Radiotherapy and radiation oncology play a key role in the clinical management of patients suffering from oncological diseases. In clinical routine, anatomic imaging such as contrast-enhanced CT and ...MRI are widely available and are usually used to improve the target volume delineation for subsequent radiotherapy. Moreover, these modalities are also used for treatment monitoring after radiotherapy. However, some diagnostic questions cannot be sufficiently addressed by the mere use standard morphological imaging. Therefore, positron emission tomography (PET) imaging gains increasing clinical significance in the management of oncological patients undergoing radiotherapy, as PET allows the visualization and quantification of tumoral features on a molecular level beyond the mere morphological extent shown by conventional imaging, such as tumor metabolism or receptor expression. The tumor metabolism or receptor expression information derived from PET can be used as tool for visualization of tumor extent, for assessing response during and after therapy, for prediction of patterns of failure and for definition of the volume in need of dose-escalation. This review focuses on recent and current advances of PET imaging within the field of clinical radiotherapy / radiation oncology in several oncological entities (neuro-oncology, head & neck cancer, lung cancer, gastrointestinal tumors and prostate cancer) with particular emphasis on radiotherapy planning, response assessment after radiotherapy and prognostication.
According to the theory of embodied simulation, mirror neurons (MN) in our brain's motor system are the neuronal basis of all social‐cognitive processes. The assumption of such a mirroring process in ...humans could be supported by results showing that within one person the same region is involved in different social cognition tasks. We conducted an fMRI‐study with 75 healthy participants who completed three tasks: imitation, empathy, and theory of mind. We analyzed the data using group conjunction analyses and individual shared voxel counts. Across tasks, across and within participants, we find common activation in inferior frontal gyrus, inferior parietal cortex, fusiform gyrus, posterior superior temporal sulcus, and amygdala. Our results provide evidence for a shared neural basis for different social‐cognitive processes, indicating that interpersonal understanding might occur by embodied simulation.
This is the first study showing a common neural basis for the different social cognitive processes: Imitation, Empathy, and Theory of Mind. Across and within participants, we find common activation in regions of the human mirror neuron system across social‐cognitive tasks. Our results indicate a simulation mechanism in humans, independent of the specific social‐cognitive task, suggesting embodied simulation at the heart of social cognition.
Real-time functional magnetic resonance imaging neurofeedback (rtfMRI NFB) is a promising method for targeted regulation of pathological brain processes in mental disorders. But most NFB approaches ...so far have used relatively restricted regional activation as a target, which might not address the complexity of the underlying network changes. Aiming towards advancing novel treatment tools for disorders like schizophrenia, we developed a large-scale network functional connectivity-based rtfMRI NFB approach targeting dorsolateral prefrontal cortex and anterior cingulate cortex connectivity with the striatum.
In a double-blind randomized yoke-controlled single-session feasibility study with N = 38 healthy controls, we identified strong associations between our connectivity estimates and physiological parameters reflecting the rate and regularity of breathing. These undesired artefacts are especially detrimental in rtfMRI NFB, where the same data serves as an online feedback signal and offline analysis target.
To evaluate ways to control for the identified respiratory artefacts, we compared model-based physiological nuisance regression and global signal regression (GSR) and found that GSR was the most effective method in our data.
Our results strongly emphasize the need to control for physiological artefacts in connectivity-based rtfMRI NFB approaches and suggest that GSR might be a useful method for online data correction for respiratory artefacts.
Chemokine CXCL12 and receptor CXCR4 control multiple steps in primary tumor growth and metastasis in breast cancer and more than 20 other human malignancies. Mechanisms that regulate availability of ...CXCL12 in tumor microenvironments will substantially impact cancer progression and ongoing efforts to target the CXCL12-CXCR4 pathway for cancer chemotherapy. We used dual luciferase imaging to investigate CXCR7-dependent scavenging of CXCL12 in breast tumors in vivo and quantify effects of CXCR7 on tumor growth and metastasis of a separate population of CXCR4+ breast cancer cells. In a mouse xenograft model of human breast cancer, in vivo imaging showed that malignant cells expressing CXCR7 reduced bioluminescent CXCL12 secreted in the primary tumor microenvironment. Capitalizing on sensitive detection of bioluminescent CXCL12, we also demonstrated that CXCR7+ cells reduced amounts of chemokine released from orthotopic tumors into the circulation. Immunofluorescence staining of human primary breast cancers showed expression of CXCR4 and CXCR7 on malignant cells in ≈30% of cases. In most cases, CXCR4 and CXCR7 predominantly were expressed on separate populations of malignant cells in a tumor. We modeled these cases of human breast cancer by co-implanting tumor xenografts with CXCR4+ breast cancer cells, human mammary fibroblasts secreting CXCL12, and CXCR7+ or control breast cancer cells. Bioluminescence imaging showed that CXCR7+ breast cancer cells enhanced proliferation of CXCR4+ breast cancer cells in orthotopic tumors and spontaneous metastases. Treatment with a small-molecule inhibitor of CXCR7 chemokine limited the growth of CXCR4+ breast cancer cells in tumors that also contained malignant CXCR7+ cells. These studies establish a new in vivo imaging method to quantify chemokine scavenging by CXCR7 in the tumor microenvironment and identify that CXCR7+ cells promote growth and metastasis of CXCR4+ breast cancer cells.
Abstract
Mature super-Earths and sub-Neptunes are predicted to be ≃ Jovian radius when younger than 10 Myr. Thus, we expect to find 5–15
R
⊕
planets around young stars even if their older ...counterparts harbor none. We report the discovery and validation of TOI 1227b, a 0.85 ± 0.05
R
J
(9.5
R
⊕
) planet transiting a very-low-mass star (0.170 ± 0.015
M
⊙
) every 27.4 days. TOI 1227's kinematics and strong lithium absorption confirm that it is a member of a previously discovered subgroup in the Lower Centaurus Crux OB association, which we designate the Musca group. We derive an age of 11 ± 2 Myr for Musca, based on lithium, rotation, and the color–magnitude diagram of Musca members. The TESS data and ground-based follow-up show a deep (2.5%) transit. We use multiwavelength transit observations and radial velocities from the IGRINS spectrograph to validate the signal as planetary in nature, and we obtain an upper limit on the planet mass of ≃0.5
M
J
. Because such large planets are exceptionally rare around mature low-mass stars, we suggest that TOI 1227b is still contracting and will eventually turn into one of the more common <5
R
⊕
planets.
Understanding of emotions and intentions are key processes in social cognition at which serotonin is an important neuromodulator. Its precursor is the essential amino acid tryptophan (TRP). Reduced ...TRP availability leads to weaker impulse control ability and higher aggression, while TRP supplementation promotes confidence. In a double-blind placebo-controlled fMRI study with 77 healthy adults, we investigated the influence of a 4 week TRP enriched diet and an acute 5-hydroxytryptophan (5-HTP) intake on two social-cognitive tasks, a moral evaluation and an emotion recognition task. With 5-HTP, immoral behavior without negative consequences was rated as more reprehensible. Additionally, during story reading, activation in insula and supramarginal gyrus was increased after TRP intake. No significant effects of TRP on emotion recognition were identified for the whole sample. Importantly, emotion recognition ability decreased with age which was for positive emotions compensated by TRP. Since the supramarginal gyrus is associated with empathy, pain and related information integration results could be interpreted as reflecting stricter evaluation of negative behavior due to better integration of information. Improved recognition of positive emotions with TRP in older participants supports the use of a TRP-rich diet to compensate for age related decline in social-cognitive processes.
Summary
Background
The contribution of hereditary factors to the development of diverticular disease (DD) of the colon is unknown. Prevalence and location of diverticula differ in Western world ...compared to in Asia and several case reports describing families with DD have been published.
Aim
To assess the heritability of DD in a large population‐based sample of twins.
Methods
The Swedish Twin Registry was cross‐linked to the Swedish Inpatient Registry. All twins, born between 1886 and 1980 and not dead before 1969, with a discharge diagnosis of DD were identified. Twins with diagnoses of colon cancer, coeliac disease or non‐infectious colitis were excluded to decrease bias. Co‐twin odds ratio (OR), concordance rates and tetrachoric correlations were calculated for monozygotic (MZ) and same gender‐dizygotic (SS‐DZ) twins. Mx‐analyses were used to estimate the relative contributions of genetic effects and environmental factors to susceptibility for DD. Calculations were based on both primary and secondary discharge diagnoses to provide estimates reflecting impact of severity of the disease.
Results
A total of 104 452 twins met the inclusion criteria. Of these, 2296 had a diagnosis of DD. The OR of developing the disease given one's co‐twin was affected was 7.15 (95% CI: 4.82–10.61) for MZ and 3.20 (95% CI: 2.21–4.63) for SS‐DZ twins. Similarly, concordance rates and tetrachoric correlations were higher in MZ than those in SS‐DZ twins. The heritability was estimated to 40% and the non shared environmental effects to 60%.
Conclusion
Genetic susceptibility is an important component, along with individual specific environmental factors, for the development of diverticular disease of the colon.
The human mirror neuron system (MNS) can be considered the neural basis of social cognition. Identifying the global network structure of this system can provide significant progress in the field. In ...this study, we use dynamic causal modeling (DCM) to determine the effective connectivity between central regions of the MNS for the first time during different social cognition tasks. Sixty-seven healthy participants completed fMRI scanning while performing social cognition tasks, including imitation, empathy, and theory of mind. Superior temporal sulcus (STS), inferior parietal lobule (IPL), and Brodmann area 44 (BA44) formed the regions of interest for DCM. Varying different connectivity patterns, 540 models were built and fitted for each participant. By applying group-level analysis, Bayesian model selection, and Bayesian model averaging, the optimal family and model for all experimental tasks were found. For all social-cognitive processes, effective connectivity from STS to IPL and from STS to BA44 was found. For imitation, additional mutual connections occurred between STS and BA44, as well as BA44 and IPL. The results suggest inverse models in which the motor regions BA44 and IPL receive sensory information from the STS. In contrast, for imitation, a sensory-loop with an exchange of motor-to-sensory and sensory-to-motor information seems to exist.
The developing brain undergoes systematic changes that occur at successive stages of maturation. Deviations from the typical neurodevelopmental trajectory are hypothesized to underlie many early ...childhood disorders; thus, characterizing the earliest patterns of normative brain development is essential. Recent neuroimaging research provides insight into brain structure during late childhood and adolescence; however, few studies have examined the infant brain, particularly in infants under 3 months of age. Using high-resolution structural MRI, we measured subcortical gray and white matter brain volumes in a cohort (
N
= 143) of 1-month infants and examined characteristics of these volumetric measures throughout this early period of neurodevelopment. We show that brain volumes undergo age-related changes during the first month of life, with the corresponding patterns of regional asymmetry and sexual dimorphism. Specifically, males have larger total brain volume and volumes differ by sex in regionally specific brain regions, after correcting for total brain volume. Consistent with findings from studies of later childhood and adolescence, subcortical regions appear more rightward asymmetric. Neither sex differences nor regional asymmetries changed with gestation-corrected age. Our results complement a growing body of work investigating the earliest neurobiological changes associated with development and suggest that asymmetry and sexual dimorphism are present at birth.
Deficits in social cognition have been proposed as a marker of schizophrenia. Growing evidence suggests especially hyperfunctioning of the right posterior superior temporal sulcus (pSTS) in response ...to neutral social stimuli reflecting the neural correlates of social-cognitive impairments in schizophrenia. We characterized healthy participants according to schizotypy (n = 74) and the single-nucleotide polymorphism rs1344706 in ZNF804A (n = 73), as they represent risk variants for schizophrenia from the perspectives of personality traits and genetics, respectively. A social-cognitive fMRI task was applied to investigate the association of right pSTS hyperfunctioning in response to neutral face stimuli with schizotypy and rs1344706. Higher right pSTS activation in response to neutral facial expressions was found in individuals with increased positive (trend) and disorganization symptoms, as well as in carriers of the risk allele of rs1344706. In addition, a positive association between right-left pSTS connectivity and disorganization symptoms during neutral face processing was revealed. Although these findings warrant replication, we suggest that right pSTS hyperfunctioning in response to neutral facial expressions presents an endophenotype of schizophrenia. We assume that right pSTS hyperfunctioning is a vulnerability to perceive neutral social stimuli as emotionally or intentionally salient, probably contributing to the emergence of symptoms of schizophrenia.
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