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1.
PLoS Comput Biol ; 20(6): e1012099, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38843298

ABSTRACT

Brain activity during the resting state is widely used to examine brain organization, cognition and alterations in disease states. While it is known that neuromodulation and the state of alertness impact resting-state activity, neural mechanisms behind such modulation of resting-state activity are unknown. In this work, we used a computational model to demonstrate that change in excitability and recurrent connections, due to cholinergic modulation, impacts resting-state activity. The results of such modulation in the model match closely with experimental work on direct cholinergic modulation of Default Mode Network (DMN) in rodents. We further extended our study to the human connectome derived from diffusion-weighted MRI. In human resting-state simulations, an increase in cholinergic input resulted in a brain-wide reduction of functional connectivity. Furthermore, selective cholinergic modulation of DMN closely captured experimentally observed transitions between the baseline resting state and states with suppressed DMN fluctuations associated with attention to external tasks. Our study thus provides insight into potential neural mechanisms for the effects of cholinergic neuromodulation on resting-state activity and its dynamics.

2.
bioRxiv ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38617301

ABSTRACT

Slow-wave sleep (SWS), characterized by slow oscillations (SO, <1Hz) of alternating active and silent states in the thalamocortical network, is a primary brain state during Non-Rapid Eye Movement (NREM) sleep. In the last two decades, the traditional view of SWS as a global and uniform whole-brain state has been challenged by a growing body of evidence indicating that SO can be local and can coexist with wake-like activity. However, the understanding of how global and local SO emerges from micro-scale neuron dynamics and network connectivity remains unclear. We developed a multi-scale, biophysically realistic human whole-brain thalamocortical network model capable of transitioning between the awake state and slow-wave sleep, and we investigated the role of connectivity in the spatio-temporal dynamics of sleep SO. We found that the overall strength and a relative balance between long and short-range synaptic connections determined the network state. Importantly, for a range of synaptic strengths, the model demonstrated complex mixed SO states, where periods of synchronized global slow-wave activity were intermittent with the periods of asynchronous local slow-waves. Increase of the overall synaptic strength led to synchronized global SO, while decrease of synaptic connectivity produced only local slow-waves that would not propagate beyond local area. These results were compared to human data to validate probable models of biophysically realistic SO. The model producing mixed states provided the best match to the spatial coherence profile and the functional connectivity estimated from human subjects. These findings shed light on how the spatio-temporal properties of SO emerge from local and global cortical connectivity and provide a framework for further exploring the mechanisms and functions of SWS in health and disease.

3.
bioRxiv ; 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38352535

ABSTRACT

Cortical stimulation with single pulses is a common technique in clinical practice and research. However, we still do not understand the extent to which it engages subcortical circuits which contribute to the associated evoked potentials (EPs). Here we find that cortical stimulation generates remarkably similar EPs in humans and mice, with a late component similarly modulated by the subject's behavioral state. We optogenetically dissect the underlying circuit in mice, demonstrating that the late component of these EPs is caused by a thalamic hyperpolarization and rebound. The magnitude of this late component correlates with the bursting frequency and synchronicity of thalamic neurons, modulated by the subject's behavioral state. A simulation of the thalamo-cortical circuit highlights that both intrinsic thalamic currents as well as cortical and thalamic GABAergic neurons contribute to this response profile. We conclude that the cortical stimulation engages cortico-thalamo-cortical circuits highly preserved across different species and stimulation modalities.

4.
JBI Evid Synth ; 22(6): 1129-1134, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38165198

ABSTRACT

OBJECTIVE: The objective of this systematic review is to evaluate the best available evidence regarding effectiveness of transoral robotic surgery in patients with recurrent head and neck cancers. INTRODUCTION: Transoral robotic surgery is now an established modality of treatment for primary head and neck cancer, showing good swallowing outcomes and quality of life for patients post-treatment. In patients with recurrent disease, conventional open surgery is often used, which prolongs recovery time and necessitates tissue disruption to gain access to the tumor site. Transoral robotic surgery is an emerging technique in this field as a minimally invasive approach to resection. INCLUSION CRITERIA: The review will include experimental or observational studies that investigated the use of transoral robotic surgery in adults (aged 18 years or older) with recurrent head and neck cancers for oncological, functional, and survival outcomes. METHODS: Three databases will be searched for evidence: PubMed, Embase, and Scopus. Search terms for each database will include transoral robotic surgery, recurrent, salvage , and head and neck cancers . Reference lists of included articles will be searched for further evidence. Critical appraisal will be conducted by 2 independent reviewers using the JBI critical appraisal tools for quantitative studies. Data will be extracted by the same reviewers. Where appropriate, meta-analysis will be conducted for all outcomes. REVIEW REGISTRATION: PROSPERO CRD42023404613.


Subject(s)
Head and Neck Neoplasms , Neoplasm Recurrence, Local , Robotic Surgical Procedures , Systematic Reviews as Topic , Humans , Robotic Surgical Procedures/methods , Head and Neck Neoplasms/surgery , Neoplasm Recurrence, Local/surgery , Quality of Life
5.
ANZ J Surg ; 94(4): 536-544, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37872745

ABSTRACT

BACKGROUND: Sensorineural hearing loss (SNHL) may occur following cardiac surgery. Although preventing post-operative complications is vitally important in cardiac surgery, there are few guidelines regarding this issue. This review aimed to characterize SNHL after cardiac surgery. METHOD: This systematic review was registered on PROSPERO and conducted in accordance with PRISMA guidelines. A systematic search of the PubMed, Embase and Cochrane Library were conducted from inception. Eligibility determination, data extraction and methodological quality analysis were conducted in duplicate. RESULTS: There were 23 studies included in the review. In the adult population, there were six cohort studies, which included 36 cases of hearing loss in a total of 7135 patients (5.05 cases per 1000 operations). In seven cohort studies including paediatric patients, there were 88 cases of hearing loss in a total of 1342 operations. The majority of cases of hearing loss were mild in the adult population (56.6%). In the paediatric population 59.2% of hearing loss cases had moderate or worse hearing loss. The hearing loss most often affected the higher frequencies, over 6000 Hz. There have been studies indicating an association between hearing loss and extracorporeal circulation, but cases have also occurred without this intervention. CONCLUSION: SNHL is a rare but potentially serious complication after cardiac surgery. This hearing loss affects both paediatric and adult populations and may have significant long-term impacts. Further research is required, particularly with respect to the consideration of screening for SNHL in children after cardiac surgery.


Subject(s)
Cardiac Surgical Procedures , Hearing Loss, Sensorineural , Adult , Humans , Child , Hearing Loss, Sensorineural/epidemiology , Hearing Loss, Sensorineural/etiology , Hearing Loss, Sensorineural/diagnosis , Cohort Studies , Postoperative Complications/epidemiology , Cardiac Surgical Procedures/adverse effects
6.
Article in English | MEDLINE | ID: mdl-38083499

ABSTRACT

The slow oscillation (SO) observed during deep sleep is known to facilitate memory consolidation. However, the impact of age-related changes in sleep electroencephalography (EEG) oscillations and memory remains unknown. In this study, we aimed to investigate the contribution of age-related changes in sleep SO and its role in memory decline by combining EEG recordings and computational modeling. Based on the detected SO events, we found that older adults exhibit lower SO density, lower SO frequency, and longer Up and Down state durations during N3 sleep compared to young and middle-aged groups. Using a biophysically detailed thalamocortical network model, we simulated the "aged" brain as a partial loss of synaptic connections between neurons in the cortex. Our simulations showed that the changes in sleep SO properties in the "aged" brain, similar to those observed in older adults, resulting in impaired memory consolidation. Overall, this study provides mechanistic insights into how age-related changes modulate sleep SOs and memory decline.Clinical Relevance- This study contributes towards finding feasible biomarkers and target mechanism for designing therapy in older adults with memory deficits, such as Alzheimer's disease patients.


Subject(s)
Electroencephalography , Sleep , Middle Aged , Humans , Aged , Sleep/physiology , Brain/physiology , Computer Simulation , Memory Disorders
7.
medRxiv ; 2023 Jun 29.
Article in English | MEDLINE | ID: mdl-37425691

ABSTRACT

Magnetoencephalography (MEG) is a non-invasive functional imaging technique for pre-surgical mapping. However, movement-related MEG functional mapping of primary motor cortex (M1) has been challenging in presurgical patients with brain lesions and sensorimotor dysfunction due to the large numbers of trails needed to obtain adequate signal to noise. Moreover, it is not fully understood how effective the brain communication is with the muscles at frequencies above the movement frequency and its harmonics. We developed a novel Electromyography (EMG)-projected MEG source imaging technique for localizing M1 during ~1 minute recordings of left and right self-paced finger movements (~1 Hz). High-resolution MEG source images were obtained by projecting M1 activity towards the skin EMG signal without trial averaging. We studied delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), and gamma (30-90 Hz) bands in 13 healthy participants (26 datasets) and two presurgical patients with sensorimotor dysfunction. In healthy participants, EMG-projected MEG accurately localized M1 with high accuracy in delta (100.0%), theta (100.0%), and beta (76.9%) bands, but not alpha (34.6%) and gamma (0.0%) bands. Except for delta, all other frequency bands were above the movement frequency and its harmonics. In both presurgical patients, M1 activity in the affected hemisphere was also accurately localized, despite highly irregular EMG movement patterns in one patient. Altogether, our EMG-projected MEG imaging approach is highly accurate and feasible for M1 mapping in presurgical patients. The results also provide insight into movement related brain-muscle coupling above the movement frequency and its harmonics.

9.
JBI Evid Synth ; 21(10): 2099-2106, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37246954

ABSTRACT

OBJECTIVE: The objective of this systematic review is to investigate oncological and functional outcomes following primary transoral surgery compared with non-surgical management in patients with small-volume (T1-2, N0-2) oropharyngeal cancer. INTRODUCTION: The incidence of oropharyngeal cancer is rising. Transoral surgery was introduced to provide a minimally invasive treatment option for patients with small-volume oropharyngeal cancer and to avoid the morbidity that results from open surgery and the potential acute and late toxicities of chemoradiotherapy. INCLUSION CRITERIA: The review will include all studies on adult patients with small-volume oropharyngeal cancer managed by transoral surgery or non-surgical management with radiotherapy and/or chemotherapy. All patients must have undergone treatment with curative intent. Participants who underwent palliative treatment will be excluded. METHODS: This review will follow the JBI methodology for systematic reviews of effectiveness. Eligible study designs will include randomized controlled trials, quasi-experimental studies, and prospective or retrospective cohort studies. Databases to be searched will include PubMed, Embase, CINAHL, Cochrane CENTRAL, and multiple trial registries from 1972. Titles and abstracts will be reviewed, and full-text articles will be retrieved if they meet the inclusion criteria. All eligible studies will be critically appraised by 2 independent reviewers using the appropriate JBI tools for experimental and observational designs. Where possible, outcome data from studies will be pooled with statistical meta-analysis to compare both oncological and functional outcomes between the two groups. All time to event to data will be converted to a common metric for oncological outcomes. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach will be followed to assess the certainty of findings. REVIEW REGISTRATION: PROSPERO CRD4202235209.


Subject(s)
Oropharyngeal Neoplasms , Adult , Humans , Prospective Studies , Retrospective Studies , Systematic Reviews as Topic , Oropharyngeal Neoplasms/surgery , Meta-Analysis as Topic , Review Literature as Topic
10.
Surg Endosc ; 37(8): 6185-6196, 2023 08.
Article in English | MEDLINE | ID: mdl-37165173

ABSTRACT

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.


Subject(s)
Magnetite Nanoparticles , Sentinel Lymph Node , Stomach Neoplasms , Animals , Swine , Sentinel Lymph Node/diagnostic imaging , Sentinel Lymph Node/surgery , Sentinel Lymph Node/pathology , Indocyanine Green , Sentinel Lymph Node Biopsy/methods , Mannose , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Coloring Agents , Lymph Node Excision , Fluorescent Dyes , Lymph Nodes/diagnostic imaging , Lymph Nodes/surgery , Lymph Nodes/pathology
11.
Nat Commun ; 13(1): 7742, 2022 12 15.
Article in English | MEDLINE | ID: mdl-36522325

ABSTRACT

Artificial neural networks are known to suffer from catastrophic forgetting: when learning multiple tasks sequentially, they perform well on the most recent task at the expense of previously learned tasks. In the brain, sleep is known to play an important role in incremental learning by replaying recent and old conflicting memory traces. Here we tested the hypothesis that implementing a sleep-like phase in artificial neural networks can protect old memories during new training and alleviate catastrophic forgetting. Sleep was implemented as off-line training with local unsupervised Hebbian plasticity rules and noisy input. In an incremental learning framework, sleep was able to recover old tasks that were otherwise forgotten. Previously learned memories were replayed spontaneously during sleep, forming unique representations for each class of inputs. Representational sparseness and neuronal activity corresponding to the old tasks increased while new task related activity decreased. The study suggests that spontaneous replay simulating sleep-like dynamics can alleviate catastrophic forgetting in artificial neural networks.


Subject(s)
Learning , Neural Networks, Computer , Learning/physiology , Sleep/physiology , Neurons/physiology , Brain
12.
Head Neck ; 44(12): 2696-2707, 2022 12.
Article in English | MEDLINE | ID: mdl-36082404

ABSTRACT

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a staging procedure dependent on accurate mapping of draining lymphatics via tracers. Robot-assisted SLNB enables access to multiple neck levels with a single incision and intraoperative fluorescence guidance to the SLN. METHODS: Lymphatic mapping in swine was done using a magnetic tracer and fluorescent dye, injected into the tongue. MRI preoperatively mapped lymphatic spread of the magnetic tracer. Dissection was performed using a da Vinci Xi robot guided by fluorescence-imaging of the dye. RESULTS: Robot-assisted SLNB was successfully performed in all animals (n = 5). A novel MRI protocol differentiated SLNs (n = 6) from lower echelon nodes (n = 11) based on flow progression. Fluorescence imaging provided valuable intraoperative guidance and correlated with magnetic-positive nodes. CONCLUSIONS: This study demonstrates preclinical feasibility of a robot-assisted approach to SLNB using magnetic and fluorescent tracers in the head and neck, enabling both preoperative mapping and intraoperative guidance.


Subject(s)
Robotics , Sentinel Lymph Node Biopsy , Animals , Swine , Sentinel Lymph Node Biopsy/methods , Fluorescence , Feasibility Studies , Indocyanine Green , Fluorescent Dyes , Lymph Nodes/diagnostic imaging , Lymph Nodes/surgery , Lymph Nodes/pathology
13.
Nanomedicine ; 42: 102546, 2022 06.
Article in English | MEDLINE | ID: mdl-35278683

ABSTRACT

Sentinel lymph node biopsy in cancers of the head and neck offers demonstrated clinical and diagnostic value, but adoption is limited by concerns about the detrimental consequence to survival of false negative results in a highly curable setting. The aim of this study was to demonstrate potential to overcome this via application of a novel mannose-labeled magnetic iron oxide tracer. In a large animal model, preoperative imaging and intraoperative magnetometer detection were used to identify magnetic lymph nodes. Iron quantification mapped the distribution of tracer within lymphatic levels. Over a 4-week test period, uptake of magnetic tracer in lymph nodes increased in a linear-like fashion, with a substantial percentage of accumulated iron (83%) being retained in the sentinel node. This result indicates a high affinity of mannose-labeled particles to the sentinel node, while providing a means for the magnetometer probe to indicate node status based on intraoperative signal.


Subject(s)
Magnetite Nanoparticles , Sentinel Lymph Node , Animals , Iron , Lymph Nodes , Magnetic Phenomena , Mannose , Sentinel Lymph Node/diagnostic imaging , Sentinel Lymph Node/surgery , Sentinel Lymph Node Biopsy/methods
14.
Adv Nutr ; 13(3): 758-791, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35134815

ABSTRACT

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.


Subject(s)
Caloric Restriction , Feeding Behavior , Circadian Rhythm/physiology , Feeding Behavior/physiology , Humans , Melanocortins/metabolism , Neurosecretory Systems/metabolism , Suprachiasmatic Nucleus/metabolism
15.
Adv Nutr ; 13(3): 792-820, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35191467

ABSTRACT

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.


Subject(s)
Ghrelin , Leptin , Caloric Restriction , Energy Intake , Fasting , Glucagon-Like Peptide 1 , Humans , Insulin
16.
J Nucl Med ; 63(8): 1162-1168, 2022 08.
Article in English | MEDLINE | ID: mdl-35027369

ABSTRACT

In head and neck cancer, a major limitation of current intraoperative margin analysis is the ability to detect areas most likely to be positive based on specimen palpation, especially for larger specimens where sampling error limits detection of positive margins. This study aims to prospectively examine the clinical value of fluorescent molecular imaging to accurately identify "the sentinel margin," the point on a specimen at which the tumor lies closest to the resected edge in real-time during frozen section analysis. Methods: Eighteen patients with oral squamous cell carcinoma were enrolled into a prospective clinical trial and infused intravenously with 50 mg of panitumumab-IRDye800CW 1-5 d before surgery. Resected specimens were imaged in a closed-field near-infrared optical imaging system in near real-time, and custom-designed software was used to identify locations of highest fluorescence on deep and peripheral margins. The surgeon identified the sentinel margin masked to optical specimen mapping, and then the regions of highest fluorescence were identified and marked for frozen analysis. Final pathology based on specimen reconstruction was used as reference standard. Results: Resected specimens were imaged in the operating room, and fluorescence had a higher interobserver agreement with pathology (Cohen κ value 0.96) than the surgeon (Cohen κ value of 0.82) for the location of the closest margin. Plotting margin distance at the predicted sentinel margin location of each observer versus the actual closest margin distance at pathology demonstrated best correlation between fluorescence and pathology (R2 = 0.98) with surgeon (R2 = 0.75). Conclusion: Fluorescence imaging can improve identification of the sentinel margin in head and neck cancer resections, holding promise for rapid identification of positive margins and improved oncologic outcomes.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Coloring Agents , Humans , Margins of Excision , Molecular Imaging , Mouth Neoplasms/diagnostic imaging , Mouth Neoplasms/surgery , Optical Imaging/methods , Prospective Studies , Squamous Cell Carcinoma of Head and Neck/diagnostic imaging , Squamous Cell Carcinoma of Head and Neck/surgery
17.
JBI Evid Synth ; 20(4): 1135-1141, 2022 04 01.
Article in English | MEDLINE | ID: mdl-34698708

ABSTRACT

OBJECTIVE: The objective of this review is to investigate overall survival in patients with human papillomavirus positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC) comparing standard- versus reduced-dose radiotherapy. INTRODUCTION: The improved survival of patients with HPV+ compared to HPV-negative OPSCC has raised the question of reducing the total radiation treatment dose delivered to patients with HPV+ OPSCC. A de-escalated radiotherapy protocol may provide equal oncological benefit, with reduced adverse events/toxicity. INCLUSION CRITERIA: We will include any adult patients aged 18years or older who have undergone curative intent treatment for HPV+ OPSCC. These patients can be at any stage at the time treatment is initiated. Exclusion criteria are as follows: pre-clinical or animal studies, patients with non-squamous cell carcinoma lesions of the oropharynx, patients with primary lesions in other head and neck sites, or patients receiving palliative treatment. METHODS: A three-step search strategy will be used to identify relevant articles for inclusion through MEDLINE, CINAHL, Embase, Web of Science, Scopus, and gray literature sources. These articles will be assessed against our inclusion and exclusion criteria at the title and abstract level as well as at full-text level. Remaining studies will be critically appraised based on their trial design. Data extraction will occur for all studies and, where possible, will be pooled with statistical meta-analysis. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021252161.


Subject(s)
Alphapapillomavirus , Carcinoma, Squamous Cell , Head and Neck Neoplasms , Oropharyngeal Neoplasms , Papillomavirus Infections , Radiation Injuries , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Head and Neck Neoplasms/complications , Humans , Meta-Analysis as Topic , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/radiotherapy , Papillomaviridae , Papillomavirus Infections/complications , Papillomavirus Infections/therapy , Radiation Injuries/complications , Review Literature as Topic , Squamous Cell Carcinoma of Head and Neck/complications , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Systematic Reviews as Topic
18.
Neural Comput ; 33(11): 2908-2950, 2021 10 12.
Article in English | MEDLINE | ID: mdl-34474476

ABSTRACT

Replay is the reactivation of one or more neural patterns that are similar to the activation patterns experienced during past waking experiences. Replay was first observed in biological neural networks during sleep, and it is now thought to play a critical role in memory formation, retrieval, and consolidation. Replay-like mechanisms have been incorporated in deep artificial neural networks that learn over time to avoid catastrophic forgetting of previous knowledge. Replay algorithms have been successfully used in a wide range of deep learning methods within supervised, unsupervised, and reinforcement learning paradigms. In this letter, we provide the first comprehensive comparison between replay in the mammalian brain and replay in artificial neural networks. We identify multiple aspects of biological replay that are missing in deep learning systems and hypothesize how they could be used to improve artificial neural networks.


Subject(s)
Deep Learning , Algorithms , Animals , Hippocampus , Neural Networks, Computer , Reinforcement, Psychology , Sleep
19.
Theranostics ; 11(15): 7188-7198, 2021.
Article in English | MEDLINE | ID: mdl-34158844

ABSTRACT

Rationale: Sentinel lymph node biopsy (SLNB) is a well-established minimally invasive staging procedure that maps the spread of tumour metastases from their primary site to the regional lymphatics. Currently, the procedure requires the local peri-tumoural injection of radiolabelled and/or optical agents, and is therefore operator dependent, disruptive to surgical workflow and restricted largely to a small subset of malignancies that can be readily accessed externally for local tracer injection. The present study set out to determine whether intravenous (IV) infusion of a tumor-targeted tracer could identify sentinel and metastatic lymph nodes (LNs) in order to overcome these limitations. Methods: We examined 27 patients with oral squamous cell carcinoma (OSCC), 18 of whom were clinically node negative (cN0). Patients were infused intravenously with 50mg of Panitumumab-IRDye800CW prior to surgical resection of their primary tumour with neck dissection and/or SLNB. Lymphadenectomy specimens underwent fluorescence molecular imaging to evaluate tracer distribution to LNs. Results: A total of 960 LNs were analysed, of which 34 (3.5%) contained metastatic disease. Panitumumab-IRDye800CW preferentially localized to metastatic and sentinel LNs as evidenced by a higher fluorescent signal relative to other lymph nodes. The median MFI of metastatic LNs was significantly higher than the median MFI of benign LNs (0.06 versus 0.02, p < 0.05). Furthermore, selecting the highest five fluorescence intensity LNs from individual specimens resulted in 100% sensitivity, 85.8% specificity and 100% negative predictive value (NPV) for the detection of occult metastases and 100% accuracy for clinically staging the neck. In the cN+ cohort, assessment of the highest 5 fluorescence LNs per patient had 87.5% sensitivity, 93.2% specificity and 99.1% NPV for the detection of metastatic nodes. Conclusion: When intravenously infused, a tumour-targeted tracer localized to sentinel and metastatic lymph nodes. Further validation of an IV tumor-targeted tracer delivery approach for SLNB could dramatically change the practice of SLNB, allowing its application to other malignancies where the primary tumour is not accessible for local tracer injection.


Subject(s)
Benzenesulfonates/administration & dosage , Head and Neck Neoplasms/pathology , Indoles/administration & dosage , Lymphatic Metastasis/pathology , Panitumumab/administration & dosage , Sentinel Lymph Node Biopsy , Squamous Cell Carcinoma of Head and Neck/pathology , Administration, Intravenous , Aged , Female , Humans , Male , Middle Aged
20.
Laryngoscope ; 131(3): 529-534, 2021 03.
Article in English | MEDLINE | ID: mdl-33593036

ABSTRACT

The rate of positive margins in head and neck cancers has remained stagnant over the past three decades and is consistently associated with poor overall survival. This suggests that significant improvements must be made intraoperatively to ensure negative margins. We discuss the important role of fluorescence imaging to guide surgical oncology in head and neck cancer. This review includes a general overview of the principles of fluorescence, available fluorophores used for fluorescence imaging, and specific clinical applications of fluorescence-guided surgery, as well as challenges and future directions in head and neck surgical oncology. Laryngoscope, 131:529-534, 2021.


Subject(s)
Head and Neck Neoplasms/surgery , Optical Imaging/methods , Squamous Cell Carcinoma of Head and Neck/surgery , Surgery, Computer-Assisted/methods , Fluorescence , Humans , Margins of Excision
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