Cytokine Immunotherapy for Neuroblastoma

Neuroblastoma (NB) is an embryonal tumor originating from the sympathetic nervous system, which occurs during fetal period or early postnatal period, and is one of the most common extracranial solid malignant tumors in children. Cytokines are pleiotropic proteins that can effectively activate tumor immune cells and counteract immune suppression, thereby suppressing tumors. Cytokine immunotherapy provides more possibilities for the application of immunotherapy through its own induction and activation of the immune system and has also been extensively studied in NB immunotherapy. This article mainly introduces the research progress of several immunotherapies based on cytokines in the treatment of children with NB

Functional MRI with active, fully implanted, deep brain stimulation systems: Safety and experimental confounds

We investigated safety issues and potential experimental confounds when performing functional magnetic resonance imaging (fMRI) investigations in human subjects with fully implanted, active, deep brain stimulation (DBS) systems. Measurements of temperature and induced voltage were performed in an in vitro arrangement simulating bilateral DBS during magnetic resonance imaging (MRI) using head transmit coils in both 1.5 and 3.0 T MRI systems. For MRI sequences typical of an fMRI study with coil-averaged specific absorption rates (SARs) less than 0.4 W/kg, no MRI-induced temperature change greater than the measurement sensitivity (0.1 °C) was detected at 1.5 T, and at 3 T temperature elevations were less than 0.5 °C, i.e. within safe limits. For the purposes of demonstration, MRI pulse sequences with SARs of 1.45 W/kg and 2.34 W/kg (at 1.5 T and 3 T, respectively) were prescribed and elicited temperature increases (> 1 °C) greater than those considered safe for human subjects. Temperature increases were independent of the presence or absence of active stimulator pulsing. At both field strengths during echo planar MRI, the perturbations of DBS equipment performance were sufficiently slight, and temperature increases sufficiently low to suggest that thermal or electromagnetically mediated experimental confounds to fMRI with DBS are unlikely. We conclude that fMRI studies performed in subjects with subcutaneously implanted DBS units can be both safe and free from DBS-specific experimental confounds. Furthermore, fMRI in subjects with fully implanted rather than externalised DBS stimulator units may offer a significant safety advantage. Further studies are required to determine the safety of MRI with DBS for other MRI systems, transmit coil configurations and DBS arrangements

Boosting Drug Named Entity Recognition using an Aggregate Classifier

AbstractObjectiveDrug named entity recognition (NER) is a critical step for complex biomedical NLP tasks such as the extraction of pharmacogenomic, pharmacodynamic and pharmacokinetic parameters. Large quantities of high quality training data are almost always a prerequisite for employing supervised machine-learning techniques to achieve high classification performance. However, the human labour needed to produce and maintain such resources is a significant limitation. In this study, we improve the performance of drug NER without relying exclusively on manual annotations.MethodsWe perform drug NER using either a small gold-standard corpus (120 abstracts) or no corpus at all. In our approach, we develop a voting system to combine a number of heterogeneous models, based on dictionary knowledge, gold-standard corpora and silver annotations, to enhance performance. To improve recall, we employed genetic programming to evolve 11 regular-expression patterns that capture common drug suffixes and used them as an extra means for recognition.MaterialsOur approach uses a dictionary of drug names, i.e. DrugBank, a small manually annotated corpus, i.e. the pharmacokinetic corpus, and a part of the UKPMC database, as raw biomedical text. Gold-standard and silver annotated data are used to train maximum entropy and multinomial logistic regression classifiers.ResultsAggregating drug NER methods, based on gold-standard annotations, dictionary knowledge and patterns, improved the performance on models trained on gold-standard annotations, only, achieving a maximum F-score of 95%. In addition, combining models trained on silver annotations, dictionary knowledge and patterns are shown to achieve comparable performance to models trained exclusively on gold-standard data. The main reason appears to be the morphological similarities shared among drug names.ConclusionWe conclude that gold-standard data are not a hard requirement for drug NER. Combining heterogeneous models build on dictionary knowledge can achieve similar or comparable classification performance with that of the best performing model trained on gold-standard annotations

Central sensitisation as a determinant of patients' benefit from total hip and knee replacement

BACKGROUND: Discrepancies exist between osteoarthritic joint changes and pain severity before and after total hip (THR) and knee (TKR) replacement. This study investigated whether the interaction between pre‐operative widespread hyperalgesia and severity of radiographic osteoarthritis (OA) was associated with pain severity before and after joint replacement. METHODS: Data were analysed from 232 patients receiving THR and 241 receiving TKR. Pain was assessed pre‐operatively and at 12 months post‐operatively using the WOMAC Pain Scale. Widespread hyperalgesia was assessed through forearm pressure pain thresholds (PPTs). Radiographic OA was evaluated using the Kellgren and Lawrence scheme. Statistical analysis was conducted using multilevel models, and adjusted for confounding variables. RESULTS: Pre‐operative: In knee patients, there was weak evidence that the effect of PPTs on pain severity was greater in patients with more severe OA (Grade 3 OA: ß = 0.96 vs. Grade 4: ß = 4.03), indicating that in these patients higher PPTs (less widespread hyperalgesia) was associated with less severe pain. In hip patients, the effect of PPTs on pain did not differ with radiographic OA (Grade 3 OA: ß = 3.95 vs. Grade 4: ß = 3.67). Post‐operative: There was weak evidence that knee patients with less severe OA who had greater widespread hyperalgesia benefitted less from surgery (Grade 3 OA: ß = 2.28; 95% CI −1.69 to 6.25). Conversely, there was weak evidence that hip patients with more severe OA who had greater widespread hyperalgesia benefitted more from surgery (Grade 4 OA: ß = −2.92; 95% CI −6.58 to 0.74). CONCLUSIONS: Widespread sensitization may be a determinant of how much patients benefit from joint replacement, but the effect varies by joint and severity of structural joint changes. SIGNIFICANCE: Pre‐operative widespread hyperalgesia and radiographic osteoarthritis (OA) severity may influence how much patients benefit from joint replacement. Patients undergoing knee replacement with less severe OA and greater widespread hyperalgesia benefitted less from surgery than patients with less hyperalgesia. Patients undergoing hip replacement with more severe OA and greater widespread hyperalgesia benefitted more than patients with less hyperalgesia