Using Artificial Intelligence to Improve the Quality and Safety of Radiation Therapy

Within artificial intelligence, machine learning (ML) efforts in radiation oncology have augmented the transition from generalized to personalized treatment delivery. Although their impact on quality and safety of radiation therapy has been limited, they are increasingly being used throughout radiation therapy workflows. Various data-driven approaches have been used for outcome prediction, CT simulation, clinical decision support, knowledge-based planning, adaptive radiation therapy, plan validation, machine quality assurance, and process quality assurance; however, there are many challenges that need to be addressed with the creation and usage of ML algorithms as well as the interpretation and dissemination of findings. In this review, the authors present current applications of ML in radiation oncology quality and safety initiatives, discuss challenges faced by the radiation oncology community, and suggest future directions.     

Crocin improved amyloid beta induced long‐term potentiation and memory deficits in the hippocampal CA1 neurons in freely moving rats

Extracellular beta‐amyloid (Aβ) accumulation and deposition is the main factor, which causes synaptic loss and eventually cells death in Alzheimer's disease (AD). Memory loss and long‐term potentiation (LTP) dysfunction in the hippocampus are involved in the AD. The involvement of crocin, as the main and active constituent of saffron extract in learning and memory processes, has been proposed. Here we investigated the probable therapeutic effect of crocin on memory, LTP, and neuronal apoptosis using in vivo Aβ models of the AD. The Aβ peptide (1–42) was bilaterally administered into the frontal‐cortex using stereotaxic apparatus. Five hours after surgery, rats were given intraperitoneal crocin (30 mg/kg) daily, which repeated for 12 days. Barnes maze results showed that administration of crocin significantly improves spatial memory indicators such as latency time to achieving the target hole and the number of errors when compared to Aβ‐group. Passive avoidance test revealed that crocin significantly increased the step‐through‐latency compared to Aβ‐treated alone. These learning deficits in Aβ‐treated animals correlated with a reduction of LTP in hippocampal CA1 synapses in freely moving rats, which crocin improved population spike amplitude and mean field excitatory postsynaptic potentials (fEPSP) slope reduction induced by Aβ. Neuronal apoptosis was detected by TUNEL assay and the expression levels of c‐Fos proteins were examined by Western blotting. Crocin significantly reduced the number of TUNEL‐positive cells in the CA1 region and decreased c‐Fos in the hippocampus compared to Aβ‐group. In vivo Aβ treatment altered significantly the electrophysiological properties of CA1 neurons and crocin further confirmed a neuroprotective action against Aβ toxicity.     

Oxidative stress and intracellular pH in the young and old erythrocytes of rat

The effects of oxidative stress (OS) on the rat erythrocytes (RBCs) that were fractionated on the percoll/BSA gradient into young and old cells were studied to find out if the altered Na ⁺ /H⁺ and Cl⁻/HCO₃ ⁻ antiporters and in turn the intracellular pH (pH_i) could act as one of the promoters of cell death. Old cells were more spherical with lesser surface area, more fragile osmotically and had lesser protein sulphydryl content than the young cells. OS was induced in RBCs by 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH). AAPH increased the superoxide dismutase (SOD) activity and MDA level and, the changes between the young and old. Interestingly, vitamin C was effective in reducing MDA in the old. Further, in the old a rapid Na⁺-dependent acidification in the presence of AAPH and a marginal acidosis in the presence of vitamin C were evident. Old RBCs exhibited higher acidosis and vitamin C was less effective in lowering the stress-induced acidosis compared to the young. Our studies suggest that increased acidosis followed by low intracellular pH could be one of the determinant factors for the disappearance of old RBCs from circulation, and perhaps of the young too under OS.     

Nitrite mediates cytoprotection after ischemia/reperfusion by modulating mitochondrial function

Nitrite, once thought to be an inert biomarker of NO formation, is now recognized as an endocrine storage pool of bioactive NO. While nitrite mediates a number of hypoxic responses, one of its most robust effects is its ability to confer cytoprotection after ischemia/reperfusion in a number of organs and models. The mechanism of this cytoprotection appears to be mediated at the level of the mitochondrion. Here we review the studies demonstrating that nitrite is cytoprotective in the heart and describe the mechanism of this cytoprotection, which involves the post-translational modification of complex I leading to the modulation of mitochondrial reactive oxygen species generation at reperfusion. The mechanism of nitrite-dependent cytoprotection will be compared to other cytoprotective agents including NO and ischemic preconditioning.     

Influence of HLA on progression of optic neuritis to multiple sclerosis: results of a four-year follow-up study

BACKGROUND: Genetic predisposition in multiple sclerosis (MS) has always been a critical concern in aetiology and progress of the disease. The present study looks into the relations between human leukocyte antigen (HLA), optic neuritis (ON) and MS in the Iranian population. METHODS: Patients with potential diagnosis of acute ON underwent a standardized clinical examination for confirming the diagnosis. Selected patients were gathered for HLA typing and clinical follow up. RESULTS: Of the 55 patients, 46 (83.6%) were female. The mean age was 25(+/-7.3) with a range of 12-43. Twenty of the 55 (36%) were confirmed for the diagnosis of clinically definite MS (CDMS). Results show that A23, B21, A11 and B51 alleles were present in 4 (20%), 6 (30%), 2 (10%) and 1 (5%) of the CDMS patients, respectively. Ten (50%) and 17 (85%) CDMS patients were positive for HLA class II alleles, DR2 and DQ1, correspondingly. CONCLUSIONS: The study strongly suggests the association among DR2, A23 and B21 allele and the evolution of ON to MS. High prevalence of A23 and DR2 alleles in CDMS patients compared with the normal population may suggest an important role for these alleles in the development of MS. The study suggests B51 as a protective factor against development of ON in the normal population. In addition, results do not confirm previous studies considering A11 as a predisposing factor. The present study finally evokes that different classes of HLA have different roles in susceptibility to MS and confirms disease heterogeneity as an important emerging concept in MS.     

Initial management of childhood brain tumors: neurosurgical considerations

Intracranial tumors are the most common solid tumors in children. The infratentorial compartment will be the primary site for 60% to 70% of these tumors, including astrocytomas, medulloblastomas, and ependymomas. Several technological advancements have increased our knowledge of the cell biology of pediatric brain tumors, facilitated earlier diagnosis, and improved neurosurgical resections while minimizing neurological deficits. These in turn have not only improved the survival of children with brain tumors but also their quality of life. Current management strategies in most cases rely on surgery coupled with adjuvant therapies, including radiation therapy and chemotherapy. The vulnerability of the immature brain to adjuvant therapies creates many challenges for the treating physician. We review current diagnostic and therapeutic approaches and outcome for children harboring the most common pediatric brain tumors: astrocytomas (low-grade and high-grade glioma), ependymoma, medulloblastoma, and craniopharyngioma. The emphasis will be on the neurosurgical management of children with these tumors.     

Basic presynaptic functions in hippocampal neurons are not affected by acute or chronic lithium treatment

Lithium is an effective mood-stabilizer in the treatment of bipolar affective disorder. While glycogen synthase kinase 3-mediated and inositol depletion-dependent effects of lithium have been described extensively in literature, there is very little knowledge about the consequences of lithium treatment on vesicle recycling and neurotransmitter availability. In the present study we have examined acute and chronic effects of lithium on synaptic vesicle recycling using primary hippocampal neurons. We found that exocytosis of readily releasable pool vesicles as well as recycling pool vesicles was unaffected by acute and chronic treatment within the therapeutic range or at higher lithium concentrations. Consistent with this observation, we also noticed that the network activity and number of active synapses within the network were also not significantly altered after lithium treatment. Taken together, as lithium treatment does not affect synaptic vesicle release at even high concentrations, our data suggest that therapeutic effects of lithium in bipolar affective disorder are not directly related to presynaptic function.     

Mitochondrial-mediated apoptosis in neural stem cells exposed to manganese.

Manganese is an essential nutrient for humans that has to be maintained at proper levels for normal brain functioning. However, manganese also acts as a toxicant to the brain, and several studies have linked exposure to excessive manganese to neurotoxicity in adults. A recent report has suggested that ingesting high doses of manganese via drinking water can impede intellectual functions in children. It is known that during development, the nervous system is particularly vulnerable to different types of injuries and toxicants. Neural stem cells (NSCs) play an essential role in both the developing nervous system and the adult brain where the capacity for self-renewal may be important. In the present study, we have used NSCs to investigate the molecular mechanisms involved in manganese developmental neurotoxicity. The results show that primary cultures of rat embryonic cortical NSCs as well as the murine-derived multipotent NSC line C17.2 undergo apoptotic cell death via a mitochondrial-mediated pathway in response to manganese. Exposed cells exhibit typical apoptotic features, such as chromatin condensation and cell shrinkage, mitochondrial cytochrome c release, activation of caspase-3, and caspase-specific cleavage of the endogenous substrate poly (ADP-ribose) polymerase. In addition, our data also show that reactive oxygen species formation plays a role in the onset of manganese toxicity in NSCs.