Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant ...chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC.
The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146).
A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable.
In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.
•In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy.•The addition of radiotherapy to chemotherapy did not significantly reduce the rate of recurrence after D2 gastrectomy.•DFS between patients treated with adjuvant chemotherapy and chemoradiotherapy was similar across all subgroups, including Lauren classification.
We present a comprehensive study of the nonproportionality of NaI(Tl) scintillation detectors within the context of dark matter search experiments. Our investigation, which integrates COSINE-100 data ...with supplementary
γ
spectroscopy, measures light yields across diverse energy levels from full-energy
γ
peaks produced by the decays of various isotopes. These
γ
peaks of interest were produced by decays supported by both long and short-lived isotopes. Analyzing peaks from decays supported only by short-lived isotopes presented a unique challenge due to their limited statistics and overlapping energies, which was overcome by long-term data collection and a time-dependent analysis. A key achievement is the direct measurement of the 0.87 keV light yield, resulting from the cascade following electron capture decay of
22
Na
from internal contamination. This measurement, previously accessible only indirectly, deepens our understanding of NaI(Tl) scintillator behavior in the region of interest for dark matter searches. This study holds substantial implications for background modeling and the interpretation of dark matter signals in NaI(Tl) experiments.
We report a new fluorescent chemosensor that displays an excellent selectivity for pyrophosphate over adenosine triphosphate or phosphate in 100% aqueous solution. A unique fluorescent change was ...observed upon formation of a 2+2 excimer of the chemosensor.
Summary Background The effects of malaria and its treatment in the first trimester of pregnancy remain an area of concern. We aimed to assess the outcome of malaria-exposed and malaria-unexposed ...first-trimester pregnancies of women from the Thai–Burmese border and compare outcomes after chloroquine-based, quinine-based, or artemisinin-based treatments. Methods We analysed all antenatal records of women in the first trimester of pregnancy attending Shoklo Malaria Research Unit antenatal clinics from May 12, 1986, to Oct 31, 2010. Women without malaria in pregnancy were compared with those who had a single episode of malaria in the first trimester. The association between malaria and miscarriage was estimated using multivariable logistic regression. Findings Of 48 426 pregnant women, 17 613 (36%) met the inclusion criteria: 16 668 (95%) had no malaria during the pregnancy and 945 (5%) had a single episode in the first trimester. The odds of miscarriage increased in women with asymptomatic malaria (adjusted odds ratio 2·70, 95% CI 2·04–3·59) and symptomatic malaria (3·99, 3·10–5·13), and were similar for Plasmodium falciparum and Plasmodium vivax . Other risk factors for miscarriage included smoking, maternal age, previous miscarriage, and non-malaria febrile illness. In women with malaria, additional risk factors for miscarriage included severe or hyperparasitaemic malaria (adjusted odds ratio 3·63, 95% CI 1·15–11·46) and parasitaemia (1·49, 1·25–1·78 for each ten-fold increase in parasitaemia). Higher gestational age at the time of infection was protective (adjusted odds ratio 0·86, 95% CI 0·81–0·91). The risk of miscarriage was similar for women treated with chloroquine (92 26% of 354), quinine (95 27%) of 355), or artesunate (20 31% of 64; p=0·71). Adverse effects related to antimalarial treatment were not observed. Interpretation A single episode of falciparum or vivax malaria in the first trimester of pregnancy can cause miscarriage. No additional toxic effects associated with artesunate treatment occurred in early pregnancy. Prospective studies should now be done to assess the safety and efficacy of artemisinin combination treatments in early pregnancy. Funding Wellcome Trust and Bill & Melinda Gates Foundation.
Salt stress negatively affects growth and development of plants. However, it is hypothesized that plant growth‐promoting endophytic bacteria can greatly alleviate the adverse effects of salinity and ...can promote growth and development of plants. In the present research, we aimed to isolate endophytic bacteria from halotolerant plants and evaluate their capacity for promoting crop plant growth.
The bacterial endophytes were isolated from selected plants inhabiting sand dunes at Pohang beach, screened for plant growth‐promoting traits and applied to rice seedlings under salt stress (NaCl; 150 mm).
Out of 59 endophytic bacterial isolates, only six isolates, i.e. Curtobacterium oceanosedimentum SAK1, Curtobacterium luteum SAK2, Enterobacter ludwigii SAK5, Bacillus cereus SA1, Micrococcus yunnanensis SA2, Enterobacter tabaci SA3, resulted in a significant increase in the growth of Waito‐C rice. The cultural filtrates of bacterial endophytes were tested for phytohormones, including indole‐3‐acetic acid, gibberellins and organic acids. Inoculation of the selected strains considerably reduced the amount of endogenous ABA in rice plants under NaCl stress, however, they increased GSH and sugar content. Similarly, these strains augmented the expression of flavin monooxygenase (OsYUCCA1) and auxin efflux carrier (OsPIN1) genes under salt stress.
In conclusion, the pragmatic application of the above selected bacterial strains alleviated the adverse effects of NaCl stress and enhanced rice growth attributes by producing various phytohormones.
Endophytic bacteria greatly enhanced growth of rice plants under 150 mm of NaCl stress by mitigating phytohormones, antioxidants, sugar content and gene expression.
Microlensing is a powerful and unique technique to probe isolated objects in the Galaxy. To study the characteristics of these interesting objects based on the microlensing method, measurement of the ...microlens parallax is required to determine the properties of the lens. Of the various methods to measure microlens parallax, the most routine way is to make simultaneous ground- and space-based observations, i.e., by measuring the space-based microlens parallax. However, space-based campaigns usually require "expensive" resources. Gould & Yee (2012) proposed an idea called the "cheap space-based microlens parallax" that can measure the lens-parallax using only two or three space-based observations of high-magnification events (as seen from Earth). This cost-effective observation strategy to measure microlens parallaxes could be used by space-borne telescopes to build a complete sample for studying isolated objects. This would enable a direct measurement of the mass function including both extremely low-mass objects and high-mass stellar remnants. However, to adopt this idea requires a test to check how it would work in actual situations. Thus, we present the first practical test of this idea using the high-magnification microlensing event OGLE-2016-BLG-1045, for which a subset of Spitzer observations fortuitously duplicates the prescription of Gould & Yee (2012). From the test, we confirm that the measurement of the lens-parallax adopting this idea has sufficient accuracy to determine the physical properties of the isolated lens.
Magma oceans were once ubiquitous in the early solar system, setting up the initial conditions for different evolutionary paths of planetary bodies. In particular, the redox conditions of magma ...oceans may have profound influence on the redox state of subsequently formed mantles and the overlying atmospheres. The relevant redox buffering reactions, however, remain poorly constrained. Using first-principles simulations combined with thermodynamic modeling, we show that magma oceans of Earth, Mars, and the Moon are likely characterized with a vertical gradient in oxygen fugacity with deeper magma oceans invoking more oxidizing surface conditions. This redox zonation may be the major cause for the Earth's upper mantle being more oxidized than Mars' and the Moon's. These contrasting redox profiles also suggest that Earth's early atmosphere was dominated by CO
and H
O, in contrast to those enriched in H
O and H
for Mars, and H
and CO for the Moon.
We present the analysis of OGLE-2016-BLG-0613, for which the lensing light curve appears to be that of a typical binary-lens event with two caustic spikes but with a discontinuous feature on the ...trough between the spikes. We find that the discontinuous feature was produced by a planetary companion to the binary lens. We find four degenerate triple-lens solution classes, each composed of a pair of solutions according to the well-known wide/close planetary degeneracy. One of these solution classes is excluded due to its relatively poor fit. For the remaining three pairs of solutions, the most-likely primary mass is about , while the planet is a super Jupiter. In all cases, the system lies in the Galactic disk, about halfway toward the Galactic bulge. However, in one of these three solution classes, the secondary of the binary system is a low-mass brown dwarf, with relative mass ratios (1:0.03:0.003), while in the two others the masses of the binary components are comparable. These two possibilities can be distinguished in about 2024 when the measured lens-source relative proper motion will permit separate resolution of the lens and source.
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. ...Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear.
Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7). Cigarette smoke extract (CSE) is an established model for studying the effects of cigarette smoke exposure in vitro. In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC) inhibitor rapidly induced autophagy. CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1) and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression. Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression. Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion. Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis. Egr-1(-/-) mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema.
We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo. The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury.
Background
Whether rescue surgery confers a survival benefit in patients undergoing non‐curative endoscopic resection of early gastric cancer remains controversial.
Methods
This was a retrospective ...review of patients who underwent non‐curative endoscopic resection of at least one lesion of differentiated‐type early gastric cancer between 2000 and 2011. Patients with a positive lateral resection margin as the only non‐curative factor were excluded. Outcome was investigated by univariable (Kaplan–Meier) and multivariable (Cox proportional hazards) analysis.
Results
Some 341 patients underwent non‐curative endoscopic resection for at least one lesion of differentiated‐type early gastric cancer. Sixty‐seven patients with a positive lateral resection margin as the only non‐curative factor were excluded, leaving 274 patients for analysis; 194 had rescue surgery and 80 had no additional treatment. The median duration of follow‐up was 60·5 months. Patients who had rescue surgery were younger, had a lower Charlson co‐morbidity index score, smaller tumours and a higher lymphovascular invasion rate than patients with no treatment. Among 194 patients who had rescue surgery, intragastric local residual tumours were found in ten (5·2 per cent) and lymph node metastases in 11 (5·7 per cent). Patients with lymph node metastasis were significantly older than those without metastasis; no other significant differences were found. Univariable analysis showed that patients aged less than 65 years, those with a Charlson co‐morbidity index score below 4 and patients undergoing rescue surgery had significantly longer overall survival. Five‐year overall survival rates in the rescue surgery and no‐treatment groups were 94·3 and 85 per cent respectively. In multivariable analysis, rescue surgery was identified as the only independent predictor of overall survival after non‐curative endoscopic resection of early gastric cancer.
Conclusion
Rescue surgery confers a survival benefit after non‐curative endoscopic resection of early gastric cancer.
Improves survival in fit patients
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