Publications by authors named "WHEELER H"

Background: To use unmanned aerial vehicles (UAVs) to deliver pesticides, new data are needed to allow regulators to conduct risk assessments. A field trial was conducted to obtain spray drift data relating to ground deposits and airborne spray resulting from a spray application delivered by a small UAV.

Results: A 12 m width area was sprayed with four passes of the UAV and spray deposits were collected within the sprayed area and up to 50 m downwind.

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Tinnitus is a common sensorineural complication that can occur de novo or after cancer treatments involving cisplatin or radiotherapy. Considering the heterogeneous etiology and pathophysiology of tinnitus, the extent to which shared genetic risk factors contribute to de novo tinnitus and cancer treatment-induced tinnitus is not clear. Here we report a GWAS for de novo tinnitus using the UK Biobank cohort with nine loci showing significantly associated variants (p < 5 × 10).

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Over two decades ago, increased levels of RNA oxidation were reported in postmortem patients with ALS, Alzheimer's, Parkinson's, and other neurodegenerative diseases. Interestingly, not all cell types and transcripts were equally oxidized. Furthermore, it was shown that RNA oxidation is an early phenomenon, altogether indicating that oxidative RNA damage could be a driver, and not a consequence, of disease.

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This article documents the contribution of peer support in reducing harms of substance use and advancing recovery. Data based on the experience of participants were collected using semi-structured interviews. Twenty-three participants were interviewed including four peer support workers.

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  • Northern herbivores significantly impact tundra ecosystems, but the effects of herbivore diversity on these ecosystems have been largely overlooked, especially with ongoing climate and land-use changes.
  • This systematic review analyzed numerous studies (201 articles and over 3700 individual comparisons) to understand how different levels of herbivore diversity (measured by functional group richness) influence ecosystem processes and functions in the tundra.
  • The findings highlight a concentrated body of research from specific locations, emphasizing the need for more comprehensive studies across diverse Arctic regions to grasp the full effects of herbivore diversity on ecosystem functionality.
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  • This clinical trial tested the effectiveness of an oral cannabis extract (THC:CBD) on adults experiencing severe nausea and vomiting from chemotherapy, despite using standard anti-nausea medications.
  • The results showed that the cannabis extract significantly increased the rate of complete responses (no vomiting or need for rescue meds) from 8% to 24% compared to a placebo.
  • While participants reported some mild side effects like sedation and dizziness, there were no serious adverse events linked to the cannabis treatment.
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  • The study looked at how climate change impacts malaria and other tropical diseases over the past 13 years.
  • Researchers found that many studies focus on malaria and dengue, but less on some other important diseases.
  • There’s still a lot we don’t know about how climate change will affect these diseases, so we need better research to figure it out.
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Aims: Therapeutic drug monitoring (TDM) has led to significant improvements in individualized medical care, although its implementation in oncology has been limited to date. Tyrosine kinase inhibitors (TKIs) are a group of therapies for which TDM has been suggested. Osimertinib is one such therapy used in the treatment of epidermal growth factor receptor (EGFR) mutation-driven lung cancer.

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Precise regulation of Type I interferon signaling is crucial for combating infection and cancer while avoiding autoimmunity. Type I interferon signaling is negatively regulated by USP18. USP18 cleaves ISG15, an interferon-induced ubiquitin-like modification, via its canonical catalytic function, and inhibits Type I interferon receptor activity through its scaffold role.

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Purpose: There remains no standard of care for patients with recurrent and chemorefractory glioblastoma. Re-irradiation (reRT) provides an additional management option. However, published series predominantly focus on small reRT volumes utilizing stereotactic hypofractionated regimens.

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  • The study aimed to evaluate how the consolidation of two rural trauma centers into one affected adult trauma patients at that center, as such an assessment had not been previously conducted.
  • Results showed a 33% increase in trauma patients and a 9% rise in transfers from other facilities after consolidation, with the post-consolidation group being older and more severely injured, leading to more ICU admissions and surgeries.
  • The conclusion indicated that consolidating trauma services improved patient outcomes, resulting in higher overall trauma volume and reduced mortality among the most severely injured patients.
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Brain cancer is a devastating and life-changing disease. Biomarkers are becoming increasingly important in addressing clinical issues, including in monitoring tumour progression and assessing survival and treatment response. The goal of this study was to identify prognostic biomarkers associated with glioma progression.

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Background: In the past decades, agricultural land abandonment and declining land-use intensity became common, especially in the Mediterranean countries of southern Europe. In some areas, this development opened up possibilities for rewilding and the recolonisation or expansion of large mammal populations. Yet, in some instances, co-occurrence of wild mammals and free-ranging domestic herbivores might lead to potential conflicts.

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Regulation of transcription and translation are mechanisms through which genetic variants affect complex traits. Expression quantitative trait locus (eQTL) studies have been more successful at identifying cis-eQTL (within 1 Mb of the transcription start site) than trans-eQTL. Here, we tested the cis component of gene expression for association with observed plasma protein levels to identify cis- and trans-acting genes that regulate protein levels.

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  • Diffuse midline glioma (DMG), particularly DIPG, is a fatal brain tumor with no effective treatments, but recent studies identified PIK3CA and MTOR as promising targets for therapy.
  • The research demonstrates that combining the PI3K/Akt/mTOR inhibitor paxalisib with the antihyperglycemic drug metformin and the PKC inhibitor enzastaurin can enhance treatment efficacy and prolong survival in animal models.
  • Advanced techniques like spatial transcriptomics and ATAC-Seq were used to evaluate the effects on tumor biology, revealing significant changes that could support a clinically relevant combination therapy for DIPG.
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  • Osimertinib, a drug for non-small cell lung cancer (NSCLC), can cause toxicity, leading to the need for dose adjustments; this study aimed to measure osimertinib and its active metabolites in dried blood spots (DBS) using a specialized hemaPEN device and compare results to plasma measurements.
  • A validated method using ultrahigh-performance liquid chromatography-tandem mass spectrometry was developed to accurately quantify osimertinib and its metabolites from both plasma and DBS, demonstrating no significant bias linked to hematocrit levels in patient samples.
  • The study concluded that measuring these drugs in DBS is a reliable and easier alternative for therapeutic drug monitoring, showing similar results to those obtained
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Nuclear clearance and cytoplasmic accumulations of the RNA-binding protein TDP-43 are pathological hallmarks in almost all patients with amyotrophic lateral sclerosis (ALS) and up to 50% of patients with frontotemporal dementia (FTD) and Alzheimer's disease. In Alzheimer's disease, TDP-43 pathology is predominantly observed in the limbic system and correlates with cognitive decline and reduced hippocampal volume. Disruption of nuclear TDP-43 function leads to abnormal RNA splicing and incorporation of erroneous cryptic exons in numerous transcripts including Stathmin-2 (STMN2, also known as SCG10) and UNC13A, recently reported in tissues from patients with ALS and FTD.

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Burgeoning evidence demonstrates that effects of environmental exposures can be transmitted to subsequent generations through the germline without DNA mutations. This phenomenon remains controversial because underlying mechanisms have not been identified. Therefore, understanding how effects of environmental exposures are transmitted to unexposed generations without DNA mutations is a fundamental unanswered question in biology.

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Transcriptome prediction models built with data from European-descent individuals are less accurate when applied to different populations because of differences in linkage disequilibrium patterns and allele frequencies. We hypothesized that methods that leverage shared regulatory effects across different conditions, in this case, across different populations, may improve cross-population transcriptome prediction. To test this hypothesis, we made transcriptome prediction models for use in transcriptome-wide association studies (TWASs) using different methods (elastic net, joint-tissue imputation [JTI], matrix expression quantitative trait loci [Matrix eQTL], multivariate adaptive shrinkage in R [MASHR], and transcriptome-integrated genetic association resource [TIGAR]) and tested their out-of-sample transcriptome prediction accuracy in population-matched and cross-population scenarios.

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Background: There is an immunologic rationale to evaluate immunotherapy in the older glioblastoma population, who have been underrepresented in prior trials. The NUTMEG study evaluated the combination of nivolumab and temozolomide in patients with glioblastoma aged 65 years and older.

Methods: NUTMEG was a multicenter 2:1 randomized phase II trial for patients with newly diagnosed glioblastoma aged 65 years and older.

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Background: Spinal neuraxis leptomeningeal metastasis (LM) relapse in glioblastoma is an uncommon event that is challenging to manage. This study aims to determine the incidence, associated factors, and outcome of LM relapse in patients with glioblastoma managed with radical intent.

Methods: Patients managed for glioblastoma using the EORTC-NCIC (Stupp) Protocol from 2007 to 2019 were entered into a prospective ethics-approved database.

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  • Genomic alterations in astrocytomas have been studied for decades, particularly the impact of homozygous deletions (HD) of specific genes, which are now critical criteria for diagnosing WHO grade 4 astrocytomas.
  • The genes in question are located on chromosome 9 and play a role in regulating cell growth; however, understanding how various alterations like heterozygous deletions and point mutations affect prognosis remains complex.
  • The literature review highlights the challenges in interpreting the prognostic value of these alterations as glioma classification evolves, emphasizing the need for standardized research methods to enhance clinical decision-making.
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Information regarding sound-source spatial location provides several speech-perception benefits, including auditory spatial cues for perceptual talker separation and localization cues to face the talker to obtain visual speech information. These benefits have typically been examined separately. A real-time processing algorithm for sound-localization degradation (LocDeg) was used to investigate how spatial-hearing benefits interact in a multitalker environment.

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Background: Predicting protein levels from genotypes for proteome-wide association studies (PWAS) may provide insight into the mechanisms underlying cancer susceptibility.

Methods: We performed PWAS of breast, endometrial, ovarian, and prostate cancers and their subtypes in several large European-ancestry discovery consortia (effective sample size: 237,483 cases/317,006 controls) and tested the results for replication in an independent European-ancestry GWAS (31,969 cases/410,350 controls). We performed PWAS using the cancer GWAS summary statistics and two sets of plasma protein prediction models, followed by colocalization analysis.

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Background: Glioblastomas are the most common and fatal primary brain malignancy in adults. There is a growing interest in identifying the molecular mechanisms of these tumors to develop novel treatments. Glioblastoma neo-angiogenesis is driven by VEGF, and another potential molecule linked to angiogenesis is PSMA.

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