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Despite all efforts to enhance safety, construction sites remain a major location for traffic accidents. Short-term construction sites, in particular, face limitations in implementing extensive safety measures due to their condensed timelines. This paper seeks to enhance safety in short-term construction sites by alerting maintenance personnel and approaching vehicles to potentially dangerous scenarios. Focusing on defining the exact dimensions of static construction sites, this method employs high-precision Real-Time-Kinematics-GNSS for localizing traffic cones and deriving the construction site geometry through respective algorithms. By analyzing the geometry, we can identify situations where maintenance personnel are in close proximity to the active lane or when vehicles enter the construction site. To increase awareness of hazardous situations, we present methods for distributing information to maintenance personnel and vehicles, along with technical solutions for warning those involved. Additionally, we discuss the distribution of the construction site’s geometry among approaching vehicles, which can provide future automated vehicles with crucial information on the site’s exact start and end points.

Medulloblastoma, a common pediatric malignant central nervous system tumour, represent a small proportion of brain tumours in adults. Previously it has been shown that in adults, Sonic Hedgehog (SHH)-activated tumours predominate, with Wingless-type (WNT) and Group 4 being less common, but molecular risk stratification remains a challenge. We performed an integrated analysis consisting of genome-wide methylation profiling, copy number profiling, somatic nucleotide variants and correlation of clinical variables across a cohort of 191 adult medulloblastoma cases identified through the Medulloblastoma Advanced Genomics International Consortium. We identified 30 WNT, 112 SHH, 6 Group 3, and 41 Group 4 tumours. Patients with SHH tumours were significantly older at diagnosis compared to other subgroups (p

PURPOSE: We sought to investigate clinical outcomes of relapsed medulloblastoma and to compare molecular features between patient-matched diagnostic and relapsed tumors. METHODS: Children and infants enrolled on either SJMB03 (NCT00085202) or SJYC07 (NCT00602667) trials who experienced medulloblastoma relapse were analyzed for clinical outcomes, including anatomic and temporal patterns of relapse and postrelapse survival. A largely independent, paired molecular cohort was analyzed by DNA methylation array and next-generation sequencing. RESULTS: A total of 72 of 329 (22%) SJMB03 and 52 of 79 (66%) SJYC07 patients experienced relapse with significant representation of Group 3 and wingless tumors. Although most patients exhibited some distal disease (79%), 38% of patients with sonic hedgehog tumors experienced isolated local relapse. Time to relapse and postrelapse survival varied by molecular subgroup with longer latencies for patients with Group 4 tumors. Postrelapse radiation therapy among previously nonirradiated SJYC07 patients was associated with long-term survival. Reirradiation was only temporizing for SJMB03 patients. Among 127 patients with patient-matched tumor pairs, 9 (7%) experienced subsequent nonmedulloblastoma CNS malignancies. Subgroup (96%) and subtype (80%) stabilities were largely maintained among the remainder. Rare subgroup divergence was observed from Group 4 to Group 3 tumors, which is coincident with genetic alterations involving MYC, MYCN, and FBXW7. Subgroup-specific patterns of alteration were identified for driver genes and chromosome arms. CONCLUSION: Clinical behavior of relapsed medulloblastoma must be contextualized in terms of up-front therapies and molecular classifications. Group 4 tumors exhibit slower biological progression. Utility of radiation at relapse is dependent on patient age and prior treatments. Degree and patterns of molecular conservation at relapse vary by subgroup. Relapse tissue enables verification of molecular targets and identification of occult secondary malignancies.

The paper reports the analysis of the stereotactic irradiation outcomes in 430 patients with pilocytic astrocytomas (PAs), who underwent treatment in 2005–2018. The comprehensive approach to treatment of patients with intracranial pilocytic astrocytomas (PAs) that includes surgical removal, drug therapy (mostly in young children) and radiation therapy, is justified. The paper defines the roles of stereotactic radiosurgery and radiotherapy as the methods of choice used in the radiation therapy of patients with pilocytic astrocytomas. These methods show high conformity and selectivity, which is of special importance in patients with the PA localization in the functionally important structures.

The improvement of neuroimaging methods and introduction of the principles of microsurgery and radiosurgery involving the use of the Gamma Knife and CyberKnife systems into clinical practice have significantly changed the treatment outcomes in patients with metastatic brain tumors, thereby allowing to formulate new principles of treating this group of patients. The reported literature review summarizes the available treatment methods for patients with metastatic brain tumors with a focus on overall survival, local control, quality of life, and the capabilities of potential combinations of the existing treatment methods. The paper shows that personalized approaches to treatment of patients with brain metastases are optimal and improve the treatment outcomes.

Abstract Intracerebral hemorrhage (ICH) remains a common and debilitating form of stroke. This neurological emergency must be diagnosed and treated rapidly yet effectively. In this article, we review the medical, surgical, repair, and regenerative treatment options for managing ICH. Topics of focus include the management of blood pressure, intracranial pressure, coagulopathy, and intraventricular hemorrhage, as well as the role of surgery, regeneration, rehabilitation, and secondary prevention. Results of various phase II and III trials are incorporated. In summary, ICH patients should undergo rapid evaluation with neuroimaging, and early interventions should include systolic blood pressure control in the range of 140 mmHg, correction of coagulopathy if indicated, and assessment for surgical intervention. ICH patients should be managed in dedicated neurosurgical intensive care or stroke units where continuous monitoring of neurological status and evaluation for neurological deterioration is rapidly possible. Extravasation of hematoma may be helpful in patients with intraventricular extension of ICH. The goal of care is to reduce mortality and enable multimodal rehabilitative therapy.

Neurofibromatoses are a group of genetic disorders with predisposing for central and peripheral nervous system tumor development. The group includes three entities: neurofibromatosis type I, neurofibromatosis type II and schwannomatosis, which are characterized by gradual phenotype development and have a partially overlapping spectrum of manifestations, which complicates diagnosis establishing, especially at the stage of clinical onset. At the same time, the emergence of new pathogenetic therapy and the high risk of transmission to descendants actualize the necessity of early diagnosis. DNA tests allow us to reliably confirm the presumed diagnosis. This article presents a review of neurofibromatoses, their clinical features and courses, modern diagnostic criteria and indications for DNA tests.

Epithelioid glioblastoma (eGBM) is a newly defined and rare GBM variant in the current WHO 2016 classification. BRAF V600E mutation is overrepresented in these tumors and there is known some morphological overlap with anaplastic epithelioid PXA (ePXA). In order to further elucidate this diagnostic category, we molecularly characterized 64 pediatric and adult examples initially diagnosed as "eGBM." Tumors were analyzed using array based methylation and direct sequencing of the BRAF and TERT genes. Our results demonstrated considerable molecular and clinical heterogeneity among eGBM cohort. Methylation patterns, copy number alterations, and mutational analysis data, in combination with clinical findings disclosed three different, well established tumor subtypes: (i) PXA-like tumors with favorable prognosis, predominantly in children and young adults (38), (ii) IDHwt GBM-like tumors with poor prognosis, mainly occurring in older adults, albeit with more frequent BRAF mutations (17), and (iii) RTK1 pediatric GBM-like neoplasms of intermediate prognosis in children and young adults, associated with chromothripsis and frequent PDGFRA amplifications (9). We conclude that the histopathologically defined eGBM do not represent a single diagnostic entity, but rather at least three molecularly and biologically distinct categories. Therefore, additional molecular testing through genome-wide molecular profiling is recommended to further stratify these rare cases.

Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies but their origin are still unclear. Here, the authors define the genomic, epigenetic and transcriptional landscape of 32 RIGs cases.

Background Electrical stimulation of the cerebellar fastigial nucleus (FN) reduces the infarct size induced by middle cerebral artery occlusion in rats. FN stimulation confers long‐lasting protection from brain injury; however, its underlying mechanism is not yet understood. We aimed to elucidate the mechanism by which FN stimulation exerts neuroprotection. We hypothesized that the neuroprotective effect of FN stimulation involves activation of cholinergic pathways, which increases reactive oxygen species (ROS) production by opening mitochondrial K+ATP channels, thus leading to an increase in UCP4 (uncoupling protein 4) expression and subsequent neuroprotection. Methods FN stimulation was performed for 1 hour in rats. The UCP4 protein and mRNA levels were measured by western blot, dot blot, and in situ hybridization. Carbachol was applied following UCP4‐promoter tdTomato reporter vector transfection of the rat primary cortical cell culture (in vitro) and rat brain (in vivo). We observed cellular UCP4 expression using fluorescence microscopy. UCP4 expression in the cell culture in response to diazoxide application was determined by a reverse transcription‐polymerase chain reaction and western blotting. Results Whereas FN stimulation increased UCP4 protein and mRNA levels, carbachol administration induced UCP4 expression in vitro and in vivo. The attenuation of this effect by atropine suggests that FN‐induced UCP4 expression involves the cholinergic pathway. The opening of mitochondrial K+ATP channels with diazoxide increased the production of ROS and led to increased UCP4 expression. In contrast, quenching ROS with superoxide dismutase reversed the effect of diazoxide on UCP4 expression. Therefore, the opening of mitochondrial K+ATP channels increased ROS production, which subsequently enhanced UCP4 expression and attenuated ROS generation. Conclusion Neuroprotective effect of FN stimulation involves activation of the cholinergic pathways, which increases ROS production by opening mitochondrial K+ATP channels, leading to increased expression of neuroprotective UCP4.

The use of quantitative mapping of diffusion characteristics carries great potential for diagnosis and therapy of brain diseases, since it potentially allows to classify tumors, determine the degree of their malignancy, differentiate various morphological structures of tumor and non-tumor pathologies (such as tumor stroma, necrotic zones, cysts, various types of edema, etc.), and predict the course and outcome of diseases, in particular, a clinical response to treatment. Based on diffusion weighted magnetic resonance imaging (MRI), it is possible to perform 3D modeling of the white matter pathways of the brain, which is called tractography. In addition to a unique ability to visualize the location of tracts in relation to intracranial pathologies, this technology allows to build and analyze complex maps of communication networks in the brain (connectomics).The review is devoted to the discussion of the physical and technical concept of diffusion weighted MRI, the key ways of its application in tumor and non-tumor processes, and problems that complicate correct interpretation of results. Since the problem of developing software for diffusion MRI data remains relevant, this review presents our own experience in developing an application as part of a project on creating effective methods for processing diffusion MRI data and modeling white matter tracts.

Radiation therapy induces double-stranded DNA breaks in tumor cells, which leads to their death. A fraction of glioblastoma cells repair such breaks and reinitiate tumor growth. It was necessary to identify the relationship between high radiation doses and the proliferative activity of glioblastoma cells, and to evaluate the contribution of DNA repair pathways, homologous recombination (HR), and nonhomologous end joining (NHEJ) to tumor-cell recovery. We demonstrated that the GO1 culture derived from glioblastoma cells from Patient G, who had previously been irradiated, proved to be less sensitive to radiation than the Sus\fP2 glioblastoma culture was from Patient S, who had not been exposed to radiation before. GO1 cell proliferation decreased with radiation dose, and MTT decreased to 35% after a single exposure to 125 Gγ. The proliferative potential of glioblastoma culture Sus\fP2 decreased to 35% after exposure to 5 Gγ. At low radiation doses, cell proliferation and the expression of RAD51 were decreased; at high doses, cell proliferation was correlated with Ku70 protein expression. Therefore, HR and NHEJ are involved in DNA break repair after exposure to different radiation doses. Low doses induce HR, while higher doses induce the faster but less accurate NHEJ pathway of double-stranded DNA break repair.

External beam radiotherapy (EBR) remained for a long time the only method of treatment in children with recurrent and resistant retinoblastoma (RB). This method often leads to serious complications, including the occurrence of secondary malignant tumors. Currently, EBR is used as second-line (salvage) therapy. There is no data in the literature of using Gamma Knife stereotactic radiosurgery (GKRS) in RB treatment.Purpose. To present 5-year experience of using GKRS in patients with RB.Material and methods. 16 children (17 eyes) were treated using GKRS in the period from 2015 to 2019. Mean patient age was 34.7 months (range, 12–114 months). The eyes were classified as group B (n=4), C (n=1), D (n=12). 3 children had the last eye. All patients received systemic and local chemotherapy, all types of local treatment modalities before using GKRS. Recurrent and resistant RB was the indication for GKRS. Marginal 50% mean dose was 22 Gу (range, 20–24 Gу), depending on tumour type and location. Radiation doses were evaluated accounting critical eye structures and the orbit bones.Results. Complete regression was achieved in 11 patients, partial in 2. Four patients underwent enucleation after GKRS. Indications for enucleation were retinoblastoma recurrence (n=2) and vitreous hemorrhage with total retinal detachment (n=2). 13 eyes were salvaged with no signs of keratopathy, uveitis or damage of orbital and surrounding tissues during mean follow-up 30.6 months (range, 7–60 months). Сomplications of different severity occurred in 13 patients, including vitreous hemorrhage in 6 patients, which was successfully treated both conservative (n=3) and using pars plana vitrectomy with simultaneous melphalan irrigation (n=3).Conclusion. The first experience of GKRS as an alternative to enucleation in patients with RB was proved to be reasonable and successful.

Positron emission tomography combined with computed tomography (PET/CT) is currently the standard imaging method in neuro-oncology for gliomas and metastatic lesions. There is much less experience with the use of PET/CT in meningioma, the most common primary tumor of the central nervous system, and there are some differences in how results are interpreted. The aim of the present work was to assess the potential for and features of the use of PET/CT to determine the degree of malignancy of meningioma, its prevalence, responses to radiotherapy, and diagnosis of relapse and/or post-radiation changes based on our own clinical experience and review of the literature. The study included 70 patients with 77 meningiomas who underwent 11C-methionine PET/CT. Mean age at investigation was 57.4 years (range 19–86 years). The main parameter evaluated, the tumor/normal ratio (T/N) of 11C-methionine (11C-MET) in tumors, averaged 3.13 (1.00–10.66). Meningiomas had high 11C-MET T/N, with values of >1.5 in 89.6% of cases. In histologically verified malignancy grade 1, 2, and 3 meningiomas (WHO scale), median T/N values were 4.06 [3.04; 4.57], 2.32 [2.12; 3.69], and 4.29 [2.60; 5.10] respectively, with no significant between-group differences. At the same time, non-growing or slowly growing histologically unverified meningiomas, i.e., incidentally discovered, had significantly lower 11C-MET T/N than grade 1 and 3 meningiomas. There was no significant difference in T/N between irradiated meningiomas with controls for tumor growth (3.81 [2.97, 3.98]) and relapse (3.62 [2.60, 4.30]). Comparison of irradiated and non-irradiated grade 1, 2, and 3 meningiomas, as well as the combined group of grade 1–3 tumors, revealed no significant differences in 11C-MET T/N. The use of PET/CT for meningiomas has a number of important characteristics. Meningiomas had high 11C-MET T/N. Our data indicate that 11C-MET PET/CT does not distinguish between meningiomas with different degrees of malignancy, i.e., WHO grades 1, 2, and 3. 11C-MET T/N in meningiomas remains stably high or shows a slight decrease in cases with effective radiotherapy and long-term local control. Comparison of growing and non-growing meningiomas revealed no significant differences in 11C-MET T/N between irradiated and non-irradiated tumors. [ABSTRACT FROM AUTHOR]

Abstract Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly malignant neoplasms posing diagnostic challenge due to a lack of defining molecular markers. CNS neuroblastoma with forkhead box R2 (FOXR2) activation (CNS_NBL) emerged as a distinct pediatric brain tumor entity from a pool previously diagnosed as primitive neuroectodermal tumors of the central nervous system (CNS-PNETs). Current standard of identifying CNS_NBL relies on molecular analysis. We set out to establish immunohistochemical markers allowing safely distinguishing CNS_NBL from morphological mimics. To this aim we analyzed a series of 84 brain tumors institutionally diagnosed as CNS-PNET. As expected, epigenetic analysis revealed different methylation groups corresponding to the (1) CNS-NBL (24%), (2) glioblastoma IDH wild-type subclass H3.3 G34 (26%), (3) glioblastoma IDH wild-type subclass MYCN (21%) and (4) ependymoma with RELA_C11orf95 fusion (29%) entities. Transcriptome analysis of this series revealed a set of differentially expressed genes distinguishing CNS_NBL from its mimics. Based on RNA-sequencing data we established SOX10 and ANKRD55 expression as genes discriminating CNS_NBL from other tumors exhibiting CNS-PNET. Immunohistochemical detection of combined expression of SOX10 and ANKRD55 clearly identifies CNS_NBL discriminating them to other hemispheric CNS neoplasms harboring “PNET-like” microscopic appearance. Owing the rarity of CNS_NBL, a confirmation of the elaborated diagnostic IHC algorithm will be necessary in prospective patient series.

After subarachnoid hemorrhage (SAH), up to 95% of surviving patients suffer from post-SAH syndrome, which includes cognitive deficits with impaired memory, executive functions, and emotional disturbances. Although these long-term cognitive deficits are thought to result from damage to temporomesial–hippocampal areas, the underlying mechanisms remain unknown. To fill this gap in knowledge, we performed a systematic RNA sequencing screen of the hippocampus in a mouse model of SAH. SAH was induced by perforation of the circle of Willis in mice. Four days later, hippocampal RNA was obtained from SAH and control (sham perforation) mice. Next-generation RNA sequencing was used to determine differentially expressed genes in the whole bilateral hippocampi remote from the SAH bleeding site. Functional analyses and clustering tools were used to define molecular pathways. Differential gene expression analysis detected 642 upregulated and 398 downregulated genes (false discovery rate

The paper deals with the questions of introducing the additive technology of selective laser melting (SLM) into the production of the main structural elements of a combustion chamber for ground-based gas pumping, power and transport gas turbines. A fundamentally new design of a low-emission two-circuit burner was developed, adapted for the manufacture of products with a complex geometry through the use of selective laser melting (SLM) of metal powders according to mathematical CAD-models with the help of an advanced production technology. Technical difficulties associated with the implementation of additive manufacturing technology were overcome. The process chain was tried out from design to manufacturing and quality control of finished structural elements under conditions of mass production. The deficiencies of the parts manufactured by the additive technology were revealed and ultimately eliminated. Successful development of burners for a low-emission combustion chamber using a new technology significantly reduces labor intensity and time of production while maintaining high quality.