The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are prognostic factors for various types of cancer. In this study, we assessed the association of NLR and PLR with the ...prognosis of small-cell lung cancer (SCLC) in patients who received the standard treatment.
We retrospectively reviewed patients who were diagnosed with SCLC and treated with platinum-based chemotherapy between July 2006 and October 2013 in Gyeongsang National University Hospital Regional Cancer Center and Changwon Samsung Hospital.
In total, 187 patients were evaluated. Compared with low NLR (<4), high NLR (⩾4) at diagnosis was associated with poor performance status, advanced stage, and lower response rate. Median overall survival (OS) and progression-free survival (PFS) were worse in the high-NLR group (high vs low, 11.17 vs 9.20 months, P=0.019 and 6.90 vs 5.49 months, P=0.005, respectively). In contrast, PLR at diagnosis was not associated with OS or PFS (P=0.467 and P=0.205, respectively). In multivariate analysis, stage, lactate dehydrogenase, and NLR at diagnosis were independent prognostic factors for OS and PFS.
NLR is easily measurable and reflects the SCLC prognosis. A future prospective study is warranted to confirm our results.
Nanotechnologies have attracted increasing attention in their application in medicine, especially in the development of new drug delivery systems. With the help of nano-sized carriers, drugs can ...reach specific diseased areas, prolonging therapeutic efficacy while decreasing undesired side-effects. In addition, recent nanotechnological advances, such as surface stabilization and stimuli-responsive functionalization have also significantly improved the targeting capacity and therapeutic efficacy of the nanocarrier assisted drug delivery system. In this review, we evaluate recent advances in the development of different nanocarriers and their applications in therapeutics delivery.
Nanomedicine is a field of science that uses nanoscale materials for the diagnosis and treatment of human disease. It has emerged as an important aspect of the therapeutics, but at the same time, ...also raises concerns regarding the safety of the nanomaterials involved. Recent applications of functionalized biodegradable nanomaterials have significantly improved the safety profile of nanomedicine.
Our goal is to evaluate different types of biodegradable nanomaterials that have been functionalized for their biomedical applications.
In this review, we used PubMed as our literature source and selected recently published studies on biodegradable nanomaterials and their applications in nanomedicine.
We found that biodegradable polymers are commonly functionalized for various purposes. Their property of being naturally degraded under biological conditions allows these biodegradable nanomaterials to be used for many biomedical purposes, including bio-imaging, targeted drug delivery, implantation and tissue engineering. The degradability of these nanoparticles can be utilized to control cargo release, by allowing efficient degradation of the nanomaterials at the target site while maintaining nanoparticle integrity at off-target sites.
While each biodegradable nanomaterial has its advantages and disadvantages, with careful design and functionalization, biodegradable nanoparticles hold great future in nanomedicine.
Purpose
To present and discuss beam characteristics and commissioning process of the first gantry‐mounted accelerator single room pencil beam scanning (PBS) proton system.
Methods
The Mevion ...HYPERSCAN employs a design configuration with a synchrocyclotron mounted on the gantry to eliminate the traditional beamline and a nozzle that contains the dosimetry monitoring chambers, the energy modulator (Energy Selector (ES)), and an Adaptive Aperture (AA). To characterize the beam, we measured the integrated depth dose (IDDs) for 12 energies, from highest energy of 227 MeV down to 28 MeV with a range difference ~ 2 cm between the adjacent energies, using a large radius Bragg peak chamber; single‐spot profiles in air at five locations along the beam central axis using radiochromic EBT3 film and cross compared with a scintillation detector; and determined the output using a densely packed spot map. To access the performance of AA, we measured interleaf leakage and the penumbra reduction effect. Monte Carlo simulation using TOPAS was performed to study spot size variation along the beam path, beam divergence, and energy spectrum.
Results
This proton system is calibrated to deliver 1 Gy dose at 5 cm depth in water using the highest beam energy by delivering 1 MU/spot to a 10 × 10 cm2 map with a 2.5 mm spot spacing. The spot size in air varies from 4 mm to 26 mm from 227 MeV to 28 MeV at the isocenter plane with the nozzle retracted 23.6 cm from isocenter. The beam divergence of 28 MeV beam is ~ 52.7 mrad, which is nearly 22 times that of 227 MeV proton beam. The binary design of the ES has resulted in shifts of the effective SSD toward the isocenter as the energy is modulated lower. The peaks of IDD curves have a constant 80%‐80% width of 8.4 mm at all energies. The interleaf leakage of the AA is less than 1.5% at the highest energy; and the AA can reduce the penumbra by 2 mm to 13 mm for the 227 and 28 MeV energies at isocenter plane in air.
Conclusions
The unique design of the HYPERSCAN proton system has yielded beam characteristics significantly different from that of other proton systems in terms of the Bragg peak shapes, spot sizes, and the penumbra sharpening effect of the AA. The combination of the ES and AA has made PBS implementation possible without using beam transport line and range shifter devices. Different considerations may be required in treatment planning optimization to account for different design and beam characteristics.
Regulatory T cells (Tregs) are essential for the establishment and maintenance of immune tolerance, suggesting a potential therapeutic role for Tregs in transplantation. However, Treg administration ...alone is insufficient in inducing long‐term allograft survival in normal hosts, likely due to the high frequency of alloreactive T cells. We hypothesized that a targeted reduction of alloreactive T effector cells would allow a therapeutic window for Treg efficacy. Here we show that preconditioning recipient mice with donor‐specific transfusion followed by cyclophosphamide treatment deleted 70–80% donor‐reactive T cells, but failed to prolong islet allograft survival. However, infusion of either 5 × 106 Tregs with direct donor reactivity or 25 × 106 polyclonal Tregs led to indefinite survival of BALB/c islets in more than 70% of preconditioned C57BL/6 recipients. Notably, protection of C3H islets in autoimmune nonobese diabetic mice required islet autoantigen‐specific Tregs together with polyclonal Tregs. Treg therapy led to significant reduction of CD8+ T cells and concomitant increase in endogenous Tregs among graft‐infiltrating cells early after transplantation. Together, these results demonstrate that reduction of the donor‐reactive T cells will be an important component of Treg‐based therapies in transplantation.
This study demonstrates that donor‐reactive regulatory T cells are more potent than polyclonal regulatory T cells in preventing rejection; however, both types require depletion of donor‐reactive T effector cells for optimal efficacy. See editorial by Bradley on page 5.
Dynamic optical isolation with all-optical switching capability is in great demand in advanced optical communications and all-optical signal processing systems. Most conventional optical isolators ...rely on Faraday rotation and are realized using micro/nanofabrication techniques, but it is not always straightforward to incorporate magneto-optical crystals into these compact systems. Here, we report the experimental demonstration of a reconfigurable all-optical isolator based on optical excitation of a gigahertz guided acoustic mode in a micrometre-sized photonic crystal fibre core. This device has remarkable advantages over its passive counterparts, including a large dynamic range of isolation, fast switching capability and reversibility, which provide new functionality that is useful in various types of all-optical systems. Devices based on similar physical principles could also be realized in CMOS-compatible silicon on-chip platforms.
Observations show Arctic sea ice has declined and midlatitude storminess has weakened during Northern Hemisphere (NH) summertime. It is currently unclear whether Arctic sea ice loss impacts ...summertime storminess because most previous work focuses on other seasons. Here we quantify the impact of Arctic sea ice loss on NH summertime storminess using equilibrium and transient climate model simulations. The equilibrium simulations show mid‐to‐late 21st century Arctic sea ice loss weakens summertime storminess, but only in the presence of ocean coupling. With ocean coupling, the equator‐to‐pole temperature and atmospheric energy gradients significantly weaken due to increased surface turbulent flux in the polar region following Arctic sea ice loss. The transient simulations show Arctic sea ice loss does not significantly weaken summertime storminess until the late 21st century. Furthermore, Arctic Amplification, which is dominated by Arctic sea ice loss in the present day, does not significantly impact the present‐day weakening of summertime storminess.
Plain Language Summary
Present‐day summertime climate change in the NH is characterized by rapid Arctic sea ice loss and weakening of weather systems. While these trends are projected to continue throughout the 21st century, their connection is not well understood. Using climate model simulations, we show mid‐to‐late 21st century Arctic sea ice loss weakens the summertime weather system by decreasing the equator‐to‐pole energy (and temperature) difference. In addition, we demonstrate transient Arctic sea ice loss does not significantly contribute to weakening summertime weather system until the late 21st century. The results suggest that present‐day Arctic sea ice loss and Arctic Amplification have not contributed significantly to the observed weakening of weather systems.
Key Points
Equilibrium and transient climate model simulations are used to quantify the summertime storminess response to Arctic sea ice loss
The equilibrium response to mid‐to‐late 21st century Arctic sea ice loss involves weaker summertime storminess due to ocean coupling
The transient weakening of present‐day summertime storminess is not significantly affected by Arctic sea ice loss and Arctic Amplification
In this study, dynamic behavior of a double-helical gear pair is investigated both experimentally and theoretically. In the experimental side, a new double-helical test set-up consisting of a test ...machine and test specimens is developed for operating a double-helical gear pair under realistic torque and speed ranges. A test gear pair formed by novel three-piece double-helical gears is developed to allow adjustable right-to-left stagger angles. A measurement system to capture three-dimensional vibratory motions and dynamic motion transmission error under high-speed conditions is implemented. A test matrix that included various combinations of key system parameters is executed under realistic torque values within a wide speed range to establish a database. In view of this experimental data, a linear, time-invariant dynamic model of double-helical gear pair systems including shafts and bearing supports is proposed, also allowing for any stagger angle between the right and left sides of a double-helical gear pair through proper definition of phasing between the two gear mesh excitations. Direct comparisons to measurements are presented to demonstrate the accuracy of the proposed model in predicting three-dimensional gear vibrations. The right-to-left stagger angle is shown to be the most critical parameter impacting dynamic response.
•Dynamics of a double-helical gear pair is investigated both experimentally and theoretically.•A test set-up is devised to measure 3D motions of the gears.•A dynamic model of the double-helical gear pair is formulated.•Model predictions are shown to agree with measurements well.•Stagger angle is found to be the key parameters impacting dynamic response.
Oxidative stress plays a key role in many physiological and pathological conditions. The intracellular oxidative homeostasis is tightly regulated by the reactive oxygen species production and the ...intracellular defense mechanisms. Increased oxidative stress could alter lipid, DNA, and protein, resulting in cellular inflammation and programmed cell death. Evidences show that oxidative stress plays an important role in the progression of various cardiovascular diseases, such as atherosclerosis, heart failure, cardiac arrhythmia, and ischemia-reperfusion injury. There are a number of therapeutic options to treat oxidative stress-associated cardiovascular diseases. Well known antioxidants, such as nutritional supplements, as well as more novel antioxidants have been studied. In addition, novel therapeutic strategies using miRNA and nanomedicine are also being developed to treat various cardiovascular diseases. In this article, we provide a detailed description of oxidative stress. Then, we will introduce the relationship between oxidative stress and several cardiovascular diseases. Finally, we will focus on the clinical implications of oxidative stress in cardiovascular diseases.
Semitransparent metal electrodes fabricated by nanoimprint lithography (NIL) in the form of nanoscale periodically perforated metal films are reported. They show high transmittance in the visible ...wavelength range as well as excellent electrical conductivities (see figure), and both characteristics can be tuned separately by changing the aperture ratio and the metal thickness. The fabrication of organic light‐emitting diodes (OLEDs) incorporating these transparent conducting electrodes demonstrates their potential use.
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