225 research outputs found
Prediction of clinical outcome in glioblastoma using a biologically relevant nine-microRNA signature
Background
Glioblastoma is the most aggressive primary brain tumor, and is associated with a very poor prognosis. In this study we investigated the potential of microRNA expression profiles to predict survival in this challenging disease.
Methods
MicroRNA and mRNA expression data from glioblastoma (n = 475) and grade II and III glioma (n = 178) were accessed from The Cancer Genome Atlas. LASSO regression models were used to identify a prognostic microRNA signature. Functionally relevant targets of microRNAs were determined using microRNA target prediction, experimental validation and correlation of microRNA and mRNA expression data.
Results
A 9-microRNA prognostic signature was identified which stratified patients into risk groups strongly associated with survival (p = 2.26e−09), significant in all glioblastoma subtypes except the non-G-CIMP proneural group. The statistical significance of the microRNA signature was higher than MGMT methylation in temozolomide treated tumors. The 9-microRNA risk score was validated in an independent dataset (p = 4.50e−02) and also stratified patients into high- and low-risk groups in lower grade glioma (p = 5.20e−03). The majority of the 9 microRNAs have been previously linked to glioblastoma biology or treatment response. Integration of the expression patterns of predicted microRNA targets revealed a number of relevant microRNA/target pairs, which were validated in cell lines.
Conclusions
We have identified a novel, biologically relevant microRNA signature that stratifies high- and low-risk patients in glioblastoma. MicroRNA/mRNA interactions identified within the signature point to novel regulatory networks. This is the first study to formulate a survival risk score for glioblastoma which consists of microRNAs associated with glioblastoma biology and/or treatment response, indicating a functionally relevant signatur
Gender balance and suitable positive actions to promote gender equality among healthcare professionals in neuro-oncology: The EANO positive action initiative
Background
The proportion of women among healthcare and biomedical research professionals in neuro-oncology is growing. With changes in cultural expectations and work-life balance considerations, more men aspire to nonfull-time jobs, yet, leadership positions remain dominated by men.
Methods
The European Association of Neuro-Oncology (EANO) disparity committee carried out a digital survey to explore gender balance and actions suitable to promote gender equality. The survey was distributed among EANO members in 2021, with responses analyzed descriptively.
Results
In total, 262 participants completed the survey (141 women, 53.8%; median age 43). Respondents were neurosurgeons (68, 26.0%); neurologists (67, 25.6%), medical oncologists (43, 16.4%), or other healthcare or research professionals; 208 participants (79.4%) worked full-time. Positive action to enforce the role of women in neuro-oncology was deemed necessary by 180 participants (68.7%), but only 28 participants (10.7%) agreed that women only should be promoted until gender balance is reached. A majority of respondents (162, 61.8%) felt that women with an equivalent CV should be prioritized over men to reach gender balance. If in the future the balance favored women at higher positions, 112 respondents (42.7%) agreed to apply positive action for men. The top indicators considered relevant to measure gender balance were: salary for similar positions (183/228, 80.3%), paid overtime (176/228, 77.2%), number of permanent positions (164/228, 71.9%), protected time for research (161/227, 70.9%), and training opportunities (157/227, 69.2%).
Conclusions
Specific indicators may help to measure and promote gender balance and should be considered for implementation among healthcare professionals in neuro-oncology
Diagnosis and management of complications from the treatment of primary central nervous system tumors in adults
Central nervous system (CNS) tumor patients commonly undergo multimodality treatment in the course of their disease. Adverse effects and complications from these interventions have not been systematically studied, but pose significant challenges in clinical practice and impact function and quality of life, especially in the management of long-term brain tumor survivors. Here, the European Association of Neuro-Oncology (EANO) has developed recommendations to prevent, diagnose, and manage adverse effects and complications in the adult primary brain CNS tumor (except lymphomas) patient population with a specific focus on surgery, radiotherapy, and pharmacotherapy. Specifically, we also provide recommendations for dose adaptations, interruptions, and reexposure for pharmacotherapy that may serve as a reference for the management of standard of care in clinical trials. We also summarize which interventions are unnecessary, inactive or contraindicated. This consensus paper should serve as a reference for the conduct of standard therapy within and outside of clinical trials
Prevalence of BRAFV600 in glioma and use of BRAF Inhibitors in patients with BRAFV600 mutation-positive glioma:systematic review
The Siren Site and the Long Transition from Archaic to Late Prehistoric Lifeways on the Eastern Edwards Plateau of Central Texas
On behalf of the Texas Department of Transportation (TxDOT), SWCA Environmental Consultants (SWCA) conducted testing and data recovery investigations at the Siren site (41WM1126), a prehistoric multi-component site in the Interstate Highway 35 right-of-way along the South Fork of the San Gabriel River in Williamson County, Texas. The work was done to fulfill TxDOT’s compliance obligations under the National Historic Preservation Act and the Antiquities Code of Texas. The testing investigations were conducted under Antiquities Permit 3834, and the subsequent data recovery was under Permit 3938. Kevin Miller served as Principal Investigator on both permits. Though the site extends far beyond the area of potential effects both horizontally and vertically, the investigations focused on Late Archaic and Late Prehistoric components within a relatively limited area that would be subject to project impacts. The investigations were conducted in February 2006.
The investigations identified five isolable components that were intermittently laid down from approximately 2600 to 900 years ago. A substantial Late Prehistoric Austin phase occupation is represented by Scallorn projectile points, stone tools, burned rock, faunal materials, and radiocarbon dates from cooking features. The component feature assemblage includes a cluster of discrete, well-preserved burned rock features that range from small fire-cracked rock concentrations to a large, slab-lined feature that dominates the cluster.
The underlying components include four cultural strata representing a series of phases in the final millennium or so of the long Archaic period. These components span approximately 2600 to 1500 b.p., though earlier, deeply buried components were also noted on the site. These deeper deposits were not the focus of the investigations, however, since they would not be affected by the project. The Archaic components revealed a suite of small side-notched dart points such as Ensor, Fairland, and Frio, as well as many earlier broad-bladed styles such as Castroville, Montell, Marshall, and Pedernales. These robust components contained numerous burned rock features of varying size and function, abundant tools, well-preserved faunal materials, macrobotanical remains including geophytes from several earth ovens, and a large suite of radiocarbon dates. The features include an incipient burned rock midden, burned rock clusters, a debitage reduction area, a biface cache, slab-lined hearths, basin-shaped hearths, and small circular hearths. The distributions of artifacts and features within the Archaic components across the excavation blocks showed significant variations. These differences reflect sequential components that provide a view of diachronic trends in technology, subsistence, economy, and a suite of other behaviors and activities during the long transition from Archaic to Late Prehistoric adaptations.
As previously determined by the testing excavations and further substantiated by the data recovery investigations, the Siren site, most notably the Late Archaic and Late Prehistoric components, is eligible for the National Register of Historic Places under Criterion D, 36 CFR 60.4, and eligible for State Archeological Landmark designation under Criteria 1 and 2 of the Rules of Practice and Procedure for the Antiquities Code of Texas, 13 TAC 26.8. The excavations and subsequent analysis have mitigated the adverse effects of the bridge construction by recovering the vast majority of the affected components within the area of potential effect. No further archaeological work is recommended. Portions of the site outside the area of potential effects have not been fully evaluated, and any future impacts beyond the mitigated areas warrant further assessment
Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.
BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution
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