Sentinel lymph node biopsy (SLNB) provides important prognostic information for early‐stage melanomas. However, statistics regarding the survival comparison between SLNB and nodal observation in ...Asia, where acral lentiginous melanoma (ALM) predominates, are limited. This study aimed to identify if SLNB offered survival benefits over nodal observation in early‐stage melanomas in Taiwan. The retrospective study included 227 patients who met the SLNB criteria according to the National Comprehensive Cancer Network guidelines and were treated at National Taiwan University Hospital from June 1997 to June 2021. Survival analysis was performed using Kaplan–Meier curves and Cox proportional hazards regression models. Of the study population, ALM accounted for 73.1%; 161 patients (70.9%) underwent SLNB and 66 patients (29.1%) were under nodal observation. Multivariate analysis showed significantly improved melanoma‐specific survival (hazard ratio HR, 0.6; p = .02) in the SLNB group. Among those who underwent completion lymph node dissection (CLND), the non‐sentinel node positivity rate was 44.4%. Immediate CLND resulted in significantly longer melanoma‐specific survival and distant‐metastasis‐free survival (DMFS) compared to nodal observation. (HR, 0.2; p = .01 for melanoma‐specific survival. HR, 0.3; p = .046 for DMFS). In conclusion, SLNB may provide survival benefits of cutaneous melanoma over nodal observation in the Taiwanese population.
Research Highlights
The sentinel lymph node biopsy group demonstrated a superior melanoma‐specific survival compared to the nodal observation group. This observation may be related to the higher prevalence of acral lentiginous melanomas in the Asian population.
The repair of the central nervous system (CNS) is a major challenge because of the difficulty for neurons or axons to regenerate after damages. Injectable hydrogels have been developed to deliver ...drugs or cells for neural repair, but these hydrogels usually require conditional stimuli or additional catalysts to control the gelling process. Self-healing hydrogels, which can be injected locally to fill tissue defects after stable gelation, are attractive candidates for CNS treatment. In the current study, the self-healing hydrogel with a semi-interpenetrating polymer network (SIPN) was prepared by incorporation of hyaluronan (HA) into the chitosan-based self-healing hydrogel. The addition of HA allowed the hydrogel to pass through a narrow needle much more easily. As the HA content increased, the hydrogel showed a more packed nanostructure and a more porous microstructure verified by coherent small-angle X-ray scattering and scanning electron microscopy. The unique structure of SIPN hydrogel enhanced the spreading, migration, proliferation, and differentiation of encapsulated neural stem cells in vitro. Compared to the pristine chitosan-based self-healing hydrogel, the SIPN hydrogel showed better biocompatibility, CNS injury repair, and functional recovery evaluated by the traumatic brain injury zebrafish model and intracerebral hemorrhage rat model. We proposed that the SIPN of HA and chitosan self-healing hydrogel allowed an adaptable environment for cell spreading and migration and had the potential as an injectable defect support for CNS repair.
Lung cancer is the leading cause of cancer‐associated death, with a global 5‐year survival rate <20%. Early metastasis and recurrence remain major challenges for lung cancer treatment. The stemness ...property of cancer cells has been suggested to play a key role in cancer plasticity, metastasis and drug‐resistance, and is a potential target for drug development. In this study, we found that in non‐small cell lung cancer (NSCLC), BMI1 and MCL1 play crucial roles of cancer stemness including invasion, chemo‐resistance and tumour initiation. JNK signalling serves as a link between oncogenic pathway or genotoxicity to cancer stemness. The activation of JNK, either by mutant EGFR or chemotherapy agent, stabilized BMI1 and MCL1 proteins through suppressing the expression of E3‐ubiquitin ligase HUWE1. In lung cancer patient samples, high level of BMI1 is correlated with poor survival, and the expression of BMI1 is positively correlated with MCL1. A novel small‐molecule, BI‐44, was developed, which effectively suppressed BMI1/MCL1 expressions and inhibited tumour formation and progression in preclinical models. Targeting cancer stemness mediated by BMI1/MCL1 with BI‐44 provides the basis for a new therapeutic approach in NSCLC treatment.
•The wettability effect on minitube flow boiling with VOF has been investigated.•The 10 mm minitubes increase average heat flux up to 324,966.9 W/m2 with CA=5∘.•The 10 mm minitubes minimize total ...pressure drop Δp lower to 698.4 Pa with CA=150∘.•Gravity and acceleration pressure drops are minor to total pressure drops.•Under higher mass flux, the hydrophilic surface can enhance heat flux, and the hydrophobic surface reduces the pressure drop.
Flow boiling within minitubes holds immense promise for efficient heat dissipation owing to its substantial latent heat exchange capacity. The performance and efficacy of the pump, crucial beyond just necessitating high heat flux, are closely tied to maintaining a low-pressure drop. Surface treatment stands out as one of the techniques to augment thermal efficiency. While the significance of microscale surface properties, particularly wettability, in influencing flow boiling has been established, only a limited number of studies have explored its impact on pressure drop. This study rigorously investigates the wettability's influence on flow boiling within minitubes using the VOF approach. It reports key parameters within a 200 ms interval, including vapor volume fraction, average heat flux, and pressure drop. Employing a mass flux of 560 kg/m2s along a 10 mm length minitube, the study attains an impressive average heat flux of up to 324,966.9 W/m2 on a hydrophilic surface exhibiting a 5° contact angle. In contrast, a hydrophobic surface boasting a 150° contact angle achieves a significantly reduced total pressure drop (∆p) of 698.4 Pa, effectively preventing tube-clogging. Simultaneously accounting for heat flux and pressure considerations, it is conceivable that selecting a surface featuring a contact angle of 105° could represent an optimal choice for a 30 mm length minitube. The findings highlight that the hydrophilic surface encourages greater liquid presence, enhancing heat exchange efficiency considerably. Conversely, hydrophobic surfaces facilitate vapor layer stabilization, leading to reduced total pressure drop and minimized fluctuations. This work offers comprehensive insights into the fundamental relationship between wettability, flow boiling, and pressure drop, thereby providing valuable guidance for future miniube design strategies in cooling applications. Such insights hold immense potential to revolutionize various industrial and engineering sectors.
The up-regulation of fucosyltransferase 8 (FUT8), the only enzyme catalyzing α1,6-fucosylation in mammals, has been observed in several malignant cancers including liver, ovarian, thyroid, and ...colorectal cancers. However, the pathological role and the regulatory mechanism of FUT8 in cancers remain largely unknown. In the current study, we report that the expression of FUT8 is up-regulated in nonsmall cell lung cancer (NSCLC) and correlates with tumor metastasis, disease recurrence, and poor survival in patients with NSCLC. Knocking down FUT8 in aggressive lung cancer cell lines significantly inhibits their malignant behaviors including in vitro invasion and cell proliferation, as well as in vivo metastasis and tumor growth. The results of glycoproteomic and microarray analyses show that FUT8 globally modifies surface antigens, receptors, and adhesion molecules and is involved in the regulation of dozens of genes associated with malignancy, suggesting that FUT8 contributes to tumor progression through multiple mechanisms. Moreover, we show that FUT8 is up-regulated during epithelial–mesenchymal transition (EMT), a critical process for malignant transformation of tumor, via the transactivation of β-catenin/lymphoid enhancer-binding factor-1 (LEF-1). These results provide a model to illustrate the relation between FUT8 expression and lung cancer progression and point to a promising direction for the prognosis and therapy of lung cancer.
An efficient host immune response against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2, COVID‐19) appears to be crucial for controlling and resolving this viral infection. However, ...many studies have reported autoimmune characteristics in severe COVID‐19 patients. Moreover, clinical observations have revealed that COVID‐19‐associated acute distress respiratory syndrome shares many features in common with inflammatory myopathy including interstitial lung disease (ILD), most particularly rapidly progressive (RP)‐ILD. This study explored this phenomenon by seeking to identify and characterize myositis‐specific and related autoantibodies in 25 COVID‐19 patients with mild or severe symptoms. Line blot analysis with the EUROLINE Myopathies Ag kit identified 9 (36%) patients with COVID‐19 with one or more autoantibodies against several myositis‐related antigens (Jo‐1, Ku, Mi‐2β, PL‐7, PL‐12, PM‐Scl 75, PM‐Scl 100, Ro‐52, and SRP); no anti‐MDA5 antibodies were detected. As the presence of antibodies identified by line blots was unrelated to disease severity, we further characterized the autoantibodies by radioimmunoassay, in which 35Smethionine‐labeled K562 cellular antigens were precipitated and visualized by gel electrophoresis. This result was confirmed by an immunoprecipitation assay and immunoblotting; 2 patients exhibited anti‐Ku70 and anti‐Ku80 antibodies. Our data suggest that it is necessary to use more than one method to characterize and evaluate autoantibodies in people recovered from COVID‐19, in order to avoid misinterpreting those autoantibodies as diagnostic markers for autoimmune diseases.
•The surface wettability on TPCT has been systematically studied by VOF.•The hydrophilic surface reduces the evaporator thermal resistance at 35.3%.•The hydrophobic surface decreases the condenser ...thermal resistance at 3.64%.•The surface wettability is critical to the thermal resistance of the evaporator.•The condenser is dominant in the overall thermal resistance.
A two-phase closed thermosyphon (TPCT) is promising for heat removal due to its simple structure and high performance in heat transfer. However, investigating the phase change process in TPCT through experiments with current technology is still challenging. To study the various surface wettability effects on TPCT, this is the first systematical volume of fluid (VOF) method-based numerical study. The wettability in terms of contact angles (5°, 40°, 120°, and 175°) is endowed on the surfaces of TPCT. The numerical results of heat transfer coefficients of the TPCT show good agreement compared with the correlations. The simulation results reveal that the hydrophilic evaporator and the hydrophobic condenser benefit heat transfer. Within the input power of 376.14 W, the hydrophilic evaporator can reduce the thermal resistance of the evaporator to 35.3 % and delays the vapor film formation. The hydrophobic condenser decreases the thermal resistance of the condenser at 3.64 % and prevents filmwise condensation. The surface wettability is critical to the temperature distribution along the evaporator, but the main temperature drop is located between the adiabatic section and the condenser. It is also noted that the thermal resistance of the condenser is dominant to the overall thermal resistance. This study provides a detailed physical insight into the surface wettability effect on TPCT and benefits the future design in thermal engineering applications.
Summary Background Both end-stage renal disease and chronic kidney disease are increasing worldwide; however, the full effect of chronic kidney disease is unknown because mortality risks for all five ...stages are unavailable. We assessed prevalence and mortality risks for all stages of chronic kidney disease and quantified its attributable mortality in Taiwan. Methods The cohort consisted of 462 293 individuals aged older than 20 years who participated in a standard medical screening programme since 1994. As of Dec 31, 2006, we identified 14 436 deaths. Chronic kidney disease was determined by glomerular filtration rate and urinary protein. We estimated national prevalence in Taiwan from the cohort by adjusting age and educational levels. Hazard ratios (HRs) were calculated with Cox proportionate hazards model. We calculated mortality attributable to chronic kidney disease for national population and for low socioeconomic status. Findings The national prevalence of chronic kidney disease was 11·93% (95% CI 11·66–12·28), but only 3·54% (3·37–3·68) of participants in the cohort were aware of their disorder. Prevalence was substantially higher in the group with low socioeconomic status than in the high status group (19·87% 19·84–19·91 vs 7·33% 7·31–7·35). 56 977 (12%) of cohort participants had chronic kidney disease; those with disease had 83% higher mortality for all cause (HR 1·83 1·73–1·93) and 100% higher for cardiovascular diseases (2·00 1·78–2·25), in a cohort that was observed for 13 years with median follow-up of 7·5 years (IQR 4·0–10·1). 10·3% (95% CI 9·57–11·03) of deaths in the entire population were attributable to chronic kidney disease, but 17·5% (16·27–18·67) of deaths in the low socioeconomic status population. 2350 (39%) deaths occurred before 65 years of age in those with chronic kidney disease. Regular users of Chinese herbal medicines had a 20% (odds ratio 1·20 1·16–1·24) increased risk of developing chronic kidney disease. Interpretation The high prevalence of chronic kidney disease and its associated all-cause mortality, especially in people with low socioeconomic status, make reduction of this disorder a public-health priority. Promotion of its recognition through the general public knowing their glomerular filtration rate and testing their urine is crucial to reduce premature deaths from all causes and to attenuate this global epidemic. Funding None.
Bioinspired muscle fiber–based wearable electronics are a breakthrough in the production of lightweight, mechanically robust next-generation smart textiles. To meet the urgent demand for next ...generation wearable electronics, the use of interpenetrating reinforced conductive fibers produced through electrospinning is proposed herein. Strain-insensitive and mechanically robust electrospun reinforced conductive fiber (ERCF) electrodes (elongation of 711 % and toughness of 10.05 MJ m−3) contain compliant mechanical reinforcements and deeply adhered conductive silver nanoparticles led to durable wearable optoelectronics. An ambient condition processable and fully solution processable ERCFs exhibits strain-insensitive conductive electrical endurance presents robust hysteresis-free smart gloves and light-emitting electrochemical cells performances, establishing the wearable cognitive human–computer interfaces. A designed ERCF-based nanogenerator can yield outstanding piezoelectric voltage (29.5 V), current (0.39 μA), and power output (11.57 μW) values, surpassing the performance of expensive, toxic, non-biocompatible dopants and technologies requiring highly energy-intensive poling processes.
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•Stretchable strain insensitive nanofibrous electrode achieved via electrospinning.•Highly adhered nanoparticles and nano reinforcements imparts greater toughness.•Fibrous smart sensors presents healthcare applications via bluetooth communication.•All fiber composed fully stretchable piezoelectric yields excellent energy outputs.
Numerous pathogenic
exon 9 mutations have been identified in myeloproliferative neoplasms (MPN), with type 1 (52bp deletion;
) and type 2 (5bp insertion;
) being the most prevalent. Despite the ...universal pathobiology of MPN driven by various
mutants, it is unclear why different
mutations result in diverse clinical phenotypes. Through RNA sequencing followed by validation at the protein and mRNA levels, we found that S100A8 was specifically enriched in
but not in
MPN-model cells. The expression of
could be regulated by STAT3 based on luciferase reporter assay complemented with inhibitor treatment. Pyrosequencing demonstrated relative hypomethylation in two CpG sites within the potential pSTAT3-targeting
promoter region in
cells as compared to
cells, suggesting that distinct epigenetic alteration could factor into the divergent S100A8 levels in these cells. The functional analysis confirmed that S100A8 non-redundantly contributed to accelerated cellular proliferation and reduced apoptosis in
cells. Clinical validation showed significantly enhanced
expression in
-mutated MPN patients compared to
-mutated cases, and thrombocytosis was less prominent in those with
upregulation. This study provides indispensable insights into how different
mutations discrepantly drive the expression of specific genes that contributes to unique phenotypes in MPN.
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