Summary
Background
Acral melanoma (AM) is the most common histopathological subtype of malignant melanoma in Asians. However, differences in the mutational profiles underlying AM and nonacral ...cutaneous melanoma (NAM) in Asians are not well understood.
Objectives
To augment the understanding of the prevalence, patterns and associations of various mutations between different subtypes of melanoma.
Methods
We performed comprehensive genomic profiling of 409 cancer‐associated genes, using next‐generation sequencing, in 66 primary melanomas comprised of 45 AMs and 21 NAMs.
Results
Most of the AMs (n = 27/45; 60%), but only five of 21 (24%) NAMs, were triple wild‐type (triple‐WT) tumours. Compared with AMs, NAMs exhibited a significantly higher frequency of BRAF mutations. The frequencies of NRAS/KRAS mutations, cell‐cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and gains of receptor tyrosine kinase genes were significantly higher in AMs. Ulceration was found at significantly higher rates in the AMs and NAMs with cell‐cycle aberrations and gains of receptor tyrosine kinase genes. Notably, cell‐cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma‐specific survival in the 66 patients with melanoma and especially in the 45 patients with AM. Multivariate analysis showed that lymph node metastasis and cell‐cycle aberrations were independent prognostic factors of melanoma‐specific survival.
Conclusions
This study strengthens our understanding of the patterns and clinical associations of oncogenic mutations in AMs and NAMs in Asians.
What's already known about this topic?
Mutation frequencies of driver genes vary between melanoma subtypes.
Acral melanoma is the most common subtype of melanoma in Asians.
KIT mutations and copy number variations occur more frequently in the acral subtype of melanoma than in the nonacral subtype
What does this study add?
NRAS/KRAS mutations, cell‐cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and amplifications of receptor tyrosine kinase genes were significantly enriched in acral melanoma and could be potential targets for treatment.
Melanomas with cell‐cycle aberrations and gains in receptor tyrosine kinase genes were significantly more likely to contain ulceration.
What is the translational message?
Cell‐cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma‐specific survival.
These observations should be explored further for future drug development.
Linked Comment: Johansson. Br J Dermatol 2020; 182:1085.
Plain language summary available online
The large-scale distribution of neutral hydrogen in the Universe will be luminous through its 21 cm emission. Here, for the first time, we use the auto-power spectrum of 21 cm intensity fluctuations ...to constrain neutral hydrogen fluctuations at z ∼ 0.8. Our data were acquired with the Green Bank Telescope and span the redshift range 0.6 < z < 1 over two fields totalling 41 deg2 and 190 h of radio integration time. The dominant synchrotron foregrounds exceed the signal by ∼103, but have fewer degrees of freedom and can be removed efficiently. Even in the presence of residual foregrounds, the auto-power can still be interpreted as an upper bound on the 21 cm signal. Our previous measurements of the cross-correlation of 21 cm intensity and the WiggleZ galaxy survey provide a lower bound. Through a Bayesian treatment of signal and foregrounds, we can combine both fields in auto- and cross-power into a measurement of ΩHI
bHI
= 0.62+0.23
−0.15 × 10−3 at 68 per cent confidence with 9 per cent systematic calibration uncertainty, where ΩHI
is the neutral hydrogen (H i) fraction and bHI
is the H i bias parameter. We describe observational challenges with the present data set and plans to overcome them.
FeFETs with 5-nm-thick Hf 0.5 Zr 0.5 O 2 (HZO) have been demonstrated in memory operations for the ON/OFF current ratio >10 4 at zero gate voltage and a memory window (MW) of 0.6-0.7 V. A gradual ...transition of the ferroelectricity with an increasing crystallization temperature for the gate-last process was presented. The excellent data retention are the <inline-formula> <tex-math notation="LaTeX">{\sim }\textsf {2}\times \textsf {10}^{\textsf {4}} </tex-math></inline-formula> ON/OFF ratio and 0.67 V extrapolated to ten years with V P/E = ±4.8 V. The MW remains >0.2 V after 10 6 cycles for read and vanishes with cycles of 10 3 −10 4 for write, which is the bottleneck for ferroelectric (FE)-type memories. The mechanism of retention and endurance is discussed. The characteristic of this letter is an unaffected coercive-field (~1 MV/cm) with scaling FE-HZO down to 5-nm thickness, which is beneficial for reducing the operation voltage. A comparable performance with thick HZO (>5 nm) on high data retention and endurance with low voltage for read is achieved. The ultrathin FE layer proposes a realistic emerging memory for 1T architecture.
Adolescents with intellectual disabilities (ID) who live a sedentary lifestyle may lead to an increased risk of chronic cardiovascular disease in adulthood. The aim of this study is to investigate ...the effects of 8-week progressive rope skipping training on physical, cardiovascular fitness and exercise tolerance of high school students with moderate ID.
Thirty-four senior high school with ID (aged 15-18 years old) were randomised into experimental group received progressive skipping rope exercise (RS, n = 17) and control group no rope skipping exercise intervention group (CON, n = 17). The RS group were received progressive rope skipping exercise for 50 min each time, three times a week, for 8 weeks. The control group was not allowed to participate in intervention activities during the study period. The physical fitness, body composition, arterial stiffness index (ASI) and blood pressure were measured before and after the 8-week intervention.
After the 8-week progressive skipping rope exercise intervention, the participants from the RS group increased in the 3-min step test, sit-up test, grip strength and sit and reach test, when compared to the baseline (P < 0.05). The RS group exhibited lower the area under curve of heart rate (HR) during post-exercise recovery (P < 0.05). The participants in the RS group showed significant decreases in systolic (SBP) and diastolic (DBP) blood pressure, mean arterial pressure (MAP) and HR when compared to the baseline (P < 0.05). Change SBP has moderate positive correlation with change ASI.
The results of this experiment suggest that progressive rope skipping exercise might improve physical fitness and promote cardiovascular health, as well as enhance exercise tolerance for adolescent students with moderate ID.
Glucose transporter GLUT1 is ubiquitously expressed in the human body from the red cells to the blood-brain barrier to the skeletal muscles. It is physiologically relevant to understand how GLUT1 ...facilitates diffusion of glucose across the cell membrane. It is also pathologically relevant because GLUT1 deficiency causes neurological disorders and anemia and because GLUT1 overexpression fuels the abnormal growth of cancer cells. This article presents a quantitative investigation of GLUT1 based on all-atom molecular-dynamics (MD) simulations of the transporter embedded in lipid bilayers of asymmetric inner-and-outer-leaflet lipid compositions, subject to asymmetric intra-and-extra-cellular environments. This is in contrast with the current literature of MD studies that have not considered both of the aforementioned asymmetries of the cell membrane. The equilibrium (unbiased) dynamics of GLUT1 shows that it can facilitate glucose diffusion across the cell membrane without undergoing large-scale conformational motions. The Gibbs free-energy profile, which is still lacking in the current literature of GLUT1, quantitatively characterizes the diffusion path of glucose from the periplasm, through an extracellular gate of GLUT1, on to the binding site, and off to the cytoplasm. This transport mechanism is validated by the experimental data that GLUT1 has low water-permeability, uptake-efflux symmetry, and 10 kcal/mol Arrhenius activation barrier around 37 °C.
Display omitted
•Model system of two membrane patches asymmetric in EC and IC salines•Model RBC membrane asymmetric in inner and outer leaflet lipid compositions•EC-gating mechanism of GLUT1 in quantitative agreement with in vitro data on glucose transport and water permeation
Background
Increasing evidence has indicated an association between immune infiltration in gastric cancer and clinical outcome. However, reliable prognostic signatures, based on systematic ...assessments of the immune landscape inferred from bulk tumour transcriptomes, have not been established. The aim was to develop an immune signature, based on the cellular composition of the immune infiltrate inferred from bulk tumour transcriptomes, to improve the prognostic predictions of gastric cancer.
Methods
Twenty‐two types of immune cell fraction were estimated based on large public gastric cancer cohorts from the Gene Expression Omnibus using CIBERSORT. An immunoscore based on the fraction of immune cell types was then constructed using a least absolute shrinkage and selection operator (LASSO) Cox regression model.
Results
Using the LASSO model, an immunoscore was established consisting of 11 types of immune cell fraction. In the training cohort (490 patients), significant differences were found between high‐ and low‐immunoscore groups in overall survival across and within subpopulations with an identical TNM stage. Multivariable analysis revealed that the immunoscore was an independent prognostic factor (hazard ratio 1·92, 95 per cent c.i. 1·54 to 2·40). The prognostic value of the immunoscore was also confirmed in the validation (210) and entire (700) cohorts.
Conclusion
The proposed immunoscore represents a promising signature for estimating overall survival in patients with gastric cancer.
Immunoscore predicts prognosis
Visualizing individual molecules with chemical recognition is a longstanding target in catalysis, molecular nanotechnology and biotechnology. Molecular vibrations provide a valuable 'fingerprint' for ...such identification. Vibrational spectroscopy based on tip-enhanced Raman scattering allows us to access the spectral signals of molecular species very efficiently via the strong localized plasmonic fields produced at the tip apex. However, the best spatial resolution of the tip-enhanced Raman scattering imaging is still limited to 3-15 nanometres, which is not adequate for resolving a single molecule chemically. Here we demonstrate Raman spectral imaging with spatial resolution below one nanometre, resolving the inner structure and surface configuration of a single molecule. This is achieved by spectrally matching the resonance of the nanocavity plasmon to the molecular vibronic transitions, particularly the downward transition responsible for the emission of Raman photons. This matching is made possible by the extremely precise tuning capability provided by scanning tunnelling microscopy. Experimental evidence suggests that the highly confined and broadband nature of the nanocavity plasmon field in the tunnelling gap is essential for ultrahigh-resolution imaging through the generation of an efficient double-resonance enhancement for both Raman excitation and Raman emission. Our technique not only allows for chemical imaging at the single-molecule level, but also offers a new way to study the optical processes and photochemistry of a single molecule.
Abstract
We report results from 21-cm intensity maps acquired from the Parkes radio telescope and cross-correlated with galaxy maps from the 2dF galaxy survey. The data span the redshift range ...0.057 < z < 0.098 and cover approximately 1300 deg2 over two long fields. Cross-correlation is detected at a significance of 5.7 σ. The amplitude of the cross-power spectrum is low relative to the expected dark matter power spectrum, assuming a neutral hydrogen (H i) bias and mass density equal to measurements from the ALFALFA survey. The decrement is pronounced and statistically significant at small scales. At k ∼ 1.5 h Mpc−1, the cross-power spectrum is more than a factor of 6 lower than expected, with a significance of 15.3 σ. This decrement indicates a lack of clustering of neutral hydrogen (H i), a small correlation coefficient between optical galaxies and H i, or some combination of the two. Separating 2dF into red and blue galaxies, we find that red galaxies are much more weakly correlated with H i on k ∼ 1.5 h Mpc−1 scales, suggesting that H i is more associated with blue star-forming galaxies and tends to avoid red galaxies.
Apoptosis induction provides a promising strategy for tumor gene therapy. Non-invasive ultrasound is a novel non-virus transfer method. In the field of cancer therapy, it has been found that ...ultrasound alone or together with microbubble represents an appealing, efficient and novel technique, which could deliver therapeutic gene or drug to specific organs or tissues in a simple and noninvasive way. Moreover, apoptosis induction mediated by the novel ultrasound-targeted microbubble destruction technique is safer and more effective than other methods, inactivating tumor cells, restraining cell proliferation and improving therapeutic effects of gene or chemotherapeutic drugs. In this paper, we reviewed apoptosis induction by ultrasound and microbubble mediated drug delivery and gene therapy in vitro and in vivo.
PDF
