Cancer immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced cancers. However, the tumor microenvironment (TME) functions as a formidable barrier that ...severely impairs the efficacy of ICIs. While the crosstalk between tumor vessels and immune cells determines the nature of anti-tumor immunity, it is skewed toward a destructive cycle in growing tumors. First, the disorganized tumor vessels hinder CD8
T cell trafficking into the TME, disable effector functions, and even kill T cells. Moreover, VEGF, the key driver of angiogenesis, interferes with the maturation of dendritic cells, thereby suppressing T cell priming, and VEGF also induces TOX-mediated exhaustion of CD8
T cells. Meanwhile, a variety of innate and adaptive immune cells contribute to the malformation of tumor vessels. Protumoral M2-like macrophages as well as T
2 and Treg cells secrete pro-angiogenic factors that accelerate uncontrolled angiogenesis and promote vascular immaturity. While CD8
T and CD4
T
1 cells suppress angiogenesis and induce vascular maturation by secreting IFN-γ, they are unable to infiltrate the TME due to malformed tumor vessels. These findings led to preclinical studies that demonstrated that simultaneous targeting of tumor vessels and immunity is a viable strategy to normalize aberrant vascular-immune crosstalk and potentiate cancer immunotherapy. Furthermore, this combination strategy has been evidently demonstrated through recent pivotal clinical trials, granted approval from FDA, and is now being used in patients with kidney, liver, lung, or uterine cancer. Overall, combining anti-angiogenic therapy and ICI is a valid therapeutic strategy that can enhance cancer immunity and will further expand the landscape of cancer treatment.
As many devices for human utility aim for fast and convenient communication with users, superb electronic devices are demonstrated to serve as hardware for human–machine interfaces in wearable forms. ...Wearable devices for daily healthcare and self‐diagnosis offer more human‐like properties unconstrained by deformation. In this sense, stretchable ionics based on flexible and stretchable hydrogels are on the rise as another means to develop wearable devices for bioapplications for two main reasons: i) ionic currents and choosing the same signal carriers for biological areas, and ii) the adoption of hydrogel ionic conductors, which are intrinsically stretchable materials with biocompatibility. Here, the current status of stretchable ionics and future applications are introduced, whose positive effects can be magnified by stretchable ionics.
Stretchable ionics are becoming central to wearable devices, adopting polymer‐based materials including hydrogels as stretchable ionic conductors. Stretchable and transparent touch panels, loudspeakers, and generators, as well as stretchable electroluminescent actuators are developed. In bridging electronics with biological studies, further progress in the development stretchable ionics for human–machine interfaces is anticipated.
Highly stretchable, transparent ionic touch panel Kim, Chong-Chan; Lee, Hyun-Hee; Oh, Kyu Hwan ...
Science (American Association for the Advancement of Science),
08/2016, Letnik:
353, Številka:
6300
Journal Article
Recenzirano
Because human-computer interactions are increasingly important, touch panels may require stretchability and biocompatibility in order to allow integration with the human body. However, most touch ...panels have been developed based on stiff and brittle electrodes. We demonstrate an ionic touch panel based on a polyacrylamide hydrogel containing lithium chloride salts. The panel is soft and stretchable, so it can sustain a large deformation. The panel can freely transmit light information because the hydrogel is transparent, with 98% transmittance for visible light. A surface-capacitive touch system was adopted to sense a touched position. The panel can be operated under more than 1000% areal strain without sacrificing its functionalities. Epidermal touch panel use on skin was demonstrated by writing words, playing a piano, and playing games.
Recent technological advances in nanomaterials have driven the development of high‐performance light‐emitting devices with flexible and stretchable form factors. Deformability in such devices is ...mainly achieved by replacing the rigid materials in the device components with flexible nanomaterials and their assemblies (e.g., carbon nanotubes, silver nanowires, graphene, and quantum dots) or with intrinsically soft materials and their composites (e.g., polymers and elastomers). Downscaling the dimensions of the functional materials to the nanometer range dramatically decreases their flexural rigidity, and production of polymer/elastomer composites with functional nanomaterials provides light‐emitting devices with flexibility and stretchability. Furthermore, monolithic integration of these light‐emitting devices with deformable sensors furnishes the resulting display with various smart functions such as force/capacitive touch‐based data input, personalized health monitoring, and interactive human–machine interfacing. These ultrathin, lightweight, and deformable smart optoelectronic devices have attracted widespread interest from materials scientists and device engineers. Here, a comprehensive review of recent progress concerning these flexible and stretchable smart displays is presented with a focus on materials development, fabrication techniques, and device designs. Brief overviews of an integrated system of advanced smart displays and cutting‐edge wearable sensors are also presented, and, to conclude, a discussion of the future research outlook is given.
The recent research developments and progress regarding flexible and stretchable smart displays are reviewed comprehensively. Important advancements concerning materials development, fabrication techniques, and device designs are summarized, compared, and discussed, with a detailed description of smart display applications. In addition, the outlook for future research in this field is discussed.
Background
With improved short-term surgical outcomes, laparoscopic distal gastrectomy has rapidly gained popularity. However, the safety and feasibility of laparoscopic total gastrectomy (LTG) has ...not yet been proven due to the difficulty of the technique. This single-arm prospective multi-center study was conducted to evaluate the use of LTG for clinical stage I gastric cancer.
Methods
Between October 2012 and January 2014, 170 patients with pathologically proven, clinical stage I gastric adenocarcinoma located at the proximal stomach were enrolled. Twenty-two experienced surgeons from 19 institutions participated in this clinical trial. The primary end point was the incidence of postoperative morbidity and mortality at postoperative 30 days. The severity of postoperative complications was categorized according to Clavien–Dindo classification, and the incidence of postoperative morbidity and mortality was compared with that in a historical control.
Results
Of the enrolled patients, 160 met criteria for inclusion in the full analysis set. Postoperative morbidity and mortality rates reached 20.6% (33/160) and 0.6% (1/160), respectively. Fifteen patients (9.4%) had grade III or higher complications, and three reoperations (1.9%) were performed. The incidence of morbidity after LTG in this trial did not significantly differ from that reported in a previous study for open total gastrectomy (18%).
Conclusions
LTG performed by experienced surgeons showed acceptable postoperative morbidity and mortality for patients with clinical stage I gastric cancer.
It is unclear whether laparoscopic distal gastrectomy for locally advanced gastric cancer is oncologically equivalent to open distal gastrectomy. The noninferiority of laparoscopic subtotal ...gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer compared with open surgery in terms of 3-year relapse-free survival rate was evaluated.
A phase III, open-label, randomized controlled trial was conducted for patients with histologically proven locally advanced gastric adenocarcinoma suitable for distal subtotal gastrectomy. The primary end point was the 3-year relapse-free survival rate; the upper limit of the hazard ratio (HR) for noninferiority was 1.43 between the laparoscopic and open distal gastrectomy groups.
From November 2011 to April 2015, 1,050 patients were randomly assigned to laparoscopy (n = 524) or open surgery (n = 526). After exclusions, 492 patients underwent laparoscopic surgery and 482 underwent open surgery and were included in the analysis. The laparoscopy group, compared with the open surgery group, suffered fewer early complications (15.7%
23.4%, respectively;
= .0027) and late complications (4.7%
9.5%, respectively;
= .0038), particularly intestinal obstruction (2.0%
4.4%, respectively;
= .0447). The 3-year relapse-free survival rate was 80.3% (95% CI, 76.0% to 85.0%) for the laparoscopy group and 81.3% (95% CI, 77.0% to 85.0%; log-rank
= .726) for the open group. Cox regression analysis after stratification by the surgeon revealed an HR of 1.035 (95% CI, 0.762 to 1.406; log-rank
= .827;
for noninferiority = .039). When stratified by pathologic stage, the HR was 1.020 (95% CI, 0.751 to 1.385; log-rank
= .900;
for noninferiority = .030).
Laparoscopic distal gastrectomy with D2 lymphadenectomy was comparable to open surgery in terms of relapse-free survival for patients with locally advanced gastric cancer. Laparoscopic distal gastrectomy with D2 lymphadenectomy could be a potential standard treatment option for locally advanced gastric cancer.
The antioxidant activities of 18 typical phenolic acids were investigated using 2, 2'-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion reducing antioxidant power (FRAP) assays. Five thermodynamic ...parameters involving hydrogen atom transfer (HAT), single-electron transfer followed by proton transfer (SET-PT), and sequential proton-loss electron transfer (SPLET) mechanisms were calculated using density functional theory with the B3LYP/UB3LYP functional and 6-311++G (d, p) basis set and compared in the phenolic acids. Based on the same substituents on the benzene ring, -CH
COOH and -CH = CHCOOH can enhance the antioxidant activities of phenolic acids, compared with -COOH. Methoxyl (-OCH
) and phenolic hydroxyl (-OH) groups can also promote the antioxidant activities of phenolic acids. These results relate to the O-H bond dissociation enthalpy of the phenolic hydroxyl group in phenolic acids and the values of proton affinity and electron transfer enthalpy (ETE) involved in the electron donation ability of functional groups. In addition, we speculated that HAT, SET-PT, and SPLET mechanisms may occur in the DPPH reaction system. Whereas SPLET was the main reaction mechanism in the FRAP system, because, except for 4-hydroxyphenyl acid, the ETE values of the phenolic acids in water were consistent with the experimental results.
Stretchable electronics are mechanically compatible with a variety of objects, especially with the soft curvilinear contours of the human body, enabling human‐friendly electronics applications that ...could not be achieved with conventional rigid electronics. Therefore, extensive research effort has been devoted to the development of stretchable electronics, from research on materials and unit device, to fully integrated systems. In particular, material‐processing technologies that encompass the synthesis, assembly, and patterning of intrinsically stretchable electronic materials have been actively investigated and have provided many notable breakthroughs for the advancement of stretchable electronics. Here, the latest studies of such material‐based approaches are reviewed, mainly focusing on intrinsically stretchable electronic nanocomposites that generally consist of conducting/semiconducting filler materials inside or on elastomer backbone matrices. Various approaches for fabricating these intrinsically stretchable electronic materials are presented, including the blending of electronic fillers into elastomer matrices, the formation of bi‐layered heterogeneous electronic‐layer and elastomer support‐layer structures, and modifications to polymeric molecular structures in order to impart stretchability. Detailed descriptions of the various conducting/semiconducting composites prepared by each method are provided, along with their electrical/mechanical properties and examples of device applications. To conclude, a brief future outlook is presented.
The latest research developments and progress regarding material‐based approaches for the fabrication of stretchable electronics are comprehensively reviewed. Detailed descriptions of various stretchable conducting/semiconducting composites are given, along with their electrical/mechanical properties, material processing strategies, and examples of device applications. In addition, the outlook for future research in this field is discussed.
infection and a family history of gastric cancer are the main risk factors for gastric cancer. Whether treatment to eradicate
can reduce the risk of gastric cancer in persons with a family history of ...gastric cancer in first-degree relatives is unknown.
In this single-center, double-blind, placebo-controlled trial, we screened 3100 first-degree relatives of patients with gastric cancer. We randomly assigned 1838 participants with
infection to receive either eradication therapy (lansoprazole 30 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, each taken twice daily for 7 days) or placebo. The primary outcome was development of gastric cancer. A prespecified secondary outcome was development of gastric cancer according to
eradication status, assessed during the follow-up period.
A total of 1676 participants were included in the modified intention-to-treat population for the analysis of the primary outcome (832 in the treatment group and 844 in the placebo group). During a median follow-up of 9.2 years, gastric cancer developed in 10 participants (1.2%) in the treatment group and in 23 (2.7%) in the placebo group (hazard ratio, 0.45; 95% confidence interval CI, 0.21 to 0.94; P = 0.03 by log-rank test). Among the 10 participants in the treatment group in whom gastric cancer developed, 5 (50.0%) had persistent
infection. Gastric cancer developed in 0.8% of participants (5 of 608) in whom
infection was eradicated and in 2.9% of participants (28 of 979) who had persistent infection (hazard ratio, 0.27; 95% CI, 0.10 to 0.70). Adverse events were mild and were more common in the treatment group than in the placebo group (53.0% vs. 19.1%; P<0.001).
Among persons with
infection who had a family history of gastric cancer in first-degree relatives,
eradication treatment reduced the risk of gastric cancer. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT01678027.).
Exohiss waves below 0.1 electron cyclotron frequency (fce) are structureless whistler‐mode emissions typically observed in the plasmatrough. Plasmaspheric hiss may possibly propagate from the ...plasmasphere into the plasmatrough and evolve into exohiss waves. We investigated the relationship of exohiss occurrence and characteristics with plasmaspheric hiss occurrence and solar wind parameters, analyzing Van Allen Probe observations from 1 October 2012 to 28 February 2018. Exohiss waves observed in the plasmatrough occurred more frequently on the dayside than the nightside, which was consistent with the plasmaspheric hiss distribution in the plasmasphere. Exohiss occurrence gradually increased up to ∼4 hr after hiss measurements and showed a magnetic local time dependence on the plasmaspheric hiss amplitude. We also determined the relative contribution of each solar wind parameter to exohiss distribution as based on exohiss measurements made 0–4 hr after plasmaspheric hiss measurements. A stronger southward interplanetary magnetic field (IMF) BZ limited the region of exohiss occurrence to the prenoon sector, again consistent with the distribution of plasmaspheric hiss. Prenoon exohiss was also observed for stronger dynamic pressure (PSW), but the plasmaspheric hiss appeared in the postnoon sector. This discrepancy indicated that prenoon exohiss is locally excited rather than a product of plasmaspheric hiss leakage. In addition, during enhanced solar wind conditions with southward IMF BZ or higher PSW, the intensity of the lower‐band chorus was enhanced even below 0.1fce, corresponding to the frequency range of the exohiss, implying that the nightside exohiss may be related to the evolution of low‐frequency chorus waves.
Key Points
Exohiss waves occur mainly on the dayside. They coincide with and increase up to 4 hr after intense plasmaspheric hiss waves
Exohiss shows magnetic local time dependence, and dayside exohiss is also dependent on solar wind conditions
A low‐frequency chorus most likely evolves into nightside exohiss