Background
Kawasaki disease is a vasculitis most commonly afflicting children <5 years of age. Many autoimmune diseases are associated with up‐regulation of T helper (Th) 17 cells, and ...down‐regulation Treg cells. Few studies have examined the Th17/Treg expression in Kawasaki disease.
Methods
Blood samples were obtained from 186 children with Kawasaki disease at 24 h before IVIG therapy, followed by 3 days and 21 days after IVIG therapy. Thirty children with an acute febrile infectious disease and 30 healthy children were obtained as control. Plasma levels of Th17‐ and Treg‐related cytokines including IL‐6, IL‐17A, IL‐10, TGF‐β, and mRNA expression levels of RORγt and Foxp3 were tested.
Results
Patients with Kawasaki disease had higher levels of plasma IL‐17A (25.35 ± 3.21 vs 7.78 ± 1.78 pg/ml, P < 0.001) and IL‐6 (152.29 ± 21.94 vs 38.63 ± 12.40 pg/ml, P < 0.001) when compared to the febrile control group. IVIG resulted in a reduction in IL‐6 and IL‐17A at both 3 and 21 days after IVIG therapy. FoxP3 levels increased significantly 3 days after IVIG therapy (2.28 ± 0.34 vs 0.88 ± 0.14, P < 0.001). IVIG resistance was associated with higher levels of IL‐10 and IL‐17A.
Conclusion
Kawasaki disease was associated with higher IL‐17A and IL‐6, a cytokine profile similar to other autoimmune diseases. IVIG therapy resulted in increased expression of Treg‐related FoxP3. IVIG resistance was associated with higher levels of IL‐10 and IL‐17A. Our findings provide further evidence that Kawasaki disease is an autoimmune‐like disease.
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
A number of patient-specific and leukemia-associated factors are related to the poor outcome in older patients with acute myeloid leukemia (AML). However, comprehensive studies regarding the impact ...of genetic alterations in this group of patients are limited. In this study, we compared relevant mutations in 21 genes between AML patients aged 60 years or older and those younger and exposed their prognostic implications. Compared with the younger patients, the elderly had significantly higher incidences of PTPN11, NPM1, RUNX1, ASXL1, TET2, DNMT3A and TP53 mutations but a lower frequency of WT1 mutations. The older patients more frequently harbored one or more adverse genetic alterations. Multivariate analysis showed that DNMT3A and TP53 mutations were independent poor prognostic factors among the elderly, while NPM1 mutation in the absence of FLT3/ITD was an independent favorable prognostic factor. Furthermore, the status of mutations could well stratify older patients with intermediate-risk cytogenetics into three risk groups. In conclusion, older AML patients showed distinct genetic alterations from the younger group. Integration of cytogenetics and molecular mutations can better risk-stratify older AML patients. Development of novel therapies is needed to improve the outcome of older patients with poor prognosis under current treatment modalities.
Background
Health‐related quality of life (QoL) is of major importance in pancreatic cancer, owing to the limited life expectation. The aim of this prospective longitudinal study was to describe QoL ...in patients undergoing resection for pancreatic or periampullary malignancy.
Methods
QoL was measured on a scale of 0–100 in patients who underwent pancreatic resection for malignancy or premalignancy at the University Medical Centre Utrecht before resection, and 1, 3, 6 and 12 months after surgery. Measures consisted of the RAND‐36, the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire (QLQ‐C30) and the EORTC pancreatic cancer‐specific module (QLQ‐PAN26).
Results
Between March 2012 and November 2013, 68 consecutive patients with a malignancy (59 patients) or premalignancy (9) were included. Physical role restriction, social and emotional domains showed a significant and clinically relevant deterioration directly after operation in 53 per cent (RAND‐36, P < 0·001), 63 and 78 per cent (QLQ‐C30 and RAND‐36 respectively, P < 0·001) and 37 per cent (RAND‐36, P < 0·001) of patients respectively. Most domains demonstrated recovery to preoperative values or better at 3 months, except for physical functioning. Emotional functioning at 3, 6 and 12 months was better than at baseline (P < 0·001). Symptom scores revealed a deterioration in vitality, pain (P = 0·002), fatigue (P < 0·001), appetite loss (P < 0·001), altered bowel habit (P = 0·001) and side‐effects (P < 0·001) after 1 month. After 3 months, only side‐effects were worse than preoperative values (P < 0·001).
Conclusion
QoL after pancreatic resection for malignant and premalignant tumours decreased considerably in the early postoperative phase. Full recovery of QoL took up to 6 months after the operation.
Quality of life recovers in 6 months
Abstract Quantum fluctuations in low-dimensional systems and near quantum phase transitions have significant influences on material properties. Yet, it is difficult to experimentally gauge the ...strength and importance of quantum fluctuations. Here we provide a resonant inelastic x-ray scattering study of magnon excitations in Mott insulating cuprates. From the thin film of SrCuO 2 , single- and bi-magnon dispersions are derived. Using an effective Heisenberg Hamiltonian generated from the Hubbard model, we show that the single-magnon dispersion is only described satisfactorily when including significant quantum corrections stemming from magnon-magnon interactions. Comparative results on La 2 CuO 4 indicate that quantum fluctuations are much stronger in SrCuO 2 suggesting closer proximity to a magnetic quantum critical point. Monte Carlo calculations reveal that other magnetic orders may compete with the antiferromagnetic Néel order as the ground state. Our results indicate that SrCuO 2 —due to strong quantum fluctuations—is a unique starting point for the exploration of novel magnetic ground states.
Abstract
The transition temperature
T
c
of unconventional superconductivity is often tunable. For a monolayer of FeSe, for example, the sweet spot is uniquely bound to titanium-oxide substrates. By ...contrast for La
2−x
Sr
x
CuO
4
thin films, such substrates are sub-optimal and the highest
T
c
is instead obtained using LaSrAlO
4
. An outstanding challenge is thus to understand the optimal conditions for superconductivity in thin films: which microscopic parameters drive the change in
T
c
and how can we tune them? Here we demonstrate, by a combination of x-ray absorption and resonant inelastic x-ray scattering spectroscopy, how the Coulomb and magnetic-exchange interaction of La
2
CuO
4
thin films can be enhanced by compressive strain. Our experiments and theoretical calculations establish that the substrate producing the largest
T
c
under doping also generates the largest nearest neighbour hopping integral, Coulomb and magnetic-exchange interaction. We hence suggest optimising the parent Mott state as a strategy for enhancing the superconducting transition temperature in cuprates.
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.
The optical design and performance of the recently opened 13A biological small‐angle X‐ray scattering (SAXS) beamline at the 3.0 GeV Taiwan Photon Source of the National Synchrotron Radiation ...Research Center are reported. The beamline is designed for studies of biological structures and kinetics in a wide range of length and time scales, from angstrom to micrometre and from microsecond to minutes. A 4 m IU24 undulator of the beamline provides high‐flux X‐rays in the energy range 4.0–23.0 keV. MoB4C double‐multilayer and Si(111) double‐crystal monochromators (DMM/DCM) are combined on the same rotating platform for a smooth rotation transition from a high‐flux beam of ∼4 × 1014 photons s−1 to a high‐energy‐resolution beam of ΔE/E ≃ 1.5 × 10−4; both modes share a constant beam exit. With a set of Kirkpatrick–Baez (KB) mirrors, the X‐ray beam is focused to the farthest SAXS detector position, 52 m from the source. A downstream four‐bounce crystal collimator, comprising two sets of Si(311) double crystals arranged in a dispersive configuration, optionally collimate the DCM (vertically diffracted) beam in the horizontal direction for ultra‐SAXS with a minimum scattering vector q down to 0.0004 Å−1, which allows resolving ordered d‐spacing up to 1 µm. A microbeam, of 10–50 µm beam size, is tailored by a combined set of high‐heat‐load slits followed by micrometre‐precision slits situated at the front‐end 15.5 m position. The second set of KB mirrors then focus the beam to the 40 m sample position, with a demagnification ratio of ∼1.5. A detecting system comprising two in‐vacuum X‐ray pixel detectors is installed to perform synchronized small‐ and wide‐angle X‐ray scattering data collections. The observed beamline performance proves the feasibility of having compound features of high flux, microbeam and ultra‐SAXS in one beamline.
The optical design and performance of the BioSAXS beamline at the Taiwan Photon Source are reported
To understand carbon cycling in marginal seas better, particulate organic carbon (POC) concentrations, POC fluxes and primary production (PP) were measured in the East China Sea (ECS) in summer 2007. ...Higher concentrations of POC were observed in the inner shelf, and lower POC values were found in the outer shelf. Similar to POC concentrations, elevated uncorrected POC fluxes (720–7300 mg C m−2 d−1) were found in the inner shelf, and lower POC fluxes (80–150 mg C m−2 d−1) were in the outer shelf, respectively. PP values (~ 340–3380 mg C m−2 d−1) had analogous distribution patterns to POC fluxes, while some of PP values were significantly lower than POC fluxes, suggesting that contributions of resuspended particles to POC fluxes need to be appropriately corrected. A vertical mixing model was used to correct effects of bottom sediment resuspension, and the lowest and highest corrected POC fluxes were in the outer shelf (58 ± 33 mg C m−2 d−1) and the inner shelf (785 ± 438 mg C m−2 d−1), respectively. The corrected POC fluxes (486 to 785 mg C m−2 d−1) in the inner shelf could be the minimum value because we could not exactly distinguish the effect of POC flux from Changjiang influence with turbid waters. The results suggest that 27–93% of the POC flux in the ECS might be from the contribution of resuspension of bottom sediments rather than from the actual biogenic carbon sinking flux. While the vertical mixing model is not a perfect model to solve sediment resuspension because it ignores biological degradation of sinking particles, Changjiang plume (or terrestrial) inputs and lateral transport, it makes significant progress in both correcting the resuspension problem and in assessing a reasonable quantitative estimate of POC flux in a marginal sea.
The 3D vertical ferroelectric tunneling junction (FTJ) of bilayer antiferroelectric (AFE) Hf 1-x Zr x O 2 (HZO) and Al 2 O 3 has been demonstrated for NAND-compatible feasibility. A bilayer-type FTJ ...is explored for the designs of the dielectric interlayer Al 2 O 3 0 nm to 4 nm and the ferroelectric type, while the current mechanism is revealed. The multilevel AFE-FTJ is exhibited for both the Program and Erase operations and realizes a synaptic device. High-density emerging memory and computing-in-memory (CiM) are in high demanded for the future era and can be feasible by the proposed vertical FTJ.
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