Pathogenicity of Highly Pathogenic Avian Influenza A(H5N1) Viruses Isolated from Cats in Mice and Ferrets, South Korea, 2023.

The prevalence of highly pathogenic avian influenza (HPAI) A(H5N1) viruses has increased in wild birds and poultry worldwide, and concomitant outbreaks in mammals have occurred. During 2023, outbreaks of HPAI H5N1 virus infections were reported in cats in South Korea. The H5N1 clade 2.3.4.4b viruses isolated from 2 cats harbored mutations in the polymerase basic protein 2 gene encoding single amino acid substitutions E627K or D701N, which are associated with virus adaptation in mammals. Hence, we analyzed the pathogenicity and transmission of the cat-derived H5N1 viruses in other mammals. Both isolates caused fatal infections in mice and ferrets. We observed contact infections between ferrets, confirming the viruses had high pathogenicity and transmission in mammals. Most HPAI H5N1 virus infections in humans have occurred through direct contact with poultry or a contaminated environment. Therefore, One Health surveillance of mammals, wild birds, and poultry is needed to prevent potential zoonotic threats.

Changes in the intrinsic severity of severe acute respiratory syndrome coronavirus 2 according to the emerging variant: a nationwide study from February 2020 to June 2022, including comparison with vaccinated populations.

BACKGROUND: As the population acquires immunity through vaccination and natural infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), understanding the intrinsic severity of coronavirus disease (COVID-19) is becoming challenging. We aimed to evaluate the intrinsic severity regarding circulating variants of SARS-CoV-2 and to compare this between vaccinated and unvaccinated individuals. METHODS: With unvaccinated and initially infected confirmed cases of COVID-19, we estimated the case severity rate (CSR); case fatality rate (CFR); and mortality rate (MR), including severe/critical cases and deaths, stratified by age and compared by vaccination status according to the period regarding the variants of COVID-19 and vaccination. The overall rate was directly standardized with age. RESULTS: The age-standardized CSRs (aCSRs) of the unvaccinated group were 2.12%, 5.51%, and 0.94% in the pre-delta, delta, and omicron period, respectively, and the age-standardized CFRs (aCFRs) were 0.60%, 2.49%, and 0.63% in each period, respectively. The complete vaccination group had lower severity than the unvaccinated group over the entire period showing under 1% for the aCSR and 0.5% for the aCFR. The age-standardized MR of the unvaccinated group was 448 per million people per month people in the omicron period, which was 11 times higher than that of the vaccinated group. In terms of age groups, the CSR and CFR sharply increased with age from the 60 s and showed lower risk reduction in the 80 s when the period changed to the omicron period. CONCLUSIONS: The intrinsic severity of COVID-19 was the highest in the delta period, with over 5% for the aCSR, whereas the completely vaccinated group maintained below 1%. This implies that when the population is vaccinated, the impact of COVID-19 will be limited, even if a new mutation appears. Moreover, considering the decreasing intrinsic severity, the response to COVID-19 should prioritize older individuals at a higher risk of severe disease.

A Surface Acoustic Wave-Based PM 1.0 Fine Dust Detection System Using Full Digital Time-Interleaved Counters.

This paper proposed a fine dust detection system using time-interleaved counters in which surface acoustic wave (SAW) sensors changed the resonance point characteristic. When fine dust was applied to the SAW sensor, the resonance point decreased. The SAW oscillator made of the SAW sensor and radio frequency (RF) amplifier generated an oscillation frequency that was the same as the resonance frequency. The oscillation frequency was transferred to digital data by a 20-bit asynchronous counter. This system has two channels: a sensing channel and a reference channel. Each channel has a SAW oscillator and a 20-bit asynchronous counter. The difference of the two channel counter results is the frequency difference. Through this, it is possible to know whether fine dust adheres to the SAW sensor. The proposed circuit achieved 0.95 ppm frequency resolution when it was operated at a frequency of 460 MHz. This circuit was implemented in a TSMC 130 nm CMOS process.

Efficacy of skin rejuvenation with a fractional 1927-nm thulium laser alone or combined with a chemical peel: a controlled histopathological preliminary study in a mouse model.

Many patients demand minimally invasive treatments for skin rejuvenation, such as nonablative laser and superficial chemical peels. Combination therapy yet has not been studied histopathologically. The purpose of this study is to assess the histopathological efficacy of a 1927-nm thulium laser-assisted salicylic acid (SA) peel in skin rejuvenation. A six-segment table was drawn on the shaved back of C57BL/6 mouse. All segments were irradiated with the thulium laser-different tips and passes were used for specific segments. A 30% SA peel was then applied to the right-hand segments. After treatment, the skin samples were collected from each segment and examined for dermal thickness, collagen density, and melanin content. Greater thickness was seen in the combination therapy group compared with the laser alone group and in those segments receiving more passes with larger beam-sized tip. Collagen density increased in all treated skin segments, irrespective of the group. No adverse events were noted in the treated areas. The sample size was small and mouse skin has histological differences with human skin. The combination of a thulium laser and 30% SA peel has a synergistic effect on dermal thickness, so that can be suggested as a novel skin rejuvenation technique.

Comparative Computational Analysis of Spike Protein Structural Stability in SARS-CoV-2 Omicron Subvariants.

The continuous emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with multiple spike (S) protein mutations pose serious threats to current coronavirus disease 2019 (COVID-19) therapies. A comprehensive understanding of the structural stability of SARS-CoV-2 variants is vital for the development of effective therapeutic strategies as it can offer valuable insights into their potential impact on viral infectivity. S protein mediates a virus' attachment to host cells by binding to angiotensin-converting enzyme 2 (ACE2) through its receptor-binding domain (RBD), and mutations in this protein can affect its stability and binding affinity. We analyzed S protein structural stability in various Omicron subvariants computationally. Notably, the S protein sequences analyzed in this work were obtained directly from our own sample collection. We evaluated the binding free energy between S protein and ACE2 in several complex forms. Additionally, we measured distances between the RBD of each chain in S protein to analyze conformational changes. Unlike most of the prior studies, we analyzed full-length S protein-ACE2 complexes instead of only RBD-ACE2 complexes. Omicron subvariants including BA.1, BA.2, BA.2.12.1, BA.4/BA.5, BA.2.75, BA.2.75_K147E, BA.4.6 and BA.4.6_N658S showed enhanced stability compared to wild type, potentially due to distinct S protein mutations. Among them, BA.2.75 and BA.4.6_N658S exhibited the highest and lowest level of stability, respectively.

SARS-CoV-2 B.1.619 and B.1.620 Lineages, South Korea, 2021.

We report the rapid emergence of severe acute respiratory syndrome coronavirus 2 lineages B.1.619 and B.1.620 in South Korea. The surge in frequency in a relatively short time emphasizes the need for ongoing monitoring for new lineages to track potential increases in transmissibility and disease severity and reductions in vaccine efficacy.

Community Transmission of SARS-CoV-2 Omicron Variant, South Korea, 2021.

In South Korea, a November 2021 outbreak caused by severe acute respiratory syndrome coronavirus 2 Omicron variant originated from 1 person with an imported case and spread to households, kindergartens, workplaces, restaurants, and hospitals, resulting in 11 clusters within 3 weeks. An epidemiologic curve indicated rapid community transmission of the Omicron variant.

Combined treatment with anti-HER2/neu and anti-4-1BB monoclonal antibodies induces a synergistic antitumor effect but requires dose optimization to maintain immune memory for protection from lethal rechallenge.

Human epidermal growth factor receptor type 2 (HER2)-positive breast cancer that is treated with anti-HER2/neu monoclonal antibody (mAb) is not free from late recurrences. Addition of anti-4-1BB mAb to anti-HER2/neu mAb has been demonstrated to strengthen the cytotoxic antitumor response. Our study expands on this by revealing the influence of anti-4-1BB mAb addition on the immune memory of anti-HER2/neu mAb. We designed murine breast cancer models by implanting TUBO and TUBO-P2J cell lines in mice, which were then treated with anti-HER2/neu and/or anti-4-1BB mAb. After complete surgical and/or chemical regression of the tumor, the mice were rechallenged with a second injection of cancer cells. Notably, anti-HER2/neu and anti-4-1BB mAb combination therapy had a synergistic antitumor effect at the initial treatment. However, the combination therapy did not evoke immune memory, allowing the tumors to thrive at rechallenge with reduced CD44+ expression in CD8+ T cells. Immune memory was also impaired when anti-4-1BB mAb was administered to naive CD8+ T cells but was sustained when this was administered to activated CD8+ T cells. In an attempt to resist the loss of immune memory, we controlled the dose of anti-4-1BB mAb to optimize the stimulation of activated CD8+ T cells. Immune memory was achieved with the dose regulation of anti-4-1BB mAb to 1 mg/kg in our model. Our study demonstrates the importance in understanding the adaptive immune mechanism of anti-HER2/neu and anti-4-1BB mAb combination therapy and suggests a dose optimization strategy is necessary to ensure development of successful immune memory.

Genomic evidence of SARS-CoV-2 reinfection in the Republic of Korea.

As the coronavirus disease 2019 (COVID-19) pandemic continues, reinfection is likely to become increasingly common. However, confirming COVID-19 reinfection is difficult because it requires whole-genome sequencing of both infections to identify the degrees of genetic differences. Since the first reported case of reinfection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the Republic of Korea in April 2020, four additional cases were classified as suspected reinfection cases. We performed whole-genome sequencing of viral RNA extracted from swabs obtained at the initial infection and reinfection stages of these four suspected cases. The interval between initial infection and reinfection of all four suspected cases was more than 3 months. All four patients were young (10-29 years), and they displayed mild symptoms or were asymptomatic during the initial infection and reinfection episodes. The analysis of genome sequences combined with the epidemiological results revealed that only two of the four cases were confirmed as reinfection, and both were reinfected with the Epsilon variant. Due to the prolonged COVID-19 pandemic, the possibility of reinfections with SARS-CoV-2 variants is increasing, as reported in our study. Therefore, continuous monitoring of cases is necessary.

Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma.

BACKGROUND & AIMS: Atezolizumab plus bevacizumab (Ate/Bev) has demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the phase III trial. Further evaluation is necessary to investigate the safety and efficacy of Ate/Bev in real settings. METHODS: This was a multicentre retrospective analysis. Between May 2020 and February 2021, 138 patients received Ate/Bev as first-line treatment for advanced HCC from 11 institutions. We excluded patients with Child-Pugh B or C and BCLC D stage, and the remaining 121 patients were included in this analysis. RESULTS: According to RECIST 1.1, the objective response and disease control rates were 24.0% and 76.0%. The median follow-up duration was 5.9 months (95% confidence interval [CI], 5.4-6.4), the median progression-free survival (PFS) was 6.5 months (95% CI, 4.1-9.0), and median overall survival (OS) was not reached (95% CI, not available). The most frequent grade 3-4 adverse event was aspartate aminotransferase elevation (10.7%). In the multivariate analyses, AFP increase (P = .037), baseline neutrophil-to-lymphocyte ratio (NLR) ≥ 5 (P = .023), and best response to stable disease or progressive disease (P = .019) were significantly associated with worse PFS. Macrovascular invasion (P = .048) and baseline NLR ≥5 (P < .001) were significantly associated with worse OS. CONCLUSIONS: Ate/Bev showed real-life efficacy and safety in Korean patients with advanced HCC, in line with results from phase III trial. Considering unfavourable survival outcomes of Ate/Bev in patients with elevated NLR, careful assessment of treatment response needs to be performed in this group.

Prognostic implication of serum AFP in patients with hepatocellular carcinoma treated with regorafenib.

Background: This multicenter study investigated the predictive value of baseline AFP and on-treatment AFP response for survival in hepatocellular carcinoma (HCC) patients with regorafenib. Materials & methods: A total of 578 patients with HCC treated with regorafenib from 12 institutions in South Korea and Italy were included. Baseline AFP (cutoff, 400 ng/ml) and AFP response (20% reduction from baseline) were analyzed for overall survival (OS) and progression-free survival (PFS). Results: Baseline AFP below 400 ng/ml was a significant factor that was independently associated with longer OS and PFS. AFP response was also a significant factor independently associated with longer OS and PFS. Conclusion: Baseline AFP and AFP response may be used as prognostic factors for survival in HCC treated with regorafenib.

Regorafenib is standard second-line therapy for patients with hepatocellular carcinoma (HCC) who show failure to sorafenib treatment, but there is no reliable factor to predict survival. In this multicenter, retrospective study with patients from South Korea and Italy, we have found that both baseline AFP level and on-treatment AFP response have independent predictive value for survival in patients with HCC under regorafenib treatment. We observed similar results when the patients were divided according to their nationality (South Korea vs Italy), despite the fact that the baseline characteristics of the patients from the two cohorts were significantly different.

Identification of the fate and regenerative mechanism of zebrafish melanocyte progenitor cells and melanocytes after laser-induced pigment ablation.

BACKGROUND AND OBJECTIVES: Lasers are known to be the most effective treatment modality for pigmentary skin diseases. However, melanocytes and melanin pigment often recur or leave post-inflammatory hyperpigmentation after the laser procedure. Studies have reported on the role of progenitor cells in pigment cell regeneration, which can be constantly replenished through mitosis. However, the response of unpigmented melanocyte progenitor cells to laser treatment is poorly understood. In this study, we used adult zebrafish skin as the melanocyte regenerative system and examined the response of melanocyte progenitor cells to laser photothermolysis. MATERIALS AND METHODS: The two groups of adult zebrafish were irradiated with 1064 nm wavelength laser system of Q-switched neodymium:yttrium-aluminum-garnet (Nd:YAG) laser with 0.3 or 0.7 J·cm-2 . We compared the regeneration of pigment at different energy levels by measuring new melanocyte counts and pigment area. We traced and quantitatively compared the melanocyte lineage cells by immunohistochemical staining using specific markers such as sox10, mitfa, and dct during the regeneration process. Three repetitive laser ablations were also held to test the postinflammatory hyperpigmentation. RESULTS: After the laser ablation of melanocytes, most of the new melanocytes appeared between Days 5 and 10. In high-energy irradiation of 0.7 J·cm-2 , the unpigmented mitfa-expressing cells showed significant decrease (p < 0.05) and showed delay in the differentiation process of melanocyte lineage cells. After repeated laser irradiation, hyperpigmentation did not appear and the final recovery ratio of the pigmented area was 87.5% and 75.3% at the 0.3 and 0.7 J·cm-2 energy levels, respectively. CONCLUSION: We suggest that laser treatment overcoming the recurrence should be planned based on the adequate energy level targeting the melanocyte progenitor cells. High-energy irradiation may induce apoptosis of progenitor cells and delay their process of differentiation. Short-term repetitive sessions of laser therapy can reduce the pigmentation in the long-term observation.

Liposomal irinotecan plus fluorouracil and leucovorin versus fluorouracil and leucovorin for metastatic biliary tract cancer after progression on gemcitabine plus cisplatin (NIFTY): a multicentre, open-label, randomised, phase 2b study.

BACKGROUND: The prognosis of patients with advanced biliary tract cancer who have progressed on gemcitabine plus cisplatin is dismal. We aimed to investigate the efficacy and safety of second-line liposomal irinotecan plus fluorouracil and leucovorin in patients with metastatic biliary tract cancer that has progressed on gemcitabine plus cisplatin. METHODS: This multicentre, open-label, randomised, phase 2b (NIFTY) study was done at five academic institutions in South Korea and included patients aged 19 years or older with histologically or cytologically confirmed metastatic biliary tract cancer that had progressed on first-line gemcitabine plus cisplatin and an Eastern Cooperative Oncology Group performance status of 0 or 1. By use of an interactive web-based response system integrated with an electronic data capture system, patients were randomly assigned (1:1) using permuted blocks (block size 4) to receive either intravenous liposomal irinotecan (70 mg/m2 for 90 min) plus intravenous leucovorin (400 mg/m2 for 30 min) and intravenous fluorouracil (2400 mg/m2 for 46 h) every 2 weeks or leucovorin and fluorouracil only every 2 weeks, and were stratified by primary tumour site, previous surgery with curative intent, and participating centre. Study treatment was continued until the patient had disease progression or unacceptable toxicities, or withdrew consent. The primary endpoint was blinded independent central review (BICR)-assessed progression-free survival. The primary endpoint and safety were assessed in the full analysis set and the safety analysis set, respectively, both of which comprised all randomly assigned patients who received at least one dose of the study treatment. This trial is registered with ClinicalTrials.gov, NCT03524508, and enrolment is complete. FINDINGS: Between Sept 5, 2018, and Feb 18, 2020, 193 patients were screened for eligibility, of whom 174 (88 in the liposomal irinotecan plus fluorouracil and leucovorin group and 86 in the fluorouracil plus leucovorin group) were enrolled and included in the full analysis and safety analysis sets. At a median follow-up of 11·8 months (IQR 7·7-18·7), the median BICR-assessed progression-free survival was significantly longer in the liposomal irinotecan plus fluorouracil and leucovorin group (7·1 months, 95% CI 3·6-8·8) than in the fluorouracil and leucovorin group (1·4 months, 1·2-1·5; hazard ratio 0·56, 95% CI 0·39-0·81; p=0·0019). The most common grade 3-4 adverse events were neutropenia (21 [24%] of 88 in the liposomal irinotecan plus fluorouracil and leucovorin group vs one [1%] of 86 in the fluorouracil and leucovorin group) and fatigue or asthenia (11 [13%] vs three [3%]). Serious adverse events occurred in 37 (42%) patients receiving liposomal irinotecan plus fluorouracil and leucovorin and 21 (24%) patients receiving fluorouracil and leucovorin. There were no treatment-related deaths. INTERPRETATION: Adding liposomal irinotecan to fluorouracil and leucovorin significantly improved BICR-assessed progression-free survival in patients with advanced biliary tract cancer. Liposomal irinotecan plus fluorouracil and leucovorin could be considered a standard-of-care second-line therapy for advanced biliary tract cancer. FUNDING: Servier and HK inno. N TRANSLATION: For the Korean translation of the abstract see Supplementary Materials section.

Implementation of a 3 × 3 directionally-unbiased linear optical multiport.

Linear optical multiports are widely used in photonic quantum information processing. Naturally, these devices are directionally-biased since photons always propagate from the input ports toward the output ports. Recently, the concept of directionally-unbiased linear optical multiports was proposed. These directionally-unbiased multiports allow photons to propagate along a reverse direction, which can greatly reduce the number of required linear optical elements for complicated linear optical quantum networks. Here, we report an experimental demonstration of a 3 × 3 directionally-unbiased linear optical fiber multiport using an optical tritter and mirrors. Compared to the previous demonstration using bulk optical elements which works only with light sources with a long coherence length, our experimental directionally-unbiased 3 × 3 optical multiport does not require a long coherence length since it provides negligible optical path length differences among all possible optical trajectories. It can be a useful building block for implementing large-scale quantum walks on complex graph networks.

Importation and Transmission of SARS-CoV-2 B.1.1.529 (Omicron) Variant of Concern in Korea, November 2021.

In November 2021, 14 international travel-related severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant of concern (VOC) patients were detected in South Korea. Epidemiologic investigation revealed community transmission of the omicron VOC. A total of 80 SARS-CoV-2 omicron VOC-positive patients were identified until December 10, 2021 and 66 of them reported no relation to the international travel. There may be more transmissions with this VOC in Korea than reported.

Nucleic Acid Testing of SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) has caused a large global outbreak. It is accordingly important to develop accurate and rapid diagnostic methods. The polymerase chain reaction (PCR)-based method including reverse transcription-polymerase chain reaction (RT-PCR) is the most widely used assay for the detection of SARS-CoV-2 RNA. Along with the RT-PCR method, digital PCR has emerged as a powerful tool to quantify nucleic acid of the virus with high accuracy and sensitivity. Non-PCR based techniques such as reverse transcription loop-mediated isothermal amplification (RT-LAMP) and reverse transcription recombinase polymerase amplification (RT-RPA) are considered to be rapid and simple nucleic acid detection methods and were reviewed in this paper. Non-conventional molecular diagnostic methods including next-generation sequencing (NGS), CRISPR-based assays and nanotechnology are improving the accuracy and sensitivity of COVID-19 diagnosis. In this review, we also focus on standardization of SARS-CoV-2 nucleic acid testing and the activity of the National Metrology Institutes (NMIs) and highlight resources such as reference materials (RM) that provide the values of specified properties. Finally, we summarize the useful resources for convenient COVID-19 molecular diagnostics.

Regorafenib in patients with advanced Child-Pugh B hepatocellular carcinoma: A multicentre retrospective study.

INTRODUCTION: Regorafenib is an approved agent in patients with advanced hepatocellular carcinoma (HCC) who progressed on sorafenib, but little is known about its clinical outcomes in Child-Pugh B patients. We aimed to investigate the safety and effectiveness of regorafenib in Child-Pugh B HCC patients. METHODS: This multicentre retrospective study included 59 patients with Child-Pugh B HCC who received regorafenib. Comparative analyses were performed with an independent cohort of Child-Pugh class A patients from the same registry (n = 440). RESULTS: The median age was 58 years (range, 19-83). All patients had progression on prior sorafenib. Regorafenib was given as 2nd line, and 3rd-4th line systemic therapy in 37 (62.7%) and 22 (37.3%) patients respectively. Compared to Child-Pugh A cohort, grade 3-4 AEs were more common in the Child-Pugh B cohort (27.1% vs 14.1%, P = .017). The median progression-free survival (PFS) and overall survival (OS) were 1.8 and 4.6 months, respectively, and these were significantly poorer than the Child-Pugh A cohort (P = .008 and P < .001 respectively). Child-Pugh B patients with albumin-bilirubin (ALBI) grade 3 had a significantly higher frequency of increased bilirubin (P = .01 for any grade and P = .01 for grade 3-4) and showed significantly poorer OS (P = .021), compared to those with ALBI grade 1 or 2. CONCLUSION: Regorafenib's poor clinical outcomes and increased frequency of severe adverse events lead us to discourage its use in the Child-Pugh B population. In particular, regorafenib should not be used in Child-Pugh B patients with ALBI grade 3.

Regorafenib in previously treated advanced hepatocellular carcinoma: Impact of prior immunotherapy and adverse events.

BACKGROUND & AIMS: Regorafenib demonstrated a clinical benefit for patients with unresectable hepatocellular carcinoma (uHCC) in the phase III RESORCE trial. Considering the heterogeneity of uHCC and discrepancies in its characteristics between prospective trials and daily practice, real-life evidence is necessary. METHODS: This multicentre, retrospective analysis was performed by the Korean Cancer Study Group. In total, 440 patients who received regorafenib between January 2017 and November 2019 were identified in nine tertiary referral hospitals in Korea. RESULTS: All patients received prior sorafenib, and the median time-to-progression (TTP) on sorafenib was 3.9 months (range, 0.2-71.6). Regorafenib was used as the second, third and fourth to seventh lines of therapy in 305 (69.3%), 115 (26.1%) and 20 (4.5%) patients respectively. According to the RECIST v1.1, the overall response rate was 7.7% (n = 34), and the median progression-free survival (PFS) and overall survival (OS) were 3.2 (95% CI, 2.8-3.5) and 12.1 (95% CI, 9.7-14.5) months respectively. Immune checkpoint inhibitors (ICIs) were given in 115 patients (26.1%) prior to regorafenib. There were no differences in PFS and OS with regorafenib according to the prior use of ICIs (PFS, P = .61; OS, P = .63). The occurrence of hand-foot skin reaction (HFSR) was associated with a better OS (P < .001). CONCLUSIONS: The real-life clinical outcomes of regorafenib for patients who progressed on prior systemic therapy including ICIs were consistent with the phase III trial results. HFSR was significantly associated with better OS with regorafenib.

Dislocation sink annihilating threading dislocations in strain-relaxed Si1-x Ge x layer.

We proposed a dislocation sink technology for achieving Si1-x Ge x multi-bridge-channel field-effect-transistor beyond 5 nm transistor design-rule that essentially needs an almost crystalline-defect-free Si1-x Ge x channel. A generation of a dislocation sink via H+ implantations in a strain-relaxed Si0.7Ge0.3 layer grown on a Si substrate and a following annealing almost annihilate completely misfit and threading dislocations located near the interface between a relaxed Si0.7Ge0.3 layer and a Si substrate. A real-time (continuous heating from room temperature to 600 °C) in situ high-resolution-transmission-electron-microscopy and inverse-fast-Fourier-transform image observation at 1.25 MV acceleration voltage obviously demonstrated the annihilation process between dislocation sinks and remaining misfit and threading dislocations during a thermal annealing, called the [SiI or GeI + V Si or V Ge â†’ Si1-x Ge x ] annihilation process, where SiI, GeI, V Si, and V Ge are interstitial Si, interstitial Ge, Si vacancy, and Ge vacancy, respectively. In particular, the annihilation process efficiency greatly depended on the dose of H+ implantation and annealing temperature; i.e. a maximum annihilation process efficiency achieved at 5 × 1015 atoms cm-2 and 800 °C.

Device-Induced Neocollagenesis: Profibrotic Response or True Neocollagenesis?

BACKGROUND AND OBJECTIVES: Many light and radiofrequency-based rejuvenation devices have claimed to increase collagen production in the skin dermal tissue. However, there has not been enough scientific evidence to prove whether the result is just a profibrotic response or not. We aimed to find the optimal skin rejuvenation device that shows true neocollagenesis. STUDY DESIGN/MATERIALS AND METHODS: We evaluated dermal collagen thickness and gene expression of procollagen type 1, 3, matrix metalloproteinase-3 (MMP-3), and transforming growth factor-ß (TGF-ß) resulting from different energy-based devices in a rat model in vivo. The wound-healing response was evaluated histologically and by real-time polymerase chain reaction (RT-PCR) at immediate, 1st, 2nd, 4th, 8th, and 12th week after the initial procedure. RESULTS: At the 12th week, the most relevant changes of the dermal thickness were found in specimens after treatment with electrosurgical unit, fractional CO2 and 1064 nm Q-switched Nd:YAG. Procollagen 1 and 3 were also found to be the highest in electrosurgical unit, fractional CO2 , and microneedle radiofrequency. Dramatic changes of MMP-3 and TGF-ß were remarkable at the early observation but went back to normal level at 12th week. The ratio of procollagen 1 and 3 was found to be the lowest with Q-Switched Nd:YAG 1064 nm and fractional CO2 . CONCLUSION: Electrosurgical unit resulted in most significant changes, but due to irreversible thermal damage and extremely high procollagen results it is considered as a profibrotic response. Fractional CO2 and Q-Switched Nd:YAG 1064 nm are applicable to face skin rejuvenation treatment considering thickening of dermal tissue and lower procollagen 1:3 ratio similar to the neocollagenesis purpose. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.