We investigated the prognostic relevance of IKZF1 deletions in 118 adult Ph-positive ALL patients who had minimal residual disease (MRD) data under a uniform treatment of allo-SCT following ...first-line imatinib-based chemotherapy. IKZF1 deletions were identified in 93 patients (78.8%). IKZF1-deleted patients had a lower proportion of early-stable molecular responders compared with wild-type patients (28.0 vs 56.0%, P=0.028). After a median follow-up of 72 months, IKZF1-deleted patients had a trend for higher cumulative incidence of relapse (CIR) (38.0 vs 13.3%, P=0.052), particularly in a subgroup of early-stable molecular responders (n=40; 21.4 vs 0%, P=0.088), but comparable disease-free survival to wild-type patients. Patients with biallelic-null deletions showed higher CIR (74.6 vs 13.3%, P=0.003) and lower disease-free survival (20.0 vs 67.5%, P=0.022) than wild-type patients. In multivariate analysis, MRD kinetics were closely related to outcomes, while neither IKZF1 deletions nor their functional subtypes retained an independent statistical power. Within the limitation of sample size, however, considering both the negative impact of IKZF1 deletions on MRD kinetics and a trend for relationship between IKZF1 deletions and relapse in early-stable molecular responders, IKZF1 deletions may have a potentially additive effect on unfavorable prognosis in a specific MRD-based subgroup of adult Ph-positive ALL transplants.
Summary
Dendritic cells (DCs) are promising therapeutic agents in the field of cancer immunotherapy due to their intrinsic immune‐priming capacity. The potency of DCs, however, is readily attenuated ...immediately after their administration in patients as tumours and various immune cells, including DCs, produce various immunosuppressive factors such as interleukin (IL)‐10 and transforming growth factor (TGF)‐β that hamper the function of DCs. In this study, we used small interfering RNA (siRNA) to silence the expression of endogenous molecules in DCs, which can sense immunosuppressive factors. Among the siRNAs targeting various immunosuppressive molecules, we observed that DCs transfected with siRNA targeting IL‐10 receptor alpha (siIL‐10RA) initiated the strongest antigen‐specific CD8+ T cell immune responses. The potency of siIL‐10RA was enhanced further by combining it with siRNA targeting TGF‐β receptor (siTGF‐βR), which was the next best option during the screening of this study, or the previously selected immunoadjuvant siRNA targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN) or Bcl‐2‐like protein 11 (BIM). In the midst of sorting out the siRNA cocktails, the cocktail of siIL‐10RA and siTGF‐βR generated the strongest antigen‐specific CD8+ T cell immunity. Concordantly, the knock‐down of both IL‐10RA and TGF‐βR in DCs induced the strongest anti‐tumour effects in the TC‐1 P0 tumour model, a cervical cancer model expressing the human papillomavirus (HPV)‐16 E7 antigen, and even in the immune‐resistant TC‐1 (P3) tumour model that secretes more IL‐10 and TGF‐β than the parental tumour cells (TC‐1 P0). These results provide the groundwork for future clinical development of the siRNA cocktail‐mediated strategy by co‐targeting immunosuppressive molecules to enhance the potency of DC‐based vaccines.
Observation of growing phase space density (PSD) peak in the outer electron radiation belt has been considered evidence for local wave‐driven acceleration as a primary cause of radiation belt ...enhancement. However, recent studies showed that strong substorm‐associated MeV electron injections can also cause significant radiation belt enhancements on fast timescales (∼10s min). Such rapid enhancements pose challenges for determining true spatial PSD profiles. To address this, we conduct a detailed spatiotemporal analysis of electron flux and PSD during an enhancement event, using Van Allen Probes data. Our analysis reveals rapid and intermittent flux enhancements. During these rapid enhancements, inbound spacecraft observed false PSD peaks, due to spacecraft's relatively slow movement. However, we identify time intervals of stable fluxes between enhancements, enabling us to determine quasi‐stationary PSD profiles with no noticeable peaks. This study provides new insights into accurate PSD analysis, critical for understanding the mechanisms underlying radiation belt enhancements.
Plain Language Summary
Radiation belt physics studies the origin and dynamics of high‐energy electrons trapped in the Earth's radiation belts. The radial profiles of these electrons' phase space density (PSD) are essential parameters for investigating their origin and dynamics. Outward‐increasing PSD profiles indicate that electrons have been transported radially (injections) from outside the radiation belt, while locally peaked profiles suggest that they were generated locally within the belt. Obtaining accurate PSD profiles is challenging due to significant temporal changes in electron flux, particularly rapid flux enhancements from injections as observed in recent studies. To examine the impact of rapid flux enhancements on PSD analysis, we closely tracked electron flux changes in space and time during an enhancement event using data from NASA's Van Allen Probes. Our results show that inbound spacecraft can observe falsely peaked PSD profiles during rapid flux enhancements, which are temporal artifacts from relatively slower spacecraft motion. By identifying time intervals of stable electron flux between enhancements, we were able to determine the true spatial PSD profiles, which overall exhibited outward‐increasing trends, consistent with injections. Our findings offer new perspective on accurately determining PSD radial profiles, which is essential for unraveling the origins of high‐energy electrons in the Earth's radiation belts.
Key Points
Rapid and intermittent electron enhancement pattern significantly impacts phase space density (PSD) analysis
Inbound spacecraft can observe a temporal PSD peak during rapid electron enhancements driven by injections
Quasi‐stationary time intervals between enhancements enable accurate determination of PSD radial profiles
Abstract
The 14
th
experimental campaign from the Korea Superconducting Tokamak Advanced Research (KSTAR) device has passed since the first experimental campaign was carried out in 2008. The basic ...diagnostic systems such as magnetic diagnostics, interferometer, inspection illuminator, visible spectrometer, ECE radiometer have been used for the first plasma experiment in KSTAR. Currently more than 50 diagnostic systems have been continuously installed including improved basic diagnostics and advanced imaging diagnostics in KSTAR. A recent progress and future plan of diagnostics for KSTAR are briefly discussed.
Fibrous dysplasia (FD) is a non-malignant condition caused by post-zygotic, activating mutations of the GNAS gene that results in inhibition of the differentiation and proliferation of bone-forming ...stromal cells and leads to the replacement of normal bone and marrow by fibrous tissue and woven bone. The phenotype is variable and may be isolated to a single skeletal site or multiple sites and sometimes is associated with extraskeletal manifestations in the skin and/or endocrine organs (McCune-Albright syndrome). The clinical behavior and progression of FD may also vary, thereby making the management of this condition difficult with few established clinical guidelines. This paper provides a clinically-focused comprehensive description of craniofacial FD, its natural progression, the components of the diagnostic evaluation and the multi-disciplinary management, and considerations for future research.
Summary
Background Psoriasis and seborrhoeic dermatitis are common erythematous‐squamous dermatoses that may present with scaly erythematous patches on the scalp. Owing to the similar ...clinicopathological features of these dermatoses, their differentiation poses a diagnostic challenge, particularly when the lesions on the scalp are isolated.
Objectives To evaluate the usefulness of dermoscopy in the clinical differentiation of scalp psoriasis and seborrhoeic dermatitis.
Methods This was a retrospective observational study to evaluate the characteristic dermoscopic features of scalp psoriasis and seborrhoeic dermatitis. The study included a total of 96 patients with lesions; these patients were recruited from two tertiary teaching hospitals in Korea (Pusan National University Hospital and Kyungpook National University Hospital). Among these, 55 patients had scalp psoriasis and 41 patients had seborrhoeic dermatitis.
Results The most significant dermoscopic features of scalp psoriasis were red dots and globules, twisted red loops, and glomerular vessels. In contrast, seborrhoeic dermatitis was characterized by arborizing vessels and atypical red vessels with the absence of red dots and globules. Featureless areas devoid of any particular vascular patterns were also frequently observed in seborrhoeic dermatitis. Dermoscopic findings of red lines and other vascular patterns were not considered useful for differentiation because these were uncommon features in both diseases. Although scales were observed commonly in both diseases, there was no significant difference in the frequency and characteristics of the scales when they were observed using dermoscopy.
Conclusions Our study shows that the investigation of vascular patterns by using dermoscopy can be valuable for the clinical diagnosis and differentiation of scalp psoriasis and seborrhoeic dermatitis.
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.
The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of early and locally-advanced non-small-cell lung ...cancer (NSCLC) was published in 2017, and covered the diagnosis, staging, management and treatment of both early stage I and II disease and locally-advanced stage III disease. At the ESMO Asia Meeting in November 2018, it was decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special face-to-face guidelines meeting in 2019 in Seoul. The aim was to adapt the ESMO 2017 guidelines to take into account potential differences related to ethnicity, cancer biology and standard practices associated with the treatment of locally-advanced, unresectable NSCLC in Asian patients. These guidelines represent the consensus opinions reached by those experts in the treatment of patients with lung cancer who represented the oncology societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and it was independent of both local current treatment practices and the treatment availability and reimbursement situations in the individual participating Asian countries.
No report has been published on the use of DSC MR imaging, DCE MR imaging, and DWI parameters in combination to create a prognostic prediction model in glioblastoma patients. The aim of this study ...was to develop a machine learning-based model to find preoperative multiparametric MR imaging parameters associated with prognosis in patients with glioblastoma. Normalized CBV, volume transfer constant, and ADC of the nonenhancing T2 high-signal-intensity lesions were evaluated using K-means clustering.
A total of 142 patients with glioblastoma who underwent preoperative MR imaging and total resection were included in this retrospective study. From the normalized CBV, volume transfer constant, and ADC maps, the parametric data were sorted using the K-means clustering method. Patients were divided into training and test sets (ratio, 1:1), and the optimal number of clusters was determined using receiver operating characteristic analysis. Kaplan-Meier survival analysis and log-rank tests were performed to identify potential parametric predictors. A multivariate Cox proportional hazard model was conducted to adjust for clinical predictors.
The nonenhancing T2 high-signal-intensity lesions were divided into 6 clusters. The cluster (class 4) with the relatively low normalized CBV and volume transfer constant value and the lowest ADC values was most associated with predicting glioblastoma prognosis. The optimal cutoff of the class 4 volume fraction of nonenhancing T2 high-signal-intensity lesions predicting 1-year progression-free survival was 9.70%, below which the cutoff was associated with longer progression-free survival. Two Kaplan-Meier curves based on the cutoff value showed a statistically significant difference (
= .037). When we adjusted for all clinical predictors, the cluster with the relatively low normalized CBV and volume transfer constant values and the lowest ADC value was an independent prognostic marker (hazard ratio, 3.04;
= .048). The multivariate Cox proportional hazard model showed a concordance index of 0.699 for progression-free survival.
Our model showed that nonenhancing T2 high-signal-intensity lesions with the relatively low normalized CBV, low volume transfer constant values, and the lowest ADC values could serve as useful prognostic imaging markers for predicting survival outcomes in patients with glioblastoma.
There remain concerns about the safety and functional benefit of laparoscopic pylorus-preserving gastrectomy (LPPG) compared with laparoscopic distal gastrectomy (LDG). This study evaluated ...short-term outcomes of a randomized clinical trial (RCT) comparing LPPG with LDG for gastric cancer.
The Korean Laparoendoscopic Gastrointestinal Surgery Study (KLASS)-04 trial was an investigator-initiated, open-label, parallel-assigned, superiority, multicentre RCT in Korea. Patients with cT1N0M0 cancer located in the middle third of the stomach at least 5 cm from the pylorus were randomized to undergo LPPG or LDG. Participants, care givers and those assessing the outcomes were not blinded to group assignment. Outcomes were 30-day postoperative morbidity rate and death at 90 days.
Some 256 patients from nine institutions were randomized (LPPG 129 patients, LDG 127 patients) between July 2015 and July 2017 and outcomes for 253 patients were analysed. Postoperative complications within 30 days were seen in 19.3 and 15.5 per cent in the LPPG and LDG groups respectively (P = 0·419). Postoperative pyloric stenosis was observed in nine (7.2 per cent) and two (1·5 per cent) patients in the LPPG and LDG groups (P = 0·026) respectively. In multivariable analysis higher BMI was a risk factor for postoperative complications (odds ratio 1·17, 95 per cent c.i. 1·04 to 1·32; P = 0·011). Death at 90 days was zero in both groups.
Postoperative complications and mortality was comparable in patients undergoing LPPG and LDG. Registration number: NCT02595086 (http://www.clinicaltrials.gov).
PDF
