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Stromal cell-derived factor-1 (SDF-1) is a chemokine that exerts multifaceted roles in atherosclerosis. However, its association with hyperlipidemia is contradictory. To date, serum SDF-1 and its correlations with lipid fractions and subfractions in heterozygous familial hypercholesterolemia (HeFH) have not been investigated. Eighty-one untreated patients with HeFH and 32 healthy control subjects were enrolled in the study. Serum SDF-1, oxidized LDL (oxLDL) and myeloperoxidase (MPO) were determined by ELISA. Lipoprotein subfractions were detected by Lipoprint. We diagnosed FH using the Dutch Lipid Clinic Network criteria. Significantly lower serum SDF-1 was found in HeFH patients compared to healthy controls. Significant negative correlations were detected between serum total cholesterol, triglycerides, LDL-cholesterol (LDL-C), apolipoprotein B100 (ApoB100) and SDF-1. Furthermore, serum SDF-1 negatively correlated with VLDL and IDL, as well as large LDL and large and intermediate HDL subfractions, while there was a positive correlation between mean LDL-size, small HDL and SDF-1. SDF-1 negatively correlated with oxLDL and MPO. A backward stepwise multiple regression analysis showed that the best predictors of serum SDF-1 were VLDL and oxLDL. The strong correlation of SDF-1 with lipid fractions and subfractions highlights the potential common pathways of SDF-1 and lipoprotein metabolism, which supports the role of SDF-1 in atherogenesis. [ABSTRACT FROM AUTHOR]

An accurate forecast of flare and coronal mass ejection (CME) initiation requires precise measurements of the magnetic energy buildup and release in the active regions of the solar atmosphere. We designed a new space weather mission that performs such measurements using new optical instruments based on the Hanle and Zeeman effects. The mission consists of two satellites, one orbiting the L1 Lagrangian point (Spacecraft Earth, SCE) and the second in heliocentric orbit at 1AU trailing the Earth by 80° (Spacecraft 80, SC80). Optical instruments measure the vector magnetic field in multiple layers of the solar atmosphere. The orbits of the spacecraft allow for a continuous imaging of nearly 73% of the total solar surface. In-situ plasma instruments detect solar wind conditions at 1AU and ahead of our planet. Earth-directed CMEs can be tracked using the stereoscopic view of the spacecraft and the strategic placement of the SC80 satellite. Forecasting of geoeffective space weather events is possible thanks to an accurate surveillance of the magnetic energy buildup in the Sun, an optical tracking through the interplanetary space, and in-situ measurements of the near-Earth environment.

High-density lipoprotein (HDL)-bound apolipoprotein M/sphingosine 1-phosphate (ApoM/S1P) complex in cardiovascular diseases serves as a bridge between HDL and endothelial cells, maintaining a healthy endothelial barrier. To date, S1P and ApoM in patients with untreated heterozygous familial hypercholesterolemia (HeFH) have not been extensively studied. Eighty-one untreated patients with HeFH and 32 healthy control subjects were included in this study. Serum S1P, ApoM, sCD40L, sICAM-1, sVCAM-1, oxLDL, and TNFα concentrations were determined by ELISA. PON1 activities were measured spectrophotometrically. Lipoprotein subfractions were detected by Lipoprint. We diagnosed FH using the Dutch Lipid Clinic Network criteria. Significantly higher serum S1P and ApoM levels were found in HeFH patients compared to controls. S1P negatively correlated with large HDL and positively with small HDL subfractions in HeFH patients and the whole study population. S1P showed significant positive correlations with sCD40L and MMP-9 levels and PON1 arylesterase activity, while we found significant negative correlation between sVCAM-1 and S1P in HeFH patients. A backward stepwise multiple regression analysis showed that the best predictors of serum S1P were large HDL subfraction and arylesterase activity. Higher S1P and ApoM levels and their correlations with HDL subfractions and inflammatory markers in HeFH patients implied their possible role in endothelial protection. [ABSTRACT FROM AUTHOR]

Background: There are no exact data about the prevalence of familial chylomicronemia syndrome (FCS) in Central Europe. We aimed to identify FCS patients using either the FCS score proposed by Moulin et al. or with data mining, and assessed the diagnostic applicability of the FCS score. Methods: Analyzing medical records of 1,342,124 patients, the FCS score of each patient was calculated. Based on the data of previously diagnosed FCS patients, we trained machine learning models to identify other features that may improve FCS score calculation. Results: We identified 26 patients with an FCS score of ≥10. From the trained models, boosting tree models and support vector machines performed the best for patient recognition with overall AUC above 0.95, while artificial neural networks accomplished above 0.8, indicating less efficacy. We identified laboratory features that can be considered as additions to the FCS score calculation. Conclusions: The estimated prevalence of FCS was 19.4 per million in our region, which exceeds the prevalence data of other European countries. Analysis of larger regional and country-wide data might increase the number of FCS cases. Although FCS score is an excellent tool in identifying potential FCS patients, consideration of some other features may improve its accuracy. [ABSTRACT FROM AUTHOR]

Background: Familial hypercholesterolemia (FH) is an autosomal dominant trait characterized by elevated LDL-C concentrations and is associated with an increased risk of premature atherosclerosis. Progranulin (PGRN) is a multifunctional protein that is known to have various anti-atherogenic effects. To date, the use of serum PGRN in patients with FH has not been studied. Methods: In total, 81 untreated patients with heterozygous FH (HeFH) and 32 healthy control subjects were included in this study. Serum PGRN, sICAM-1, sVCAM-1, oxLDL and TNFα concentrations were determined by ELISA. Lipoprotein subfractions were detected by Lipoprint. We diagnosed FH using the Dutch Lipid Clinic Network criteria. Results: We could not find a significant difference between the PGRN concentrations of the HeFH patients and controls (37.66 ± 9.75 vs. 38.43 ± 7.74 ng/mL, ns.). We found significant positive correlations between triglyceride, TNFα, sVCAM-1, the ratio of small HDL subfraction and PGRN, while significant negative correlations were found between the ratio of large HDL subfraction and PGRN both in the whole study population and in FH patients. PGRN was predicted by sVCAM-1, logTNFα and the ratio of small HDL subfraction. Conclusions: The strong correlations between HDL subfractions, inflammatory markers and PGRN suggest that PGRN may exert its anti-atherogenic effect in HeFH through the alteration of HDL composition and the amelioration of inflammation rather than through decreasing oxidative stress. [ABSTRACT FROM AUTHOR]

Background and aims: Premature mortality due to atherosclerotic vascular disease is very high in Hungary in comparison with international prevalence rates, though the estimated prevalence of familial hypercholesterolemia (FH) is in line with the data of other European countries. Previous studies have shown that high lipoprotein(a)- Lp(a) levels are associated with an increased risk of atherosclerotic vascular diseases in patients with FH. We aimed to assess the associations of serum Lp(a) levels and such vascular diseases in FH using data mining methods and machine learning techniques in the Northern Great Plain region of Hungary. Methods: Medical records of 590,500 patients were included in our study. Based on the data from previously diagnosed FH patients using the Dutch Lipid Clinic Network scores (≥7 was evaluated as probable or definite FH), we trained machine learning models to identify FH patients. Results: We identified 459 patients with FH and 221 of them had data available on Lp(a). Patients with FH had significantly higher Lp(a) levels compared to non-FH subjects [236 (92.5; 698.5) vs. 167 (80.2; 431.5) mg/L, p <.01]. Also 35.3% of FH patients had Lp(a) levels >500 mg/L. Atherosclerotic complications were significantly more frequent in FH patients compared to patients without FH (46.6 vs. 13.9%). However, contrary to several other previous studies, we could not find significant associations between serum Lp(a) levels and atherosclerotic vascular diseases in the studied Hungarian FH patient group. Conclusion: The extremely high burden of vascular disease is mainly explained by the unhealthy lifestyle of our patients (i.e., high prevalence of smoking, unhealthy diet and physical inactivity resulting in obesity and hypertension). The lack of associations between serum Lp(a) levels and atherosclerotic vascular diseases in Hungarian FH patients may be due to the high prevalence of these risk factors, that mask the deleterious effect of Lp(a). [ABSTRACT FROM AUTHOR]

It is challenging, yet important, to measure the—ever‐changing—cold electron density in the plasmasphere. The cold electron density inside and outside of the plasmapause is a key parameter for radiation belt dynamics. One indirect measurement is through finding the velocity dispersion relation exhibited by lightning induced whistlers. The main difficulty of the method comes from low signal‐to‐noise ratios for most of the ground‐based whistler components. To provide accurate electron density and L $L$‐shell measurements, whistler components need to be detectable in the noisy background, and their characteristics need to be reliably determined. For this reason, precise segmentation is needed on a spectrogram image. Here, we present a fully automated way to perform such an image segmentation by leveraging the power of convolutional neural networks, a state‐of‐the‐art method for computer vision tasks. Testing the proposed method against a manually, and semi‐manually segmented whistler data set achieved < $< $10% relative electron density prediction error for 80% of the segmented whistler traces, while for the L $L$ shell, the relative error is < $< $5% for 90% of the cases. By segmenting more than 1 million additional real whistler traces from Rothera station Antarctica, logged over 9 years, seasonal changes in the average electron density were found. The variations match previously published findings, and confirm the capabilities of the image segmentation technique. Plain Language Summary: When lightning strikes on the Earth, electromagnetic waves are generated, that can travel along the magnetic field lines of the Earth and can be observed in the other hemisphere. As the waves are in the 1–30 kHz range, they can be measured with radio antennas and exhibit a whistling sound, thus their name, whistlers. As the electromagnetic waves travel, they are distorted due to the velocity dispersion in the ionosphere and the magnetosphere. As the rate of dispersion depends on the physical parameters of the above‐mentioned regions, the precise measurement of the whistlers can be a method to monitor the electron density on different magnetic field lines. The cold electron density inside and outside of the plasmasphere is a key parameter for radiation belt dynamics, that can affect satellites negatively, their precise measurement can be fruitful in many applications. Whistlers have been measured and collected for decades, however, due to the noisy nature of the detection data, the precise, automated estimation of the physical parameters through whistler traces has been a challenging task. We trained a convolutional neural network based model to accurately mark the whistlers on a frequency‐time spectrogram. The trained model can find and segment the whistlers, which allows accurate physical parameter estimation, within 10% error in electron density for 80% of the time. Key Points: Monitoring the electron density along different L‐shells by measuring the dispersion relation via whistlersConvolutional neural network based method to accurately segment the whistler traces from spectrogram imagesSeasonal variation of plasmaspheric equatorial electron density based on more than 1 million analyzed whistler traces over 9 years [ABSTRACT FROM AUTHOR]

In this study we present an inversion method which provides thermal plasma population parameters from characteristics of chorus emissions only. Our ultimate goal is to apply this method to ground‐based data in order to derive the lower‐energy boundary condition for many radiation belt models. The first step is to test the chorus inversion method on in situ data of the Van Allen Probes in the generation region. The density and thermal velocity of energetic electrons (few kiloelectron volts to 100 keV) are derived from frequency sweep rate and starting frequencies of chorus emissions through analysis of wave data from the Electric and Magnetic Field Instrument Suite and Integrated Science on board the Van Allen Probes. The nonlinear wave growth theory of Omura and Nunn (2011, https://doi.org/10.1029/2010JA016280) serves as the basis for our inversion method, assuming that the triggering wave is originated by the linear cyclotron instability. We present 16 consecutive rising‐tone emissions recorded in the generation region between 11 and 12 UT on 14 November 2012. The results of the inversion are compared with density and thermal velocities (parallel and perpendicular) of energetic electrons derived from the unidirectional flux data of the Helium, Oxygen, Proton, and Electron instrument, showing a good agreement: The normalized root‐mean‐square deviation between the measured and predicted values are less than ∼15%. We found that the theoretical amplitudes are consistent with the measured ones. The relation between linear and nonlinear wave growth agrees with our basic assumption; namely, linear growth is a preceding process of nonlinear wave growth. We analyze electron distributions at the relativistic resonant energy ranges. Key Points: Linear growth of whistler mode waves forms triggering waves for nonlinear chorus emissionsWe have developed an inversion method to derive energetic electron properties from observation of chorus emissionsThe particle properties derived from chorus inversion agree with energetic particle measurements [ABSTRACT FROM AUTHOR]

Continuous burst mode very low frequency (VLF) measurements were recorded on the Van Allen Probes satellites and are analyzed to detect pulses from the Russian Alpha (RSDN‐20) ground‐based navigational system between January and March 2016. Based on the wave characteristics of these pulses and on the position of the spacecraft, the signals propagated mostly in ducted mode in the plasmasphere. Knowledge of the propagation path allowed us to carry out a monochromatic wave propagation inversion to obtain plasmaspheric electron densities. We compared the obtained densities with independent in situ measurements on the spacecraft. The results show good agreement, validating our inversion process. This contributes to validating the field‐aligned density profile model routinely used in the inversion of whistlers detected on the ground. Furthermore, our method can provide electron densities at regimes where no alternative measurements are available on the spacecraft. This raises the possibility of using this method as an additional tool to measure and monitor plasmaspheric electron densities. Key Points: Satellite observation of guided VLF transmitter signals in the plasmasphere, based on wave characteristics, are presentedPropagation inversion method of guided VLF transmitter signals yield electron densities in agreement with reference measurementsThis method can be an alternative tool for measuring plasmaspheric electron densities [ABSTRACT FROM AUTHOR]

Background: Afamin is a plasma vitamin E‐binding glycoprotein partially associated with ApoA1‐containing high‐density lipoprotein (HDL) subfractions. In a previous study, the serum vitamin E decreased after low‐density lipoprotein (LDL) apheresis, while vitamin E/cholesterol ratio increased. We aimed to study the effect of LDL apheresis on serum afamin level. Methods: The serum level of afamin and oxidized LDL were measured by enzyme‐linked immunosorbent assay in six severe heterozygous FH patients before and after their first LDL apheresis treatments and in seven healthy controls. We also investigated the changes in total cholesterol, LDL‐C, HDL‐C, ApoB, ApoA1, HDL subfractions, and α‐ and γ‐tocopherol levels during the treatment. HDL subfractions were detected by an electrophoretic method on polyacrylamide gel (Lipoprint). Serum α‐ and γ‐tocopherol levels were detected by gas chromatography‐mass spectrometry. Results: The first treatment sessions decreased serum afamin levels by an average of 9.4%. Total cholesterol, LDL‐C, HDL‐C and ApoA1 levels decreased by 52.6; 61.8; 10.5; and 14.1%, respectively. We found that α‐ and γ‐tocopherol levels markedly decreased (by 34.1 and 32.9%, respectively), while α‐ tocopherol/cholesterol and γ‐tocopherol/cholesterol ratios significantly increased (by 41.4 and 40.3%, respectively). Oxidized LDL levels significantly decreased. There was a shift toward the larger HDL subfractions. Conclusion: LDL apheresis moderately decreases the circulating levels of afamin parallel to lowering HDL‐C and ApoA1 levels. Tocopherol levels decreases markedly compared to afamin levels, however, beneficial changes in vitamin E/cholesterol ratios, oxidized LDL levels and HDL subfraction distribution were detected. These additional effects of LDL apheresis may result in further cardiovascular risk reduction in FH patients. [ABSTRACT FROM AUTHOR]

Familial hypercholesterolemia (FH) is one of the most common autosomal, dominantly inherited diseases affecting cholesterol metabolism, which, in the absence of treatment, leads to the development of cardiovascular complications. The disease is still underdiagnosed, even though an early diagnosis would be of great importance for the patient to receive proper treatment and to prevent further complications. No studies are available describing the genetic background of Hungarian FH patients. In this work, we present the clinical and molecular data of 44 unrelated individuals with suspected FH. Sequencing of five FH-causing genes (LDLR, APOB, PCSK9, LDLRAP1 and STAP1) has been performed by next-generation sequencing (NGS). In cases where a copy number variation (CNV) has been detected by NGS, confirmation by multiplex ligation-dependent probe amplification (MLPA) has also been performed. We identified 47 causal or potentially causal (including variants of uncertain significance) LDLR and APOB variants in 44 index patients. The most common variant in the APOB gene was the c.10580G>A p.(Arg3527Gln) missense alteration, this being in accordance with literature data. Several missense variants in the LDLR gene were detected in more than one index patient. LDLR variants in the Hungarian population largely overlap with variants detected in neighboring countries. [ABSTRACT FROM AUTHOR]