Association between insulin resistance and cardiac remodeling in HER2-positive breast cancer patients: a real-world study.

BACKGROUND: Insulin resistance is an overlapping risk factor for both heart and breast cancer, while its interaction with cardiotoxicity in breast cancer (BC) patients is not clear. This study investigated the impact of insulin resistance on cardiac remodeling in patients with human epidermal growth factor receptor 2 (HER2)-positive BC during and after trastuzumab therapy in real-world clinical practice. METHODS: HER2-positive BC patients who received trastuzumab treatment between December 2012 and December 2017 were reviewed and 441 patients with baseline metabolic indices and serial echocardiographic measurements (baseline, 6, 12, and 18 months) after trastuzumab therapy initiation were included. Repeated measurement analysis of variance was used to evaluate temporal trends in multiparameter echocardiography. Linear mixed model was applied to further evaluate the role of insulin resistance in forementioned changes. Correlation of homeostasis model assessment-estimated insulin resistance (HOMA-IR) and triglyceride-glucose index (TyG) levels to changes in echocardiography parameters was explored. RESULTS: Of 441 patients (mean age 54 ± 10 [SD] years), 61.8% received anthracycline-based chemotherapy, 33.5% received left-sided radiotherapy, 46% received endocrine therapy. No symptomatic cardiac dysfunction was observed over the therapy course. A total of 19 (4.3%) participants experienced asymptomatic cancer therapy-related cardiac dysfunction (CTRCD), and the peak onset time was 12 months after the initiation of trastuzumab. Albeit relatively low CTRCD incidence, cardiac geometry remodeling, especially left atrial (LA) dilation over therapy was notable and was more severe in high HOMA-IR and TyG level groups (P < 0.01). Noteworthy, a partial reversibility of cardiac remodeling was observed with treatment cessation. Additionally, HOMA-IR level positively correlated to changes in LA diameter from baseline to 12 months (r = 0.178, P = 0.003). No significant association (all P > 0.10) was detected between HOMA-IR or TyG level and dynamic left ventricular parameter evaluation. Multivariate linear regression analysis demonstrated that higher HOMA-IR level was an independent determinant for LA enlargement in BC patients during anti-HER2 targeted therapy course after adjusting for confounding risk factors (P = 0.006). CONCLUSION: Insulin resistance was associated with left atrial adverse remodeling (LAAR) in HER2-positive BC patients that received standard trastuzumab therapy, indicating that insulin resistance could be a supplementation to baseline cardiovascular risk stratification proforma for HER2-targeted antitumor therapies.

Pulmonary embolism and bradycardia in a NSCLC patient treated with crizotinib for a rare mutation.

INTRODUCTION: Lung cancer is a major global health problem because of its high incidence and mortality. Targeted therapies have transformed treatment of driver-mutated metastatic non-small cell lung cancer (NSCLC). Nevertheless, recent studies demonstrated that cardiovascular disease (CVD) was the second leading cause of mortality in cancer survivors now, management of patients' cardiovascular health during the course of anticancer therapy has become a great challenge faced by the oncologists. Anticancer related cardiovascular (CV) complications are not limited to traditional chemotherapy, but are also increasingly recognized in targeted therapy. CASE REPORT: We present a case of pulmonary embolism (PE) and bradycardia in a 91-year-old NSCLC patient treated with crizotinib for a rare MET Y1003S mutation. To our knowledge, this is the second report to show antitumor response of crizotinib in lung cancer patients with such a rare mutation. However, the patient complained chest tightness and shortness of breath after a month of standard dose crizotinib therapy. Non-invasive examination revealed new onset bradycardia and PE. MANAGEMENT & OUTCOME: Such clinical manifestations were associated with targeted therapy-related CV toxicity, on which the emerging discipline cardio-oncology focused, and a multidisciplinary investigation and treatment was conducted. DISCUSSION: This case highlights the CV adverse events of novel therapies and the current challenges to be tackled in cardio-oncology.

Copper (II) Ion-Modified Gold Nanoclusters as Peroxidase Mimetics for the Colorimetric Detection of Pyrophosphate.

Copper (II) ions have been shown to greatly improve the chemical stability and peroxidase-like activity of gold nanoclusters (AuNCs). Since the affinity between Cu2+ and pyrophosphate (PPi) is higher than that between Cu2+ and AuNCs, the catalytic activity of AuNCs-Cu2+ decreases with the introduction of PPi. Based on this principle, a new colorimetric detection method of PPi with high sensitivity and selectivity was developed by using AuNCs-Cu2+ as a probe. Under optimized conditions, the detection limit of PPi was 0.49 nM with a linear range of 0.51 to 30,000 nM. The sensitivity of the method was three orders of magnitude higher than that of a fluorescence method using AuNCs-Cu2+ as the probe. Finally, the AuNCs-Cu2+ system was successfully applied to directly determine the concentration of PPi in human urine samples.

A Joint Strategy To Evaluate the Microscopic Origin of the Second-Harmonic-Generation Response in Nonpolar ABCO3F Compounds.

In this paper, a joint strategy was proposed to investigate the microscopic origin of the second-harmonic-generation (SHG) response in nonpolar ABCO3F compounds. The SHG coefficients of ABCO3F were evaluated using finite-field and sum-over-states methods. The tendency of the obtained SHG tensors is in good agreement with the powder SHG response. The atomic contribution was investigated using variation of the atomic charges and bandwidth of occupied atomic states. The results show that oxygen states play a key role in determining the SHG response, and the neighboring divalent cations exert a indirect influence via covalent interaction. The bidentate bonding pattern is beneficial to obtaining a largely enhanced SHG response.

Pb2Ba3(BO3)3Cl: A Material with Large SHG Enhancement Activated by Pb-Chelated BO3 Groups.

Pb(II) has long been associated with lone pair activity and is often substituted in alkali earth metal borates to create new nonlinear optical (NLO) materials with enhanced second harmonic generation (SHG) capabilities. However, large enhancement in isomorphic Pb-free analogues is rare. Here we report a new NLO material Pb2Ba3(BO3)3Cl with a phase-matching SHG response approximately 3.2× that of KDP and 6× higher than its isomorphic compound Ba5(BO3)3Cl. We show that the enhanced SHG response originates from a unique edge-sharing connection between lead-oxygen polyhedra and boron-oxygen groups, making the dielectric susceptibility more easily affected by the external electric field of an incident photon. This understanding provides a route to identify systems that would benefit from SHG-active cation substitution in isomorphic structures that exhibit weak or null SHG responses.

Na11B21O36X2 (X = Cl, Br): halogen sodium borates with a new graphene-like borate double layer.

Borate not graphene: The [B6O12]∞(6-) single borate layer is a graphene-like layer (see figure). The weak Na(+)-Br(Cl)(-) ionic connection between the layers leads to the layer cleavage, and difficulty of the block crystal growth.

Cellular Membrane-Engineered Nanovesicles as a Three-Stage Booster to Target the Lesion Core.

The lesion core is the area with the most serious injury and vigorous repair. Existing nanocarriers are difficult to break through the targeted delivery to the lesion core for precise treatment in the intracellular and extracellular microenvironment. Herein, a cellular membrane-engineered nanovesicle (CMEV) with a hierarchical structure is constructed using the double emulsion-extrusion method by integrating a neutrophil membrane, functional antibody, and gelled drug-loaded core as a three-stage booster to target the lesion core and deliver catestatin (CST), a small therapeutic peptide, for ischemic cardiomyopathy therapy. By coating the neutrophil membrane outside the shell, CMEV is endowed with the function of neutrophil-like migration to achieve the first stage of tissue targeting. Based on the specific anchoring to injured myocardium, a myosin light chain 3 (MLC3) antibody is embedded to fulfill the second stage of CMEV accumulation in the lesion core. The gelled core containing CST-sodium alginate (NaAlg) with a pH-responsive shell is prepared by ionic cross-linking to accomplish the third stage of precise CST administration. Triggered by the microenvironment, NaAlg electrostatically adheres to the lesion core for sustained release, enhancing the efficacy of CST in improving cardiomyocyte apoptosis, excessive fibrosis, macrophage polarization, and angiogenesis. Thus, the "three-stage booster" nanovesicle significantly ameliorates cardiac function and adverse remodeling to treat ischemic cardiomyopathy.

High Piezoelectricity in Eco-Friendly NaNbO3-Based Ferroelectric Relaxor Ceramics via Phase and Domain Engineering.

To meet the requirements of environmental friendliness, high-performance lead-free piezoelectric materials have become important materials for next-generation electronic devices. Here, lead-free and potassium-free NaNbO3 (NN)-based ceramics with high piezoelectric (d33 = 361 ± 10 pC/N) and dielectric (εr = 4500) properties were obtained by tolerant preparation techniques. The excellent piezoelectric and dielectric properties can be attributed to the relaxor morphotropic phase boundaries (R-MPB) and coexisting domain regions, which are beneficial in lowering the free energy and greatly improving the dielectric response and domain switching capability. Furthermore, the d33 of NaNbO3-10Ba(Ti0.7Sn0.3)O3-1.5NaSbO3 (NN-10BTS-1.5NS) ceramics can be maintained at 350 pC/N over the range of 25-80 °C with a change rate of less than 10%, exhibiting excellent temperature stability. Based on a series of in situ characterizations, the variations of the phase and domain structures of NN-based relaxor piezoelectric ceramics with temperature are clearly demonstrated. This work not only proposes new materials for sensors and actuators but also provides an excellent strategy for designing high-performance piezoelectric ceramics through phase and domain engineering.

Value of the HFA-PEFF diagnostic algorithms for heart failure with preserved ejection fraction to the inflammatory myopathy population.

OBJECTIVES: The HFA-PEFF score has been validated to hold great diagnostic and prognostic utility for heart failure with preserved ejection fraction (HFpEF). Idiopathic inflammatory myopathy (IIM) is recognized as one of the potential etiologies underlying HFpEF. Here, we intended to investigate the real prevalence of HFpEF in IIM via the HFA-PEFF score and explore the prognostic value of this score. METHODS: Two hundred twenty IIM patients were enrolled for assessment. The cohort was divided into low, intermediate and high tertiles of the HFA-PEFF score. Spearman's correlation analysis was used to explore the association between the score and disease activity. Chi-square test was applied to investigate the distribution discrepancy of HFA-PEFF tertiles among patients with different myositis-specific antibodies (MSAs) or myositis-associated antibodies (MAAs). Univariate and multivariate ordinal regression analyses were performed to screen risk factors for high HFA-PEFF scores. Survival curves were obtained using the Kaplan-Meier method and log-rank tests. RESULTS: In total, 79 (35.9%), 107 (48.6%) and 34 (15.5%) patients were rated low, intermediate and high probability of HFpEF, respectively. The HFA-PEFF score correlated well with disease activity. Patients with positive AMA-M2 scored higher in the HFA-PEFF score (p = 0.011). During follow-up, patients with positive AMA-M2 or anti-SRP antibody developed an inclination towards concentric hypertrophy on echocardiography. Additionally, palpitation symptom, AMA-M2 positivity and elevated serum levels of LDH, cTnI were independent risk factors for high HFA-PEFF scores. Finally, a high-tertile HFA-PEFF score was related to lower overall survival rate (p < 0.001). Patients with positive AMA-M2 had poorer outcomes (p = 0.002). CONCLUSION: HFpEF was prevailing in IIM patients according to the HFA-PEFF score. The HFA-PEFF score correlated well with disease activity and held significant prognostic value. Patients with AMA-M2 antibody were prone to have poor outcomes.

Further examples of the P-O-P connection in borophosphates: synthesis and characterization of Li2Cs2B2P4O15, LiK2BP2O8, and Li3M2BP4O14 (M = K, Rb).

A new series of anhydrous mixed alkali-metal borophosphates--Li(2)Cs(2)B(2)P(4)O(15) (1), LiK(2)BP(2)O(8) (2), Li(3)K(2)BP(4)O(14) (3), and Li(3)Rb(2)BP(4)O(14) (4)--have been successfully synthesized by using the conventional solid-state reaction method. Compound 1 contains a novel fundamental building unit (FBU), [B(4)P(8)O(30)], with B/P = 1:2. Compound 2 contains an FBU of [B(2)P(4)O(16)] with B/P = 1:2. Compounds 3 and 4 are isotypic, and they have a [B(P(2)O(7))(2)] unit as their FBU. In all four compounds, their FBUs are connected through corner sharing to generate layered anionic partial structures, and then further linked with metallic polyhedra to form three-dimensional (3D) frameworks. Most interestingly, three of the four compounds contain direct P-O-P connections in their structures, which is extremely rare among borophosphates. Thermal analyses, IR spectroscopy, and UV/Vis/near-IR diffuse reflectance spectroscopy have also been performed on the four title compounds.

Na3Cd3B(PO4)4: a new noncentrosymmetric borophosphate with zero-dimensional anion units.

A new noncentrosymmetric borophosphate, Na(3)Cd(3)B(PO(4))(4), has been successfully synthesized by conventional solid state reaction for the first time. It crystallizes in the orthorhombic space group Pmc2(1) with unit cell parameters of a = 13.6854(3) Å, b = 5.3346(11) Å, c = 18.2169(4) Å, and Z = 4. Na(3)Cd(3)B(PO(4))(4) features zero-dimensional [B(PO(4))(4)](9-) anion units with Cd(2+) and Na(+)/Cd(2+) cations located around them, in which the BO(4) tetrahedron is surrounded by four PO(4) tetrahedra by sharing the vertexes of O atoms. Second harmonic generation (SHG) measurements show that Na(3)Cd(3)B(PO(4))(4) exhibits a SHG response 1.1 times larger than that of KH(2)PO(4) (KDP) and is phase matchable.

The effect of perfectionism on test anxiety and the mediating role of sense of coherence in adolescent students.

BACKGROUND: Previous research has shown that perfectionism is closely associated with stress. However, limited research has examined the longitudinal relationship between perfectionism and test anxiety. In addition, no study has investigated the possible mediators for the effects of perfectionism on test anxiety in school contexts. OBJECTIVE: Utilizing a three-wave longitudinal design, this study employed a sample of Chinese junior high school students as participants to examine the longitudinal relationship between perfectionism, sense of coherence, and test anxiety. METHODS: 427 Chinese junior high school students (212 girls, 215 boys) participated in all three measurement times. The Frost Multidimensional Perfectionism scale, sense of coherence scale (SOC), and Test Anxiety scale were administered to the participants. The students completed questionnaires about once every two months from the beginning of a school semester to the end of the semester. RESULTS: Results from structural equation modeling indicated that negative perfectionism significantly contributed to test anxiety in the adolescent students. The lagged effect of perfectionism (T1) on SOC (T2) was significant, and the lagged effect of SOC (T2) on test anxiety (T3) was significant, indicating that SOC played a significant mediating role in the effect of perfectionism on test anxiety. CONCLUSION: The longitudinal effects of negative perfectionism on test anxiety were mediated by sense of coherence. The findings of the study have general implications for mitigating test anxiety and improving school adjustment and academic achievement.

Tunable Domain Switching Features of Incommensurate Antiferroelectric Ceramics Realizing Excellent Energy Storage Properties.

An incommensurate modulated antiferroelectric phase is a key part of ideal candidate materials for the next generation of dielectric ceramics with excellent energy storage properties. However, there is less research carried out when considering its relatively low polarization response. Here, the incommensurate phase is modulated by stabilizing the antiferroelectric phase and the energy storage performance of the incommensurate phase under ultrahigh electric field is studied. The tape-casting method is applied to construct dense and thin ceramics. La3+ doping induces a room-temperature incommensurate antiferroelectric orthorhombic matrix. With little Cd2+ , the extremely superior energy storage performances arose as follows: when 0.03, the recoverable energy storage density reaches ≈19.3 J cm-3 , accompanying an ultrahigh energy storage efficiency of ≈91% (870 kV cm-1 ); also, a giant discharge energy density of ≈15.4 J cm-3 emerges during actual operation. In situ observations demonstrate that these superior energy storage properties originate from the phase transition from the incommensurate antiferroelectric orthorhombic phase to the induced rhombohedral relaxor ferroelectric one. The adjustable incommensurate period affects the depolarization response. The revealed phase-transition mechanism enriches the existing antiferroelectric-ferroelectric transition. Attention to the incommensurate phase can provide a reference for the selection of the next generation of high-performance antiferroelectric materials.

Cu-Doped Alloy Layer Guiding Uniform Li Deposition on a Li-LLZO Interface under High Current Density.

Li7La3Zr2O12(LLZO)-based ceramics as promising solid-state electrolytes (SSEs) have received much attention for use in high-energy lithium (Li) metal batteries. However, the Li growth through the solid garnet electrolyte under a low current density hinders its practical application. In this work, the Cu doped Li3Zn was designed to guide uniform Li deposition by magnetron cosputtering and an in situ alloying reaction on Li6.5La3Zr1.5Ta0.5O12 (LLZTO) pellets. After introducing the composite layer, a small interfacial area specific resistance (∼30 Ω·cm2) can be obtained. Improved lithium plating/stripping performance, including a long-life span of 450 h (under a current density of 0.8 mA cm-2 without short circuit) and a high critical current density (CCD) of 2.8 mA cm-2 is performed by the composite interlayer with a Zn:Cu ratio of 10:1. And the Li/Cu-Li3Zn SSEs/LFP full cell exhibits good electrochemical performance. Accordingly, the Li deposited behavior in the Li plating/stripping process at the intermediate layer is discussed in detail. This work provides a new sight for the alloy interface designed on the solid-state garnet SSEs for high performance lithium metal batteries under high current density.

Potential High-Temperature Piezoelectric Ceramics with Remarkable Performances Enhanced by the Second-Order Jahn-Teller Effect.

Herein, the second-order Jahn-Teller effect was applied to the design of the bismuth ferrite-based ceramics. A large distortion of an electron structure arranged along the z axis and an asymmetric distribution of charge density were calculated in 0.80(0.725BiFeO3-0.275BaTiO3)-0.20PT (0.20 PT) based on the density functional theory, indicating good ferro/piezoelectric properties. The top experimental polarization of 36.89 µC/cm2, optimal d33 value of 258 pC/N measured at room temperature, and ultrahigh d33 value of 303 pC/N measured at 370 °C were obtained at 0.20 PT, thereby further confirming the calculations. Furthermore, a high Curie point of 488 °C, as well as outstanding temperature stability ranging from room temperature to 430 °C of the 0.20 PT ceramic was observed. The domain of the 0.20 PT exhibited greater order and smaller size, resulting in easy switching when applying voltage. The distorted electron structure, plumb grains, ordered and easily switchable domains, and coexistences of tetragonal (T) and rhombohedral (R) phases contributed to the large piezoelectric constant of the 0.2 PT ceramic. BFBT-xPT ceramics are potentially promising for high-temperature piezoelectric field applications.

Enhanced piezoelectric properties of (1 -x)BiFe0.98(Zn0.5Hf0.5)0.02O3-xBaTiO3 ceramics near the morphotropic phase boundary.

Here, (1 -x)BiFe0.98(Zn0.5Hf0.5)0.02O3-xBaTiO3 + 1 mol% MnO2 (x = 0.225, 0.250, 0.265, 0.275, 0.285, and 0.300) (BFZH-xBT) ceramics were synthesized using a traditional ceramic sintering technique. A morphotropic phase boundary (MPB) consisting of rhombohedral (R) and tetragonal (T) phases was formed in the BFZH-xBT ceramics when x = 0.285. The suitable content of BT was conducive to enlarge the particle size, improve ferroelectric and piezoelectric properties, and reduce the leakage current density. For the optimal component at x = 0.285, we observed the largest grain size, a lowest leakage current density value of ∼1.93 × 10-5 A cm-2, minimum content of oxygen vacancies, high temperature of 478 °C and the highest piezoelectric coefficient (d33) of 130 pC N-1.

MBaYB6O12 (M = Rb, Cs): two new rare-earth borates with large birefringence and short ultraviolet cutoff edges.

Two new rare-earth borates, MBaYB6O12 (M = Rb, Cs), which are the first reported compounds in M2O-BaO-RE2O3-B2O3 (M = Rb, Cs; RE = rare-earth) quaternary systems, have been discovered through a high-temperature solution method and their structures were determined by single-crystal X-ray diffraction. These two compounds are isostructural with the centrosymmetric space group R3[combining macron] (no. 148) and the fundamental building blocks are the B3O6 groups which are nearly parallel to each other. The spectral measurement shows that the cutoff edges of the two compounds are all down to the deep-ultraviolet (deep-UV) region (below 200 nm). And the experimental birefringence of RbBaYB6O12 and RbBaYB6O12 is about 0.12 at 589 nm. Moreover, first-principles theoretical studies were carried out to gain a better understanding of the structure-property relationships. The calculation results demonstrate that both the compounds have a large birefringence of 0.100 at 589 nm, which corresponds to the experimental value. Both experimental and theoretical studies suggest that MBaYB6O12 (M = Rb, Cs) are potential birefringent materials for UV and deep-UV applications.