•WES of a Taiwan stage I LUAD cohort identified 16 mutations associated with poor RFS.•These 16 mutations were harbored at EGFR, KRAS, TP53, CTNNB1 and six other genes.•An index, maxVAF, summarized ...the overall mutation load from genes other than EGFR.•Higher relapse risk was found for stage I patients with high maxVAF or high miR-31.•At stage IB, miR-182, -183, and -196a correlated with EGFR mutation and poor RFS.
About 20% of stage I lung adenocarcinoma (LUAD) patients suffer a relapse after surgical resection. While finer substages have been defined and refined in the AJCC staging system, clinical investigations on the tumor molecular landscape are lacking.
We performed whole exome sequencing, DNA copy number and microRNA profiling on paired tumor-normal samples from a cohort of 113 treatment-naïve stage I Taiwanese LUAD patients. We searched for molecular features associated with relapse-free survival (RFS) of stage I or its substages and validated the findings with an independent Caucasian LUAD cohort.
We found sixteen nonsynonymous mutations harbored at EGFR, KRAS, TP53, CTNNB1 and six other genes associated with poor RFS in a dose-dependent manner via variant allele fraction (VAF). An index, maxVAF, was constructed to quantify the overall mutation load from genes other than EGFR. High maxVAF scores discriminated a small group of high-risk LUAD at stage I (median RFS: 4.5 versus 69.5 months; HR = 10.5, 95% CI = 4.22–26.12, P < 0.001). At the substage level, higher risk was found for patients with high maxVAF or high miR-31; IA (median RFS: 32.1 versus 122.8 months, P = 0.005) and IB (median RFS: 7.1 versus 26.2, P = 0.049). MicroRNAs, miR-182, miR-183 and miR-196a were found correlated with EGFR mutation and poor RFS in stage IB patients.
Distinctive features of somatic gene mutation and microRNA expression of stage I LUAD are characterized to complement the survival prognosis by substaging. The findings open up more options for precision management of stage I LUAD patients.
The experimental demonstrations of light-emitting diode (LED) fabrication with surface plasmon (SP) coupling with the radiating dipoles in its quantum wells are first reviewed. The SP coupling with a ...radiating dipole can create an alternative emission channel through SP radiation for enhancing the effective internal quantum efficiency when the intrinsic non-radiative recombination rate is high, reducing the external quantum efficiency droop effect at high current injection levels, and producing partially polarized LED output by inducing polarization-sensitive SP for coupling. Then, we report the theoretical and numerical study results of SP-dipole coupling based on a simple coupling model between a radiating dipole and the SP induced on a nearby Ag nanoparticle (NP). To include the dipole strength variation effect caused by the field distribution built in the coupling system (the feedback effect), the radiating dipole is represented by a saturable two-level system. The spectral and dipole-NP distance dependencies of dipole strength variation and total radiated power enhancement of the coupling system are demonstrated and interpreted. The results show that the dipole-SP coupling can enhance the total radiated power. The enhancement is particularly effective when the feedback effect is included and hence the dipole strength is increased.
Esophageal cancer has extreme worldwide demographic and histologic variations in occurrence; thus, understanding the pathogenesis of esophageal cancer must be region- or country-based. We examined ...the incidence and tumor stage at diagnosis of esophageal cancer in relation to patients' socioeconomic status (SES) in Taiwan.
This retrospective cohort study used data from Taiwan's National Health Insurance Research Database and Taiwan Cancer Registry collected between January 2008 and December 2014. The records of 40- to 79-year-old patients diagnosed with esophageal cancer were retrieved. The distribution of the crude incidence rates of esophageal cancer by occupation and income variables was studied retrospectively. Cox proportional hazard model was used to adjust for potential confounders and compare the esophageal cancer incidence among four independent variables: age, gender, occupation, and income. Logistic regression analysis was applied to find the power of the independent variables on the odds ratio of late-stage presentation.
The analysis included 7763 subjects. Esophageal squamous cell carcinoma (ESCC) was the predominant histological type (96.6%) and 94.4% of patients were male. The peak affected age for ESCC was 50 to 59 years, whereas the risk of esophageal adenocarcinoma increased progressively with age. The risk of ESCC was significantly unfavorable for the most disadvantaged group, either in occupation or income, while in EAC, risk was unrelated to either factor. The stage of cancer at diagnosis was lower in the highest income groups than in the other two groups.
Significant SES disparities in esophageal cancer incidence, based on occupation and income, are present in Taiwan. Low SES populations have a higher percentage of late-stage diagnosis. Resolution of the increasing socioeconomic disparities and narrowing the gaps in health inequities in Taiwan are needed.
Symmetry and balance in nasal reconstruction can be hard to achieve. Traditionally, a foil template modeled after the unaffected contralateral side is used in the design of a forehead flap. Crude ...two-dimensional models often generate underwhelming results. To better simulate complex nasal topography, three-dimensional printing technology was applied to nasal reconstruction.
Between May 2012 and October 2016, twenty patients underwent forehead flap nasal reconstruction for heminasal deformities. Ten reconstructions were guided with prefabricated three-dimensional templates (CAD/CAM), and ten patients underwent traditional nasal reconstruction without CAD/CAM. In the CAD/CAM group, two templates were printed: contour guide and framework guide. These were a reference for skin flap design and cartilage framework design, respectively. Photographic records and photogrammetry was used to evaluate results.
The mean follow-up time was 19.3 months (range, 6 months to 38 months) in the control group and 17.4 months (range, 7 months to 35 months) in the CAD/CAM group. Without CAD/CAM, there was asymmetry in alar width, alar area, nostril height, width and area (p < 0.05) between reconstructed and native structures. In the CAD/CAM group, there were asymmetries of nostril-related parameters only. After quantifying asymmetries as a percentage, the CAD/CAM group demonstrated more symmetric reconstructions, particularly in alar width (p = 0.043) and alar area (p = 0.003).
When CAD/CAM guidance and three-dimensional printing was used, there was greater symmetry between reconstructed and native structures of the nose.
Background
This study aimed to propose a novel four-type deformity and treatment-oriented classification of the lower eyelids that directs the therapeutic combination of three-step lower ...blepharoplasty for Asian populations.
Methods
We reviewed 183 patients who underwent a therapeutic combination of three steps of lower blepharoplasty after being diagnosed with four types of lower eyelid deformities between July 2018 and April 2021. The three-step lower blepharoplasty includes: (1) mid-face and lower eyelid augmentation, (2) transconjunctival eye bag removal, and (3) skin pinch removal. Consecutive digital images, detailed fat graft volume, fat removal amount, skin pinch removal amount, complications, and patient’s satisfaction and aesthetic improvement score were recorded.
Results
The overall patient’s satisfy score is 91. Aesthetic improvement score is 80.2 and 83.3 among lay persons and experts, respectively. The volume of the fat graft ranges from 2 to 3 mL per orbit according to the severity of the deformity. The amount of fat removed was 0.53 ± 0.36 and 0.61 ± 0.40 mL per orbit in types II and III patients, respectively. There is no lower lid malposition. Eleven patients had over-correction of fat grafting, and they need steroid injection; 20 patients had under-correction of fat grafting, and they need secondary fat grafting. Ten patients need secondary skin pinch excision due to post-op skin redundancy. Two patients had conjunctiva wound granuloma.
Conclusions
The combination of three-step lower blepharoplasty according to the novel classification is a straightforward and effective method to correct lower eyelid deformities. The complication rate was low with high patient satisfaction.
Level of Evidence IV
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors
www.springer.com/00266
.
Background
Several materials can serve as spacer grafts in the repair of retracted lower eyelids. However, previous studies did not reveal any of these to be superior to the others. From our ...perspective, autologous dermal grafts are ideal because they are biologically compatible and abundantly available. However, the absorption of these grafts is an issue, and the thickness of the dermal grafts is crucial. We evaluated the dermal thickness at five potential donor sites using ultrasonography and the efficacy and safety of the posterior neck dermis as a spacer graft in the correction of retracted lower eyelids.
Methods
In 20 healthy volunteers, the dermal thickness was assessed using ultrasonography and compared between the posterior neck, upper arm, inguinal area, intergluteal cleft, and gluteal sulcus. Between January 2018 and June 2021, eight retracted lower eyelids in eight patients were repaired using a posterior neck dermal graft. The surgical results of these grafts were also evaluated.
Results
The mean age of the volunteers was 37.8 years, and the mean body mass index was 24.45 kg/m
2
. The intergluteal cleft provided the thickest dermis followed by the posterior neck and gluteal sulcus, which were not significantly different. The upper arm and inguinal area had the thinnest dermis without significant differences between them. The mean marginal reflex distance 2/iris ratio decreased by 0.15 (
p
=0.008). The mean cosmetic score (0–10) for evaluation of lower eyelid reconstruction increased by 3.38 (
p
=0.011). The mean Vancouver Scar Scale score for evaluation of donor site scarring was 3.21.
Conclusions
Although the posterior neck dermis is the second thickest, it is an ideal spacer graft in the reconstruction of retracted lower eyelids. Adequate thickness, uncomplicated methods, and a closer surgical field are its advantages. Additionally, donor site morbidity is minimal, with acceptable scarring.
Level of evidence IV
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors
www.springer.com/00266
.
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To manufacture tissue engineering-based functional tissues, scaffold materials that can be sufficiently vascularized to mimic the functionality and complexity of native tissues are ...needed. Currently, vascular network bioengineering is largely carried out using natural hydrogels as embedding scaffolds, but most natural hydrogels have poor mechanical stability and durability, factors that critically limit their widespread use. In this study, we examined the suitability of gelatin-phenolic hydroxyl (gelatin-Ph) hydrogels that can be enzymatically crosslinked, allowing tuning of the storage modulus and the proteolytic degradation rate, for use as injectable hydrogels to support the human progenitor cell-based formation of a stable and mature vascular network. Porcine gelatin-Ph hydrogels were found to be cytocompatible with human blood-derived endothelial colony-forming cells and white adipose tissue-derived mesenchymal stem cells, resulting in >87% viability, and cell proliferation and spreading could be modulated by using hydrogels with different proteolytic degradability and stiffness. In addition, gelatin was extracted from mouse dermis and murine gelatin-Ph hydrogels were prepared. Importantly, implantation of human cell-laden porcine or murine gelatin-Ph hydrogels into immunodeficient mice resulted in the rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, the degree of enzymatic crosslinking of the gelatin-Ph hydrogels could be used to modulate cell behavior and the extent of vascular network formation in vivo. Our report details a technique for the synthesis of gelatin-Ph hydrogels from allogeneic or xenogeneic dermal skin and suggests that these hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues.
Trophocytes and oenocytes of honeybees are used in studies of cellular senescence, but their cellular energy metabolism with age is poorly understood. In this study, the molecules involved in ...cellular energy metabolism were evaluated in the trophocytes and oenocytes of young and old worker bees. The results revealed that (i) β-oxidation and protein synthesis decreased with age, (ii) fat and glycogen accumulation increased with age, and (iii) glycolysis did not change with age. These results indicate that the trophocytes and oenocytes of young bees have higher activity of cellular energy metabolism compared with old worker bees and that aging results in a decline in the cellular energy metabolism of worker bees.