Publications by authors named "Cahill D"

Cerebrospinal fluid (CSF) has emerged as a valuable liquid biopsy source for glioma biomarker discovery and validation. CSF produced within the ventricles circulates through the subarachnoid space, where the composition of glioma-derived analytes is influenced by the proximity and anatomical location of sampling relative to tumor, in addition to underlying tumor biology. The substantial gradients observed between lumbar and intracranial CSF compartments for tumor-derived analytes underscore the importance of sampling site selection.

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Background: Following surgery, patients with newly diagnosed glioblastoma frequently enter clinical trials. Nuanced risk assessment is warranted to reduce imbalances between study arms. Here, we aimed (I) to analyze the interactive effects of residual tumor with clinical and molecular factors on outcome and (II) to define a postoperative risk assessment tool.

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Purpose: Mutations in the Isocitrate Dehydrogenase (IDH) genes, IDH1 or IDH2, define a group of adult diffuse gliomas associated with a younger age at diagnosis and better prognosis than IDH wild-type glioblastoma. Within IDH mutant gliomas, a small fraction of astrocytic tumors present with grade 4 histologic features and poor prognosis. In molecular studies, homozygous deletion of CDKN2A/B is independently predictive of poor prognosis and short survival.

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Opportunistic pathogenic microbial infections pose a significant danger to human health, which forces people to use riskier, more expensive, and less effective drugs compared to traditional treatments. These may be attributed to several factors, such as overusing antibiotics in medicine and lack of sanitization in hospital settings. In this context, researchers are looking for new options to combat this worrying condition and find a solution.

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Background: MR spectroscopic imaging (MRSI) can be used to quantify an extended brain metabolic profile but is confounded by changes in tissue water levels due to disease.

Purpose: To develop a fast absolute quantification method for metabolite concentrations combining whole-brain MRSI with echo-planar time-resolved imaging (EPTI) relaxometry in individuals with glioma and healthy individuals.

Materials And Methods: In this prospective study performed from August 2022 to August 2023, using internal water as concentration reference, the MRSI-EPTI quantification method was compared with the conventional method using population-average literature relaxation values.

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Early diagnosis remains a major limitation of cancer outcomes with ethnicity and deprivation being determinants of inequalities that impact outcomes. Prostate cancer suffers from lower incidence rates and higher mortality rates in the most deprived versus the least deprived groups. We developed the 'Man Van' to enable high-risk male patients' from deprived communities and ethnic minorities increased access to health care to address these health inequalities.

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Glioma resection is associated with prolonged survival, but neuro-oncological trials have frequently refrained from quantifying the extent of resection. The Response Assessment in Neuro-Oncology (RANO) resect group is an international, multidisciplinary group that aims to standardise research practice by delineating the oncological role of surgery in diffuse adult-type gliomas as defined per WHO 2021 classification. Favourable survival effects of more extensive resection unfold over months to decades depending on the molecular tumour profile.

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Supramaximal resection beyond the contrast-enhancing tumor borders represents an emerging surgical strategy for patients with newly diagnosed glioblastoma. A recent study provides evidence detailing the interactive effects of more aggressive surgery on other clinical predictors of outcome, supporting guidance for surgical decision-making and informing clinical trialists about the need to stratify for extent of resection. See related article by Park et al.

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Article Synopsis
  • Glioma is the most common brain tumor in adults, and current methods for classifying it rely on molecular changes like IDH1.R132H, which can be risky and may not fully capture the complexity of the tumor.
  • A new liquid biopsy test called mt-IDH1 is introduced, allowing for a minimally invasive blood test that detects tumor RNA using just 2 ml of plasma.
  • In a study with 133 participants, the mt-IDH1 test showed a sensitivity of 75% and specificity of 88.7%, proving its potential for diagnosis and monitoring of gliomas, with results available in under 4 hours.
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  • Mutations in IDH1 and IDH2 genes play important roles in diagnosing and predicting outcomes in diffuse gliomas, particularly regarding their effects on immune cell populations within tumors.
  • This study used RNA sequencing and preclinical models to analyze the impact of IDH mutations on myeloid cells in glioma specimens, revealing that IDH-mutant tumors have fewer suppressive myeloid cells compared to IDH-wild-type tumors.
  • The research suggests that targeting the myeloid cell populations affected by mutant IDH could be a potential therapeutic approach for treating high-grade gliomas.
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  • The gene IDH1 often changes in many cancers, leading to a harmful substance that messes with the body's natural defenses.
  • Tumors with this change often keep immune cells out, but blocking the mutant IDH1 can help the body's immune system attack the cancer.
  • The study shows that the mutant IDH1 silences certain genes that would usually help the immune system work, but stopping this mutation can help reactivate those genes and boost immunity against tumors.
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Delays and risks associated with neurosurgical biopsies preclude timely diagnosis and treatment of central nervous system (CNS) lymphoma and other CNS neoplasms. We prospectively integrated targeted rapid genotyping of cerebrospinal fluid (CSF) into the evaluation of 70 patients with CNS lesions of unknown cause. Participants underwent genotyping of CSF-derived DNA using a quantitative polymerase chain reaction-based approach for parallel detection of single-nucleotide variants in the MYD88, TERT promoter, IDH1, IDH2, BRAF, and H3F3A genes within 80 minutes of sample acquisition.

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Purpose: Treatment paradigms for isocitrate dehydrogenase (IDH)-mutant gliomas are rapidly evolving. Although typically indolent and responsive to initial treatment, these tumors invariably recur at a higher grade and require salvage treatment. Homozygous deletion of the tumor suppressor gene CDKN2A/B frequently emerges at recurrence in these tumors, driving poor patient outcomes.

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Phytophthora cinnamomi is an oomycete plant pathogen with a host range of almost 5000 plant species worldwide and therefore poses a serious threat to biodiversity. Omics technology has provided significant progress in our understanding of oomycete biology, however, transformation studies of Phytophthora for gene functionalisation are still in their infancy. Only a limited number of Phytophthora species have been successfully transformed and gene edited to elucidate the role of particular genes.

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Gliomas with Isocitrate dehydrogenase (IDH) mutation represent a discrete category of primary brain tumors with distinct and unique characteristics, behaviors, and clinical disease outcomes. IDH mutations lead to aberrant high-level production of the oncometabolite D-2-hydroxyglutarate (D-2HG), which act as a competitive inhibitor of enzymes regulating epigenetics, signaling pathways, metabolism, and various other processes. This review summarizes the significance of IDH mutations, resulting upregulation of D-2HG and the associated molecular pathways in gliomagenesis.

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Article Synopsis
  • Survival rates for glioblastoma IDH wild-type (GBM) vary, emphasizing the need for improved surgical strategies, particularly given that most recurrences occur close to the resection margin.
  • A predictive model was created to determine which GBMs could achieve radiographic gross-total resection (GTR), showing strong accuracy in forecasting surgical outcomes based on tumor characteristics.
  • Analysis of surgical margins using a rapid method revealed that patients with undetected TERT promoter mutations after GTR had significantly better survival rates compared to those with detectable mutations.
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Article Synopsis
  • * Researchers used advanced RNA-sequencing techniques on tumor samples taken from patients after four weeks of IDHi treatment to examine cellular changes.
  • * Findings reveal that IDHi promotes differentiation of tumor cells toward a specific brain cell type (astrocytes), reduces stem-like cells, and highlights a mutation (NOTCH1) that may hinder this differentiation and affect treatment response.
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The epidermal growth factor receptor, EGFR, is frequently activated in lung cancer and glioblastoma by genomic alterations including missense mutations. The different mutation spectra in these diseases are reflected in divergent responses to EGFR inhibition: significant patient benefit in lung cancer, but limited in glioblastoma. Here, we report a comprehensive mutational analysis of EGFR function.

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Unlabelled: A protocol has been established for genetic transformation of the chloroplasts in two new cultivars of tomato ( L.) grown in India and Australia: Pusa Ruby and Yellow Currant. Tomato cv.

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An iterative algorithm for the diffusion of heat in layered structures is solved in cylindrical coordinates for the geometry used in measurements of thermophysical properties of materials by the modified transient plane source (MTPS) method. This solution for the frequency-domain temperature response is then used to model the transient temperature excursion and evaluate the accuracy of the measurements. We evaluate when the MTPS method is capable of separately determining the thermal conductivity and heat capacity per unit volume of a material.

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Unlabelled: Recent clinical trials have highlighted the limited efficacy of T cell-based immunotherapy in patients with glioblastoma (GBM). To better understand the characteristics of tumor-infiltrating lymphocytes (TIL) in GBM, we performed cellular indexing of transcriptomes and epitopes by sequencing and single-cell RNA sequencing with paired V(D)J sequencing, respectively, on TILs from two cohorts of patients totaling 15 patients with high-grade glioma, including GBM or astrocytoma, IDH-mutant, grade 4 (G4A). Analysis of the CD8+ TIL landscape reveals an enrichment of clonally expanded GZMK+ effector T cells in the tumor compared with matched blood, which was validated at the protein level.

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Introduction: Intra-detrusor botulinum toxin (Botox) injection is a minimally invasive alternative to augmentation cystoplasty in patients with refractory neurogenic bladder. Botox was first used for neurogenic bladder children two decades ago. However, there are no existing guidelines on indications or use among patients with spina bifida.

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