Construction of oncogenetic tree models reveals multiple pathways of oral cancer progression

Oral cancer develops and progresses by accumulation of genetic alterations. The interrelationship between these alterations and their sequence of occurrence in oral cancers has not been thoroughly understood. In the present study, we applied oncogenetic tree models to comparative genomic hybridization (CGH) data of 97 primary oral cancers to identify pathways of progression. CGH revealed the most frequent gains on chromosomes 8q (72.4%) and 9q (41.2%) and frequent losses on 3p (49.5%) and 8p (47.5%). Both mixture and distance‐based tree models suggested multiple progression pathways and identified +8q as an early event. The mixture model suggested two independent pathways namely a major pathway with ?8p and a less frequent pathway with +9q. The distance‐based tree identified three progression pathways, one characterized by ?8p, another by ?3p and the third by alterations +11q and +7p. Differences were observed in cytogenetic pathways of node‐positive and node‐negative oral cancers. Node‐positive cancers were characterized by more non‐random aberrations (n = 11) and progressed via ?8p or ?3p. On the other hand, node‐negative cancers involved fewer non‐random alterations (n = 6) and progressed along ?3p. In summary, the tree models for oral cancers provided novel information about the interactions between genetic alterations and predicted their probable order of occurrence. © 2009 UICC     

Dosimetric impacts of gantry angle misalignment on prostate cancer treatment using helical tomotherapy

During helical tomotherapy, gantry angle accuracy is one of the vital geometric factors that assure accurate dose delivery to the target and organs at risk adjacent to it. The purpose of this study is to investigate the dosimetric impact of gantry angle misalignment on the target volume and critical organs during helical tomotherapy treatment. Five prostate cases were chosen to calculate the effects of gantry angle deviations on both patient-specific delivery quality assurance (DQA) and helical tomotherapy treatment plans. For DQA plans, the cheese phantom was rotated for up to +/-5 degrees from the preset position to simulate the gantry angle deviations during tomotherapy. Point doses at 5 mm below the isocenter and the dose distribution for each gantry angle were measured and reconstructed, respectively. For helical tomotherapy treatment plans, the same gantry misalignment effect was simulated by adjusting the automatic roll correction for up to +/-5 degrees using Planned Adaptive software. Variations of dose volume histograms (DVHs) and isodose lines were evaluated for both target and critical organs. There was no significant difference found, however, among the point dose measurements for gantry rotation up to +/-5 degrees in DQA plans. Shifts of isodose lines could be observed for gantry rotations larger than +/-27 degrees. Dosimetric discrepancies (less than 2%) were also found among DVHs of the PTV in the cases when gantry angle misalignment was larger than +/-2 degrees. However, for DVHs of either bladder or rectum under different gantry rotations, no significant differences were detected when gantry angle errors were up to +/-5 degrees. In summary, point dose measurements alone cannot reveal the dosimetric deviation due to gantry angle misalignment in DQA plans. For a 5 degrees gantry deviation, the dose to PTV increased by 0.5% comparing to the planned dose. The influence on organs at risk, i.e., rectum and bladder, is also negligible. Further studies are needed on the dosimetric impacts of gantry angle deviations for other treatment sites.     

Physiological instability is linked to mortality in primary central nervous system lymphoma: A case–control fMRI study

Primary central nervous system lymphoma (PCNSL) is an aggressive brain disease where lymphocytes invade along perivascular spaces of arteries and veins. The invasion markedly changes (peri)vascular structures but its effect on physiological brain pulsations has not been previously studied. Using physiological magnetic resonance encephalography (MREG_BOLD) scanning, this study aims to quantify the extent to which (peri)vascular PCNSL involvement alters the stability of physiological brain pulsations mediated by cerebral vasculature. Clinical implications and relevance were explored. In this study, 21 PCNSL patients (median 67y; 38% females) and 30 healthy age‐matched controls (median 63y; 73% females) were scanned for MREG_BOLD signal during 2018–2021. Motion effects were removed. Voxel‐by‐voxel Coefficient of Variation (CV) maps of MREG_BOLD signal was calculated to examine the stability of physiological brain pulsations. Group‐level differences in CV were examined using nonparametric covariate‐adjusted tests. Subject‐level CV alterations were examined against control population Z‐score maps wherein clusters of increased CV values were detected. Spatial distributions of clusters and findings from routine clinical neuroimaging were compared [contrast‐enhanced, diffusion‐weighted, fluid‐attenuated inversion recovery (FLAIR) data]. Whole‐brain mean CV was linked to short‐term mortality with 100% sensitivity and 100% specificity, as all deceased patients revealed higher values (n = 5, median 0.055) than surviving patients (n = 16, median 0.028) (p < .0001). After adjusting for medication, head motion, and age, patients revealed higher CV values (group median 0.035) than healthy controls (group median 0.024) around arterial territories (p ≤ .001). Abnormal clusters (median 1.10 × 10⁵mm³) extended spatially beyond FLAIR lesions (median 0.62 × 10⁵mm³) with differences in volumes (p = .0055).     

A ridge-to-reef ecosystem microbial census reveals environmental reservoirs for animal and plant microbiomes

Microbes are found in nearly every habitat and organism on the planet, where they are critical to host health, fitness, and metabolism. In most organisms, few microbes are inherited at birth; instead, acquiring microbiomes generally involves complicated interactions between the environment, hosts, and symbionts. Despite the criticality of microbiome acquisition, we know little about where hosts’ microbes reside when not in or on hosts of interest. Because microbes span a continuum ranging from generalists associating with multiple hosts and habitats to specialists with narrower host ranges, identifying potential sources of microbial diversity that can contribute to the microbiomes of unrelated hosts is a gap in our understanding of microbiome assembly. Microbial dispersal attenuates with distance, so identifying sources and sinks requires data from microbiomes that are contemporary and near enough for potential microbial transmission. Here, we characterize microbiomes across adjacent terrestrial and aquatic hosts and habitats throughout an entire watershed, showing that the most species-poor microbiomes are partial subsets of the most species-rich and that microbiomes of plants and animals are nested within those of their environments. Furthermore, we show that the host and habitat range of a microbe within a single ecosystem predicts its global distribution, a relationship with implications for global microbial assembly processes. Thus, the tendency for microbes to occupy multiple habitats and unrelated hosts enables persistent microbiomes, even when host populations are disjunct. Our whole-watershed census demonstrates how a nested distribution of microbes, following the trophic hierarchies of hosts, can shape microbial acquisition.

Microbial partners metabolize our food, fight off disease, and run the machinery that sustains the air we breathe, water we drink, and soil under our feet. Despite their importance, most host-associated microbes are generally not present at birth and are instead acquired (1). Because microbial symbionts can influence host health and fitness, the processes that determine how different microbiomes assemble within different hosts is a matter of active and urgent inquiry. Microbial ecologists have made great progress in determining how factors such as abiotic conditions (2–4), host evolution (5, 6), and microbial traits (7–9) shape environmental microbiomes, but considerably less is known about how surrounding environments or different guilds of host organisms contribute to host-associated microbiome composition. Longitudinal studies show that microbial richness accumulates and community composition changes over time across a wide diversity of hosts and habitats (1), but we know comparatively little about from where these microbes originate. To better understand microbial transmission and its role in community composition, we propose a framework that relies on theory from foodweb and landscape ecology.The concept of a foodweb has had a place in the ecological lexicon since at least the time of Elton (1927; (10)), and others such as Lindeman (11) and Odum (12) significantly expanded upon this notion to include how macroorganisms interact within their environments, in addition to their feeding relationships. The units of study for foodwebs are ecosystems, which are spatially explicit and include all organisms along with their abiotic environments and their interactions within its bounds (13). This definition was born from the efforts of the founders of the Hubbard Brook Ecosystem Study (HBES; 1963), who recognized that a watershed naturally delineates the boundaries of an ecosystem, an idea that parallels the Hawaiian ahupuaʻa concept. Since then, the HBES and its framework have led to numerous milestones in our understanding of processes such as the effects of long-term changes in acidification (14) and ecosystem impacts of global warming (15). Here, we adopt the notion of the watershed as an entire discrete ecosystem to better understand the landscape ecology of microbes. Landscape ecology is a means to understand how spatial processes affect biodiversity (16). In classic landscape ecology theory, the structure (heterogeneity) and fragmentation of habitats (or patches) within a matrix of otherwise inhospitable areas affect species’ dispersal ability and establishment. This ultimately shapes species’ abundance and distributions across the landscape (17). Contemporary landscape ecology theory extends this idea to include the concept of a landscape continuum, where continuous environmental variables, as opposed to discrete habitat patches surrounded by a matrix, better describe species’ distributions. Connecting these concepts, foodwebs are embedded in landscapes, and watersheds constitute a useful unit of measure to better understand their interactions.To expand concepts from foodweb and landscape ecology to be inclusive of microbes, we must first consider the following: a landscape for microbes can be both structural (e.g., different land covers or hydrology) and biotic (e.g., variation in the distribution of host populations). Also, microbes might better fit a continuous landscape model rather than a patch model if their distributions are not governed merely by the presence of a compatible host or habitat, but rather, if they exist among multiple hosts across a gradient of environmental conditions. This requires microbes to be generalists to some degree and/or a matrix that is at least partially hospitable (18). These considerations are important because while microbial transmission among related hosts is one obvious means of microbiome assembly, this model, in and of itself, is insufficient to sustain microbiomes (defined here as communities of bacteria and archaea) across a dynamic landscape. For example, many plants and animals are either sparse, seasonal, or ephemeral, requiring that their symbiotic microbes be capable of residing, at times, in alternate nearby hosts or environments. This potential for a microbe to persist in, and disperse among, hosts of different kingdoms and guilds, or even between liquid and land, is a trait with the potential to add an additional dimension to microbiome assembly theory (19). Where, then, might a host’s microbes reside when not inside that host? In addition, what factors might predict microbiome distributions among potentially interacting hosts and environments?Variability in matrix suitability and host specialization may result in differing microbial communities reflected in one of three nonmutually exclusive patterns, each of which leaves a diagnostic imprint on microbiome structure. If any host or environment has an equal likelihood of harboring microbes that are present in any other host or environment, we might expect host–microbe interaction networks that are randomly structured. Alternatively, if microbes are more likely to co-occur among related hosts or guilds, we might expect these to contain unique and specific consortia of microbes (modules) that are not found elsewhere in the interaction network. Finally, host–microbe interactions might be best characterized as stratified, resulting in a network topology in which microbial diversity is nested such that taxa-poor microbiomes are subsets of those that are taxa-rich. In this scenario, nonhost environmental matrices (e.g., soil, sediment, water) serve as reservoirs of broad microbial diversity that is subsequently, and hierarchically, partitioned into simpler microbiomes. While this concept is fairly intuitive, there are actually few, if any, studies that demonstrate transmission among environmental microbiomes and multiple hosts at ecosystem scales. Instead, many of the insights gleaned into assembly processes of microbiomes are owed to studies of single hosts, tractable model systems, or global syntheses (20). We address this gap by sampling microbiomes from aquatic, marine, and terrestrial foodwebs within a single watershed to examine the dynamics of sources and sinks of microbial diversity.Here, we present a microbial census of a model ecosystem metacommunity in which continental-scale environmental heterogeneity is recapitulated within a comparatively small watershed. Because of this, we can surmise the distribution limits of microbiomes across land, stream, and sea, a feat that would not be plausible in most other landscapes of similar size or environmental variability. From ridge to reef, our compact watershed spans a roughly 3.5 m rainfall differential, ∼27 times that encountered along the Mississippi, the largest watershed in continental North America. Also, our model ecosystem is located on the most isolated archipelago on the planet, making exogenous microbial inputs infrequent, if not unlikely. Furthermore, owing to parallels in environmental heterogeneity and foodweb structure across this compact watershed compared to others, our findings are potentially relevant for highly connected ecosystems that span substantially larger geographic areas.For example, a long-standing question in biogeography is the relationship between organisms’ local distributions and those at larger scales. Many factors influence the distributions of microbes, including their physiology, size, population density, and dispersal abilities (21–23). A common assumption is that niche breadth should also predict the range size of an organism, since the ability to survive in broader environments, and to use a greater array of resources, should indicate the ability to occupy more habitats that occur over greater distances (24, 25). This is an important component of source and sink dynamics, because it suggests that local occupancy should predict global distributions. This relationship is seldom tested empirically, however, because small areas rarely contain, or are sampled for, broad climatic variability and host diversity. In the absence of phenotypic, genomic, or even well-resolved taxonomic information about the majority of the earth’s microbial biodiversity, geographic range is one of the few traits that can be directly inferred from short environmental DNA sequence reads. By examining our ecosystem-wide microbiome census within the context of the global survey of the Earth Microbiome Project (26), we assess the relationship between global and local microbial distributions.     

Problematic Gaming Is Associated with Some Health-Related Behaviors Among Finnish Vocational School Students

International Journal of Mental Health and Addiction - The objective of this work was to examine the connections between problematic digital gaming and various health-related behavior...     

Size matters: effects of stimulus size, duration and eccentricity on the visual gamma-band response.

OBJECTIVE: The effects of stimulus size, duration and eccentricity on the visual gamma-band response (GBR) in human EEG were investigated and compared to visual evoked potentials (VEPs) in order to differentiate in future (and past) experiments whether changes in GBRs are due to stimulus-related (exogenous) or cognitive effects. METHODS: EEG was recorded from 23 subjects while they performed a simple choice reaction time task requiring discrimination of squares and circles. In separate blocks stimulus size, duration, and eccentricity were manipulated. EEG was recorded from 64 electrodes. A wavelet transform based on Morlet wavelets was employed for the analysis of gamma-band activity. RESULTS: Amplitude of the GBR was diminished for small and peripheral stimuli. With short stimulus durations ON and OFF responses of the GBR merged into one peak. In comparison, VEP amplitudes were less susceptible to stimulus features. In contrast to VEP latencies, however, GBR latency did not show a lateralization for eccentric stimuli. CONCLUSIONS: In addition to previous experiments which have shown a modulation of the GBR by various cognitive processes, the present results demonstrate the susceptibility of the GBR in human EEG to exogenous factors, as numerous intracortical recordings in non-human primates have shown before. The results suggest that the human GBR resides in early visual areas. SIGNIFICANCE: The demonstration of the susceptibility of the GBR to stimulus properties implies that studies aimed at exploring the involvement of the GBR in information processing have to be designed carefully. It also constrains the localization of the human GBR.