Forkhead box O (FOXO) transcription factors are involved in multiple signaling pathways and play critical roles in a number of physiological and pathological processes including cancer. The ...importance of FOXO factors ascribes them under multiple levels of regulation including phosphorylation, acetylation/deacetylation, ubiquitination and protein-protein interactions. As FOXO factors play a pivotal role in cell fate decision, mounting evidence suggests that FOXO factors function as tumor suppressors in a variety of cancers. FOXOs are actively involved in promoting apoptosis in a mitochondria-independent and -dependent manner by inducing the expression of death receptor ligands, including Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand, and Bcl-2 family members, such as Bim, bNIP3 and Bcl-X(L), respectively. An understanding of FOXO proteins and their biology will provide new opportunities for developing more effective therapeutic approaches to treat cancer.
The past decade has witnessed adoption of conservative gynecologic treatments, including minimally invasive surgery (MIS), alongside steady declines in inpatient hysterectomies. It remains unclear ...what factors have contributed to trends in outpatient benign hysterectomy (BH), as well as whether these trends exacerbate disparities.
Retrospective cohort of 527,964 women ≥18 years old who underwent BH from 2008 to 2014. BH surgical approaches included: open/abdominal hysterectomy (AH), vaginal hysterectomy (VH), laparoscopic hysterectomy (LH), and robotic-assisted hysterectomy (RH). Quarterly frequencies were calculated by care setting and surgical approach. We used multilevel logistic regression (MLR) using the most recent year of data (2014) to examine the influence of patient-, physician-, and hospital-level preoperative factors and surgical approaches on outpatient migration.
From 2008-2014, surgical approaches for LH and RH increased, which coincided with decreases in VH and AH. Overall, a 44.2% shift was observed from inpatient to outpatient settings (P<0.0001). Among all outpatient visits MIS increased, particularly for RH (3.6% to 41.07%). We observed increases in the proportion of non-Hispanic Black and Medicaid patients who obtained MIS in 2014 vs. 2008 (P<0.001). Surgical approach (51.8%) and physician outpatient MIS experience (19.9%) had the greatest influence on predicting outpatient BH. Compared with LH, RH was associated with statistically significantly higher likelihood of outpatient BH overall (OR 1.23; 95% CI, 1.16-1.31), as well as in sub-analyses of more complex cases and hospitals that performed ≥1 RH (P<0.05).
From 2008-2014, rates of LH and RH significantly increased. A significant shift from inpatient to outpatient setting was observed. These findings suggest that RH may facilitate the shift to outpatient BH, particularly for patients with complexities. The adoption of MIS in outpatient settings may improve access to disadvantaged patient groups.
The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross section is by far the largest of all low-energy neutrino couplings. This ...mode of interaction offers new opportunities to study neutrino properties and leads to a miniaturization of detector size, with potential technological applications. We observed this process at a 6.7σ̃ confidence level, using a low-background, 14.6-kilogram CsINa scintillator exposed to the neutrino emissions from the Spallation Neutron Source at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the standard model for this process, were observed in high signal-to-background conditions. Improved constraints on nonstandard neutrino interactions with quarks are derived from this initial data set.
Sub-picosecond magnetisation manipulation via femtosecond optical pumping has attracted wide attention ever since its original discovery in 1996. However, the spatial evolution of the magnetisation ...is not yet well understood, in part due to the difficulty in experimentally probing such rapid dynamics. Here, we find evidence of a universal rapid magnetic order recovery in ferrimagnets with perpendicular magnetic anisotropy via nonlinear magnon processes. We identify magnon localisation and coalescence processes, whereby localised magnetic textures nucleate and subsequently interact and grow in accordance with a power law formalism. A hydrodynamic representation of the numerical simulations indicates that the appearance of noncollinear magnetisation via optical pumping establishes exchange-mediated spin currents with an equivalent 100% spin polarised charge current density of 10
A cm
. Such large spin currents precipitate rapid recovery of magnetic order after optical pumping. The magnon processes discussed here provide new insights for the stabilization of desired meta-stable states.
The paper focuses on the impact of emission ‘cap-and-trade’ mechanism in a so-called emission-dependent supply chain with the emission permit supplier and the emission-dependent firm. In the ...cap-and-trade system, emission permit becomes one of key factors of production for emission-dependent firms. Two major sources of emission permits are considered—emission cap/quota imposed by the government, and permits purchased via emission trading. If the quota is insufficient to satisfy the target production, extra permits should be purchased via trading. In this case, the traditional non-profit green organizations may be endowed with the role of emission permit suppliers. Thus, the introduction of market mechanism injects new life into environment protection. In the context of newsvendor, the paper investigates the behavior and decision-making of each member in the emission-dependent supply chain. A game-theoretical analytical model is proposed and the unique Nash equilibrium is derived. In their own self-interest, the emission permit supplier and the emission-dependent firm make their optimal decisions on permits pricing and production quantity respectively. Players’ bargaining power in the game is affected by several exogenous factors, such as the governmental environment policy, the market risk, etc. Several valuable managerial insights on bargaining power affected by external factors (such as environmental policies, market risks, etc.) are further concluded.
Apelin has been reported to regulate mitochondrial function in myocardial ischemia-reperfusion injury and cerebral ischemia-reperfusion injury. However, the role of apelin-13 in lung ...ischemia-reperfusion injury (LIRI) remains unclear. This study established an experimental rat model to evaluate the underlying mechanisms of apelin-13 on LIRI. Twenty-four rats were randomly divided to sham operation group (group SM), ischemia/reperfusion group (group IR), and apelin-13 treatment group (group APL). The effects of apelin-13 on LIRI were determined histologically using H&E staining, while the wet/dry weight ratio was used to assess lung edema caused by LIRI. Inflammatory cytokines were also detected in Bronchoalveolar lavage (BAL) fluid by ELISA. The protein expression of UCP2 and the morphological changes of mitochondria were determined by western blotting and electromicroscopy, respectively. The results demonstrated the structural damage of lung tissues and lung edema in group IR. An increased level of inflammatory cytokines including IL-1β, IL-6 and TNF-α was observed in rats with LIRI using ELISA. After that, oxidative stress and morphological damage of mitochondria were also shown in group IR. Yet, the application of apelin-13 reversed all these deleterious effects in group APL. The protective effects of apelin-13 were indicated by decreased reactive oxygen species (ROS) and elevated UCP2 expression levels in rats. In conclusion, this study revealed that apelin-13 had protective effects against LIRI via attenuating lung edema, the production of inflammatory cytokines, oxidative stress and mitochondrial dysfunction.
A survey of the key issues associated with the development in the Chinese iron and steel industry and current situations of energy consumption are described in this paper. The apparent production of ...crude steel in China expanded to 418.78 million tonnes in 2006, which was about 34% share of the world steel production. The iron and steel industry in China is still one of the major high energy consumption and high pollution industries, which accounts for the consumption of about 15.2% of the national total energy, and generation of 14% of the national total wastewater and waste gas and 6% of the total solid waste materials. The average energy consumption per unit of steel is about 20% higher than that of other advanced countries due to its low energy utilization efficiency. However, the energy efficiency of the iron and steel industry in China has made significant improvement in the past few years and significant energy savings will be achieved in the future by optimizing end-use energy utilization. Finally, some measures for the industry in terms of the economic policy of China's 11th five-year plan are also presented.
The KamLAND-Zen experiment has provided stringent constraints on the neutrinoless double-beta (0νββ) decay half-life in ^{136}Xe using a xenon-loaded liquid scintillator. We report an improved search ...using an upgraded detector with almost double the amount of xenon and an ultralow radioactivity container, corresponding to an exposure of 970 kg yr of ^{136}Xe. These new data provide valuable insight into backgrounds, especially from cosmic muon spallation of xenon, and have required the use of novel background rejection techniques. We obtain a lower limit for the 0νββ decay half-life of T_{1/2}^{0ν}>2.3×10^{26} yr at 90% C.L., corresponding to upper limits on the effective Majorana neutrino mass of 36-156 meV using commonly adopted nuclear matrix element calculations.
Resting-state functional magnetic resonance imaging is currently the mainstay of functional neuroimaging and has allowed researchers to identify intrinsic connectivity networks (aka functional ...networks) at different spatial scales. However, little is known about the temporal profiles of these networks and whether it is best to model them as continuous phenomena in both space and time or, rather, as a set of temporally discrete events. Both categories have been supported by series of studies with promising findings. However, a critical question is whether focusing only on time points presumed to contain isolated neural events and disregarding the rest of the data is missing important information, potentially leading to misleading conclusions. In this work, we argue that brain networks identified within the spontaneous blood oxygenation level-dependent (BOLD) signal are not limited to temporally sparse burst moments and that these event present time points (EPTs) contain valuable but incomplete information about the underlying functional patterns.
We focus on the default mode and show evidence that is consistent with its continuous presence in the BOLD signal, including during the event absent time points (EATs), i.e., time points that exhibit minimum activity and are the least likely to contain an event. Moreover, our findings suggest that EPTs may not contain all the available information about their corresponding networks. We observe distinct default mode connectivity patterns obtained from all time points (AllTPs), EPTs, and EATs. We show evidence of robust relationships with schizophrenia symptoms that are both common and unique to each of the sets of time points (AllTPs, EPTs, EATs), likely related to transient patterns of connectivity. Together, these findings indicate the importance of leveraging the full temporal data in functional studies, including those using event-detection approaches.
Reduction in cardiovascular death and hospitalization for heart failure (HHF) was recently reported with the sodium-glucose cotransporter-2 inhibitor (SGLT-2i) empagliflozin in patients with type 2 ...diabetes mellitus who have atherosclerotic cardiovascular disease. We compared HHF and death in patients newly initiated on any SGLT-2i versus other glucose-lowering drugs in 6 countries to determine if these benefits are seen in real-world practice and across SGLT-2i class.
Data were collected via medical claims, primary care/hospital records, and national registries from the United States, Norway, Denmark, Sweden, Germany, and the United Kingdom. Propensity score for SGLT-2i initiation was used to match treatment groups. Hazard ratios for HHF, death, and their combination were estimated by country and pooled to determine weighted effect size. Death data were not available for Germany.
After propensity matching, there were 309 056 patients newly initiated on either SGLT-2i or other glucose-lowering drugs (154 528 patients in each treatment group). Canagliflozin, dapagliflozin, and empagliflozin accounted for 53%, 42%, and 5% of the total exposure time in the SGLT-2i class, respectively. Baseline characteristics were balanced between the 2 groups. There were 961 HHF cases during 190 164 person-years follow-up (incidence rate, 0.51/100 person-years). Of 215 622 patients in the United States, Norway, Denmark, Sweden, and the United Kingdom, death occurred in 1334 (incidence rate, 0.87/100 person-years), and HHF or death in 1983 (incidence rate, 1.38/100 person-years). Use of SGLT-2i, versus other glucose-lowering drugs, was associated with lower rates of HHF (hazard ratio, 0.61; 95% confidence interval, 0.51-0.73;
<0.001); death (hazard ratio, 0.49; 95% confidence interval, 0.41-0.57;
<0.001); and HHF or death (hazard ratio, 0.54; 95% confidence interval, 0.48-0.60;
<0.001) with no significant heterogeneity by country.
In this large multinational study, treatment with SGLT-2i versus other glucose-lowering drugs was associated with a lower risk of HHF and death, suggesting that the benefits seen with empagliflozin in a randomized trial may be a class effect applicable to a broad population of patients with type 2 diabetes mellitus in real-world practice.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02993614.