Corrigendum: ITGB5 promotes innate radiation resistance in pancreatic adenocarcinoma by promoting DNA damage repair and the MEK/ERK signaling pathway.

[This corrects the article DOI: 10.3389/fonc.2022.887068.].

Extended adjuvant temozolomide in newly diagnosed glioblastoma: A single-center retrospective study.

Objective: To investigate whether extending adjuvant temozolomide (TMZ) improved the prognosis of newly diagnosed glioblastoma (GBM) patients with different mutation statuses of O6-methylguanine DNA methyltransferase (MGMT), isocitrate dehydrogenase 1 (IDH1), p53 and different expression level of Ki67. Methods: This study was a retrospective cohort study that postoperative patients with newly diagnosed GBM who did not progress after receiving radiotherapy with concomitant and 6 cycles of adjuvant TMZ were enrolled in control group, and those received more than 6 cycles of adjuvant TMZ were incorporated in extended group. Patients were stratified by MGMT expression, IDH1 mutation, p53 mutation and expression level of Ki67. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Result: A total of 93 postoperative patients with newly diagnosed GBM were included in this study, 40 and 53 cases were included in control group and extended group, respectively. On the whole, extended adjuvant TMZ chemotherapy significantly prolonged OS and PFS of patients with newly diagnosed GBM [median OS (mOS): 29.00 months vs. 16.70 months, P < 0.001; median PFS (mPFS): 13.80 months vs. 9.60 months, P = 0.002]. The results of subgroup analysis showed that patients with methylated MGMT in extended group had significantly longer OS and PFS than those in control group; patients with IDH1 mutation benefited more from extended adjuvant TMZ chemotherapy than those with wild-type IDH1; there was no significant difference in the effect of extended TMZ chemotherapy on OS between GBM patients with wild-type p53 and those with mutant p53; compared with GBM patients with lower expression of Ki67, extended adjuvant TMZ treatment dramatically improved the OS and PFS of those with higher expression of Ki67. Conclusion: The therapeutic schedule of extended adjuvant TMZ significantly prolonged OS and PFS of patients with newly diagnosed GBM regardless of p53 mutation status, and patients with different MGMT methylation, IDH1 mutation and Ki67 expression level benefited differently from extended adjuvant TMZ chemotherapy.

Experimental Demonstration of Double Emittance Exchange toward Arbitrary Longitudinal Beam Phase-Space Manipulations.

Many of the most significant advances in accelerator science have been due to improvements in our ability to manipulate beam phase space. Despite steady progress in beam phase-space manipulation over the last several decades, future accelerator applications continue to outpace the ability to manipulate the phase space. This situation is especially pronounced for longitudinal beam phase-space manipulation, and is now getting increased attention. Herein, we report the first experimental demonstration of the double emittance exchange concept, which allows for the control of the longitudinal phase space using relatively simple transverse manipulation techniques. The double emittance exchange beamline enables extensive longitudinal manipulation, including tunable bunch compression, time-energy correlation control, and nonlinearity correction, in a remarkably flexible manner. The demonstration of this new method opens the door for arbitrary longitudinal beam manipulations capable of responding to the ever increasing demands of future accelerator applications.

ITGB5 promotes innate radiation resistance in pancreatic adenocarcinoma by promoting DNA damage repair and the MEK/ERK signaling pathway.

Pancreatic adenocarcinoma (PAAD) is one of the most aggressive digestive system tumors in the world, with a low early diagnosis rate and a high mortality. Integrin beta 5 (ITGB5) is demonstrated to be a potent tumor promoter in several carcinomas. However, it is unknown whether ITGB5 participates in the occurrence and development of PAAD. In this study, we confirmed a high expression of ITGB5 in PAAD and its role in promoting invasiveness and transitivity in PAAD. Besides, the knockdown of ITGB5 increased cell sensitivity to radiation by promoting DNA damage repair and the MEK/ERK signaling pathway. Collectively, these results show that ITGB5 plays an essential role in pancreatic cancer growth and survival.

Different classes of antibiotics exhibit disparate negative impacts on the therapeutic efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer patients.

It has been reported that antibiotics (ATBs) have adverse effect on the efficacy of treatment with immune checkpoint inhibitors (ICIs) in cancer patients. Since different classes of ATBs have different antibacterial spectrum, we aimed to study whether all ATBs had similar or different negative effects on the clinical outcomes of ICIs in patients with advanced non-small cell lung cancer (NSCLC). Patients with advanced NSCLC who received ICIs were included in this retrospective study and grouped by the class of ATBs they had used around the ICIs treatment time. The overall survival (OS) and the progression free survival (PFS) of patients among these groups were compared using Kaplan-Meier method and Cox proportional hazards model. A total of 148 eligible patients were enrolled, and 80 patients used ATBs. The results indicated that quinolones had no significant negative consequence on the clinical outcomes, while ß-lactams significantly shortened the OS and PFS of patients. Furthermore, patients exposed to the combination of ß-lactams and quinolones suffered the worst OS and PFS. Moreover, the subgroup analysis of ß-lactams revealed that only penicillins, but not carbapenems and cephalosporins, markedly reduced both OS and PFS. In addition to the class of ATBs used, the time frame of ATBs used also affected the clinical outcomes of ICIs therapy. Patients receiving ATBs within 60 days prior to and 30 days after the initiation of ICI treatment had significantly shorter OS and PFS compared with those who did not use ATBs. This study demonstrated that different classes of ATBs had disparate negative impacts on the clinical outcomes, and the use of ß-lactams, especially penicillins, should be avoided in advanced NSCLC patients who are receiving or scheduled to receive ICIs within 60 days.

Systematic pan-cancer analysis identifies RBM39 as an immunological and prognostic biomarker.

RNA-binding Motif Protein39 (RBM39) is identified as a splicing factor and transcription coactivator. Despite mounting evidence that RBM39 plays a critical role in the development of specific malignancies, no systematic pan-cancer investigation of RBM39 has been conducted. As a result, we set out to investigate RBM39's prognostic significance and putative immunological activities in 33 different cancers. Based on TCGA and CCLE, GTEx, cBioportal and HPA, we used a series of bioinformatics approaches to explore the potential oncogenic role of RBM39, including analysis of the expression of the pan-cancer species RBM39, the prognostic relationship between RBM39 expression and overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI), the relationship between RBM39 expression and clinical phenotype, analysis of the relationship between RBM39 expression and tumour mutational burden (TMB), microsatellite instability (MSI), DNA methylation and immune cell infiltration. Our results showed that RBM39 is overexpressed in most cancers. RBM39 was positively or negatively correlated with the prognosis of different tumours. RBM39 expression was associated with TMB and MSI in 9 and 12 cancer types. In addition, RBM39 expression was associated with DNA methylation in almost all tumours. There are eight tumours were screened for further study, including BRCA, COAD, HNSC, LIHC, LUSC, SKCM, STAD, UCEC. In the screed tumours, RBM39 was found to be negatively correlated with the infiltration of most immune cells. In addition, the correlation with RBM39 expression varied by immune cell subtype. Based on RBM39's role in tumorigenesis and tumour immunity, we suggest it can serve as a surrogate prognostic marker.

A novel preoperative MRI-based radiomics nomogram outperforms traditional models for prognostic prediction in pancreatic ductal adenocarcinoma.

To develop an efficient prognostic model based on preoperative magnetic resonance imaging (MRI) radiomics for patients with pancreatic ductal adenocarcinoma (PDAC), the preoperative MRI data of PDAC patients in two independent centers (defined as development cohort and validation cohort, respectively) were collected retrospectively, and the radiomics features of tumors were then extracted. Based on the optimal radiomics features which were significantly related to overall survival (OS) and progression-free survival (PFS), the score of radiomics signature (Rad-score) was calculated, and its predictive efficiency was evaluated according to the area under receiver operator characteristic curve (AUC). Subsequently, the clinical-radiomics nomogram which incorporated the Rad-score and clinical parameters was developed, and its discrimination, consistency and application value were tested by calibration curve, concordance index (C-index) and decision curve analysis (DCA). Moreover, the predictive value of the clinical-radiomics nomogram was compared with traditional prognostic models. A total of 196 eligible PDAC patients were enrolled in this study. The AUC value of Rad-score for OS and PFS in development cohort was 0.724 and 0.781, respectively, and the value of Rad-score was negatively correlated with PDAC's prognosis. Moreover, the developed clinical-radiomics nomogram showed great consistency with the C-index for OS and PFS in development cohort was 0.814 and 0.767, respectively. In addition, the DCA demonstrated that the developed nomogram displayed better clinical predictive usefulness than traditional prognostic models. We concluded that the preoperative MRI-based radiomics signature was significantly related to the poor prognosis of PDAC patients, and the developed clinical-radiomics nomogram showed better predictive ability, it might be used for individualized prognostic assessment of preoperative patients with PDAC.

Turn-key constrained parameter space exploration for particle accelerators using Bayesian active learning.

Particle accelerators are invaluable discovery engines in the chemical, biological and physical sciences. Characterization of the accelerated beam response to accelerator input parameters is often the first step when conducting accelerator-based experiments. Currently used techniques for characterization, such as grid-like parameter sampling scans, become impractical when extended to higher dimensional input spaces, when complicated measurement constraints are present, or prior information known about the beam response is scarce. Here in this work, we describe an adaptation of the popular Bayesian optimization algorithm, which enables a turn-key exploration of input parameter spaces. Our algorithm replaces  the need for parameter scans while minimizing prior information needed about the measurement's behavior and associated measurement constraints. We experimentally demonstrate that our algorithm autonomously conducts an adaptive, multi-parameter exploration of input parameter space, potentially orders of magnitude faster than conventional grid-like parameter scans, while making highly constrained, single-shot beam phase-space measurements and accounts for costs associated with changing input parameters. In addition to applications in accelerator-based scientific experiments, this algorithm addresses challenges shared by many scientific disciplines, and is thus applicable to autonomously conducting experiments over a broad range of research topics.

Transition Radiation in Photonic Topological Crystals: Quasiresonant Excitation of Robust Edge States by a Moving Charge.

We demonstrate, theoretically and experimentally, that a traveling electric charge passing from one photonic crystal into another generates edge waves-electromagnetic modes with frequencies inside the common photonic band gap localized at the interface-via a process of transition edge-wave radiation (TER). A simple and intuitive expression for the TER spectral density is derived and then applied to a specific structure: two interfacing photonic topological insulators with opposite spin-Chern indices. We show that TER breaks the time-reversal symmetry and enables valley- and spin-polarized generation of topologically protected edge waves propagating in one or both directions along the interface. Experimental measurements at the Argonne Wakefield Accelerator Facility are consistent with the excitation and localization of the edge waves. The concept of TER paves the way for novel particle accelerators and detectors.

Observation of Field-Emission Dependence on Stored Energy.

Field emission from a solid metal surface has been continuously studied for a century over macroscopic to atomic scales. It is general knowledge that, other than the surface properties, the emitted current is governed solely by the applied electric field. A pin cathode has been used to study the dependence of field emission on stored energy in an L-band rf gun. The stored energy was changed by adjusting the axial position (distance between the cathode base and the gun back surface) of the cathode while the applied electric field on the cathode tip is kept constant. A very strong correlation of the field-emission current with the stored energy has been observed. While eliminating all possible interfering sources, an enhancement of the current by a factor of 5 was obtained as the stored energy was increased by a factor of 3. It implies that under certain circumstances a localized field emission may be significantly altered by the global parameters in a system.

Dipole-mode wakefields in dielectric-loaded rectangular waveguide accelerating structures.

By applying different symmetric boundary conditions, we found that the transverse wakefields generated by an electron bunch traveling through a partially loaded rectangular dielectric structure at an off center position can be decomposed into corresponding orthogonal longitudinal section electric (LSE) and longitudinal section magnetic (LSM) modes for guided waves as in the case of longitudinal wakefields treated previously. The wakefields are characterized using the normalized shunt impedance R/Q, a function of the geometry of the accelerating structure, for both LSE and LSM modes. A numerical example is given for an X-band waveguide structure and detailed results are given for the several leading transverse wakefield terms. The analytic results obtained are in agreement with the results from the time domain simulation tool MAFIA.