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
Four 2-(styryl)triphenylene derivatives (TSs) were synthesized for deep-blue dopant materials. By using a pyrene-containing compound, DMPPP, as the host, the TS-doped devices exhibited significant ...delayed fluorescence via triplet-triplet annihilation, providing the highest quantum efficiency of 10.2% and a current efficiency of 12.3 cd A(-1).
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.
MicroRNAs (miRNAs) are thought to control tumor metastasis through direct interactions with target genes. Thyroid hormone (T3) and its receptor (TR) are involved in cell growth and cancer ...progression. However, the issue of whether miRNAs participate in T3/TR-mediated tumor migration is yet to be established. In the current study, we demonstrated that T3/TR negatively regulates mature miR-17 transcript expression, both in vitro and in vivo. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays localized the regions responding to TR-mediated repression to positions -2234/-2000 of the miR-17 promoter sequence. Overexpression of miR-17 markedly inhibited cell migration and invasion in vitro and in vivo, mediated via suppression of matrix metalloproteinases (MMP)-3. Moreover, p-AKT expression was increased in miR-17-knockdown cells that led to enhanced cell invasion, which was blocked by LY294002. Notably, low miR-17 expression was evident in highly metastatic cells. The cell migration ability was increased by T3, but partially reduced upon miR-17 overexpression. Notably, TRα1 was frequently upregulated in hepatocellular carcinoma (HCC) samples and associated with low overall survival (P=0.023). miR-17 expression was significantly negatively associated with TRα1 (P=0.033) and MMP3 (P=0.043) in HCC specimens. Data from our study suggest that T3/TR, miR-17, p-AKT and MMP3 activities are interlinked in the regulation of cancer cell metastasis.
We report the experimental generation of highly energetic carbon ions up to 48 MeV per nucleon by shooting double-layer targets composed of well-controlled slightly underdense plasma and ultrathin ...foils with ultraintense femtosecond laser pulses. Particle-in-cell simulations reveal that carbon ions are ejected from the ultrathin foils due to radiation pressure and then accelerated in an enhanced sheath field established by the superponderomotive electron flow. Such a cascaded acceleration is especially suited for heavy ion acceleration with femtosecond laser pulses. The breakthrough of heavy ion energy up to many tens of MeV/u at a high repetition rate would be able to trigger significant advances in nuclear physics, high energy density physics, and medical physics.
Background Previous reports have indicated that statins could prevent bone loss in ovariectomized (OVX) rats and increase the expressions of osteogenic genes in cultured osteoblasts. In this study, ...we hypothesized that simvastatin might increase osteoblast number and protein expressions of osteogenic markers localized in bones in concomitance with the prevention of bone loss in OVX rats.
Materials and methods Fifty‐four 3‐month‐old OVX and sham‐operated (SHAM) female Sprague–Dawley rats were used. Simvastatin (10–20 mg kg−1 day−1) was administrated orally for 6 weeks. Trabecular volume, osteoblast number and osteogenic proteins including BMP2, collagen type I and osteocalcin on bone sections obtained from lumbar vertebral body, distal femur and proximal tibia were measured.
Results The results showed that SHAM rats had significantly less trabecular bone volume and osteoblast number than that of OVX rats 6 weeks after operation. Oral simvastatin treatment (10–20 mg kg−1 day−1) increased bone volume and osteoblast number in the distal femurs, proximal tibiae and vertebrae of OVX rats. Furthermore, the osteoblastic cells with immuno‐stained BMP2, collagen type I and osteocalcin in vertebral bones were significantly increased by simvastatin treatment (20 mg kg−1 day−1) in OVX rats.
Conclusions This study demonstrates that simvastatin enhances the production of osteogenic proteins in bone and this effect may contribute to the prevention of bone loss in OVX rats.
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.
Summary Objective Dietary loading has been reported to have an effect on temporomandibular joint (TMJ) remodeling via periodontal-muscular reflex. We therefore examined whether reducing dietary ...loading decreased TMJ degradation induced by the unilateral anterior crossbite prosthesis as we recently reported. Methods Forty 6-week-old female C57BL/6J mice were randomly divided into two experimental and two control groups. One experimental and one control group received small-size diet and the other two groups received large-size diet. Unilateral anterior crossbite prosthesis was created in the two experimental groups. The TMJ samples were collected 3 weeks after experimental operation. Histological changes in condylar cartilage and subchondral bone were assessed by Hematoxylin & Eosin, toluidine blue, Safranin O and tartrate-resistant acid phosphatase staining. Real-time polymerase chain reaction (PCR) and/or immunohistochemistry were performed to evaluate the expression levels of Collagen II, Aggrecan, a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5) and RANKL/RANK/OPG in TMJ condylar cartilage and/or subchondral bone. Results Thinner and degraded cartilage, reduced cartilage cellular density, decreased expression levels of Collagen II and Aggrecan, loss of subchondral bone and enhanced osteoclast activity were observed in TMJs of both experimental groups. However, the cartilage degradation phenotype was less severe and cartilage ADAMTS-5 mRNA was lower while OPG/RANKL ratio in cartilage and subchondral bone was higher in the small-size than large-size diet experimental group. No differences of histomorphology and the tested molecules were found between the two control groups. Conclusions The current findings suggest that a lower level of functional loading by providing small-size diet could reduce TMJ degradation induced by the biomechanical stimulation from abnormal occlusion.
We report temporal patterns of viral shedding in 94 patients with laboratory-confirmed COVID-19 and modeled COVID-19 infectiousness profiles from a separate sample of 77 infector-infectee ...transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% (95% confidence interval, 25-69%) of secondary cases were infected during the index cases' presymptomatic stage, in settings with substantial household clustering, active case finding and quarantine outside the home. Disease control measures should be adjusted to account for probable substantial presymptomatic transmission.
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