The Neurogenome study: Comprehensive molecular profiling to optimize treatment for Danish glioblastoma patients.

Background: Glioblastoma is an aggressive brain cancer with no possibility for cure. Treatment and survival have only improved slightly since 2005 when the current regime was implemented. The limited improvements in the treatment of glioblastoma may reflect our poor understanding of the disease. We hypothesize that systematically collected translational data will improve knowledge and hereby treatment. Methods: We have been performing whole exome sequencing in glioblastoma tumor tissue since 2016 and whole genome sequencing (WGS) since 2020 with the aim of offering experimental treatment. Results: We have sequenced 400+ GBM patients and from these 100+ are paired tumor samples from relapse surgery. To develop genomic profiling and to increase the information on each patient´s contribution, we have initiated the Neurogenome study as of June 2022. The Neurogenome protocol is a national, comprehensive, translational, and omic protocol. It is a continuation of 2 previous protocols from 2016 and forth in our department, but with more substudies added, focusing on the translational and clinical utility. We collect and analyze data from an out-patient clinic in a systematic approach to a number of subprojects ranging from basic science to applied clinical science, including clinical trials. Conclusions: The protocol will act as a backbone for future projects in the national research center, Danish Comprehensive Cancer Center-Brain Tumor Center with the overall aim to select eligible patients for experimental treatment based upon genomic alterations. The article will present the Neurogenome setup and a presentation of selected projects that are based upon inclusion.

Characteristics of Recurrent Visions of the Nonphysical World Among Cognitively Unimpaired Elders of the Ojibwe Tribal Nation.

Importance: Visual hallucinations are a core feature of dementia with Lewy bodies and primary psychiatric disease, yet identification of a hallucination vs normal spiritual experience depends on cultural context. Almost no information exists in the medical literature regarding normal spiritual experiences in American Indian participants in the context of a neurocognitive evaluation. Objective: To assess the characteristics of a normal spiritual experience in an Ojibwe Tribal Nation. Design, Setting, and Participants: This prospective, cross-sectional study was conducted between August 1, 2021, and August 31, 2022, among an Ojibwe Tribal Nation in northern Minnesota. Participants were evaluated at their tribal nation clinic. Cognitively unimpaired tribal Elders who were enrolled members of the tribal nation and aged 55 years or older were invited to participate via fliers, radio advertisements, and health fair presentations. Thirty-seven tribal Elders volunteered. Main Outcomes and Measures: Each participant was asked whether they experienced hallucinations or visions of people, animals, or objects that are not part of the physical world. This was an a priori formulated question and part of a comprehensive neurocognitive evaluation consisting of history and physical examination (including cognitive screening with a subspecialty-trained behavioral neurologist); blood tests for metabolic, nutritional, and thyroid conditions; and noncontrast magnetic resonance imaging brain scan. Four patients were excluded from the present analysis due to having mild cognitive impairment or dementia. Results: Thirty-three cognitively unimpaired tribal Elders (mean [SD] age, 66.0 [7.5] years; 22 women [67%]) were included. Sixteen (48%) answered affirmatively, reporting recurrent visions of the nonphysical world. Generally, these visions were well formed, benevolent in nature, and transient; started in preadolescence; involved spirits or ancestors; and were congruent with cultural and spiritual beliefs of the Ojibwe people. No patients had accompanying dream enactment behavior, dysautonomia, parkinsonism, sleep transition-related hallucinations, or moderate to severe depression to suggest a prodrome of an α-synucleinopathy, hypnopompic or hypnagogic hallucinations, or psychosis. Conclusions and Relevance: Although based on only 1 Ojibwe Tribal Nation, this study suggests that formed visions of the nonphysical world are common among cognitively healthy Ojibwe individuals and can represent normal spiritual experiences. Clinicians would benefit from careful consideration of cultural or spiritual context to avoid misdiagnosis of neuropsychiatric disease.

The feeding habits of small-bodied fishes mediate the strength of top-down effects on plankton and water quality in shallow subtropical lakes.

The proliferation of small-bodied fishes in lakes is often accompanied by deterioration of water quality and ecosystem function. However, the potential impacts of different types of small-bodied fish species (e.g., obligate zooplanktivores and omnivores) on subtropical lake ecosystems in particular have been overlooked mainly due to their small size, shorter life spans and lower economic value. Therefore, we conducted a mesocosm experiment to elucidate how plankton communities and water quality respond to different types of small-bodied fishes, including a common zooplanktivorous fish (thin sharpbelly Toxabramis swinhonis) and other small-bodied omnivorous fishes (bitterling Acheilognathus macropterus, crucian carp Carassius auratus and sharpbelly Hemiculter leucisculus). During the experiment, the mean weekly total nitrogen (TN), total phosphorus (TP), chemical oxygen demand (CODMn), turbidity, chlorophyll-a (Chl.α) and trophic level index (TLI) values were generally higher in treatments where fish were present compared to treatments where fish were absent, but responses varied. At the end of the experiment, phytoplankton abundance and biomass and the relative abundance and biomass of cyanophyta were higher while the abundance and biomass of large-bodied zooplankton were lower in the fish-present treatments. Moreover, the mean weekly TP, CODMn, Chl.α and TLI values were generally higher in treatments with the obligate zooplanktivore, thin sharpbelly, when compared to treatments with omnivorous fishes. Also, the ratio of zooplankton to phytoplankton biomass was the lowest, and the ratio of Chl.α to TP was the highest in treatments with thin sharpbelly. Collectively, these general findings indicate that an overabundance of small-bodied fishes can have adverse effects on water quality and plankton communities and that small-bodied zooplanktivorous fishes likely induce stronger top-down effects on plankton and water quality than omnivorous fishes. Our results emphasise that small-bodied fishes should be monitored and controlled if overabundant when managing or restoring shallow subtropical lakes. From the perspective of environmental protection, the combined stocking of different piscivorous fish species that feed in different habitat types could be a way forward to control small-bodied fishes with different feeding habits, but more research is needed to assess the feasibility of this approach.

An fMRI-compatible system for targeted electrical stimulation.

BACKGROUND: Neuromodulation is a rapidly expanding therapeutic option considered within neuropsychiatry, pain and rehabilitation therapy. Combining electrostimulation with feedback from fMRI can provide information about the mechanisms underlying the therapeutic effects, but so far, such studies have been hampered by the lack of technology to conduct safe and accurate experiments. Here we present a system for fMRI compatible electrical stimulation, and the first proof-of-concept neuroimaging data with deep brain stimulation (DBS) in pigs obtained with the device. NEW METHOD: The system consists of two modules, placed in the control and scanner room, connected by optical fiber. The system also connects to the MRI scanner to timely initiate the stimulation sequence at start of scan. We evaluated the system in four pigs with DBS in the subthalamic nucleus (STN) while we acquired BOLD responses in the STN and neocortex. RESULTS: We found that the system delivered robust electrical stimuli to the implanted electrode in sync with the preprogrammed fMRI sequence. All pigs displayed a DBS-STN induced neocortical BOLD response, but none in the STN. COMPARISONS WITH EXISTING METHOD: The system solves three major problems related to electric stimuli and fMRI examinations, namely preventing distortion of the fMRI signal, enabling communication that synchronize the experimental conditions, and surmounting the safety hazards caused by interference with the MRI scanner. CONCLUSIONS: The fMRI compatible electrical stimulator circumvents previous problems related to electroceuticals and fMRI. The system allows flexible modifications for fMRI designs and stimulation parameters, and can be customized to electroceutical applications beyond DBS.

Manipulation of fish community structure effectively restores submerged aquatic vegetation in a shallow subtropical lake.

Fish community manipulation and regulation has been largely overlooked as a mitigation strategy for restoring submerged aquatic vegetation (SAV) in shallow lakes of the middle and lower Yangtze River Basin (MLYRB). An in-situ fish exclusion experiment and a large-scale lake manipulation were conducted to test the hypothesis that the reasonable removal of benthivorous and herbivorous fish would facilitate the restoration and reconstruction of SAV in shallow lakes within the MLYRB. The in-situ exclusion experiment was conducted from April to October in 2017. Electrofishing was used to remove benthivorous and herbivorous fish from the exclosures. SAV were then artificially planted in the same pattern and density in both exclosures and adjacent open sites, and responses were measured for seven consecutive months. The mean percent coverage and biomass of SAV in the exclosures increased quickly and remained significantly higher than those in open sites over the duration of the experiment. Water quality also improved as turbidity, chlorophyll-a, total phosphorus and total nitrogen in the exclosures remained significantly lower than those in the open sites. After the in-situ experiment, a larger scale manipulation of fish in the entire submerged macrophyte zone (SMZ) was implemented from 2017 to 2020. After removing more than 2/3 of the benthivorous and herbivorous fish biomass by October 2020 in the SMZ, both the species richness and spatial coverage of SAV increased from 2 to 9 and from 1.7% to 32.2%, respectively. Our results provided clear evidence that fish are strong regulators of SAV productivity and that their reasonable removal facilitates ecological recovery. Therefore, we propose that fish community manipulation as implemented in this study be given more attention in addition to the reduction of external nutrient loading when designing projects to restore SAV in shallow lakes of the MLYRB.

Simultaneous evaluation of brain tumour metabolism, structure and blood volume using [(18)F]-fluoroethyltyrosine (FET) PET/MRI: feasibility, agreement and initial experience.

PURPOSE: Both [(18)F]-fluoroethyltyrosine (FET) PET and blood volume (BV) MRI supplement routine T1-weighted contrast-enhanced MRI in gliomas, but whether the two modalities provide identical or complementary information is unresolved. The aims of the study were to investigate the feasibility of simultaneous structural MRI, BV MRI and FET PET of gliomas using an integrated PET/MRI scanner and to assess the spatial and quantitative agreement in tumour imaging between BV MRI and FET PET. METHODS: A total of 32 glioma patients underwent a 20-min static simultaneous PET/MRI acquisition on a Siemens mMR system 20 min after injection of 200 MBq FET. The MRI protocol included standard structural MRI and dynamic susceptibility contrast (DSC) imaging for BV measurements. Maximal relative tumour FET uptake (TBRmax) and BV (rBVmax), and Dice coefficients were calculated to assess the quantitative and spatial congruence in the tumour volumes determined by FET PET, BV MRI and contrast-enhanced MRI. RESULTS: FET volume and TBRmax were higher in BV-positive than in BV-negative scans, and both VOLBV and rBVmax were higher in FET-positive than in FET-negative scans. TBRmax and rBVmax were positively correlated (R (2) = 0.59, p < 0.001). FET and BV positivity were in agreement in only 26 of the 32 patients and in 42 of 63 lesions, and spatial congruence in the tumour volumes as assessed by the Dice coefficients was generally poor with median Dice coefficients exceeding 0.1 in less than half the patients positive on at least one modality for any pair of modalities. In 56 % of the patients susceptibility artefacts in DSC BV maps overlapped the tumour on MRI. CONCLUSION: The study demonstrated that although tumour volumes determined by BV MRI and FET PET were quantitatively correlated, their spatial congruence in a mixed population of treated glioma patients was generally poor, and the modalities did not provide the same information in this population of patients. Combined imaging of brain tumour metabolism and perfusion using hybrid PET/MR systems may provide complementary information on tumour biology, but the potential clinical value remains to be determined in future trials.