Endocrine treatment is recommended by clinical guidelines as the preferred treatment option for premenopausal as well as postmenopausal women with hormone receptor-positive, HER2-negative metastatic ...breast cancer. In real-world clinical practice, however, a substantial number of patients are treated with chemotherapy. We aimed to compare the clinical antitumour activity and safety of palbociclib plus endocrine therapy with that of capecitabine chemotherapy in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer.
This multicentre, open-label, randomised, phase 2 study was done in 14 academic institutions in South Korea. Premenopausal women aged 19 years or older with hormone receptor-positive, HER2-negative breast cancer that had relapsed or progressed during previous tamoxifen therapy and with an Eastern Cooperative Oncology Group performance status of 0–2 were included. One line of previous chemotherapy for metastatic breast cancer was allowed. Patients were randomly assigned, using a random permuted block design (with a block size of two), to receive palbociclib plus combination endocrine therapy (oral exemestane 25 mg per day for 28 days and oral palbociclib 125 mg per day for 21 days every 4 weeks plus leuprolide 3·75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1250 mg/m2 twice daily for 2 weeks every 3 weeks). Randomisation was stratified by previous chemotherapy for metastatic breast cancer and visceral metastasis. The primary endpoint was progression-free survival. All analyses were done in a modified intention-to-treat population that excluded patients who did not receive study medication. This study is registered with ClinicalTrials.gov, NCT02592746, and is ongoing for follow-up of overall survival.
Between June 15, 2016, and Dec 10, 2018, 189 patients were enrolled, of whom 184 were randomly assigned to the palbociclib plus endocrine therapy group (n=92) or the capecitabine group (n=92). Six patients in the capecitabine group withdrew from the study before drug administration; therefore, 92 patients in the palbociclib plus endocrine therapy group and 86 patients in the capecitabine group were included in the modified intention-to-treat analyses. 46 (50%) of 92 patients in the palbociclib plus endocrine therapy group and 45 (51%) of 92 in the capecitabine group were treatment naive for metastatic breast cancer. During a median follow-up of 17 months (IQR 9–22), median progression-free survival was 20·1 months (95% CI 14·2–21·8) in the palbociclib plus endocrine therapy group versus 14·4 months (12·1–17·0) in the capecitabine group (hazard ratio 0·659 95% CI 0·437–0·994, one-sided log-rank p=0·0235). Treatment-related grade 3 or worse neutropenia was more common in the palbociclib plus endocrine therapy group than in the capecitabine group (69 75% of 92 vs 14 16% of 86 patients). 2 (2%) patients in the palbociclib plus endocrine therapy group and 15 (17%) patients in the capecitabine group had treatment-related serious adverse events. No treatment-related deaths occurred.
Exemestane plus palbociclib with ovarian function suppression showed clinical benefit compared with capecitabine in terms of improved progression-free survival in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Palbociclib plus exemestane with ovarian suppression is an active treatment option in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer who have been pretreated with tamoxifen.
Pfizer, Shinpoong, and Daewoong Korea and Takeda.
The self-discharge behaviour of Li–S cell, is investigated through changes in the open-circuit voltage (OCV) and discharge capacity with storage time. A fresh Li–S cell experiences 72% sulfur ...utilization during the first discharge, as based on the theoretical capacity for the formation of Li
2S. After 30 days of storage, the OCV has fallen from 2.48 to 2.16
V and the discharge capacity has decreased from 1206 to 924
mAh
g
−1 (based on sulfur). Analysis of the self-discharged sample by a variety of techniques shows the formation of lithium polysulfides, such as Li
2S
n
(
n ≥ 1) from the reaction of lithium and sulfur, which is related to the corrosion of the stainless current-collector. Stainless steel is not the most appropriate current-collector material for Li–S cells. The extent of self-discharge can be decreased by using a gold-coated current-collector that offers protection against corrosion.
To evaluate validity and reliability of the food-frequency questionnaire (FFQ) developed for the Korean Genome Epidemiologic Study (KoGES).
FFQ was administered twice at 1-year interval (first FFQ ...(FFQ1) at the beginning and second FFQ (FFQ2) at the end of the study) and diet records (DRs) were collected for 3 days during each of the four seasons from December 2002 to May 2004 for those who attended the health examination center. At the end of the study period, we collected the 12-day DRs of 124 participants. The nutrient intakes from the DRs were compared with both FFQ1 and FFQ2.
The intakes of energy and some nutrients estimated from FFQ1 and FFQ2 were different from those assessed by the DRs. Especially, the consumption of carbohydrates was higher in FFQ1 and FFQ2 than in the DRs. The de-attenuated, age, sex and energy intake adjusted correlation coefficients between the FFQ2 and the 12-day DRs in Korean population ranged between 0.23 (Vitamin A) and 0.64 (carbohydrate). The median for all nutrients was 0.39. The correlations were similar when we compared nutrient densities of both methods. Joint classification of calorie-adjusted nutrient intakes assessed by FFQ2 and 12-day DRs by quartile ranged from 25.8% (vitamin A) to 39.5% (carbohydrate, iron) for exact concordance. Except vitamin A, the proportion of subjects classified into distant quartile was less than 7% in all nutrients. The median of correlations between the two FFQs 1 year apart were 0.45 for all nutrient intakes and 0.39 for nutrient densities.
We conclude that the FFQ we have developed appears to be an acceptable tool for assessing the nutrient intakes in this population. Further studies for calibration of the FFQ collected from multicenters participating in the KoGES are needed.
This study was supported by the budget of the National Genome Research Institute, Korea National Institute of Health (2002-347-6111-221).
There has been reported that the association between nodal spread and tumor size was disrupted in triple-negative breast cancer (TNBC) and it showed characteristically early relapse. The TNM ...(tumor–node–metastasis) staging system might not be equally effective as a prognostic indicator for all subtypes. The aim of our study was to evaluate the usefulness of the staging according to subtypes.
We conducted a retrospective analysis of invasive breast cancer patients who received curative surgery at Samsung Medical Center from 2000 to 2004. Relapse-free survivals (RFS) by stage were analyzed.
Thousand eight hundred and seventy-nine patients who were available clinicopathologic data were included. These patients were divided into three subtypes: hormone receptor (HR)+, human epidermal growth factor receptor 2+, and triple negative groups. As the stage became more advanced, the slope of each stage of the RFS curves of patients with HR+ and HER2+ steadily increased. In contrast, RFS curves intermingled and showed overlap from stage 1 to 3A in TNBC patients. There was only wide separation of RFS curves between stage 1-3A and 3B-3C in TNBC.
The current TNM staging system might not be enough for encompassing the tumor biology and for predicting outcomes to make therapeutic decisions for all BCs, especially for TNBC patients.
To evaluate the performance of a machine learning based algorithm tool for chest radiographs (CXRs), applied to a consecutive cohort of historical clinical cases, in comparison to expert chest ...radiologists.
The study comprised 1,960 consecutive CXR from primary care referrals and the emergency department (992 and 968 cases respectively), obtained in 2015 at a UK hospital. Two chest radiologists, each with >20 years of experience independently read all studies in consensus to serve as a reference standard. A chest artificial intelligence (AI) algorithm, Lunit INSIGHT CXR, was run on the CXRs, and results were correlated with those by the expert readers. The area under the receiver operating characteristic curve (AUROC) was calculated for the normal and 10 common findings: atelectasis, fibrosis, calcification, consolidation, lung nodules, cardiomegaly, mediastinal widening, pleural effusion, pneumothorax, and pneumoperitoneum.
The ground truth annotation identified 398 primary care and 578 emergency department datasets containing pathologies. The AI algorithm showed AUROC of 0.881–0.999 in the emergency department dataset and 0.881–0.998 in the primary care dataset. The AUROC for each of the findings between the primary care and emergency department datasets did not differ, except for pleural effusion (0.954 versus 0.988, p<0.001).
The AI algorithm can accurately and consistently differentiate normal from major thoracic abnormalities in both acute and non-acute settings, and can serve as a triage tool.
•Validation of this AI tool shows accuracy for 10 common chest radiographic findings.•AI chest radiograph assessment has similar accuracy to expert chest radiologists.•AI chest radiograph assessment can be rolled out for clinical implementation.
We aimed to compare tissue-specific expression profiles and biological pathways of RNA from amniocytes and amniotic fluid supernatant (AFS) from second-trimester pregnancies by using transcriptome ...analysis. Additionally, we wanted to explore whether cell-free RNA from AFS exhibits a unique gene expression signature that more adequately reflects the fetal developmental process than amniocyte RNA.
Amniotic fluid samples were prospectively collected in the second trimester of pregnancy from euploid fetuses. Total RNA was extracted from amniocytes and AFS and hybridized to Affymetrix GeneChip Human Arrays. Significantly differentially expressed transcripts between amniocytes and AFS were obtained by using Welch's t-test. Unsupervised hierarchical clustering was used to visualize overall expression characteristics and differences in transcripts between AFS and amniocytes. The biological functions of selected genes were analyzed using various online Gene Ontology databases.
A total of 3,072 and 15,633 transcripts were detected in the second-trimester AFS and amniocytes, respectively. Hierarchical clustering revealed differential transcript expression between AFS and amniocytes. We found 353 genes that were specifically enriched in the AFS only, and tissue expression analysis showed enrichment of brain-specific genes in the AFS. Biological pathway analysis revealed that AFS-specific transcripts were mainly involved in embryonic development, cardiovascular development, and cellular morphology pathways.
This study demonstrated differential tissue-specific gene expression profiles and biological pathways between AFS and amniocytes. The results suggested that AFS is the preferred RNA source to investigate potential biomarkers of fetal neurodevelopment.
The continuous growth of atmospheric nitrous oxide (N2O) is of concern for its potential role in global warming and future stratospheric ozone destruction. Climate feedbacks that enhance N2O ...emissions in response to global warming are not well understood, and past records of N2O from ice cores are not sufficiently well resolved to examine the underlying climate‐N2O feedbacks on societally relevant time scales. Here, we present a new high‐resolution and high‐precision N2O reconstruction obtained from the Greenland NEEM (North Greenland Eemian Ice Drilling) and the Antarctic Styx Glacier ice cores. Covering the N2O history of the past two millennia, our reconstruction shows a centennial‐scale variability of ~10 ppb. A pronounced minimum at ~600 CE coincides with the reorganizations of tropical hydroclimate and ocean productivity changes. Comparisons with proxy records suggest association of centennial‐ to millennial‐scale variations in N2O with changes in tropical and subtropical land hydrology and marine productivity.
Plain Language Summary
Nitrous oxide (N2O) is a greenhouse and ozone‐depleting gas. The growing level of N2O in the atmosphere is of global concern, and records of past N2O variations can provide an important context for understanding the links between N2O and climate change. In this study, we report new, high‐quality N2O records covering the last two millennia using ice cores obtained from Greenland and Antarctica. Our N2O records show rapid centennial‐scale changes in atmospheric N2O and confirm a pronounced minimum near 600 CE. Comparison with climate records suggests that hydroclimate change on land and changes in marine productivity contribute to centennial‐ to millennial‐scale N2O variations.
Key Points
We report records of N2O concentration for the last 2,000 yr from the Styx ice core in Antarctca and NEEM ice core in Greenland
The data accurately reveal the timing and magnitude of N2O variations on centennial time scales
Variations in N2O are associated with changes in tropical and subtropical land hydrology and marine productivity
Status of LAMPS at RAON Hong, B.; Ahn, D.S.; Ahn, J.K. ...
Nuclear instruments & methods in physics research. Section B, Beam interactions with materials and atoms,
August 2023, 2023-08-00, Letnik:
541
Journal Article
Recenzirano
A new radioactive ion-beam accelerator facility, RAON, is under construction in Korea. Among the seven experimental systems being built, the Large Acceptance Multi-Purpose Spectrometer (LAMPS) in the ...high-energy experimental hall is the versatile detector system for nuclear physics. Its primary goal is to study the nuclear equation of state (EoS) and the symmetry energy of the compressed nuclear matter, which should be essential to understand the effective nuclear interactions and structure of the astrophysical objects like neutron stars. The basic LAMPS system consists of the beam diagnostic elements such as the starting counters and beam drift chambers, the time-projection chamber, the barrel and forward time-of-flight systems, the forward neutron detector array, and the superconducting solenoid magnet. In this paper the overview of the present status of each detector component for LAMPS will be given with some prospects.
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