Background: We conducted a prospective randomized controlled trial comparing surgery alone (S) with concurrent chemoradiotherapy followed by surgery (CRT-S) for resectable esophageal squamous cell ...carcinoma (SCC) based on our previous report. Patients and methods: One hundred and one patients with stage II/III esophageal SCC were randomized to receive either S (50 patients) or CRT-S (51 patients). The chemoradiotherapy (CRT) consisted of cisplatin 60 mg/m2 intravenously (i.v.) on day 1, 5-fluorouracil (5-FU) 1000 mg/m2 i.v. on days 2–5, cisplatin 60 mg/m2 i.v. on day 22 combined with radiation therapy (45.6 Gy, 1.2 Gy b.i.d. on days 1–28). Surgery was performed 3–4 weeks after radiotherapy was completed. For patients with disease that was stable or responsive to CRT, three additional cycles of chemotherapy (cisplatin 60 mg/m2 i.v. on day 1, 5-FU 1000 mg/m2 on days 2–5 every 4 weeks) were given after surgical resection. Results: The median age was 62 years. The toxicity of CRT was acceptable and did not affect the post-operative morbidity and the duration of hospital stay. Clinical response was 86% including 21% of complete response (CR) rate. Pathological CR was achieved in 43% 95% confidence interval (CI) 27–59 of the patients who underwent surgery after CRT. At a median follow-up of 25 months, median overall survival (OS) was 27.3 months in S and 28.2 months in CRT-S (P = 0.69). Event-free survival (EFS) at 2 years was 51% in S and 49% in CRT-S (P = 0.93). This trial, which was statistically powered to detect a relatively large difference in 2-year survival rate from 30% to 50% with 80% power, was discontinued at interim analysis because of the unexpectedly high drop-out rate for esophagectomy (31%) and resultant excessive locoregional failure rate in CRT-S arm (22% versus 12%, P = 0.31), though it was not statistically significant. Conclusion: Although preoperative CRT induced high clinical and pathological response, there was no statistically significant benefit in OS and EFS.
A superconducting transition temperature (Tc) as high as 100 K was recently discovered in one monolayer FeSe grown on SrTiO3. The discovery ignited efforts to identify the mechanism for the markedly ...enhanced Tc from its bulk value of 8 K. There are two main views about the origin of the Tc enhancement: interfacial effects and/or excess electrons with strong electron correlation. Here, we report the observation of superconductivity below 20 K in surface electron-doped bulk FeSe. The doped surface layer possesses all the key spectroscopic aspects of the monolayer FeSe on SrTiO3. Without interfacial effects, the surface layer state has a moderate Tc of 20 K with a smaller gap opening of 4.2 meV. Our results show that excess electrons with strong correlation cannot induce the maximum Tc, which in turn reveals the need for interfacial effects to achieve the highest Tc in one monolayer FeSe on SrTiO3.
Migraine carries an increased risk for cardiovascular and cerebrovascular diseases that cannot be explained by traditional cardiovascular risk factors. The circulating endothelial progenitor cell ...(EPC) number is a surrogate biologic marker of vascular function, and diminished EPC counts are associated with higher cardiovascular risk. We investigated whether abnormalities in EPC levels and functions are present in migraine patients.
Consecutive headache patients (n =166) were enrolled, including those with tension type headache (TTH; n = 74), migraine without aura (MO; n = 67), and migraine with aura (MA; n = 25). EPC colony-forming units in peripheral blood samples and migratory capacity to chemoattractants (stromal cell-derived factor 1 and vascular endothelial growth factor) and cellular senescence levels were assayed in risk factor-matched subjects (n = 6 per group).
The TTH group had more cardiovascular risk factors, more headache days, and higher Framingham risk scores than the other two groups. Mean numbers of EPC colony-forming units were 47.8 +/- 24.3 in TTH, 20.4 +/-22.2 in MO, and 8.6 +/- 10.1 in MA patients (p < 0.001 in TTH vs MO; p = 0.001 in MO vs MA). EPC colony counts of normal subjects (n = 37) were not significantly different from those with TTH. Multiple linear regression models identified only MO, MA, and the presence of migraine (MO + MA) as significant predictors of EPC levels. In addition, EPCs from migraine patients (MO and MA) showed reduced migratory capacity and increased cellular senescence compared with EPCs from TTH or normal subjects.
Circulating endothelial progenitor cell (EPC) numbers and functions are reduced in migraine patients, suggesting that EPCs can be an underlying link between migraine and cardiovascular risk.
Recent studies have suggested potential roles of the microbiome in cervicovaginal diseases. However, there has been no report on the cervical microbiome in cervical intraepithelial neoplasia (CIN). ...We aimed to identify the cervical microbiota of Korean women and assess the association between the cervical microbiota and CIN, and to determine the combined effect of the microbiota and human papillomavirus (HPV) on the risk of CIN. The cervical microbiota of 70 women with CIN and 50 control women was analysed using pyrosequencing based on the 16S rRNA gene. The associations between specific microbial patterns or abundance of specific microbiota and CIN risk were assessed using multivariate logistic regression, and the relative excess risk due to interaction (RERI) and the synergy index (S) were calculated. The phyla Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, Tenericutes, Fusobacteria and TM7 were predominant in the microbiota and four distinct community types were observed in all women. A high score of the pattern characterized by predominance of Atopobium vaginae, Gardnerella vaginalis and Lactobacillus iners with a minority of Lactobacillus crispatus had a higher CIN risk (OR 5.80, 95% CI 1.73‒19.4) and abundance of A. vaginae had a higher CIN risk (OR 6.63, 95% CI 1.61‒27.2). The synergistic effect of a high score of this microbial pattern and oncogenic HPV was observed (OR 34.1, 95% CI 4.95‒284.5; RERI/S, 15.9/1.93). A predominance of A. vaginae, G. vaginalis and L. iners with a concomitant paucity of L. crispatus in the cervical microbiota was associated with CIN risk, suggesting that bacterial dysbiosis and its combination with oncogenic HPV may be a risk factor for cervical neoplasia.
Aortic pulse wave velocity (AoPWV) and augmentation index (AIx) are commonly used measures of large elastic artery stiffness and wave reflection, respectively. Recently, a new cuff-based SphygmoCor ...device (Xcel) has been developed to measure both AoPWV and AIx. We sought to examine the following: (1) the validity of Xcel compared with the well-validated tonometry-based SphygmoCor device (MM3); (2) the intratest and day-to-day reliability of Xcel; (3) the influence of body side (right or left) on Xcel measurements; and (4) the relation of Xcel measurements to carotid artery compliance, distensibility and β-stiffness index. We found that measurements of AoPWV and AIx between Xcel and MM3 were not different (P=0.26 and P=0.43, N=22 and 26, respectively) and were strongly related (r=0.85 and 0.75, P<0.0001), and based on Bland-Altman plots there was good agreement between them. Intra-test (intraclass correlation=0.996 and 0.983, P<0.0001; AoPWV and AIx, N=24 and 26, respectively) and day-to-day reliability (intraclass correlation=0.979 and 0.939, P<0.0001) were high. Xcel AoPWV and AIx on the left versus right body side were not different (P=0.19 and P=0.58, N=14 and 15, respectively) and were highly correlated (r=0.99 and 0.94, P<0.0001). AoPWV and AIx measured with Xcel were positively related with β-stiffness index (r=0.62 and 0.51, P< or = 0.005, N=23 and 24, respectively) and negatively related with distensibility (r = -0.58 and -0.44, P < or = 0.02, N=23 and 24, respectively). In conclusion, Xcel measures of AIx and AoPWV are valid, highly reliable and not affected by body side. Xcel is a useful tool for use in research and the clinic.
Summary
Oxidative stress is involved in the pathophysiology of rheumatoid arthritis (RA). We investigated the therapeutic potential of rebamipide, a gastroprotective agent with a property of reactive ...oxygen species scavenger, on the development of inflammatory polyarthritis and the pathophysiological mechanisms by which rebamipide might confer anti‐arthritic effects in SKG mice, an animal model of RA. Intraperitoneal (i.p.) injection of rebamipide attenuated the severity of clinical and histological arthritis. Rebampide treatment reduced the number of T helper type 1 (Th1), Th2, Th17, inducible T cell co‐stimulator (ICOS)+ follicular helper T (Tfh) transitional type (T2) and mature B cells in the spleen, but increased the number of regulatory T (Treg), CD19+ CD1dhigh CD5high, CD19+ CD25high forkhead box protein 3 (FoxP3)+ regulatory B (Breg) cells, memory B cells, and transitional type 1 (T1) B cells. In addition, flow cytometric analysis revealed significantly decreased populations of FAS+GL‐7+ germinal centre B cells and B220− CD138+ plasma cells in the spleens of rebamipide‐treated SKG mice compared to controls. Rebamipide decreased germinal centre B cells and reciprocally induced Breg cells in a dose‐dependent manner in vitro. Rebamipide‐induced Breg cells had more suppressive capacity in relation to T cell proliferation and also inhibited Th17 differentiation from murine CD4+ T cells. Together, these data show that i.p. administration of rebamipide suppresses arthritis severity by inducing Breg and Treg cells and suppressing Tfh and Th17 cells in a murine model of RA.
The path of tokamak fusion and International thermonuclear experimental reactor (ITER) is maintaining high-performance plasma to produce sufficient fusion power. This effort is hindered by the ...transient energy burst arising from the instabilities at the boundary of plasmas. Conventional 3D magnetic perturbations used to suppress these instabilities often degrade fusion performance and increase the risk of other instabilities. This study presents an innovative 3D field optimization approach that leverages machine learning and real-time adaptability to overcome these challenges. Implemented in the DIII-D and KSTAR tokamaks, this method has consistently achieved reactor-relevant core confinement and the highest fusion performance without triggering damaging bursts. This is enabled by advances in the physics understanding of self-organized transport in the plasma edge and machine learning techniques to optimize the 3D field spectrum. The success of automated, real-time adaptive control of such complex systems paves the way for maximizing fusion efficiency in ITER and beyond while minimizing damage to device components.
The presence of a di-unsaturated highly branched isoprenoid (HBI) lipid biomarker (diene II) in Southern Ocean sediments has previously been proposed as a proxy measure of palaeo Antarctic sea ice. ...Here we show that a source of diene II is the sympagic diatom Berkeleya adeliensis Medlin. Furthermore, the propensity for B. adeliensis to flourish in platelet ice is reflected by an offshore downward gradient in diene II concentration in >100 surface sediments from Antarctic coastal and near-coastal environments. Since platelet ice formation is strongly associated with super-cooled freshwater inflow, we further hypothesize that sedimentary diene II provides a potentially sensitive proxy indicator of landfast sea ice influenced by meltwater discharge from nearby glaciers and ice shelves, and re-examination of some previous diene II downcore records supports this hypothesis. The term IPSO25-Ice Proxy for the Southern Ocean with 25 carbon atoms-is proposed as a proxy name for diene II.
New limits are presented on the cross section for weakly interacting massive particle (WIMP) nucleon scattering in the KIMS CsI(Tℓ) detector array at the Yangyang Underground Laboratory. The exposure ...used for these results is 24 524.3 kg·days. Nuclei recoiling from WIMP interactions are identified by a pulse shape discrimination method. A low energy background due to alpha emitters on the crystal surfaces is identified and taken into account in the analysis. The detected numbers of nuclear recoils are consistent with zero and 90% confidence level upper limits on the WIMP interaction rates are set for electron equivalent energies from 3 to 11 keV. The 90% upper limit of the nuclear recoil event rate for 3.6-5.8 keV corresponding to 2-4 keV in NaI(Tℓ) is 0.0098 counts/kg/keV/day, which is below the annual modulation amplitude reported by DAMA. This is incompatible with interpretations that enhance the modulation amplitude such as inelastic dark matter models. We establish the most stringent cross section limits on spin-dependent WIMP-proton elastic scattering for the WIMP masses greater than 20 GeV/c2.
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