Clinical significance of HER2-low expression in early breast cancer: a nationwide study from the Korean Breast Cancer Society.

BACKGROUND: There is an increasing interest in HER2-low breast cancer with promising data from clinical trials using novel anti-HER2 antibody-drug conjugates. We explored the differences in clinicopathological characteristics and survival outcomes between HER2-low and HER2-IHC 0 breast cancer. METHODS: Using nationwide data from the Korean Breast Cancer Registry between 2006 and 2011, 30,491 patients with stages I to III breast cancer were included in the analysis: 9,506 (31.2%) in the HER2-low group and 20,985 (68.8%) in the HER2-IHC 0 group. Kaplan-Meier and Cox proportional hazards regression survival analysis were used to compare breast cancer-specific survival between the two groups. RESULTS: HER2-low breast cancer was more frequent in patients with hormone receptor-positive breast cancer than in those with triple-negative breast cancer. In patients with hormone receptor-positive breast cancer, HER2-low breast cancer was associated with fewer T4 tumors, higher histological grade, and a negative lymphatic invasion. In patients with triple-negative breast cancer, HER2-low breast cancer was associated with a high lymph node ratio and positive lymphatic invasion. HER2-low breast cancer was significantly associated with a lower Ki-67 labeling index. No significant difference was observed in overall survival between the two groups. HER2-low breast cancer showed significantly better breast cancer-specific survival than HER2-IHC 0 breast cancer, regardless of the hormone receptor status. In multivariate analysis, the impact of low HER2 expression on breast cancer-specific survival was significant only in triple-negative breast cancer (HRs, 0.68; 95% CI, 0.49-0.93; P = 0.019). CONCLUSIONS: These findings suggest that the biology and clinical impact of low HER2 expression can differ according to the hormone receptor status and support the need for further investigation on the understanding of the biology of HER2-low breast cancer.

Origin of the different degradation mechanisms of LNCM and LNCA cathodes in Li-ion batteries.

Lithium nickel cobalt manganese oxide (LNCM) and lithium nickel cobalt aluminum oxide (LNCA) display similar performances and characteristics as cathode materials, but their degradation behaviors differ. To investigate the origin of these differences, the properties of LNCM and LNCA are comparatively examined computationally. Their structural, electronic, and transport properties show no significant differences, indicating that the degradation mechanisms cannot be explained through these intrinsic properties. Phase equilibria simulation shows that Mn embedment in the crystal is thermodynamically and kinetically favored; thus, the Mn concentration should be homogeneous over the LNCM particles. However, the Al distribution varies based on synthetic conditions, which can cause uneven concentration distributions or secondary-phase formation. In addition, the LNCA volume change with variations in Al concentration is more severe than that of LNCM with Mn concentration. Thus, LNCA particles may experience higher internal mechanical stresses, whereas the surfaces are protected by the secondary-phase coating effect. These features give LNCA robust surfaces but vulnerability to internal stress-induced particle breakage, while LNCM has relatively stable bulk properties but suffers surface-related degradation owing to bare surface exposure. This interpretation agrees well with the reported characteristic degradation behaviors of LNCM and LNCA, thus properly explaining the underlying mechanisms.

Understanding the Chemical Composition with Doping Aliovalent Ions, Followed by the Electrochemical Behavior for Surface-Modified Ni-Rich NMC Cathode Materials.

A comparative study of doping aliovalent ions, Zr- or Al-, into Ni-rich Li(Ni,Co,Mn)O2 cathode materials is conducted in terms of the electrochemical properties and chemical analysis, especially on the surface region. The solubility and chemical composition for the given sol-gel treatment matches well with the computational results with which the infinitesimal Zr-coating is identified as exhibiting increased charge capacity with prolonged cycle life. Specifically, the whole process can be understood by the suppressed lithium-ion charge transfer resistance (RCT) during the cycles, which can be facilitated by the decreased NiO formation during the cyclic reactions.

Surface Density Dependent Catalytic Activity of Single Palladium Atoms Supported on Ceria*.

The analogy between single-atom catalysts (SACs) and molecular catalysts predicts that the specific catalytic activity of these systems is constant. We provide evidence that this prediction is not necessarily true. As a case in point, we show that the specific activity over ceria-supported single Pd atoms linearly increases with metal atom density, originating from the cumulative enhancement of CeO2 reducibility. The long-range electrostatic footprints (≈1.5 nm) around each Pd site overlap with each other as surface Pd density increases, resulting in an observed deviation from constant specific activity. These cooperative effects exhaust previously active O atoms above a certain Pd density, leading to their permanent removal and a consequent drop in reaction rate. The findings of our combined experimental and computational study show that the specific catalytic activity of reducible oxide-supported single-atom catalysts can be tuned by varying the surface density of single metal atoms.

Theoretical investigation of the cation antisite defect in layer-structured cathode materials for Li-ion batteries.

The formation of cation antisite defects in layer-structured LiTMO2 cathode materials for Li-ion batteries is investigated, where TM represents Ni or Co. Energetically possible arrangements of cation antisite defects are searched by a bottom-up method in which cations are added to a frame supercell that contains some vacant cation lattice points, using a particle swarm optimization algorithm combined with a density functional theory method. The equilibrium concentration of antisite defects is quantified through a calculation model in which an ensemble crystal system is assembled by statistically combining the constructed supercell units. The behavior of antisite defect formation in LiNiO2 and LiCoO2 is compared, and the effect of Co or Mn introduction to LiNiO2 is examined. The underlying mechanism is investigated in terms of the covalent and ionic bonding characteristics, TM oxidation state, and structural changes in the cation sites, based on analyses of the crystal orbital Hamilton population, partial charge, and bond lengths. It is concluded that the structural distortion of the cation sites and the superexchange interaction involved with cation mixing are the two main factors determining the concentration of cation antisite defects in layer-structured cathode materials.

Effects and distribution of Zr introduced in Ni-based cathode material for Li-ion batteries.

The spatial and site distribution of Zr introduced to the LiNiO2 (LNO) host material and the related mechanism of performance improvement as a Li-ion battery electrode are theoretically investigated. It is found that the equilibrium doping limit of Zr is higher near the (012) surface than that near (003) among the main surface planes of LNO, and that the diffusion energy barrier in the [012] direction is lower than that in [003]. The thermodynamic and kinetic aspects indicate the main Zr diffusion pathway into crystalline LNO via the (012) surface in the perpendicular direction and its crystallographic equivalents. Regarding the site-distribution in the bulk crystal, Zr preferentially substitutes Ni, but becomes located at Li sites as the composition of the LNO host becomes Li-deficient. It is observed that Zr doping suppresses O release from the LNO surface, thus suppressing side reactions at the cathode-electrolyte interface. This is attributed to the mechanism of increased covalent and electrostatic interactions with the O ions by the introduction of Zr. The pillar effect of Zr is achievable with a suitable Li-deficient composition during heating, which induces Zr localization at Li sites. The distribution of Zr is found to be determined by the physical and chemical factors of the doping site size and the chemical bonding characteristics of Zr with neighboring O ions.

Self-assembly of core-shell structures driven by low doping limit of Ti in LiCoO2: first-principles thermodynamic and experimental investigation.

Introducing additives is a general method of performance improvement in materials engineering, but details regarding whether the additive is doped in the host crystal or present as a secondary phase are usually examined from experimental experience, with a systematic theoretical prediction lacking, which sometimes causes controversy on the role of additives. In this study, the dopability of Ti in crystalline LiCoO2 (LCO) is investigated by a first-principles simulation method, and the doping limit is quantitatively calculated. The probability of Ti substitution for Co is examined and related to point-defect formation in LCO as a function of the general experimental variables of temperature and gas-phase partial pressures, enabling practical use of the theoretical model for real experiments. It was found that Ti substitution for Co, accompanied by the formation of a Li vacancy, is the most probable Ti doping form in LCO, but the doping limit is very low and most Ti would segregate into secondary phases. The theoretical prediction showed good agreement with the experimental results. Based on theoretical predictions, particles having LCO cores and Ti-rich shells are obtained from a simple sol-gel route followed by one-step firing without additional surface treatment. The high-voltage cyclability of LCO is greatly improved. The method demonstrated in this study may be a useful tool for screening suitable coating or doping elements for various material systems and provide a guide for designing simple spontaneous coating processes, as in this study.

Dual spectra band emissive Eu2+/Mn2+ co-activated alkaline earth phosphates for indoor plant growth novel phosphor converted-LEDs.

This paper reports designing a novel single composition blue/red color illuminating phosphor followed by fabricating "smart" agricultural/horticultural LED lighting. Color-tunable Eu2+/Mn2+ co-activated alkaline earth phosphates, Na(Sr,Ba)PO4 and Ca3Mg3(PO4)4, are considered, and the stable doping sites for the corresponding activators are identified by using first-principle DFT calculations. We can realize the designated color purity with stable thermal quenching preserved luminescence behavior is induced by the Eu2+ center positioned at different coordination states with intermixed Sr2+/Ba2+ sites in Na(Sr,Ba)PO4 hosts. Moreover, we demonstrate that the resultant LED lighting adopting the proposed novel phosphor composition stimulates the enhanced photosynthesis reaction for indoor hydroponics plants, such as oats and onions, which is superior to the narrow line emission band induced by the mixture of conventional red/green/blue LEDs. Thus, using the color-tunable single composition luminescent material may produce an innovative energy-efficient artificial lighting for indoor plant growth.

Eu(2+)-Activated Phase-Pure Oxonitridosilicate Phosphor in a Ba-Si-O-N System via Facile Silicate-Assisted Routes Designed by First-Principles Thermodynamic Simulation.

Eu(2+)-activated single phase Ba(2+)-oxonitridosilicate phosphors were prepared under a mild synthetic condition via silicate precursors, and their luminescent properties were investigated. Both the preferred oxonitridosilicate formation as for the available host compounds and thermodynamic stability within the Ba-Si-O-N system were elucidated in detail by the theoretical simulation based on the first-principles density functional theory. Those results can visualize the optimum synthetic conditions for Eu(2+)-activated highly luminescent Ba(2+)-oxonitridosilicates, especially Ba3Si6O12N2, as promising conversion phosphors for white LEDs, including Ba3Si6O9N4 and BaSi2O2N2 phases. To prove the simulated design rule, we synthesized the Ba3Si6O12N2:Eu(2+) phosphor using various silicate precursors, Ba2Si4O10, Ba2Si3O8, and BaSiO3, in a carbothermal reduction ambient and finally succeeded in obtaining a phase of pure highly luminescent oxonitridosilicate phosphor without using any solid-state nitride addition and/or high pressure synthetic procedures. Our study provides useful guidelines for robust synthetic procedures for developing thermally stable rare-earth-ion activated oxonitridosilicate phosphors and an established simulation method that can be effectively applied to other multigas systems.

Encapsulation of LiNi0.5Co0.2Mn0.3O2 with a thin inorganic electrolyte film to reduce gas evolution in the application of lithium ion batteries.

Emission of gas at charged states of lithium ion batteries (LIBs) is a significant problem because it causes swelling and deformation of LIBs. In this study, the gas generation mechanism is investigated and preventative measures are developed. Decomposition of the electrolyte solution related to residual lithium compounds on the surface of LiNi0.5Co0.2Mn0.3O2 (NCM523) and to the structural change in the cathode active material is investigated as two main mechanisms of gas generation in LIB cells. NCM523 particles are encapsulated in a continuous lithium lanthanum titanium oxide (LLTO) thin layer to inhibit gas-generating reactions. The LLTO layer fixes free lithium of the cathode surface and effectively suppresses side reactions between the charged cathode active material and the electrolyte solution, resulting in substantial reduction of the gas generation. In addition, LLTO-coated NCM523 shows improved capacity retention without any loss of capacity or rate performance because LLTO is a good conductor of Li ions.

Subcutaneous implantation of thyroid carcinoma and benign tissue after thyroidectomy: report on two cases and review of the current literature.

Background: Subcutaneous implantation of thyroid tissue after thyroidectomy is a rare occurrence involving both benign and malignant thyroid tissue. Clinically, subcutaneous implantation of thyroid tissue can be challenging to diagnose. We present two cases of subcutaneous implantation of thyroid tissue following thyroidectomy and discuss the differential diagnosis, clinicopathological characteristics, and the possible mechanism of implantation. Case Description: A 35-year-old woman (age in 2009) who underwent total thyroidectomy in 2009 whose histopathological examination revealed a nodular hyperplasia and lymphocytic thyroiditis complained of palpable mass in her neck 10 years after operation and underwent excision. Follicular adenoma was confirmed in histopathological results. A 58-year-old woman (age in 2010) who underwent lobectomy in 2010 for nodular hyperplasia had a 6 cm sized huge mass in her anterior neck 9 years after operation. Anterior neck mass excision was done and poorly differentiated carcinoma was confirmed in histopathological results. The patient showed no sign of recurrence after 3 years follow-up. Conclusions: Subcutaneous implantation of benign thyroid tissue or thyroid cancer can occur after thyroidectomy. Minimizing the likelihood of subcutaneous implantation requires careful consideration of various factors at every stage of the surgical procedure. Surgeons should be aware of this potential long-term complication that can occur in both conventional thyroidectomy and remote access surgery, effectively communicate and provide appropriate guidance to their patients, and try to avoid seeding of both malignant and benign thyroid tissue.

Investigation of the effect of point defects on the Li-ion conductivity of Li3InCl6.

The effect of point defects on the performance of the Li3InCl6 solid electrolyte was investigated using first-principles simulations. The Li-ion conductivity of Li3InCl6 was improved by the presence of point defects, such as a 4g site occupation by In or a Cl vacancy. The diffusion of Li ions was activated by the movement of some Li ions to vacant sites in the In layer, and the point defects reduced the energy barrier of this step, resulting in an overall increase in Li-ion diffusivity. The underlying mechanism of this effect was examined in terms of the structural and chemical properties of Li-Cl and In-Cl bonds, which indicated the energy barrier was closely related to changes in the bond distance and covalent interaction between the migrating Li and nearby Cl ions and nonuniformity among In-Cl bonds. Thermodynamic analysis showed that defect formation was unfavorable during conventional high-temperature synthesis; therefore, it is suggested that heating is applied at low temperatures only as a supplementary process to modify the crystallinity after preparing defective Li3InCl6 crystals by mechanical or solution-based routes to practically implement the effect of point defects and improve the solid electrolyte performance of Li3InCl6.

Is Gross Extrathyroidal Extension to Strap Muscles (T3b) Only a Risk Factor for Recurrence in Papillary Thyroid Carcinoma? A Propensity Score Matching Study.

The presence of extrathyroidal extension (ETE) is associated with locoregional recurrence and distant metastases in papillary thyroid carcinoma (PTC). This study was designed to compare the recurrence risk between minimal ETE (mETE) and gross ETE (gETE) in patients with PTC using propensity score matching. In this study, 4452 patients with PTC who underwent thyroid surgery in a single center were retrospectively analyzed, and clinicopathological characteristics were compared according to the ETE status. Disease-free survival (DFS) and recurrence risk were compared between mETE and gETE after propensity score matching. The mean follow-up duration was 122.7 ± 22.5 months. In multivariate analysis, both mETE and gETE were not associated with recurrence risk before propensity score matching (p = 0.154 and p = 0.072, respectively). After propensity score matching, no significant difference in recurrence rates was observed between the two groups (p = 0.668). DFS of the gETE group did not significantly differ from that of the mETE group (log-rank p = 0.531). This study revealed that both mETE and gETE are not independent risk factors for the risk of recurrence in PTC. Our findings suggest that gETE invading strap muscles only might not be associated with worse oncological outcomes in PTC.

Effectiveness Analysis for Smart Construction Safety Technology (SCST) by Test Bed Operation on Small- and Medium-Sized Construction Sites.

In the global construction industry, government policies have recently focused on smart construction technologies, such as those concerning the "smartization" of construction, improvements of productivity, and automation technologies. In addition, smart construction safety technologies (SCSTs) have been developed to ensure workers' safety, under the initiative of the private sector. In regards to overseas occupational safety, wearable technologies have been developed for various types of industries, and the integrated platform developments needed to link them have become mainstream. In South Korea, individual companies are focusing on developing basic SCSTs and platforms for integrated control, aiming to prevent accidents in the construction field. The goal of this study was to identify the pros and cons of SCSTs through test bed operation and to derive improvement directions. Therefore, a test bed embedded with SCSTs was built and operated to provide effective safety management for small- and medium-sized sites exposed to fatal accidents. From analyzing the data from the test bed, it was found that it is difficult to change the tendencies of workers' behaviors based solely on the introduction of SCSTs. This indicates that the effects of SCSTs are insignificant without the cooperation of workers. In addition, technical problems in field application were identified for each sensor and equipment, and the necessity, problems, and effectiveness of SCSTs were analyzed. As a result, both the installation and attachment types were found to be effective; however, workers avoided wearing certain attachment types. Based on the results derived through analysis of the pros and cons of SCSTs, the directions and guidelines were suggested for future use. This result can be used for future technology development directions, and policy establishment. Additionally, for the activation of SCSTs in the field, the cooperation of workers and the interest of managers remain essential factors, and improvements to the equipment are required.

Analysis of Genomic Alterations Associated with Recurrence in Early Stage HER2-Positive Breast Cancer.

We aimed to compare gene expression in primary tumors of patients with recurrence and nonrecurrence to gain insight into the biology of high-risk HER2-positive early breast cancer. Patients who underwent curative resection and received adjuvant trastuzumab for HER2-positive early breast cancer were evaluated. Gene expression analyses were performed using NanoString Technologies' nCounter Breast Cancer 360 Panel. PAM50 intrinsic subtypes and Breast Cancer Signatures including tumor inflammation signature (TIS) were evaluated. Of 247 patients, 28 (11.3%) had recurrence at a median follow-up of 54.2 months. Patients with pathological stage III, tumor size > 5 cm, axillary lymph node metastases, and hormone receptor-negativity were more frequently observed in the recurrent group compared with the nonrecurrent group. In patients with recurrence, seven genes were upregulated significantly, including WNT11, HAPLN1, FGF10, BBOX1, CXADR, NDP, and EREG, and two genes were downregulated, including CXCL9 and GNLY. TIS score was significantly lower in patients with recurrence compared with controls without recurrence. These findings suggest that activation of oncogenic signaling pathways related to cell proliferation, adhesion, cancer stemness, and noninflamed tumor microenvironment are associated with the risk of recurrence in early stage, HER2-positive breast cancer.

Design of a Metal/Oxide/Carbon Interface for Highly Active and Selective Electrocatalysis.

Sustainable energy-conversion and chemical-production require catalysts with high activity, durability, and product-selectivity. Metal/oxide hybrid structure has been intensively investigated to achieve promising catalytic performance, especially in neutral or alkaline electrocatalysis where water dissociation is promoted near the oxide surface for (de)protonation of intermediates. Although catalytic promise of the hybrid structure is demonstrated, it is still challenging to precisely modulate metal/oxide interfacial interactions on the nanoscale. Herein, we report an effective strategy to construct rich metal/oxide nano-interfaces on conductive carbon supports in a surfactant-free and self-terminated way. When compared to the physically mixed Pd/CeO2 system, a much higher degree of interface formation was identified with largely improved hydrogen oxidation reaction (HOR) kinetics. The benefits of the rich metal-CeO2 interface were further generalized to Pd alloys for optimized adsorption energy, where the Pd3Ni/CeO2/C catalyst shows superior performance with HOR selectivity against CO poisoning and shows long-term stability. We believe this work highlights the importance of controlling the interfacial junctions of the electrocatalyst in simultaneously achieving enhanced activity, selectivity, and stability.

Enhancement of UV emission in ZnO nanorods by growing additional ZnO layers on the surface.

Ultraviolet (UV) photoluminescence emission from ZnO nanorod arrays was greatly enhanced by growing additional thin ZnO layers on the surface after thermal reduction of the nanorods. Appropriate selection of additives based on the shape of the original ZnO samples was found to be an important factor in designing the solution composition for growing the additional ZnO layers. This is because the additives modify the growth rates with respect to crystallographic planes. Adding ethylene glycol to the solution was effective for rod-shaped ZnO nanorods in enhancing the UV emission, whereas adding polyethylenimine was better for plate-like particles. These results can be explained by the presence of non-luminescent regions near the surface, where UV emission is thought to be suppressed by non-radiative surface centers. Growing additional layers on side planes increases the volume of the optically active region of ZnO nanorods, with a lower transmittance loss; thus, it effectively enhances the UV emission intensity.

Synthesis and Surface Coating of LiMn2O4 Nanorods for the Cathode of the Lithium-Ion Battery.

MnO2 nanorods are prepared using a hydrothermal method, and used as precursors for the synthesis of LiMn2O4 nanorod-based active material for the cathode of lithium-ion batteries. The effects of additives, pressure, reactant concentration in the solution, and reaction time during the hydrothermal synthesis on the morphology of MnO2 are examined. For the synthesis of the LiMn2O4 nanorods, two synthetic methods, hydrothermal processing of the MnO2 precursor in a Li-containing solution, and the solid-state reaction of the precursor with LiOH·H2O powder are tested. The morphological and electrochemical properties of the resulting materials are then analyzed. The rate and cycle performances of the LiMn2O4 nanorods are considerably improved by a composite coating of Li-ion-conductive Li2O-2B2O3 and electrically conductive carbon. Because the conductive properties of these coating materials can be obtained with low crystallinity of them, superior coating performance is attainable with relatively low-temperature of after heating, which is advantageous in preserving the morphology of LiMn2O4 nanorods.

High-performance and stable photoelectrochemical water splitting cell with organic-photoactive-layer-based photoanode.

Considering their superior charge-transfer characteristics, easy tenability of energy levels, and low production cost, organic semiconductors are ideal for photoelectrochemical (PEC) hydrogen production. However, organic-semiconductor-based photoelectrodes have not been extensively explored for PEC water-splitting because of their low stability in water. Herein, we report high-performance and stable organic-semiconductors photoanodes consisting of p-type polymers and n-type non-fullerene materials, which is passivated using nickel foils, GaIn eutectic, and layered double hydroxides as model materials. We achieve a photocurrent density of 15.1 mA cm-2 at 1.23 V vs. reversible hydrogen electrode (RHE) with an onset potential of 0.55 V vs. RHE and a record high half-cell solar-to-hydrogen conversion efficiency of 4.33% under AM 1.5 G solar simulated light. After conducting the stability test at 1.3 V vs. RHE for 10 h, 90% of the initial photocurrent density are retained, whereas the photoactive layer without passivation lost its activity within a few minutes.

Defects on the Surface of Ti-Doped MgAl2O4 Nanophosphor.

Ti-doped nano MgAl2O4 for white emission was synthesized by combustion method. Extrinsic Schottky defects, Al vacancies and Ti4+ dopant in Al sites, which are considered to be responsible for bluish-white emission, were observed by STEM on the surface of Ti-doped nano MgAl2O4 powder. The stabilities of the Schottky defect associates, (TiAl·-VAl''')'', were demonstrated by DFT calculation. The emission behavior was interpreted with these results.