•Main factors impacting feature stability: Image acquisition, reconstruction, tumor segmentation, and interpolation.•Textural features are less robust than morphological or statistical features.•A ...checklist is provided including items that should be reported in a radiomic study.
Although quantitative image biomarkers (radiomics) show promising value for cancer diagnosis, prognosis, and treatment assessment, these biomarkers still lack reproducibility. In this systematic review, we aimed to assess the progress in radiomics reproducibility and repeatability in the recent years.
Four hundred fifty-one abstracts were retrieved according to our search pattern criteria, with the publication dates ranging from 2017/05/01 to 2020/12/01. Each abstract including the keywords was independently screened by four observers. Forty-two full-text articles were selected for further analysis. Patient population data, radiomic feature classes, feature extraction software, image preprocessing, and reproducibility results were extracted from each article. To support the community with a standardized reporting strategy, we propose a specific reporting checklist to evaluate the feasibility to reproduce each study.
Many studies continue to under-report essential reproducibility information: all but one clinical and all but two phantom studies missed to report at least one important item reporting image acquisition. The studies included in this review indicate that all radiomic features are sensitive to image acquisition, reconstruction, tumor segmentation, and interpolation. However, the amount of sensitivity is feature dependent, for instance, textural features were, in general, less robust than statistical features.
Radiomics repeatability, reproducibility, and reporting quality can substantially be improved regarding feature extraction software and settings, image preprocessing and acquisition, cutoff values for stable feature selection. Our proposed radiomics reporting checklist can serve to simplify and improve the reporting and, eventually, guarantee the possibility to fully replicate and validate radiomic studies.
Metazoan arrestins bind to seven-transmembrane (7TM) receptors to regulate function. Aspergillus nidulans PalF, a protein involved in the fungal ambient pH signaling pathway, contains arrestin ...N-terminal and C-terminal domains and binds strongly to two different regions within the C-terminal cytoplasmic tail of the 7TM, putative pH sensor PalH. Upon exposure to alkaline ambient pH, PalF is phosphorylated and, like mammalian β-arrestins, ubiquitinated in a signal-dependent and 7TM protein-dependent manner. Substitution in PalF of a highly conserved arrestin N-terminal domain Ser residue prevents PalF-PalH interaction and pH signaling in vivo. Thus, PalF is the first experimentally documented fungal arrestin-related protein, dispelling the notion that arrestins are restricted to animal proteomes. Epistasis analyses demonstrate that PalF posttranslational modification is partially dependent on the 4TM protein Pall but independent of the remaining pH signal transduction pathway proteins PalA, PalB, and PalC, yielding experimental evidence bearing on the order of participation of the six components of the pH signal transduction pathway. Our data strongly implicate PalH as an ambient pH sensor, possibly with the cooperation of PalI.
Abstract Background and purpose Patients with advanced NSCLC have survival rates <15%. The NOTCH pathway plays an important role during lung development and physiology but is often deregulated in ...lung cancer, making it a potential therapeutic target. We investigated NOTCH signaling in NSCLC and hypothesized that high NOTCH activity contributes to radiation resistance. Materials and methods NOTCH signaling in NSCLC patient samples was investigated using quantitative RT-PCR. H460 NSCLC cells with either high or blocked NOTCH activity were generated and their radiation sensitivity monitored using clonogenic assays. In vivo, xenograft tumors were irradiated and response assessed using growth delay. Microenvironmental parameters were analyzed by immunohistochemistry. Results Patients with high NOTCH activity in tumors showed significantly worse disease-free survival. In vitro, NOTCH activity did not affect the proliferation or intrinsic radiosensitivity of NSCLC cells. In contrast, xenografts with blocked NOTCH activity grew slower than wild type tumors. Tumors with high NOTCH activity grew significantly faster, were more hypoxic and showed a radioresistant phenotype. Conclusions We demonstrate an important role for NOTCH in tumor growth and correlate high NOTCH activity with poor prognosis and radioresistance. Blocking NOTCH activity in NSCLC might be a promising intervention to improve outcome after radiotherapy.
Summary
The Aspergillus nidulans PacC transcription factor mediates gene regulation in response to alkaline ambient pH which, signalled by the Pal pathway, results in the processing of PacC72 to ...PacC27 via PacC53. Here we investigate two levels at which the pH regulatory system is transcriptionally moderated by pH and identify and characterise a new component of the pH regulatory machinery, PacX. Transcript level analysis and overexpression studies demonstrate that repression of acid‐expressed palF, specifying the Pal pathway arrestin, probably by PacC27 and/or PacC53, prevents an escalating alkaline pH response. Transcript analyses using a reporter and constitutively expressed pacC trans‐alleles show that pacC preferential alkaline‐expression results from derepression by depletion of the acid‐prevalent PacC72 form. We additionally show that pacC repression requires PacX. pacX mutations suppress PacC processing recalcitrant mutations, in part, through derepressed PacC levels resulting in traces of PacC27 formed by pH‐independent proteolysis. pacX was cloned by impala transposon mutagenesis. PacX, with homologues within the Leotiomyceta, has an unusual structure with an amino‐terminal coiled‐coil and a carboxy‐terminal zinc binuclear cluster. pacX mutations indicate the importance of these regions. One mutation, an unprecedented finding in A. nidulans genetics, resulted from an insertion of an endogenous Fot1‐like transposon.
The Aspergillus nidulans pH response, mediated by PacC which is proteolytically activated in response to Pal mediated alkaline pH signalling, moderates itself. pacC is negatively autoregulated by the acid prevalent form PacC72 and a runaway pH response is prevented by negative feedback at signalling gene palF. PacX, a zinc binuclear cluster protein with unusual architecture and restricted taxonomic distribution, tempers PacC activity and is required to tether the pH response to the ambient pH signal.
Over the last decades, the incidence of human papilloma virus (HPV) positive head and neck squamous-cell carcinoma (HNSCC) has significantly increased. Infection with high-risk HPV types drives ...tumourigenesis through expression of the oncoproteins E6 and E7. Currently, the primary treatment of HNSCC consists of radiotherapy, often combined with platinum-based chemotherapeutics. One of the common features of HNSCC is the occurrence of tumour hypoxia, which impairs the efficacy of radiotherapy and is a negative prognostic factor. Therefore, it is important to detect and quantify the severity of hypoxia, as well as develop strategies to specifically target hypoxic tumours. HPV-positive tumours are remarkably radiosensitive compared to HPV-negative tumours and consequently the HPV-positive patients have a better prognosis. This provides an opportunity to elucidate mechanisms of radiation sensitivity, which may reveal targets for improved therapy for HPV-negative head and neck cancers. In this review, we will discuss the differences between HPV-positive and HPV-negative head and neck tumours and methods of hypoxia detection and targeting in these disease types. Particular emphasis will be placed on the mechanisms by which HPV infection impacts radiosensitivity.
We addressed the question of whether Aspergillus nidulans has more than one cyclin‐dependent kinase gene and identified such a gene, phoA, encoding two PSTAIRE‐containing kinases (PHOAM1 and PHOAM47) ...that probably result from alternative pre‐mRNA splicing. PHOAM47 is 66% identical to Saccharomyces cerevisiae Pho85. The function of this gene was studied using phoA null mutants. It functions in a developmental response to phosphorus‐limited growth but has no effect on the regulation of enzymes involved in phosphorus acquisition. Aspergillus nidulans shows both asexual and sexual reproduction involving temporal elaboration of different specific cell types. We demonstrate that developmental decisions in confluent cultures depend upon both the initial phosphorus concentration and the inoculation density and that these factors influence development through phoA. In the most impressive cases, absence of phoA resulted in a switch from asexual to sexual development (at pH 8), or the absence of development altogether (at pH 6). The phenotype of phoA deletion strains appears to be specific for phosphorus limitation. We propose that PHOA functions to help integrate environmental signals with developmental decisions to allow ordered differentiation of specific cell types in A.nidulans under varying growth conditions. The results implicate a putative cyclin‐dependent kinase in the control of development.
Background
Improving survival in non-small cell lung cancer (NSCLC) will require new strategies or new drugs. Sequential administration of conventional non-cross-resistant cytotoxic drugs offers an ...opportunity to increase drug diversity while maintaining dose intensity. This Phase II trial was designed to assess the efficacy and feasibility of such a regimen in advanced NSCLC.
Methods
Patients with NSCLC stage IIIB or IV received as first-line treatment four cycles of carboplatin (AUC 5) (day 1) plus gemcitabine 1000 mg/m
2
(days 1 and 8) every 3 weeks. Thereafter, treatment continued with 12 weekly cycles of paclitaxel 80 mg/m
2
.
Results
In total, 46 patients were included. Median age was 59.6 years (range 41.3–74.3 years) and 93.5 % (
n
= 43) had Eastern Cooperative Oncology Group performance score of 0 or 1. All but 6 had stage IV disease, and 13 (28.3 %) had squamous cell carcinomas. Thirty-six (78 %) patients completed 4 cycles of carboplatin–gemcitabine and 35 patients received at least 1 cycle of paclitaxel, of whom 16 (46 % of total) patients completed 12 cycles of paclitaxel. The overall objective response rate was 49 %. Sixteen (37 %) patients had a response to carboplatin–gemcitabine, increasing to 21 (49 %) patients after administration of paclitaxel. Of the 13 assessable patients who showed a partial response (PR) on carboplatin–gemcitabine, 12 (92 %) patients showed also a PR on paclitaxel. Of 19 assessable patients with stable disease (SD) on carboplatin–gemcitabine, 4 (21 %) had a PR and 13 (68 %) SD on paclitaxel. Toxicity was moderate: 24 % stopped because of toxicity.
Conclusion
Sequential chemotherapy with carboplatin–gemcitabine and weekly paclitaxel is active and feasible in advanced NSCLC patients.
An Aspergillus nidulans kinase gene, which encodes a protein kinase with high similarity to mitogen-activated protein kinases involved in cell wall construction and morphogenesis in yeast species, ...was cloned and sequenced. Targeted deletion of the Aspergillus nidulans kinase gene indicates that this kinase is involved in germination of conidial spores and polarized growth. These defects were largely remedied on complex high osmolarity media, although abnormal swellings of hyphal tips were still observed. Glycerol (1 M) only supported the growth of compact colonies. The Aspergillus nidulans kinase gene is, thus, required for normal polarized growth at several stages of colony formation in the filamentous fungus A. nidulans.
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