Association between postoperative nadir platelet count and postoperative cardiovascular complications following septal myectomy in patients with hypertrophic cardiomyopathy: a retrospective cohort study.

BACKGROUND: Platelet count is associated with cardiovascular risk and mortality in several cardiovascular diseases, but the association of the nadir platelet counts post-septal myectomy with the cardiovascular complication risk in hypertrophic obstructive cardiomyopathy patients remains unclear. METHODS: This retrospective cohort study reviewed all adult patients who underwent septal myectomy at a single tertiary referral center over a 5-year period. Postoperative nadir platelet count was defined as the lowest platelet count in the first 4 postoperative days or until hospital discharge. The composite outcome included cardiovascular death, myocardial infarction, heart failure, malignant arrhythmia, cardiac tamponade, and major bleeding events within 30 days postoperatively. Univariable and multivariable logistic regression and restricted cubic spline models were used to assess the association between postoperative nadir platelet count and the 30-day postoperative cardiovascular complication risk. RESULTS: Among the 113 enrolled patients, 23 (20.4%) developed cardiovascular events within 30 days postoperatively. The incidence of postoperative cardiovascular complications was significantly higher in patients with a nadir platelet count ≤ 99 × 109/L than in those with a nadir platelet count > 99 × 109/L (33.3% vs. 7.1%, crude risk ratio: 4.67, 95% confidence interval: 1.69-12.85, P < 0.001). Multivariable logistic regression revealed that postoperative nadir platelet count was negatively associated with 30-day postoperative cardiovascular complications (adjusted odds ratio: 0.97; 95% confidence interval: 0.95-0.99; P = 0.005) and the association was linear (Pnonlinearity = 0.058) after full adjustment. The association between nadir platelet count and cardiovascular complications within 30 days post-surgery was consistent in all predefined subgroups (Pinteraction > 0.05). CONCLUSION: The postoperative nadir platelet count was significantly associated with the 30-day post-myectomy risk of cardiovascular complications in hypertrophic obstructive cardiomyopathy patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT04275544).

Rimegepant orally disintegrating tablet 75 mg for acute treatment of migraine in adults from China: a subgroup analysis of a double-blind, randomized, placebo-controlled, phase 3 clinical trial.

BACKGROUND: Rimegepant orally disintegrating tablet (ODT), an oral small-molecule calcitonin gene-related peptide receptor antagonist, is indicated for acute and preventive treatment of migraine in the United States and other countries. Previously, a large clinical trial assessed the efficacy and safety of rimegepant ODT 75 mg for the acute treatment of migraine in adults living in China or South Korea. A post hoc subgroup analysis of this trial was performed to evaluate the efficacy and safety of rimegepant for acute treatment of migraine in adults living in China. METHODS: Eligible participants were ≥ 18 years of age and had a ≥ 1-year history of migraine, with 2 to 8 attacks of moderate or severe pain intensity per month and < 15 headache days per month during the 3 months before screening. Participants self-administered rimegepant ODT 75 mg or matching placebo to treat a single migraine attack of moderate or severe pain intensity. The co-primary endpoints were pain freedom and freedom from the most bothersome symptom (MBS) at 2 h post-dose. Key secondary endpoints included pain relief at 2 h post-dose, ability to function normally at 2 h post-dose, use of rescue medication within 24 h post-dose, and sustained pain freedom from 2 to 24 h and 2 to 48 h post-dose. All p values were nominal. Safety was assessed via treatment-emergent adverse events (TEAEs), electrocardiograms, vital signs, and routine laboratory tests. RESULTS: Overall, 1075 participants (rimegepant, n = 538; placebo, n = 537) were included in the subgroup analysis. Rimegepant was more effective than placebo for the co-primary endpoints of pain freedom (18.2% vs. 10.6%, p = 0.0004) and freedom from the MBS (48.0% vs. 31.8%, p <  0.0001), as well as all key secondary endpoints. The incidence of TEAEs was comparable between the rimegepant (15.2%) and placebo (16.4%) groups. No signal of drug-induced liver injury was observed, and no study drug-related serious TEAEs were reported in the rimegepant group. CONCLUSIONS: A single dose of rimegepant 75 mg rimegepant was effective for the acute treatment of migraine in adults living in China, with safety and tolerability similar to placebo. TRIAL REGISTRATION: Clinicaltrials.gov NCT04574362 Date registered: 2020-10-05.

Growth hormone treatment in pre-pubertal short Chinese children with chronic kidney disease prior to transplantation.

BACKGROUND: The effect of recombinant human GH (rhGH) in Chinese children with chronic kidney disease (CKD) is unclear. METHODS: This was a 52-week, multicenter, randomized, open-label, negative-controlled phase 3 study. Prepubertal subjects were randomized 1:1 to either daily subcutaneous injections of rhGH 0.05 mg/kg/day or no treatment for 52 weeks. RESULTS: A total of 68 subjects with a mean age of 7.8 ± 3.27 years were enrolled. At week 52, the height standard deviation score (HT-SDS) in the treated group increased by 0.75 ± 0.58, which was significantly higher compared with 0.17 ± 0.47 in the untreated group (least squares mean 0.58, 95% confidence interval, 0.32-0.84; P < 0.001). At week 52, significant improvements were observed in other growth parameters (height velocity [P < 0.001]), insulin-like growth factor 1 (IGF-1) SDS [P < 0.001], IFG-1/insulin-like growth factor binding protein-3 molar ratio [P < 0.001], and height [P < 0.001]) compared with the untreated control. Seven patients reported treatment-related adverse events (TRAEs) and most TRAEs were mild in severity. Most subjects recovered without further intervention. CONCLUSIONS: Daily rhGH for 52 weeks in children with CKD-induced growth retardation significantly improved HT-SDS and other growth parameters without compromising safety. IMPACT: The efficacy and safety of growth hormone (GH) therapy in Chinese children with chronic kidney disease (CKD) are unclear. This study found that giving short stature Chinese children with CKD daily recombinant human growth hormone (rhGH) for 52 weeks improved growth parameters without compromising safety. This study's information can give physicians the confidence to treat these patients in their clinical practice.

A severe complication of J-tip guide wire during catheterization: A case report and discussion.

J-tip guide wire entrapment within the heart is a serious and dangerous complication that is rarely mentioned. We present a case in which the J-tip guide wire was entrapped in the right atrium during tunneled cuffed venous catheterization. We were unable to remove the guide wire using previously reported methods and concluded with surgery. Owing to the special structure of the guide wire itself, a safe removal process needs to be discussed. Patient consent for publication was obtained prior to the submission of the manuscript.

The high magnetoresistance performance of epitaxial half-metallic CrO2-based magnetic junctions.

Half-metallic chromium dioxide (CrO2) is an ideal spintronic material due to its near-full spin polarization and ultralow Gilbert damping at room temperature. Based on theoretical calculations, we found that the tunneling magnetoresistance (TMR) ratios of the CrO2/XO2/CrO2 (X= Ti and Sn) magnetic tunnel junctions (MTJs) can reach up to the order of magnitude of 105%, and the magnetoresistance (MR) ratio of CrO2/RuO2/CrO2 magnetic junctions (MJs) can reach the order of magnitude of 104%. In addition, we succeeded in fabricating epitaxial CrO2-based MTJs (CrO2/TiO2/CrO2 and CrO2/TiO2/Co2FeAl) with TiO2 tunnel barriers of varying thickness. Evident TMR effects were observed for all CrO2-based MTJs with the highest MR ratio of 8.55% for the CrO2/TiO2/Co2FeAl MTJ at 10 K. The MR ratios of CrO2-based MTJs in our studies were lower than theoretical expectations, which could be due to the possible mixture of interface atoms and Cr magnetization reversal. Moreover, the existence of oxygen vacancies in the TiO2 tunnel barrier also weakened the TMR effect significantly due to increased spin scattering, and the annealing treatment in an oxygen atmosphere led to an increase in the MR ratio of the CrO2/TiO2/Co2FeAl MTJ by about 33% in comparison with the unannealed MTJ, which is consistent with theoretical calculations.

The effect of four-phonon interaction on phonon thermal conductivity of hexagonal VTe2 and puckered pentagonal VTe2.

The traditional view is that complex structures have lower lattice thermal conductivity. However, it is observed that complex structures have higher lattice thermal conductivity than simple atomic structures in VTe2 systems after considering the four-phonon scattering effect. In this work, we calculate the lattice thermal conductivity of an H-VTe2 monolayer with a simple atomic structure and that of a PP-VTe2 monolayer with a complex atomic arrangement using first-principles calculations combined with the Boltzmann transport theory under the conditions of with and without the four-phonon scattering process. Our findings reveal that the lattice thermal conductivity of the PP-VTe2 monolayer along the x or y direction is 3-4 times lower than that of the H-VTe2 monolayer when only considering the three-phonon scattering process. After taking into account the four-phonon scattering process, the lattice thermal conductivity of both monolayers decreases. For the H-VTe2 monolayer, the lattice thermal conductivity decreases by 88.7% (from 1.33 to 0.15 W m-1 K-1) compared to only considering the three-phonon scattering process, mainly due to strong four-phonon scattering. In addition, the PP-VTe2 monolayer experiences a lower decrease in lattice thermal conductivity, with reductions of 12.5% (from 0.4 to 0.35 W m-1 K-1) and 11.7% (from 0.34 to 0.3 W m-1 K-1) in the x and y directions, respectively, because of the weak four-phonon scattering. Notably, the lattice thermal conductivity with the four-phonon scattering process of the H-VTe2 monolayer is twice as low as that of the PP-VTe2 monolayer. Hence, our findings suggest that even simple atomic structures can exhibit lower lattice thermal conductivity than complex structures when considering four-phonon interaction.

Accessing the thermal conductivities of Sb2Te3 and Bi2Te3/Sb2Te3 superlattices by molecular dynamics simulations with a deep neural network potential.

Phonon thermal transport is a key feature for the operation of thermoelectric materials, but it is challenging to accurately calculate the thermal conductivity of materials with strong anharmonicity or large cells. In this work, a deep neural network potential (NNP) is developed using a dataset based on density functional theory (DFT) and applied to describe the lattice dynamics of Sb2Te3 and Bi2Te3/Sb2Te3 superlattices. The lattice thermal conductivities of Sb2Te3 are first predicted using equilibrium molecular dynamics (EMD) simulations combined with an NNP and the results match well with experimental values. Then, through further exploration of weighted phase spaces and the Grüneisen parameter, we find that there is a stronger anharmonicity in the out-of-plane direction in Sb2Te3, which is the reason why the thermal conductivities are overestimated more in the out-of-plane direction than in the in-plane direction by solving the phonon Boltzmann transport equation (BTE) with only three-phonon scattering processes being considered. More importantly, the lattice thermal conductivities of Bi2Te3/Sb2Te3 superlattices with different periods are accurately predicted using non-equilibrium molecular dynamics (NEMD) simulations together with an NNP, which serves as a good example to explore the thermal transport physics of superlattices using a deep neural network potential.

Tuning the lattice thermal conductivity of Sb2Te3 by Cr doping: a deep potential molecular dynamics study.

Element doping is a prominent method for reducing the lattice thermal conductivity and optimizing the thermoelectric performance of materials in the thermoelectric field. However, determination of the thermal conductivity of element-doped systems is a challenging task, especially when the elements are randomly doped. In this work, a first-principles based deep neural network potential (NNP) is developed to investigate the lattice thermal transport properties of Cr-doped Sb2Te3 using molecular dynamics simulations. Compared with pure Sb2Te3, the thermal conductivity of orderly Cr-doped Sb2Te3 with Cr atoms locating at specific atomic layer positions decreases slightly in the in-plane direction, but sharply in the out-of-plane direction. The decrease of the low frequency phonon density of states and the enhancement of phonon scattering near 2.5 THz are the primary reasons for the decrease in the thermal conductivity of Cr-doped Sb2Te3, while the decrease of phonon velocity due to band flattening is the reason for the sharp decrease of thermal conductivity in the out-of-plane direction. Moreover, the thermal conductivities of randomly Cr-doped Sb2Te3 with different Cr concentrations are also investigated using the NNP. It is found that the thermal conductivities in both the in-plane and out-of-plane directions are reduced by 76% and 80%, respectively, for Sb36Cr36Te108. Furthermore, the influence of different Cr dopant arrays on the thermal conductivity of Sb2Te3 is also predicted using the NNP. Our work provides a good example for predicting the thermal conductivity of element-doped systems using the NNP combined with molecular dynamics simulations.

Association of intraoperative cerebral and somatic tissue oxygen saturation with postoperative acute kidney injury in adult patients undergoing multiple valve surgery.

BACKGROUND: The association between tissue oxygenation with postoperative acute kidney injury (AKI) in adult patients undergoing multiple valve surgery has not been specifically studied. METHODS: In this prospective exploratory cohort study, 99 patients were enrolled. The left forehead, the left forearm, the left upper thigh, and the left renal region tissue oxygen saturation using near-infrared spectroscopy were monitored. The association between each threshold and AKI was assessed. The relative and absolute thresholds were < 70%, < 75%, < 80%, < 85%, < 90%, < 95%, and < 100% baseline, and baseline-standard deviation (SD), -1.5 SD, -2 SD, -2.5 SD, and -3 SD. Multivariate logistic regression analysis was adopted to explore the association. RESULTS: AKI occurred in 53 (54%) patients. The absolute value-based SrrO2 thresholds associated with AKI were baseline-3 SD (odds ratio [OR], 4.629; 95% confidence interval [CI], 1.238-17.314; P = 0.023) and baseline-2.5 SD (OR, 2.842; 95% CI, 1.025-7.881; P = 0.045) after adjusting for the potential confounders, those are renal region tissue oxygen saturation of 55% and 60%, but not statistically significant after correcting for multiple testing (corrected P = 0.114 and 0.179, respectively). CONCLUSION: The SrrO2 desaturation, defined as < baseline - 2.5 SD or < baseline - 3 SD, may be associated with AKI. The thresholds need to be verified in future large-scale studies. TRIAL REGISTRATIONS: The study was registered at ClinicalTrials.gov, first trial registration: 26/10/2017, identifier: NCT03323203.

Genotype-Phenotype Correlation Reanalysis in 83 Chinese Cases with OCRL Mutations.

Background: Both Lowe syndrome and Dent-2 disease are caused by variants in the OCRL gene. However, the reason why patients with similar OCRL gene mutations presented with different phenotypes remains uncertain. Methods: Children with hemizygous pathogenic or likely pathogenic variants in OCRL were compiled from published and unpublished consecutive cases from China. Furthermore, a Chi-square test was employed to analyze the correlation of the location and types of mutations on the phenotype of children with Lowe syndrome or Dent-2 disease. Results: Among the total 83 patients, 70.8% (34/48) cases of Lowe syndrome presented with truncating mutations, while only 31.4% (11/35) cases of Dent-2 disease presented with truncating mutation (Χ2 = 12.662; P < 0.001). Meanwhile, the majority of mutations in Dent-2 disease are located in Exon 2-12 (21/35, 60.0%), while the majority of mutations in Lowe syndrome are located in Exon 13-23 (39/48, 81.3%; Χ2 = 14.922; P < 0.001). Conclusions: Truncating mutations of the OCRL gene were more common in patients with Lowe syndrome than in Dent-2 disease, while mutation is more likely located at exon 2-12 in Dent-2 disease than that in Lowe syndrome. The type and location of mutation are important indicators for the phenotypes in patients with OCRL mutation. This is a large cohort study analyzing the genotype-phenotype correlation in patients with Lowe syndrome and Dent-2 disease in China. Our data may improve the interpretation of new OCRL variants and genetic counseling. Furthermore, a large international study would be necessary to illustrate the genotype-phenotype correlation in patients with OCRL mutations.

Edaravone Dexborneol Versus Edaravone Alone for the Treatment of Acute Ischemic Stroke: A Phase III, Randomized, Double-Blind, Comparative Trial.

BACKGROUND AND PURPOSE: Edaravone dexborneol, comprised of 2 active ingredients, edaravone and (+)-borneol, has been developed as a novel neuroprotective agent with synergistic effects of antioxidant and anti-inflammatory in animal models. The present clinical trial aimed at testing the effects of edaravone dexborneol versus edaravone on 90-day functional outcome in patients with acute ischemic stroke (AIS). METHODS: A multicenter, randomized, double-blind, comparative, phase III clinical trial was conducted at 48 hospitals in China between May 2015 and December 2016. Inclusion criteria included patients diagnosed as AIS, 35 to 80 years of age, National Institutes of Health Stroke Scale Score between 4 and 24, and within 48 hours of AIS onset. AIS patients were randomized in 1:1 ratio into 2 treatment arms: 14-day infusion of edaravone dexborneol or edaravone injection. The primary end point was the proportion of patients with modified Rankin Scale score ≤1 on day 90 after randomization. RESULTS: One thousand one hundred sixty-five AIS patients were randomly allocated to the edaravone dexborneol group (n=585) or the edaravone group (n=580). The edaravone dexborneol group showed significantly higher proportion of patients experiencing good functional outcomes on day 90 after randomization, compared with the edaravone group (modified Rankin Scale score ≤1, 67.18% versus 58.97%; odds ratio, 1.42 [95% CI, 1.12-1.81]; P=0.004). The prespecified subgroup analyses indicated that a greater benefit was observed in female patients than their male counterparts (2.26, 1.49-3.43 versus 1.14, 0.85-1.52). CONCLUSIONS: When edaravone dexborneol versus edaravone was administered within 48 hours after AIS, 90-day good functional outcomes favored the edaravone dexborneol group, especially in female patients. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02430350.

Antiangiogenic antibody BD0801 combined with immune checkpoint inhibitors achieves synergistic antitumor activity and affects the tumor microenvironment.

BACKGROUND: Signaling through VEGF/VEGFR induces cancer angiogenesis and affects immune cells. An increasing number of studies have recently focused on combining anti-VEGF/VEGFR agents and immune checkpoint inhibitors (ICIs) to treat cancer in preclinical and clinical settings. BD0801 is a humanized rabbit anti-VEGF monoclonal antibody in the clinical development stage. METHODS: In this study, the anti-cancer activities of BD0801 and its potential synergistic anti-tumor effects when combined with different immunotherapies were assessed by using in vitro assays and in vivo tumor models. Ex vivo studies were conducted to reveal the possible mechanisms of actions (MOA) underlying the tumor microenvironment modification. RESULTS: BD0801 showed more potent antitumor activity than bevacizumab, reflected by stronger blockade of VEGF/VEGFR binding and enhanced inhibitory effects on human umbilical vein endothelial cells (HUVECs). BD0801 exhibited dose-dependent tumor growth inhibitory activities in xenograft and murine syngeneic tumor models. Notably, combining BD0801 with either anti-PD-1 or anti-PD-L1 antibodies showed synergistic antitumor efficacy in both lung and colorectal cancer mouse models. Furthermore, the mechanistic studies suggested that the MOA of the antitumor synergy involves improved tumor vasculature normalization and enhanced T-cell mediated immunity, including increased tumor infiltration of CD8+ and CD4+ T cells and reduced double-positive CD8+PD-1+ T cells. CONCLUSIONS: These data provide a solid rationale for combining antiangiogenic agents with immunotherapy for cancer treatment and support further clinical development of BD0801 in combination with ICIs.

Repeated Preoperative Intranasal Administration of Insulin Decreases the Incidence of Postoperative Delirium in Elderly Patients Undergoing Laparoscopic Radical Gastrointestinal Surgery: A Randomized, Placebo-Controlled, Double-Blinded Clinical Study.

STUDY OBJECTIVES: This study aimed to investigate the effects of repeated preoperative intranasal administration of insulin on the incidence of postoperative delirium (POD) and the levels of serum pro-inflammatory markers in elderly patients undergoing laparoscopic radical gastrointestinal surgery. DESIGN: Prospective, randomized, double-blinded, placebo-controlled clinical study. SETTING: General Hospital of Western Theater Command from August 2019 to December 2019. PATIENTS: Ninety elderly patients underwent laparoscopic radical gastrointestinal tumor resections under general anesthesia. INTERVENTIONS: Patients were randomly divided into a control group (0.5 mL saline administered intranasally) or an insulin group (20 U/0.5 mL insulin administered intranasally) for 2 days prior to surgery, with 45 patients in each group. MEASUREMENTS: The incidence of delirium was measured at postoperative day 1 (T2), day 3 (T3), and day 5 (T4) using the Confusion Assessment Method for the intensive care unit (CAM-ICU). Plasma levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α were measured at T0 (before insulin or saline administration), T1 (at the end of surgery), T2, T3, and T4 by enzyme-linked immunosorbent assay. MAIN RESULTS: Compared with the control group, the insulin group demonstrated a decreased POD incidence (12.5% vs. 47.5%, p = 0.001) within 5 days after surgery. The incidence of POD was significantly lower in the Ins group than in the Con group at T2 (12.5% vs. 32.5%, p = 0.032) and at T3 (2.5% vs. 20%, p = 0.034). The incidence of POD decreased in both groups over time and was similar at T4 (0% vs 10%, p = 0.116). Compared with the baseline value at T0, serum TNF-α, IL-6 and IL-1ß concentrations increased significantly at T1-4 (p <0.05). Compared with the control group at the same time point, the expression levels of TNF-α, IL-6 and IL-1ß in group I at T2 and T3 were significantly reduced (p <0.05). The incidence rates of adverse events were similar in the two groups. CONCLUSIONS: Repeated preoperative intranasal administration of insulin prevented the occurrence of delirium after laparoscopic radical gastrointestinal surgery in elderly patients and reduced TNF-α, IL-1ß, and IL-6 levels.

Manipulation of precession modes in all-permalloy nanostripe-nanopillar structured spin torque nano-oscillator driven by direct current.

We investigated the dynamical behaviors of an all-permalloy structured spin-torque nano-oscillator (STNO) composed of a nanostripe with in-plane magneto-anisotropy and a free magnetized nanopillar in the absence of a non-magnetic spacer via a micro-magnetic simulation. It is found the newly-devised STNO exhibits two stable precession modes of magnetization in the nanopillar: out-of-plane precession mode and in-plane precession mode under varying applied DC current densities. The switching between the two modes is generated in a certain current density, depending on geometries of the nanopillar as well as the nanostripe. Given a special nanopillar geometry, both modes demonstrate stable oscillation properties in a certain range of current densities. Pulsed magnetic field can effectively realize transformation of the two modes under application of a proper current density. The realization of synchronous oscillations to significantly enhance the output power is verified in this new type of STNO by etching plenty of nanopillars on the nanostripe to build STNOs array.

The large perpendicular magnetic anisotropy induced at the Co2FeAl/MgAl2O4interface and tuned with the strain, voltage and charge doping by first principles study.

The heterostructures with high perpendicular magnetic anisotropy (PMA) have advantages for the application of the nonvolatile memories with long data retention time and small size. The interface structure and magnetic anisotropy energy (MAE) of Co2FeAl/MgAl2O4heterostructures were studied by first principles calculations. The stable interface atomic arrangement is the Co or FeAl layer located above the equatorial oxygen coordinate in the distorted oxygen octahedrons. The Co-O interface can induce large effective PMA up to 4.54 mJ m-2, but this structure is a metastable structure. Meanwhile, the effective MAE decreases linearly as the thickness of the ferromagnetic layer increase. The effective MAE for the FeAl-O interface is only 1.3 mJ m-2, while the maximum thickness of Co2FeAl layer that maintains the PMA effect is about 1.717 nm. These values are very close to the experimental results. Throughd-orbital-resolved MAE, we confirm that the interface PMA is mainly originated from the hybridization betweendxy,dyzanddz2orbitals of interface 3datoms. In addition, the compressive strain, negative electric field and hole doping can significantly enhance the effective PMA of FeAl-O interface. At the same time, Co-O interface will become the most stable structure by tuning the Mg/Al ratio in the spinel layers. The large effective PMA makes the Co2FeAl/MgAl2O4junction a perfect candidate for the next-generation of non-volatile spintronic devices.

A method for magnetocardiography functional localization based on boundary element method and Nelder-Mead simplex algorithm.

BACKGROUND: The magnetocardiography (MCG) functional localization can transfer the biomagnetic signal to the electrical activity information inside the heart. The electrical activity is directly related to the physiological function of the heart. METHODS: This study proposes a practical method for MCG functional localization based on the boundary element method (BEM) and the Nelder-Mead (NM) simplex algorithm. Single equivalent moving current dipole (SEMCD) is served as the equivalent cardiac source. The parameters of SEMCD are adapted using the NM simplex algorithm by fitting the measured MCG with the calculated MCG obtained based on BEM. The SEMCD parameters are solved in the sense that the difference between measured and calculated MCG is minimized. RESULTS: The factors affecting the localization accuracy of this BEM-NM method were first explored with synthetic signals. Then, the results with real MCG signals show a good agreement between the SEMCD location and the region where ventricle depolarization starts, demonstrating the feasibility of this idea. CONCLUSIONS: This is the first three-dimensional localization of the onset of ventricular depolarization with the BEM-NM method. The method is promising in the noninvasive localization of lesions for heart diseases.

Degradation of MCL-1 by bufalin reverses acquired resistance to osimertinib in EGFR-mutant lung cancer.

Although osimertinib, an EGFR tyrosine kinase inhibitor, has become the standard therapy for treating non-small cell lung cancer (NSCLC) patients with EGFR-activating mutation, upregulation of MCL-1 induces acquired resistance to osimertinib. Bufalin, a natural digoxin-like ingredient isolated from a traditional Chinese medicine Chan Su, has been shown to downregulate MCL-1 in NSCLC cells. However, whether bufalin reverses this acquired resistance to osimertinib in NSCLC cells remains unclear. In this study, bufalin reduced cell viability and promoted apoptosis in osimertinib-resistant cells. Moreover, co-treatment with bufalin and osimertinib restored the sensitivity of osimertinib-resistant cells to osimertinib-induced growth regression and apoptosis in vitro and in vivo. Mechanistically, MEK/ERK-dependent MCL-1 phosphorylation and Ku70-mediated MCL-1 overexpression confer osimertinib resistance in EGFR-mutant NSCLC cells. In osimertinib-resistant cells, bufalin modulates Ku70-mediated MCL-1 degradation, but not MEK/ERK/MCL-1 signaling. In conclusion, our study suggests that bufalin eliminates resistance to osimertinib by inhibiting Ku70-mediated MCL-1 overexpression, indicating that a combination of osimertinib and bufalin could be an effective additional treatment to overcome acquired resistance to osimertinib in NSCLC cells.

Domain-wall motion at an ultrahigh speed driven by spin-orbit torque in synthetic antiferromagnets.

In this article, we present our numerical investigation about the spin-orbit-torque induced domain-wall (DW) motion in a synthetic antiferromagnetic multilayer nanotrack. This nanotrack was composed by two ferromagnetic (FM) layers with a RKKY inter-layer antiferromagnetic (AFM) exchange coupling. The velocity of DW was well manipulated by varying parameters including inter-layer exchange constant, the Dzyaloshinskii-Moriya interaction (DMI) strength, the current density and the magnetic anisotropy. The DW velocity was found to be strictly related to the orientation of the moments in the two FM layers. When the interlayer exchange constant or the DMI constant were larger than a critical value, there was a large angle between the moments in one FM layer and that in the other one under the current, and the DW was driven to move at an ultrahigh speed (around 10 000 m s-1). However, when the DMI or the AFM exchange coupling was weaker than the critical value, the moments in one FM layer were parallel to that in the other one under the current, and the velocity was significantly reduced.

Magnetoresistance and Hall resistivity of semimetal WTe2 ultrathin flakes.

This article reports the characterization of WTe2 thin flake magnetoresistance and Hall resistivity. We found it does not exhibit magnetoresistance saturation when subject to high fields, in a manner similar to their bulk characteristics. The linearity of Hall resistivity in our devices confirms the compensation of electrons and holes. By relating experimental results to a classic two-band model, the lower magnetoresistance values in our samples is demonstrated to be caused by decreased carrier mobility. The dependence of mobility on temperature indicates the main role of optical phonon scattering at high temperatures. Our results provide more detailed information on carrier behavior and scattering mechanisms in WTe2 thin films.

Evaluation of Mycophenolate Mofetil and Low-Dose Steroid Combined Therapy in Moderately Severe Henoch-Schönlein Purpura Nephritis.

BACKGROUND The most appropriate management of Henoch-Schönlein Purpura (HSP) nephritis with nephrotic-range proteinuria remains uncertain. The aim of this study was to evaluate the clinical therapeutic effects of mycophenolate mofetil and low-dose steroid in Henoch-Schönlein purpura nephritis (HSPN) with nephrotic-range proteinuria and pathological classification less than IV in children. MATERIAL AND METHODS The clinical effects of MMF and low-dose steroid therapy were studied in children with Henoch-Schönlein purpura nephritis manifested with nephrotic-range proteinuria, normal kidney function, and <50% crescents or sclerosing lesions on renal biopsy. We enrolled 32 boys and 29 girls with nephrotic-range proteinuria, normal kidney function, and pathological classification less than IV on renal biopsy. We treated 41 cases (67.2%) with mycophenolate mofetil and low-dose prednisone combined therapy and 20 cases (32.8%) were treated with full-dose prednisone alone. RESULTS Short-term response was significantly different between 2 groups (χ²=4.371, P=0.037), while no significant difference was found in long-term prognosis (χ²=0.419, P=0.522) after follow-up. The ROC curve showed that the most appropriate cutoff value was 30.67 µg·h/ml for MPA-AUC and the area under the ROC curve was 0.731, with 85.2% sensitivity and 64.3% specificity. CONCLUSIONS Mycophenolate mofetil and low-dose prednisone combined therapy is a reasonable treatment choice which can promote the remission of proteinuria without increasing obvious adverse reactions in pediatric HSPN with nephrotic state and pathological classification less than grade IV. MPA-AUC more than 30 µg·h/ml was an appropriate value for MMF in the combined therapy with MMF and steroid for treating children with HSPN.