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Cancers Aug 2023Glioblastoma (GB) is a malignant brain tumour that is challenging to treat, often relapsing even after aggressive therapy. Evaluating therapy response relies on magnetic...
BACKGROUND
Glioblastoma (GB) is a malignant brain tumour that is challenging to treat, often relapsing even after aggressive therapy. Evaluating therapy response relies on magnetic resonance imaging (MRI) following the Response Assessment in Neuro-Oncology (RANO) criteria. However, early assessment is hindered by phenomena such as pseudoprogression and pseudoresponse. Magnetic resonance spectroscopy (MRS/MRSI) provides metabolomics information but is underutilised due to a lack of familiarity and standardisation.
METHODS
This study explores the potential of spectroscopic imaging (MRSI) in combination with several machine learning approaches, including one-dimensional convolutional neural networks (1D-CNNs), to improve therapy response assessment. Preclinical GB (GL261-bearing mice) were studied for method optimisation and validation.
RESULTS
The proposed 1D-CNN models successfully identify different regions of tumours sampled by MRSI, i.e., normal brain (N), control/unresponsive tumour (T), and tumour responding to treatment (R). Class activation maps using Grad-CAM enabled the study of the key areas relevant to the models, providing model explainability. The generated colour-coded maps showing the N, T and R regions were highly accurate (according to Dice scores) when compared against ground truth and outperformed our previous method.
CONCLUSIONS
The proposed methodology may provide new and better opportunities for therapy response assessment, potentially providing earlier hints of tumour relapsing stages.
PubMed: 37568818
DOI: 10.3390/cancers15154002 -
Current Oncology (Toronto, Ont.) Aug 2023Gliomas are the most frequent intrinsic central nervous system tumors. The new 2021 WHO Classification of Central Nervous System Tumors brought significant changes into... (Review)
Review
Gliomas are the most frequent intrinsic central nervous system tumors. The new 2021 WHO Classification of Central Nervous System Tumors brought significant changes into the classification of gliomas, that underline the role of molecular diagnostics, with the adult-type diffuse glial tumors now identified primarily by their biomarkers rather than histology. The status of the isocitrate dehydrogenase (IDH) 1 or 2 describes tumors at their molecular level and together with the presence or absence of 1p/19q codeletion are the most important biomarkers used for the classification of adult-type diffuse glial tumors. In recent years terminology has also changed. IDH-mutant, as previously known, is diagnostically used as astrocytoma and IDH-wildtype is used as glioblastoma. A comprehensive understanding of these tumors not only gives patients a more proper treatment and better prognosis but also highlights new difficulties. MR imaging is of the utmost importance for diagnosing and supervising the response to treatment. By monitoring the tumor on followup exams better results can be achieved. Correlations are seen between tumor diagnostic and clinical manifestation and surgical administration, followup care, oncologic treatment, and outcomes. Minimal resection site use of functional imaging (fMRI) and diffusion tensor imaging (DTI) have become indispensable tools in invasive treatment. Perfusion imaging provides insightful information about the vascularity of the tumor, spectroscopy shows metabolic activity, and nuclear medicine imaging displays tumor metabolism. To accommodate better treatment the differentiation of pseudoprogression, pseudoresponse, or radiation necrosis is needed. In this report, we present a literature review of diagnostics of gliomas, the differences in their imaging features, and our radiology's departments accumulated experience concerning gliomas.
Topics: Humans; Adult; Brain Neoplasms; Diffusion Tensor Imaging; Mutation; Glioma; Biomarkers
PubMed: 37754483
DOI: 10.3390/curroncol30090568 -
International Journal of Molecular... Jan 2024Plants monitor day length and memorize changes in temperature signals throughout the day, creating circadian rhythms that support the timely control of physiological and... (Review)
Review
Plants monitor day length and memorize changes in temperature signals throughout the day, creating circadian rhythms that support the timely control of physiological and metabolic processes. The () transcription factors are known as master regulators for the acquisition of cold stress tolerance, whereas () is involved in plant adaptation to heat stress through thermomorphogenesis. Recent studies have shown that circadian clock genes control plant responses to temperature. Temperature-responsive transcriptomes show a diurnal cycle and peak expression levels at specific times of throughout the day. Circadian clock genes play essential roles in allowing plants to maintain homeostasis by accommodating temperature changes within the normal temperature range or by altering protein properties and morphogenesis at the cellular level for plant survival and growth under temperature stress conditions. Recent studies revealed that the central oscillator genes / () and // (//), as well as the () genes (/), were involved in the pathway of the cold signaling transcription factor and regulated the thermomorphogenesis gene . Further studies showed that another central oscillator, (), and the regulatory protein () are also involved. These studies led to attempts to utilize circadian clock genes for the acquisition of temperature-stress resistance in crops. In this review, we highlight circadian rhythm regulation and the clock genes involved in plant responses to temperature changes, as well as strategies for plant survival in a rapidly changing global climate.
Topics: Temperature; Circadian Clocks; Cold Temperature; Circadian Rhythm; Climate
PubMed: 38255990
DOI: 10.3390/ijms25020918 -
International Journal of Molecular... Nov 2023() play key roles in the circadian rhythms and flowering in plants. Here, we identified the four members of the family in , including , , and , and isolated their...
() play key roles in the circadian rhythms and flowering in plants. Here, we identified the four members of the family in , including , , and , and isolated their retrotransposon-tagged mutants. They were expressed in different organs and were nuclear-localized. The four genes played important roles in normal clock rhythmicity maintenance by negatively regulating the expression of and . Surprisingly, the four functioned redundantly in regulating flowering time under long-day conditions, and the quadruple mutant flowered earlier. Moreover, MtPRR can recruit the MtTPL/MtTPR corepressors and the other MtPRRs to form heterodimers to constitute the core mechanism of the circadian oscillator.
Topics: Circadian Clocks; Medicago truncatula; Arabidopsis; Circadian Rhythm; Photoperiod; Gene Expression Regulation, Plant
PubMed: 38069157
DOI: 10.3390/ijms242316834 -
European Journal of Nuclear Medicine... May 2024To summarize evidence on the comparative value of amino acid (AA) PET and conventional MRI for prediction of overall survival (OS) in patients with recurrent high grade... (Comparative Study)
Comparative Study
PURPOSE
To summarize evidence on the comparative value of amino acid (AA) PET and conventional MRI for prediction of overall survival (OS) in patients with recurrent high grade glioma (rHGG) under bevacizumab therapy.
METHODS
Medical databases were screened for studies with individual data on OS, follow-up MRI, and PET findings in the same patient. MRI images were assessed according to the RANO criteria. A receiver operating characteristic curve analysis was used to predict OS at 9 months.
RESULTS
Five studies with a total of 72 patients were included. Median OS was significantly lower in the PET-positive than in the PET-negative group. PET findings predicted OS with a pooled sensitivity and specificity of 76% and 71%, respectively. Corresponding values for MRI were 32% and 82%. Area under the curve and sensitivity were significantly higher for PET than for MRI.
CONCLUSION
For monitoring of patients with rHGG under bevacizumab therapy, AA-PET should be preferred over RANO MRI.
Topics: Humans; Bevacizumab; Glioma; Magnetic Resonance Imaging; Positron-Emission Tomography; Brain Neoplasms; Amino Acids; Recurrence; Female; Neoplasm Grading; Male; Survival Analysis; Middle Aged
PubMed: 38228970
DOI: 10.1007/s00259-024-06601-4 -
Plant Biotechnology Journal May 2024Soybean is a short-day plant that typically flowers earlier when exposed to short-day conditions. However, the identification of genes associated with earlier flowering...
Soybean is a short-day plant that typically flowers earlier when exposed to short-day conditions. However, the identification of genes associated with earlier flowering time but without a yield penalty is rare. In this study, we conducted genome-wide association studies (GWAS) using two re-sequencing datasets that included 113 wild soybeans (G. soja) and 1192 cultivated soybeans (G. max), respectively, and simultaneously identified a candidate flowering gene, qFT13-3, which encodes a protein homologous to the pseudo-response regulator (PRR) transcription factor. We identified four major haplotypes of qFT13-3 in the natural population, with haplotype H4 (qFT13-3) being lost during domestication, while qFT13-3 underwent natural and artificial selection, increasing in proportion from 4.5% in G. soja to 43.8% in landrace and to 81.9% in improve cultivars. Notably, most cultivars harbouring qFT13-3 were located in high-latitude regions. Knockout of qFT13-3 accelerated flowering and maturity time under long-day conditions, indicating that qFT13-3 functions as a flowering inhibitor. Our results also showed that qFT13-3 directly downregulates the expression of GmELF3b-2 which is a component of the circadian clock evening complex. Field trials revealed that the qft13-3 mutants shorten the maturity period by 11 days without a concomitant penalty on yield. Collectively, qFT13-3 can be utilized for the breeding of high-yield cultivars with a short maturity time suitable for high latitudes.
Topics: Glycine max; Genome-Wide Association Study; Plant Breeding; Haplotypes; Photoperiod; Flowers; Gene Expression Regulation, Plant; Plant Proteins
PubMed: 38070185
DOI: 10.1111/pbi.14254 -
Plant Communications May 2024The circadian clock entrained by environmental light-dark cycles allows plants to fine-tune diurnal growth and developmental responses. Here, we show that physical...
The circadian clock entrained by environmental light-dark cycles allows plants to fine-tune diurnal growth and developmental responses. Here, we show that physical interactions among evening clock components, including PSEUDO-RESPONSE REGULATOR5 (PRR5), TIMING OF CAB EXPRESSION1 (TOC1), and the Evening Complex (EC) component EARLY FLOWERING 3 (ELF3), define a diurnal repressive chromatin structure specifically at the PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) locus in Arabidopsis. These three clock components act interdependently as well as independently to repress nighttime hypocotyl elongation, as hypocotyl elongation rate dramatically increased specifically at nighttime in the prr5-1 toc1-21 elf3-1 mutant concomitant with a substantial increase in PIF4 expression. Transcriptional repression of PIF4 by ELF3, PRR5, and TOC1 is mediated by the SWI2/SNF2-RELATED (SWR1) chromatin remodeling complex, which incorporates histone H2A.Z at the PIF4 locus, facilitating robust epigenetic suppression of PIF4 during the evening. Overall, these findings demonstrate that the PRR-EC-SWR1 complex represses hypocotyl elongation during the night through a distinctive chromatin domain covering the PIF4 chromatin.
PubMed: 38816994
DOI: 10.1016/j.xplc.2024.100981