Search

Background: Gastrectomy with extended (D2) lymphadenectomy is considered standard of care for gastric cancer to provide the best possible outcomes and pathologic staging. However, D2 gastrectomy is a technically demanding operation and reported to be associated with increased complications and mortality. Application of sentinel lymph node (SLN) concept in gastric cancer has the potential to reduce patient morbidity; however, SLN techniques are not established for gastrectomy, in part due to lack of practical tracers. An effective and convenient tracer with enhanced SLN accumulation is critically needed. Methods: Mannose-labelled magnetic tracer ‘FerroTrace’ and fluorescent dye indocyanine green (ICG) were injected laparoscopically into the stomach submucosa of 8 healthy swine under general anaesthesia. Intraoperative fluorescence imaging was used to highlight draining lymphatic pathways containing ICG, while preoperative T2-weighted MRI and ex vivo magnetometer probe measurements were used to identify nodes containing FerroTrace. Lymphadenectomy was performed either robotically (n= 2) or via laparotomy (n= 6). Results: Mixing ICG and FerroTrace ensured concurrence of fluorescent and magnetic signals in SLNs. An initial trial with robotic dissection removed all magnetic LNs (n= 4). In the subsequent laparotomy study that targeted all ICG-LNs based on intraoperative fluorescence imaging, dissection removed an average of 4.7 ± 1.2 fluorescent, and 2.0 ± 1.3 magnetic LNs per animal. Both MRI and magnetometer detected 100% of SLNs (n= 7). FerroTrace demonstrated high specificity to SLNs, which contained 76 ± 30% of total lymphotropic iron, and 88 ± 20 % of the overall magnetometer signal. Conclusions: Through utilisation of this dual tracer approach, SLNs were identified via preoperative MRI, visualised intraoperatively with fluorescence imaging, and confirmed with a magnetometer. This combination pairs the sensitivity of ICG with SLN-specific FerroTrace and can be used for reliable SLN detection in gastric cancer, with potential applications in neoadjuvant therapy. Graphical abstract:

Objective: Cannabis use may produce neurophysiological disturbances similar to those observed in schizophrenia, particularly in relation to altered neural synchronization. Therefore, the current experiment examined the effect of cannabis use on EEG neural synchronization using the auditory steady-state evoked potential. Method: Auditory steady-state evoked potentials were assessed using varying rates of stimulation (auditory click-trains of 20, 30, 40 Hz) in current cannabis users (N=17) and drug-naive comparison subjects (N=16). EEG spectral power and signal-to-noise ratio at each stimulation frequency were compared between groups. Results: Cannabis users showed decreased EEG power and signal-to-noise ratio at the stimulation frequency of 20 Hz. In addition, current cannabis users demonstrated increased schizotypal personality characteristics as assessed with the Schizotypal Personality Questionnaire, which positively correlated with total years of cannabis use. Finally, within the cannabis group, 20-Hz power values were negatively correlated with Schizotypal Personality Questionnaire scores. Conclusions: These data provide evidence for neural synchronization and early-stage sensory processing deficits in cannabis use. This finding, along with the observed increased rates of schizotypy in cannabis users, adds support for a cannabinoid link to schizophrenia spectrum disorders.

Calorie restriction (CR) is a common approach to inducing negative energy balance. Recently, time-restricted feeding (TRF), which involves consuming food within specific time windows during a 24-h day, has become popular owing to its relative ease of practice and potential to aid in achieving and maintaining a negative energy balance. TRF can be implemented intentionally with CR, or TRF might induce CR simply because of the time restriction. This review focuses on summarizing our current knowledge on how TRF and continuous CR affect gut peptides that influence satiety. Based on peer-reviewed studies, in response to CR there is an increase in the orexigenic hormone ghrelin and a reduction in fasting leptin and insulin. There is likely a reduction in glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and cholecystokinin (CCK), albeit the evidence for this is weak. After TRF, unlike CR, fasting ghrelin decreased in some TRF studies, whereas it showed no change in several others. Further, a reduction in fasting leptin, insulin, and GLP-1 has been observed. In conclusion, when other determinants of food intake are held equal, the peripheral satiety systems appear to be somewhat similarly affected by CR and TRF with regard to leptin, insulin, and GLP-1. But unlike CR, TRF did not appear to robustly increase ghrelin, suggesting different influences on appetite with a potential decrease of hunger after TRF when compared with CR. However, there are several established and novel gut peptides that have not been measured within the context of CR and TRF, and studies that have evaluated effects of TRF are often short-term, with nonuniform study designs and highly varying temporal eating patterns. More evidence and studies addressing these aspects are needed to draw definitive conclusions.Statement of Significance: An in-depth review of current literature on the effects of time-restricted feeding and calorie restriction on the endocrine system involved in satiety. Along with the companion article, our reviews weave together information on both central and peripheral systems of satiety, which tend to be examined separately, in hopes to guide future research in this area.

This review focuses on summarizing current knowledge on how time-restricted feeding (TRF) and continuous caloric restriction (CR) affect central neuroendocrine systems involved in regulating satiety. Several interconnected regions of the hypothalamus, brainstem, and cortical areas of the brain are involved in the regulation of satiety. Following CR and TRF, the increase in hunger and reduction in satiety signals of the melanocortin system [neuropeptide Y (NPY), proopiomelanocortin (POMC), and agouti-related peptide (AgRP)] appear similar between CR and TRF protocols, as do the dopaminergic responses in the mesocorticolimbic circuit. However, ghrelin and leptin signaling via the melanocortin system appears to improve energy balance signals and reduce hyperphagia following TRF, which has not been reported in CR. In addition to satiety systems, CR and TRF also influence circadian rhythms. CR influences the suprachiasmatic nucleus (SCN) or the primary circadian clock as seen by increased clock gene expression. In contrast, TRF appears to affect both the SCN and the peripheral clocks, as seen by phasic changes in the non-SCN (potentially the elusive food entrainable oscillator) and metabolic clocks. The peripheral clocks are influenced by the primary circadian clock but are also entrained by food timing, sleep timing, and other lifestyle parameters, which can supersede the metabolic processes that are regulated by the primary circadian clock. Taken together, TRF influences hunger/satiety, energy balance systems, and circadian rhythms, suggesting a role for adherence to CR in the long run if implemented using the TRF approach. However, these suggestions are based on only a few studies, and future investigations that use standardized protocols for the evaluation of the effect of these diet patterns (time, duration, meal composition, sufficiently powered) are necessary to verify these preliminary observations.Statement of Significance: This is an in-depth review of current literature on the effects of time-restricted feeding and calorie restriction on central neuroendocrine systems involved in satiety. Our reviews weave together information on both central and peripheral systems of satiety, which tend to be examined separately, in hopes of guiding future research in this area.

The presence of duplicated code in software systems is significant and several studies have shown that clones can be potentially harmful with respect to the maintainability and evolution of the source code. Despite the significance of the problem, there is still limited support for eliminating software clones through refactoring, because the unification and merging of duplicated code is a very challenging problem, especially when software clones have gone through several modifications after their initial introduction. In this work, we propose an approach for automatically assessing whether a pair of clones can be safely refactored without changing the behavior of the program. In particular, our approach examines if the differences present between the clones can be safely parameterized without causing any side-effects. The evaluation results have shown that the clones assessed as refactorable by our approach can be indeed refactored without causing any compile errors or test failures. Additionally, the computational cost of the proposed approach is negligible (less than a second) in the vast majority of the examined cases. Finally, we perform a large-scale empirical study on over a million clone pairs detected by four different clone detection tools in nine open-source projects to investigate how refactorability is affected by different clone properties and tool configuration options. Among the highlights of our conclusions, we found that a) clones in production code tend to be more refactorable than clones in test code, b) clones with a close relative location (i.e., same method, type, or file) tend to be more refactorable than clones in distant locations (i.e., same hierarchy, or unrelated types), c) Type-1 clones tend to be more refactorable than the other clone types, and d) clones with a small size tend to be more refactorable than clones with a larger size.

When a moving stimulus is presented at a specific temporal frequency, both steady-state responses and induced activity may be elicited in the electroencephalogram. The electroencephalogram was recorded when study participants viewed random dot kinematograms under three conditions coherent motion, incoherent motion and stationary. Dot position was changed at a rate of 9.3 Hz in the coherent and incoherent conditions. Induced power at 40 Hz was increased during coherent motion compared with the other conditions. In contrast, the steady-state response at 9.3 Hz showed a trend for increased power during the incoherent condition. These results suggest that steady-state responses to moving stimuli reflect sensory activation, while the induced activity indexes perceptual processes.

Patients with bipolar disorder show cognitive deficits and disorganized behavior, which may reflect a disturbance in neural synchronization. We tested whether EEG measures of auditory neural synchronization were abnormal in bipolar disorder. Nineteen symptomatic patients with bipolar disorder and 32 non-psychiatric control subjects were evaluated. Click trains (500 ms duration) presented at 20, 30, 40 and 50 Hz were used to evoke EEG synchronization. Patients with bipolar disorder showed reduced power across the frequencies of stimulation. Phase-locking across trials was also disturbed in bipolar disorder, consistent with poor phase synchronization between the stimulus and EEG. Abnormal high frequency neural synchronization may contribute to cognitive deficits in bipolar disorder.