The hard X-ray free-electron laser at the Pohang Accelerator Laboratory (PAL-XFEL) in the Republic of Korea achieved saturation of a 0.144 nm free-electron laser beam on 27 November 2016, making it ...the third hard X-ray free-electron laser in the world, following the demonstrations of the Linac Coherent Light Source (LCLS) and the SPring-8 Angstrom Compact Free Electron Laser (SACLA). The use of electron-beam-based alignment incorporating undulator radiation spectrum analysis has allowed reliable operation of PAL-XFEL with unprecedented temporal stability and dispersion-free orbits. In particular, a timing jitter of just 20 fs for the free-electron laser photon beam is consistently achieved due to the use of a state-of-the-art design of the electron linear accelerator and electron-beam-based alignment. The low timing jitter of the electron beam makes it possible to observe Bi(111) phonon dynamics without the need for timing-jitter correction, indicating that PAL-XFEL will be an extremely useful tool for hard X-ray time-resolved experiments. The Pohang Accelerator Laboratory X-ray Free Electron Laser (PAL-XFEL) in South Korea has now entered operation with a timing jitter of just 20 fs.
Biomarkers on the basis of tumor-infiltrating lymphocytes (TIL) are potentially valuable in predicting the effectiveness of immune checkpoint inhibitors (ICI). However, clinical application remains ...challenging because of methodologic limitations and laborious process involved in spatial analysis of TIL distribution in whole-slide images (WSI).
We have developed an artificial intelligence (AI)-powered WSI analyzer of TIL in the tumor microenvironment that can define three immune phenotypes (IPs): inflamed, immune-excluded, and immune-desert. These IPs were correlated with tumor response to ICI and survival in two independent cohorts of patients with advanced non-small-cell lung cancer (NSCLC).
Inflamed IP correlated with enrichment in local immune cytolytic activity, higher response rate, and prolonged progression-free survival compared with patients with immune-excluded or immune-desert phenotypes. At the WSI level, there was significant positive correlation between tumor proportion score (TPS) as determined by the AI model and control TPS analyzed by pathologists (
< .001). Overall, 44.0% of tumors were inflamed, 37.1% were immune-excluded, and 18.9% were immune-desert. Incidence of inflamed IP in patients with programmed death ligand-1 TPS at < 1%, 1%-49%, and ≥ 50% was 31.7%, 42.5%, and 56.8%, respectively. Median progression-free survival and overall survival were, respectively, 4.1 months and 24.8 months with inflamed IP, 2.2 months and 14.0 months with immune-excluded IP, and 2.4 months and 10.6 months with immune-desert IP.
The AI-powered spatial analysis of TIL correlated with tumor response and progression-free survival of ICI in advanced NSCLC. This is potentially a supplementary biomarker to TPS as determined by a pathologist.
Coronavirus disease 2019 (COVID-19) sequelae (or long COVID) has become a clinically significant concern. Several studies have reported the relationship between heart rate variability (HRV) ...parameters and COVID-19. This review investigates the long-term association between COVID-19 and HRV parameters. Four electronic databases were searched up to 29 July 2022. We included observational studies comparing HRV parameters (measurement durations: 1 min or more) in participants with and without a history of COVID-19. We used assessment tools developed by the National Heart, Lung, and Blood Institute group to evaluate the methodological quality of included studies. Eleven cross-sectional studies compared HRV parameters in individuals who recovered from acute COVID-19 infection to controls (n = 2197). Most studies reported standard deviation of normal-to-normal intervals (SDNN) and root mean square of the successive differences. The methodological quality of the included studies was not optimal. The included studies generally found decreased SDNN and parasympathetic activity in post-COVID-19 individuals. Compared to controls, decreases in SDNN were observed in individuals who recovered from COVID-19 or had long COVID. Most of the included studies emphasized parasympathetic inhibition in post-COVID-19 conditions. Due to the methodological limitations of measuring HRV parameters, the findings should be further validated by robust prospective longitudinal studies.
In a power plant that uses seawater as a coolant, a debris filter (DF) is required to remove foreign substances from the seawater, and differential pressure leads to a decrease in the coolant flow ...rate, leading to a decrease in the power generation efficiency. In this study, an analysis was performed for the cases wherein the initial flow velocity conditions of the DF used in the condenser tube cleaning system (CTCS) were 1.5 m/s, 2.0 m/s, and 2.5 m/s using Ansys Fluent 2021, and the flow characteristics were identified. The flow and differential pressure characteristics of a CTCS with an installed DF were considered in a comparative analysis of the velocity, pressure, and turbulence kinetic energy (TKE) distributions. The results confirmed that a vortex was generated in the pipe with the DF, apparently due to the collision of the flow with the bracket of the DF. As the flow rate increased, the range of the vortex increased, causing a loss in flow.
The construction of Pohang Accelerator Laboratory X-ray Free-Electron Laser (PAL-XFEL), a 0.1-nm hard X-ray free-electron laser (FEL) facility based on a 10-GeV S-band linear accelerator (LINAC), is ...achieved in Pohang, Korea by the end of 2016. The construction of the 1.11 km-long building was completed by the end of 2014, and the installation of the 10-GeV LINAC and undulators started in January 2015. The installation of the 10-GeV LINAC, together with the undulators and beamlines, was completed by the end of 2015. The commissioning began in April 2016, and the first lasing of the hard X-ray FEL line was achieved on 14 June 2016. The progress of the PAL-XFEL construction and its commission are reported here.
Airports strive to prevent safety issues, such as foreign object debris (FOD), by pavement management using the pavement condition index (PCI). The index is used in decision-making processes for ...overall pavement maintenance and repair, such as the prevention of additional damage due to cracks and the like. However, considering the current situation in Korea where mostly mid-sized and large commercial airports exist, problems regarding direct applications of the existing PCI deduct value have been consistently pointed out. In addition, as the relationship between the PCI and whether maintenance and repair are required is unrealistic, there have been difficulties in communication between maintenance and repair staff and decision makers. Therefore, to resolve these problems, this study first analyzed the calculation procedure of the existing PCI and then redefined the main distress type of Korean airport pavements. In addition, a deduct value curve (DVC) in terms of the severity level for six main distress factors of asphalt pavements and eight main distress factors of concrete pavements and a corrected deduct value curve (CDVC) for multiple distresses in terms of the pavement form were developed using panel rating, which is an engineering approach, by forming an airport pavement expert panel. Finally, a Korea airport pavement condition index (KPCI) was proposed using the curves, and the field application results were compared against the existing PCI to examine the adequacy of the KPCI. As a result, the developed criteria showed an overall trend lower than existing PCI. Moreover, it was verified that this trend increases with worsening pavement condition. It appears that a more discriminating evaluation may be possible when determining pavement conditions by PCI results of the developed criteria.
Objectives. To analyze the efficacy and safety of auricular acupuncture (AA) in patients with cognitive impairment and dementia. Methods. Twelve electronic databases were searched for randomized ...controlled trials evaluating effects of AA in patients with cognitive impairment and/or dementia, from their inception to August 2017. The primary outcome was cognitive function, and secondary outcomes were self-care ability, quality of life, clinical efficacy rate, and incidences of adverse events. Results. Nine studies were included, and five involving 677 participants were analyzed quantitatively. Compared with Western medications (WM), AA had mixed effects on cognitive functions (Mini-Mental State Examination MMSE, mean difference MD 0.73, 95% confidence interval CI −0.02 to 1.48; Hierarchic Dementia Scale HDS, MD 2.21, 95% CI 1.09 to 3.33); there was no significant improvement in the activities of daily living (ADL) score (MD 0.20, 95% CI −3.51 to 3.91) in patients with vascular dementia (VD). Compared to WM, AA combined with WM showed better clinical efficacy rate (risk ratio RR 1.42, 95% CI 1.06 to 1.91) in patients with VD; there was no significant improvement in cognitive functions (MMSE, MD 0.97, 95% CI −0.44 to 2.38; Montreal Cognitive Assessment MoCA, MD 0.22, 95% CI −1.83 to 2.27) in patients with mild cognitive impairment (MCI). Compared to herbal medicine (HM), AA plus HM showed significant improvements in cognitive function (MMSE, MD 1.31, 95% CI 0.13 to 2.49) in patients with MCI and patients with vascular cognitive impairment, no dementia (VCIND) and in ADL score (MD −6.70, 95% CI −8.78 to −4.62) in patients with MCI. No adverse event associated with AA was reported. Conclusion. The evidence reveals mixed efficacy of AA in patients with cognitive impairment and/or dementia. However, the results were inconclusive because of the small number and poor methodological quality of the included studies.
Although immune checkpoint inhibitors (ICIs) can induce durable responses in non-small-cell lung cancer (NSCLC) patients, a significant proportion of responders still experience progressive disease ...after a period of response. Limited data are available on the clinical patterns of acquired resistance (AR) to ICIs. Clinical and radiologic data from 125 NSCLC patients treated with anti-PD-1 or PD-L1 antibodies between 2011 and 2018 at two tertiary academic institutions were retrospectively reviewed. Overall, 63 (50.4%) patients experienced AR after ICI treatment in a median of 10.7 months. Among the 13 patients with a partial response with ICI, 12 (32.4%) had only lymph node progression. Most patients (n = 52, 82.5%) had one or two sites with progression (oligo-progression). The median overall survival (OS) after progression was significantly longer in the extrathoracic group than in the thoracic and liver progression groups (30.2 months 95% confidence interval (CI), 13.4 to not reached (NR), 11.7 months 95% CI, 9.5-21.1, and 5.4 months 95% CI, 2.6-NR, respectively, P < 0.001). Patients with oligo-progression had significantly longer OS after AR than did the multi-progression patients (18.9 months 95% CI, 10.6-NR vs. 8.8 months 95% CI, 5.7-NR, P = 0.04). No significant difference in progression-free survival was observed between the subsequent chemotherapy and the ICI after AR groups (P = 0.723). Patients with AR after ICI treatment had a unique progression pattern with oligo-progression and high rates of progression only in the lymph nodes. Local treatment and/or continuation of ICIs beyond AR might be an effective option.
OBJECTIVE:To investigate the molecular characteristics of AGEJ compared with EAC and gastric adenocarcinoma.
SUMMARY OF BACKGROUND DATA:Classification of AGEJ based on differential molecular ...characteristics between EAC and gastric adenocarcinoma has been long-standing controversy but rarely conducted due to anatomical ambiguity and epidemiologic difference.
METHODS:The molecular classification model with Bayesian compound covariate predictor was developed based on differential mRNA expression of EAC (N = 78) and GCFB (N = 102) from the Cancer Genome Atlas (TCGA) cohort. AGEJ/cardia (N = 48) in TCGA cohort and AGEJ/upper third GC (N = 46 pairs) in Seoul National University cohort were classified into the EAC-like or GCFB-like groups whose genomic, transcriptomic, and proteomic characteristics were compared.
RESULTS:AGEJ in both cohorts was similarly classified as EAC-like (31.2%) or GCFB-like (68.8%) based on the 400-gene classifier. The GCFB-like group showed significantly activated phosphoinositide 3-kinase-AKT signaling with decreased expression of ERBB2. The EAC-like group presented significantly different alternative splicing including the skipped exon of RPS24, a significantly higher copy number amplification including ERBB2 amplification, and increased protein expression of ERBB2 and EGFR compared with GCFB-like group. High-throughput 3D drug test using independent cell lines revealed that the EAC-like group showed a significantly better response to lapatinib than the GCFB-like group (P = 0.015).
CONCLUSIONS:AGEJ was the combined entity of the EAC-like and GCFB-like groups with consistently different molecular characteristics in both Seoul National University and TCGA cohorts. The EAC-like group with a high Bayesian compound covariate predictor score could be effectively targeted by dual inhibition of ERBB2 and EGFR.
PDF
