An experiment to search for light sterile neutrinos is conducted at a reactor with a thermal power of 2.8 GW located at the Hanbit nuclear power complex. The search is done with a detector consisting ...of a ton of Gd-loaded liquid scintillator in a tendon gallery approximately 24 m from the reactor core. The measured antineutrino event rate is 1976 per day with a signal to background ratio of about 22. The shape of the antineutrino energy spectrum obtained from the eight-month data-taking period is compared with a hypothesis of oscillations due to active-sterile antineutrino mixing. No strong evidence of 3+1 neutrino oscillation is found. An excess around the 5 MeV prompt energy range is observed as seen in existing longer-baseline experiments. The mixing parameter sin^{2}2θ_{14} is limited up to less than 0.1 for Δm_{41}^{2} ranging from 0.2 to 2.3 eV^{2} with a 90% confidence level.
The RENO experiment reports more precisely measured values of θ_{13} and |Δm_{ee}^{2}| using ∼2200 live days of data. The amplitude and frequency of reactor electron antineutrino (νover ¯_{e}) ...oscillation are measured by comparing the prompt signal spectra obtained from two identical near and far detectors. In the period between August 2011 and February 2018, the far (near) detector observed 103 212 (850 666) νover ¯_{e} candidate events with a background fraction of 4.8% (2.0%). A clear energy and baseline dependent disappearance of reactor νover ¯_{e} is observed in the deficit of the measured number of νover ¯_{e}. Based on the measured far-to-near ratio of prompt spectra, we obtain sin^{2}2θ_{13}=0.0896±0.0048(stat)±0.0047(syst) and |Δm_{ee}^{2}|=2.68±0.12(stat)±0.07(syst)×10^{-3} eV^{2}.
Scedosporium spp. is the most common mold infection in pneumonia resulting from near‐drowning. Three fatal scedosporiosis cases developed after solid organ transplantation, probably transmitted from ...the nearly‐drowned donor. One heart transplant recipient and two kidney transplant recipients developed fatal scedosporiosis following deceased donor transplantation from the same donor, a nearly‐drowned victim of a suicide attempt. Genotypically, indistinguishable strains of Scedosporium auratiacum were recovered from the three recipients. Two liver transplant recipients from the same donor received prophylactic voriconazole without any subsequent signs of infection. To determine the safety of donation from nearly‐drowned donors, a national traceback investigation was also performed of the causes of deaths in all transplant recipients who received organs from drowned donors between 2001 and 2013. Over 13 years, 2600 deceased donor transplants were performed in Korea. Among these 2600 deceased donor transplants, 27 (1%) victims of drowning donated their organs. From these 27 donors, 84 patients received organ transplants and 18 died, including the above three. We found no microbiologic evidence of invasive mold transmission from the nearly‐drowned donors to the other 15 recipients. Although disseminated infection in the donor could not be demonstrated by culture, undiagnosed disseminated donor infection and transmission of Scedosporium spp. should be considered in near‐drowning events.
The authors describe their experience of one heart recipient and two kidney recipients with fatal scedosporiosis following deceased donor transplantation from the same donor, a nearly drowned victim of a suicide attempt.
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.
Summary Objective Runt-related transcription factor 2 (Runx2) and Osterix (Osx) are the master transcription factors in bone formation. Nonetheless, genes acting downstream of both Runx2 and Osx have ...yet to be fully characterized. Here, we investigate the downstream targets of both Runx2 and Osx in osteoblasts. Materials and methods DNA microarray analysis was conducted on calvarial RNA from wild-type, Runx2 heterozygous, Osx heterozygous, and Runx2 / Osx double heterozygous embryos. Expression and transcriptional responses of the selected target gene were analyzed in MC3T3-E1 osteoblastic cells. Results The expression of unique cartilage matrix-associated protein ( Ucma ) was decreased in Runx2 / Osx double heterozygous embryos. In contrast, Ucma expression was increased in osteoblasts overexpressing both Runx2 and Osx. Ucma expression was initiated mid-way through osteoblast differentiation and continued throughout the differentiation process. Transcriptional activity of the Ucma promoter was increased upon transfection of the cells with both Runx2 and Osx . Runx2-and Osx-mediated activation of the Ucma promoter was directly regulated by Runx2-and/or Sp1-binding sites within its promoter. During osteoblast differentiation, the formation of mineralized nodules in Ucma -overexpressing stable clones occurred earlier and was more enhanced than that in the mock-transfected control. Mineralized nodule formation was strongly augmented in the cells cultured in a medium containing secretory Ucma proteins. Conclusion Ucma is a novel downstream gene regulated by both Runx2 and Osx and it stimulates osteoblast differentiation and nodule formation.
Summary
Background
Atrophic gastritis and intestinal metaplasia are premalignant conditions for gastric cancer. Their reversibility by Helicobacter pylori eradication remains controversial.
Aim
To ...evaluate the reversibility of atrophic gastritis and intestinal metaplasia by H. pylori eradication with long‐term follow‐up.
Methods
598 subjects were prospectively enrolled and followed for up to 10 years. They were categorised as H. pylori‐negative (n = 65), H. pylori non‐eradicated (n = 91), and H. pylori‐eradicated (n = 442). Histological assessment was performed for antrum and corpus by Sydney classification.
Results
Histological follow‐up was performed regularly at 1, 2, 3‐4 and ≥5 years, with mean follow‐up of 1.07 ± 0.21, 2.29 ± 0.83, 3.93 ± 1.02, and 6.45 ± 1.28 years, respectively. Atrophic gastritis in antrum and corpus gradually and significantly (both P < .05 for all timepoints) improved only in the H. pylori‐eradicated group compared to that at baseline. Significant difference in atrophic gastritis between H. pylori‐eradicated and H. pylori‐negative groups disappeared from 1‐year follow‐up. Similarly, intestinal metaplasia in antrum and corpus improved significantly (both P < .05 for all timepoints) only in the H. pylori‐eradicated group in comparison with that at baseline. Significant difference in intestinal metaplasia between H. pylori‐eradicated and H. pylori‐negative groups disappeared from ≥5 years of follow‐up in the antrum and from 3 years of follow‐up in the corpus.
Conclusion
H. pylori eradication may be a preventative strategy for intestinal‐type gastric cancer by regression of atrophic gastritis and intestinal metaplasia.
Linked ContentThis article is linked to Genta and Kim and Hwang papers. To view these articles visit https://doi.org/10.1111/apt.14491 and https://doi.org/10.1111/apt.14524.
The mechanism of primary resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small-cell lung cancer (NSCLC) has not been clearly understood.
...Eleven patients exhibiting primary resistance (disease progression <3 months) were identified among 197 consecutive NSCLC patients with TKI-sensitive EGFR mutations who received EGFR TKIs at Seoul National University Hospital. Treatment-naïve tumors were examined for concurrent genetic alterations using fluorescence in situ hybridization and targeted deep sequencing of cancer-related genes. Deletion polymorphism of Bcl-2-interacting mediator of cell death (BIM) gene was examined to validate its predictive role for TKI outcome.
The median progression-free survival (PFS) for patients receiving EGFR TKIs was 11.9 months, and the response rate 78.8%. Among the 11 patients exhibiting primary resistance, a de novo T790M mutation was identified in one patient, and two exhibited mesenchymal-epithelial transition amplification and anaplastic lymphoma kinase fusion. Targeted deep sequencing identified no recurrent, coexistent drivers of NSCLC. Survival analysis revealed that patients with recurrent disease after surgery had a longer PFS than those with initial stage IV disease. However, BIM deletion polymorphism, line of treatment, EGFR genotype, and smoking were not predictive of PFS for EGFR TKIs.
We identified coexistent genetic alterations of cancer-related genes that could explain primary resistance in a small proportion of patients. Our result suggests that the mechanism of primary resistance might be heterogeneous.
We report a fuel-dependent reactor electron antineutrino (νover ¯_{e}) yield using six 2.8 GW_{th} reactors in the Hanbit nuclear power plant complex, Yonggwang, Korea. The analysis uses 850 666 ...νover ¯_{e} candidate events with a background fraction of 2.0% acquired through inverse beta decay (IBD) interactions in the near detector for 1807.9 live days from August 2011 to February 2018. Based on multiple fuel cycles, we observe a fuel ^{235}U dependent variation of measured IBD yields with a slope of (1.51±0.23)×10^{-43} cm^{2}/fission and measure a total average IBD yield of (5.84±0.13)×10^{-43} cm^{2}/fission. The hypothesis of no fuel-dependent IBD yield is ruled out at 6.6σ. The observed IBD yield variation over ^{235}U isotope fraction does not show significant deviation from the Huber-Mueller (HM) prediction at 1.3 σ. The measured fuel-dependent variation determines IBD yields of (6.15±0.19)×10^{-43} and (4.18±0.26)×10^{-43} cm^{2}/fission for two dominant fuel isotopes ^{235}U and ^{239}Pu, respectively. The measured IBD yield per ^{235}U fission shows the largest deficit relative to the HM prediction. Reevaluation of the ^{235}U IBD yield per fission may mostly solve the reactor antineutrino anomaly (RAA) while ^{239}Pu is not completely ruled out as a possible contributor to the anomaly. We also report a 2.9 σ correlation between the fractional change of the 5 MeV excess and the reactor fuel isotope fraction of ^{235}U.
Identifying the extent of environmental contamination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for infection control and prevention. The extent of environmental ...contamination has not been fully investigated in the context of severe coronavirus disease (COVID-19) patients.
To investigate environmental SARS-CoV-2 contamination in the isolation rooms of severe COVID-19 patients requiring mechanical ventilation or high-flow oxygen therapy.
Environmental swab samples and air samples were collected from the isolation rooms of three COVID-19 patients with severe pneumonia. Patients 1 and 2 received mechanical ventilation with a closed suction system, while patient 3 received high-flow oxygen therapy and non-invasive ventilation. Real-time reverse transcription–polymerase chain reaction (rRT–PCR) was used to detect SARS-CoV-2; viral cultures were performed for samples not negative on rRT–PCR.
Of the 48 swab samples collected in the rooms of patients 1 and 2, only samples from the outside surfaces of the endotracheal tubes tested positive for SARS-CoV-2 by rRT–PCR. However, in patient 3's room, 13 of the 28 environmental samples (fomites, fixed structures, and ventilation exit on the ceiling) showed positive results. Air samples were negative for SARS-CoV-2. Viable viruses were identified on the surface of the endotracheal tube of patient 1 and seven sites in patient 3's room.
Environmental contamination of SARS-CoV-2 may be a route of viral transmission. However, it might be minimized when patients receive mechanical ventilation with a closed suction system. These findings can provide evidence for guidelines for the safe use of personal protective equipment.
Neutrino elastic scattering observation with NaI (NEON) is an experiment designed to detect neutrino-nucleus coherent scattering using reactor electron antineutrinos. NEON is based on an array of six ...NaI(Tl) crystals with a total mass of 13.3 kg, located at the tendon gallery that is 23.7 m away from a reactor core with a thermal power of 2.8 GW in the Hanbit nuclear power complex. The installation of the NEON detector was completed in December 2020, and since May 2021, the detector has acquired data at full reactor power. Based on the observed light yields of the NaI crystals of approximately 22, number of photoelectrons per unit keV electron-equivalent energy (keVee), and 6 counts/kg/keV/day background level at 2–6 keVee energy, coherent elastic neutrino-nucleus scattering (CE
ν
NS) observation sensitivity is evaluated as more than 3
σ
assuming 1-year reactor-on and 100 days reactor-off data, 0.2 keVee energy threshold, and 7 counts/keV/kg/day background in the signal region of 0.2
-
0.5 keVee. This paper describes the design of the NEON detector, including the shielding arrangement, configuration of NaI(Tl) crystals, and associated operating systems. The initial performance and associated sensitivity of the experiment are also presented.
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