Pemetrexed plus vinorelbine versus vinorelbine monotherapy in patients with metastatic breast cancer (KCSG-BR15-17): A randomized, open-label, multicenter, phase II trial.

INTRODUCTION: Metastatic breast cancer refractory to anthracycline and taxanes often shows rapid progression. The development of effective and tolerable combination regimens for these patients is needed. This phase II trial investigated the efficacy of pemetrexed plus vinorelbine in patients with metastatic breast cancer. METHODS: This randomized, open-label, phase II trial was conducted in 17 centers in Korea. Patients with advanced breast cancer who had previously been treated with anthracyclines and taxanes were randomly assigned in a 1:1 ratio to receive either vinorelbine or pemetrexed plus vinorelbine. Randomization was stratified by prior capecitabine treatment and hormone receptor status. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included the objective response rate, overall survival, safety, and quality of life. RESULTS: Between March 2017 and August 2019, a total of 125 patients were enrolled. After a median follow-up duration of 14.1 months, 118 progression events and 88 death events had occurred. Sixty-two patients were assigned to the pemetrexed plus vinorelbine arm, and 63 were assigned to the vinorelbine arm. Pemetrexed plus vinorelbine significantly prolonged PFS compared to vinorelbine (5.7 vs. 1.5 months, p < 0.001). The combination arm had higher disease control rate (76.8% vs. 45.9%, p = 0.001) and a tendency toward longer overall survival (16.8 vs. 10.5 months, p = 0.102). Anemia was more frequent in the pemetrexed plus vinorelbine arm per cycle compared with vinorelbine (7.9% vs. 1.9%, p < 0.001), but there was no difference in the incidence of grade 3-4 neutropenia per cycle between the pemetrexed plus vinorelbine arm and the vinorelbine single arm (14.7% vs. 19.5%, p = 0.066). CONCLUSIONS: This phase II study showed that pemetrexed plus vinorelbine led to a longer PFS than vinorelbine. Adverse events of pemetrexed plus vinorelbine were generally manageable.

Clinical activity of nivolumab in combination with eribulin in HER2-negative metastatic breast cancer: A phase IB/II study (KCSG BR18-16).

AIM: We evaluated the efficacy and safety of nivolumab and eribulin combination therapy for metastatic breast cancer (BC) in Asian populations. METHODS: In this parallel phase II study, adult patients with histologically confirmed recurrent/metastatic hormone receptor-positive/HER2-negative (HR+HER2-) or triple-negative BC (TNBC) were prospectively enroled from 10 academic hospitals in Korea (ClinicalTrials.gov Identifier: NCT04061863). They received nivolumab (360 mg) on day 1 plus eribulin (1.4 mg/m2) on days 1 and 8 every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was the investigator-assessed 6-month progression-free survival (PFS) rate in each subtype. Secondary endpoints included investigator-assessed objective response rate (ORR) as per Response Evaluation Criteria in Advanced Solid Tumors version 1.1, disease control rate, overall survival, and treatment toxicity. The association between PD-L1 expression and efficacy was investigated. RESULTS: Forty-five patients with HR+HER2- BC and 45 with TNBC were enroled. Their median age was 51 (range, 31-71) years, and 74 (82.2%) received one or two prior treatments before enrolment. Six-month PFS was 47.2% and 25.1% in the HR+HER2- and TNBC cohorts, respectively. Median PFS was 5.6 (95% confidence interval [CI]: 5.3-7.4) and 3.0 (95% CI: 2.1-5.2) months in the HR+HER2- and TNBC groups, respectively. ORRs were 53.3% (complete response [CR]: 0, partial response [PR]: 24) and 28.9% (CR: 1, PR: 12). Patients with PD-L1+ tumours (PD-L1 expression ≥1%) and PD-L1- tumours (ORR 50% versus 53.8% in HR+HER2-, 30.8% versus 29.0% in TNBC) had similar ORRs. Neutropenia was the most common grade 3/4 adverse event; the most common immune-related adverse events (AEs) were grades 1/2 hypothyroidism and pruritus. Five patients discontinued therapy because of immune-related AEs. CONCLUSION: Nivolumab plus eribulin showed promising efficacy and tolerable safety in previously treated HER2- metastatic BC. TRIAL REGISTRATION: NCT04061863.

Seeking and Providing Social Support on Twitter for Trauma and Distress During the COVID-19 Pandemic: Content and Sentiment Analysis.

BACKGROUND: The COVID-19 pandemic can be recognized as a traumatic event that led to stressors, resulting in trauma or distress among the general population. Social support is vital in the management of these stressors, especially during a traumatic event, such as the COVID-19 pandemic. Because of the limited face-to-face interactions enforced by physical distancing regulations during the pandemic, people sought solace on social media platforms to connect with, and receive support from, one another. Hence, it is crucial to investigate the ways in which people seek and offer support on social media for mental health management. OBJECTIVE: The research aimed to examine the types of social support (eg, emotional, informational, instrumental, and appraisal) sought and provided for trauma or distress on Twitter during the COVID-19 pandemic. In addition, this study aimed to gain insight into the difficulties and concerns of people during the pandemic by identifying the associations between terms representing the topics of interest related to trauma or distress and their corresponding sentiments. METHODS: The study methods included content analysis to investigate the type of social support people sought for trauma or distress during the pandemic. Sentiment analysis was also performed to track the negative and positive sentiment tweets posted between January 1, 2020, and March 15, 2021. Association rule mining was used to uncover associations between terms and sentiments in tweets. In addition, the research used Kruskal-Wallis and Mann-Whitney U tests to determine whether the retweet count and like count varied based on the social support type. RESULTS: Most Twitter users who indicated trauma or distress sought emotional support. Regarding sentiment, Twitter users mostly posted negative sentiment tweets, particularly in January 2021. An intriguing observation was that wearing masks could trigger and exacerbate trauma or distress. The results revealed that people mostly sought and provided emotional support on Twitter regarding difficulties with wearing masks, mental health status, financial hardships, and treatment methods for trauma or distress. In addition, tweets regarding emotional support received the most endorsements from other users, highlighting the critical role of social support in fostering a sense of community and reducing the feelings of isolation during the pandemic. CONCLUSIONS: This study demonstrates the potential of social media as a platform to exchange social support during challenging times and to identify the specific concerns (eg, wearing masks and exacerbated symptoms) of individuals with self-reported trauma or distress. The findings provide insights into the types of support that were most beneficial for those struggling with trauma or distress during the pandemic and may inform policy makers and health organizations regarding better practices for pandemic response and special considerations for groups with a history of trauma or distress.

Dynamics of Moiré Trion and Its Valley Polarization in a Microfabricated WSe2/MoSe2 Heterobilayer.

The moiré potential, induced by stacking two monolayer semiconductors with slightly different lattice mismatches, acts as periodic quantum confinement for optically generated excitons, resulting in spatially ordered zero-dimensional quantum systems. However, there are limitations to exploring intrinsic optical properties of moiré excitons due to ensemble emissions and broadened emissions from many peaks caused by the inhomogeneity of the moiré potential. In this study, we proposed a microfabrication technique based on focused Ga+ ion beams, which enables us to control the number of peaks originating from the moiré potential and thus explore unknown moiré optical characteristics of WSe2/MoSe2 heterobilayer. By taking advantage of this approach, we reveal emissions from a single moiré exciton and charged moiré exciton (trion) under electrostatic doping conditions. We show the momentum dark moiré trion state above the bright trion state with a splitting energy of approximately 4 meV and clarify that the dynamics are determined by the initial trion population in the bright state. Furthermore, the degree of negative circularly polarized emissions and their valley dynamics of moiré trions are dominated by a very long valley relaxation process lasting ∼700 ns. Our findings on microfabricated heterobilayer could be viewed as an extension of our groundbreaking efforts in the field of quantum optics application using moiré superlattices.

Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer.

We explored accumulated genomic alterations in patients with heavily treated HER2 + metastatic breast cancer enrolled in the KCSG BR18-14/KM10B trial. Targeted sequencing was performed with circulating tumor DNAs (ctDNAs) collected before the treatment of 92 patients. ctDNAs collected at the time of disease progression from seven patients who had a durable response for > 12 months were also analyzed. Sixty-five genes were identified as pathogenic alterations in 99 samples. The most frequently altered genes were TP53 (n = 48), PIKCA (n = 21) and ERBB3 (n = 19). TP53 and PIK3CA mutations were significantly related with shorter progression free survival (PFS), and patients with a higher ctDNA fraction showed a worse PFS. The frequency of homologous recombination deficiency (HRD)-related gene mutations was higher than that in matched tumor tissues, and these mutations tended to be associated with shorter PFS. New pathogenic variants were found at the end of treatment in all seven patients, including BRCA2, VHL, RAD50, RB1, BRIP1, ATM, FANCA, and PIK3CA mutations. In conclusion, TP53 and PIK3CA mutations, as well as a higher ctDNA fraction, were associated with worse PFS with trastuzumab and cytotoxic chemotherapy. The enrichment of HRD-related gene mutations and newly detected variants in ctDNA may be related to resistance to treatment.

Comparison of initial and sequential salvage brain-directed treatment in patients with 1-4 vs. 5-10 brain metastases from breast cancer (KROG 16-12).

PURPOSE: We aimed to compare the initial and salvage brain-directed treatment and overall survival (OS) between patients with 1-4 brain metastases (BMs) and those with 5-10 from breast cancer (BC). We also organized a decision tree to select the initial whole-brain radiotherapy (WBRT) for these patients. METHODS: Between 2008 and 2014, 471 patients were diagnosed with 1-10 BMs. They were divided into two groups based on the number of BM: 1-4 BMs (n = 337) and 5-10 BMs (n = 134). Median follow-up duration was 14.0 months. RESULTS: Stereotactic radiosurgery (SRS)/fractionated stereotactic radiotherapy (FSRT) was the most common treatment modality (n = 120, 36%) in the 1-4 BMs group. In contrast, 80% (n = 107) of patients with 5-10 BMs were treated with WBRT. The median OS of the entire cohort, 1-4 BMs, and 5-10 BMs was 18.0, 20.9, and 13.9 months, respectively. In the multivariate analysis, the number of BM and WBRT were not associated with OS, whereas triple-negative BC and extracranial metastasis decreased OS. Physicians determined the initial WBRT based on four variables in the following order: number and location of BM, primary tumor control, and performance status. Salvage brain-directed treatment (n = 184), mainly SRS/FSRT (n = 109, 59%), prolonged OS by a median of 14.3 months. CONCLUSION: The initial brain-directed treatment differed notably according to the number of BM, which was chosen based on four clinical factors. In patients with ≤ 10 BMs, the number of BM and WBRT did not affect OS. The major salvage brain-directed treatment modality was SRS/FSRT and increased OS.

Near dissolved organic matter microfiltration (NDOM MF) coupled with UVC LED disinfection to maximize the efficiency of water treatment for the removal of Giardia and Cryptosporidium.

Microfiltration (MF) membranes with a mean pore size same as or smaller than 0.45 µm have been typically used to separate pathogenic protozoa in water since materials larger than 0.45 µm are considered particulates. However, 0.45 µm is too small to separate protozoa which are 4-6 µm (Cryptosporidium oocyst) or 8-15 µm (Giardia cyst) in size. In this study, we optimized the mean pore size of MF membranes to maximize the producibility and guarantee a high removal rate simultaneously and proposed the membrane filtration using an MF membrane with an optimum mean pore size larger than but close to dissolved organic matter (DOM), which is called near DOM MF (NDOM MF). According to the MF test using polystyrene surrogate beads with diameters of 3 and 8 µm, an MF membrane with a 0.8 µm mean pore size was the best in that it showed 52% to 146% higher water fluxes than a 0.45 µm MF membrane while maintaining the removal rate at 3-4 log. It was also the case for a low-temperature MF test, revealing the NDOM MF is highly effective regardless of temperature changes. Lastly, we tried to find the possibility of combining the NDOM MF with disinfection by an ultraviolet light emitting diode (UVC LED) to further guarantee the high quality of treated water while providing high process efficiency.

Prophylactic Femoral Neck Fixation in an Osteoporosis Femur Model: A Novel Surgical Technique with Biomechanical Study.

Intramedullary nailing (IMN) is a popular treatment for elderly patients with femoral shaft fractures. Recently, prophylactic neck fixation has been increasingly used to prevent proximal femoral fractures during IMN. Therefore, this study aimed to investigate the biomechanical strength of prophylactic neck fixation in osteoporotic femoral fractures. An osteoporotic femur model was created to simulate the union of femoral shaft fractures with IMN. Two study groups comprising six specimens each were created for IMN with two standard proximal locking screws (SN group) and IMN with two reconstruction proximal locking screws (RN group). Axial loading was conducted to measure the stiffness, load-to-failure, and failure modes. There were no statistically significant differences in stiffness between the two groups. However, the load-to-failure in the RN group was significantly higher than that in the SN group (p < 0.05). Femoral neck fractures occurred in all specimens in the SN group. Five constructs in the RN group showed subtrochanteric fractures without femoral neck fractures. However, one construct was observed in both subtrochanteric and femoral neck fractures. Therefore, prophylactic neck fixation may be considered an alternative biomechanical solution to prevent proximal femoral fractures when performing IMN for osteoporotic femoral fractures.

Bamboo Shoot and Artemisia capillaris Extract Mixture Ameliorates Dextran Sodium Sulfate-Induced Colitis.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract and is characterized by recurrent chronic inflammation and mucosal damage of the gastrointestinal tract. Recent studies have demonstrated that bamboo shoot (BS) and Artemisia capillaris (AC) extracts enhance anti-inflammatory effects in various disease models. However, it is uncertain whether there is a synergistic protective effect of BS and AC in dextran sodium sulfate (DSS)-induced colitis. In the current study, we tested the combined effects of BS and AC extracts (BA) on colitis using in vivo and in vitro models. Compared with control mice, oral administration of DSS exacerbated colon length and increased the disease activity index (DAI) and histological damage. In DSS-induced colitis, treatment with BA significantly alleviated DSS-induced symptoms such as colon shortening, DAI, histological damage, and colonic pro-inflammatory marker expression compared to single extracts (BS or AC) treatment. Furthermore, we found BA treatment attenuated the ROS generation, F-actin formation, and RhoA activity compared with the single extract (BS or AC) treatment in DSS-treated cell lines. Collectively, these findings suggest that BA treatment has a positive synergistic protective effect on colonic inflammation compared with single extracts, it may be a highly effective complementary natural extract mixture for the prevention or treatment of IBD.

In vivo functional effects of Weissella confusa VP30 exopolysaccharides on loperamide-induced constipation in rats.

In this work, the in vivo functionalities of milk fermented with Weissella confusa VP30 (VP30-EPS) and purified exopolysaccharide (pEPS) from the milk fermented with Weissella confusa VP30 were evaluated for their effect on constipation using an experimental constipated rat model. Rats were randomly divided into four groups: (i) control group (PBS administered normal group), (ii) loperamide treated group (constipation group), (iii) constipation with loperamide plus VP30-EPS (1 g/kg), and (iv) constipation with loperamide plus pEPS (0.6 g/kg) groups. Loperamide treatment induced animal constipation and significantly reduced the frequency of defecation, intestinal transit ratio, and water content of feces. However, all four fecal parameters were improved in both the loperamide plus VP30-EPS and pEPS administered groups as compared to the loperamide group. These results suggest that the addition of VP30-EPS potentially improves the functional laxative effects of commercial products. This study suggests the possibility that VP30-EPS can be applied to fermented and/or functional foods to relieve constipation.

Cold plasma-assisted regeneration of biochar for dye adsorption.

Environmental remedies, including adsorption-based water purification, are now being asked to meet the requirement for a low-carbon circular economy requiring low energy and low material consumption. In this regard, we tested the possibility of regenerating adsorbents via cold plasma (CP) treatment for less use of adsorbents and no washing solution. In the adsorption of methylene blue (MB) using carbonized rice husk (CRH) and five successive regeneration cycles by CP treatment, the removal efficiencies were maintained at a moderate level (∼70% of the initial performance), unlike five consecutive adsorption without CP treatment (∼9-13% of the initial performance). The regeneration of CRH by CP treatment was also double-checked by the FESEM, EDS, BET, FTIR, XPS, and surface zeta potential measurements. The successfully recovered adsorption capability is related to the remediation of adsorption sites. It is also worth noting that the required power consumption for recycling by CP treatment was about 6.4 times lower than carbonizing new rice husks. This work provides insights into recovering adsorbents using CP without rigorous, costly, and energy-intensive processes.

Impairment of Neuronal Mitochondrial Quality Control in Prion-Induced Neurodegeneration.

Mitochondrial dynamics continually maintain cell survival and bioenergetics through mitochondrial quality control processes (fission, fusion, and mitophagy). Aberrant mitochondrial quality control has been implicated in the pathogenic mechanism of various human diseases, including cancer, cardiac dysfunction, and neurological disorders, such as Alzheimer's disease, Parkinson's disease, and prion disease. However, the mitochondrial dysfunction-mediated neuropathological mechanisms in prion disease are still uncertain. Here, we used both in vitro and in vivo scrapie-infected models to investigate the involvement of mitochondrial quality control in prion pathogenesis. We found that scrapie infection led to the induction of mitochondrial reactive oxygen species (mtROS) and the loss of mitochondrial membrane potential (ΔΨm), resulting in enhanced phosphorylation of dynamin-related protein 1 (Drp1) at Ser616 and its subsequent translocation to the mitochondria, which was followed by excessive mitophagy. We also confirmed decreased expression levels of mitochondrial oxidative phosphorylation (OXPHOS) complexes and reduced ATP production by scrapie infection. In addition, scrapie-infection-induced aberrant mitochondrial fission and mitophagy led to increased apoptotic signaling, as evidenced by caspase 3 activation and poly (ADP-ribose) polymerase cleavage. These results suggest that scrapie infection induced mitochondrial dysfunction via impaired mitochondrial quality control processes followed by neuronal cell death, which may have an important role in the neuropathogenesis of prion diseases.

Effects of Filler Functionalization on Filler-Embedded Natural Rubber/Ethylene-Propylene-Diene Monomer Composites.

Natural rubber (NR) presents a number of advantages over other types of rubber but has poor resistance to chemicals and aging. The incorporation of ethylene propylene diene monomer (EPDM) into the NR matrix may be able to address this issue. Mineral fillers, such as carbon black (CB) and silica are routinely incorporated into various elastomers owing to their low cost, enhanced processability, good functionality, and high resistance to chemicals and aging. Other fillers have been examined as potential alternatives to CB and silica. In this study, phlogopite was surface-modified using 10 phr of compatibilizers, such as aminopropyltriethoxysilane (A1S), aminoethylaminopropyltrimethoxysilane (A2S), or 3-glycidoxypropyltrimethoxysilane (ES), and mixed with NR/EPDM blends. The effects of untreated and surface-treated phlogopite on the mechanical properties of the rubber blend were then compared with those of common fillers (CB and silica) for rubbers. The incorporation of surface-modified phlogopite into NR/EPDM considerably enhanced various properties. The functionalization of the phlogopite surface using silane-based matters (amino- and epoxide-functionalized) led to excellent compatibility between the rubber matrix and phlogopite, thereby improving diverse properties of the elastomeric composites, with effects analogous to those of CB. The tensile strength and elongation at break of the phlogopite-embedded NR/EPDM composite were lower than those of the CB-incorporated NR/EPDM composite by 30% and 10%, respectively. Among the prepared samples, the ES-functionalized phlogopite showed the best compatibility with the rubber matrix, exhibiting a tensile strength and modulus of composites that were 35% and 18% higher, respectively, compared with those of the untreated phlogopite-incorporated NR/EPDM composite. The ES-functionalized phlogopite/NR/EPDM showed similar strength and higher modulus (by 18%) to the CB/NR/EPDM rubber composite, despite slightly lower elongation at break and toughness. The results of rebound resilience and compression set tests indicated that the elasticity of the surface-modified phlogopite/NR/EPDM rubber composite was higher than that of the silica- and CB-reinforced composites. These improvements could be attributed to enhancements in the physical and chemical interactions among the rubber matrix, stearic acid, and functionalized (compatibilized) phlogopite. Therefore, the functionalized phlogopite can be utilized in a wide range of applications for rubber compounding.

Phase II study to investigate the efficacy of trastuzumab biosimilar (Herzuma®) plus treatment of physician's choice (TPC) in patients with heavily pretreated HER-2+ metastatic breast cancer (KCSG BR 18-14/KM10B).

We investigated the efficacy and safety of a trastuzumab biosimilar, Herzuma®, in combination with treatment of physician's choice (TPC) in patients with HER2+ metastatic breast cancer (MBC) who had failed at least two HER2 directed chemotherapies.

Cultural and linguistic adaption and testing of the Health Literacy Questionnaire (HLQ) among healthy people in Korea.

BACKGROUNDS: This study administered the Health Literacy Questionnaire (HLQ) among Korean adults to examine its factor structure, reliability, and validity. METHODS: The HLQ items were translated and culturally adapted to the Korean context. The convenience sampling method was used, and data were collected. The difficulty level, confirmatory factor analysis (CFA) using diagonal weighted least squares (DWLS) estimator in R, discriminant validity, and composite reliability were performed. RESULTS: The easiest scale to obtain a high score was "Scale 4. Social support for health" and the hardest was "Scale 7. Navigating the healthcare system." Nine one-factor models fitted well. The nine-factor structural equation model fitted the data well. All HLQ scales were homogenous, with composite reliability. CONCLUSIONS: The Korean version of the HLQ has a strong construct and high composite reliability when applied to Korean adults.

Zero Discharge of Dyes and Regeneration of a Washing Solution in Membrane-Based Dye Removal by Cold Plasma Treatment.

Although dye removal from wastewater streams has been investigated via several approaches using adsorbents, resins, or membranes, it is still hard to avoid the fact that dyes are persistently left in the adsorption materials or washing solutions used to regenerate the used adsorbents. In particular, given that cleaning agents are composed of acid/base, organic solvents, or electrolytes, dye adsorption and adsorbent regeneration processes leave behind more hard-to-manage wastewater containing dyes. In this study, we demonstrated that cold plasma (CP) treatment, which is one of the advanced oxidation processes (AOPs), can be used for zero discharge of dyes and regeneration of a washing solution in a membrane-based dye removal process. Specifically, CP treatment was found to successfully remove dyes released from a washing process to regenerate a used membrane, thereby effectively recycling a cleaning solution. As a result, the regenerated washing solution was more favorable for the adsorbed dyes' elution, leading to the successful regeneration of a used membrane without a significant loss of dye removal efficiency. This fact was evidenced by a comparative study on the effect of CP treatment on the reusability of membranes and washing solutions and the kinetic analysis of the AOP of the desorbed dyes. We hope that this study contributes to opening a new door for environmentally friendly and sustainable dye removal.

Concurrent validity, test-retest reliability, and sensitivity of a PostureRite system measurement on dynamic postural sway and risk of fall in cerebral palsy.

BACKGROUND: Accurately diagnosing dynamic postural sway (DPS) is essential for effective and sustainable intervention in children with cerebral palsy (CP). We developed an accurate, inexpensive, and wearable DPS measurement system to measure DPS accurately and consistently during walking and functional activities of daily living. OBJECTIVE: We investigated the validity and reliability of this PostureRite system in children with CP, and the link between PostureRite and clinical measures including gross motor function measure (GMFM), pediatric balance scale (PBS), and fall efficacy scale (FES). METHODS: Twenty-one participants were categorized as follows: 11 healthy adults (3 females, mean age, 25.00±1.00 years) and 10 children with CP (mean age, 11.10±6.28 years). We determined the concurrent validity of PostureRite by comparing DPS data to the gold standard accelerometer measurement results. We determined test-retest reliability by measuring DPS data on three occasions at 2-h intervals. We assessed PostureRite measurement sensitivity to ascertain differences between healthy children and children with CP DPS measurements. RESULTS: Random and mixed intraclass correlation coefficients (ICC2,k and ICC3,k) were obtained; an independent T-test was performed (P < 0.05). Concurrent validity analysis showed a good relationship between the gold standard accelerometer and PostureRite (ICC2,k = 0.973, P < 0.05). Test-retest reliability demonstrated a good relationship across the three repeated measures of the DPS data (ICC3,k = 0.816-0.924, P < 0.05). Independent T-test revealed a significant difference in DPS data between healthy adults and children with CP (P < 0.05). CONCLUSIONS: We developed a portable, wireless, and affordable PostureRite system to measure DPS during gross motor function associated with daily activity and participation, and established the concurrent validity, test-retest reliability as sensitivity, and clinical relevance by comparing the DPS obtained from the participants with and without CP.

Design and Synthesis of Conformationally Diverse Pyrimidine-Embedded Medium/Macro- and Bridged Cycles via Skeletal Transformation.

The rigidity and flexibility of small molecules are complementary in 3-dimensional ligand-protein interaction. Therefore, the chemical library with conformational diversity would be a valuable resource for investigating the influence of skeletal flexibility on the biological system. In this regard, we designed and synthesized ten conformationally diverse pyrimidine-embedded medium/macro- and bridged cyclic scaffolds covering 7- to 14-member rings via an efficient skeletal transformation strategy. Their high conformational and shape diversity was confirmed by chemoinformatic analysis.

Magnon-Coupled Intralayer Moiré Trion in Monolayer Semiconductor-Antiferromagnet Heterostructures.

Moiré fringe patterns created by stacking different 2D layered materials as artificial van der Waals (vdW) heterostructures have become a novel platform to study and engineer optically generated excitonic properties. The moiré patterns contribute to the formation of spatially ordered excitonic states (excitons and trions), which can be used in the quantum simulation of many-body systems and ensembles of coherent quantum light emitters. The intriguing moiré excitonic properties are affected by and controlled via the interaction with magnetic elements. Here, a moiré excitonic system interacting with the magnetic elementary excitation of antiferromagnetic orders in MoSe2 /MnPS3 vdW heterostructures is reported. The low-temperature photoluminescence spectra with additional fine spectral structures on the low-energy side, which are coupled magnon-trion peaks below the Néel temperature of MnPS3 , are carefully investigated. The fine spectral structures with long lifetime and coherence time are assigned to intralayer trion-magnon complexes trapped in the moiré potentials (moiré trion-magnon complexes). These findings highlight the emergence of moiré trion-magnon complexes and provide a new way to explore novel quantum phenomena in moiré excitonic systems with magnetic functionalities.

The Pattern of Care for Brain Metastasis from Breast Cancer over the Past 10 Years in Korea: A Multicenter Retrospective Study (KROG 16-12).

PURPOSE: We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea. MATERIALS AND METHODS: We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients). RESULTS: Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance. CONCLUSION: The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years.