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Microarray analysis identifies cerebellar genes sensitive to chronic ethanol treatment in PKCgamma mice.

Neuroadaptive changes that occur in the development of ethanol tolerance may be the result of alterations in gene expression. We have shown that PKCgamma wild-type mice develop tolerance to the sedative-hypnotic effects of ethanol after chronic ethanol treatment; whereas, mutant mice do not, making these genotypes a suitable model for identifying changes in gene expression related to tolerance development. Using a two-stage process, several genes were initially identified using microarray analyses of cerebellar tissue from ethanol-treated PKCgamma mutant and wild-type mice. Subsequent confirmation of a subset of these genes using quantitative real time reverse transcriptase polymerase chain reactions (qRT-PCR) was done to verify gene expression changes. A total of 109 genes from different functional classifications were identified in these groups on the microarrays. Eight genes were selected for verification as follows: three, Twik-1, Plp, and Adk2, were chosen as genes related to tolerance; another three, Hsp70.2, Bdnf, and Th, were chosen as genes related to resistance to tolerance; and two genes, JunB and Nur77, were selected as candidate genes sensitive to chronic ethanol. The results from the verification experiments indicated that Twik-1, which codes for a potassium channel, was associated with tolerance and appeared to be dependent on the presence of PKCgamma. No genes were confirmed to be related to resistance to tolerance; however, expression of two of these, Hsp70.2 and Th, were found to be sensitive to chronic ethanol and were added to the transcription factors, JunB and Nur77, confirmed by qRT-PCR, as a subset of genes that respond to chronic ethanol.

Alcoholism↗

Cytochrome P450 expression and catalytic activity in coronary arteries and liver of cattle.

There is increasing evidence that cytochrome P450 (CYP) enzymes are involved not only in the metabolism of xenobiotics, but also in vascular homeostasis. Among the CYP-derived vasoactive agents, special importance is assigned to endogenous products from arachidonic acid (AA). Specifically, the vasodilator epoxyeicosatrienoic acids (EETs), being linked to the CYP 2B, 2C, and 2J subfamilies, and the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE) connected instead to the CYP 4A subfamily and, to a lesser degree, to isoforms of the CYP 1A and 2E subfamilies. Here, we have examined the occurrence of functional CYP isoforms in the coronary arteries of cattle by RT-PCR with sequence verification, Western immunoblotting, and analysis of distinct catalytic activities with fluorescent substrate probes. Liver tissue was examined comparatively. Coronary tissue expressed mRNA transcripts and immunoreactive proteins belonging to the CYP 1A, 2C, 2E, and 2J subfamilies. Appropriate catalytic activity was ascertained with all these CYP species except 2J. A broader spectrum of CYP enzymes (CYP 1A, 2B, 2C, 2D, 2E, 2J, 3A, 4A subfamilies) was found in liver tissue with catalytic activities exceeding many fold those of coronary tissue. We conclude that bovine coronary arteries are endowed with a full-fledged CYP system with potential for AA-linked vasoregulation through dilator rather than constrictor agents. The same tissue and, to a much larger degree, liver tissue possess the capability of metabolizing xenobiotics via the CYP pathway.

Amino Acid Sequence↗

Identification and external validation of a prognostic signature based on myeloid-derived suppressor cells-related LncRNAs to evaluate survival prognosis and treatment efficacy in invasive breast carcinoma.

BACKGROUND: Originating in the hematopoietic tissue, myeloid-derived suppressor cells (MDSCs) significantly contribute to tumor-related immunological processes. However, their relationship with long noncoding RNAs (lncRNAs) and breast cancer remains incompletely understood. In this study, we introduced MDSCs-associated lncRNAs as novel prognostic biomarkers to assess outcomes in patients with invasive breast carcinoma (BRCA). METHODS: Information regarding BRCA cases, including clinical and genomic details, was obtained from the TCGA repository. Predictive indicators were discovered, and their reliability underwent thorough verification. A clinically useful nomogram was developed following application-based validation. Additional investigations encompassed functional analysis, TMB assessment, TME profiling, immunotherapy efficacy forecasting, and drug sensitivity testing along with target identification. Long non-coding RNA expression was measured using reverse transcription quantitative PCR. RESULTS: A risk stratification model incorporating eight MDSCs-related lncRNAs effectively predicted patient outcomes. Kaplan-Meier (K-M) survival analysis clearly indicated a much worse prognosis among patients classified as high-risk (p&#xa0;<&#xa0;0.001). The nomogram accurately forecasted overall survival (OS). Analysis of functional enrichment revealed that pathways associated with epithelial cells showed activity among patients at higher risk. Characterization of the tumor microenvironment showed increased immune cell presence in those classified as low-risk. Conversely, individuals with greater risk displayed higher tumor mutational burden. TIDE and IPS analyses indicated superior immunotherapy responsiveness in the low-risk BRCA subgroup. Among 47 drugs with notable IC50 variations, Ribociclib, PD173074, KU-55933, NU7441, and nutlin-3a exhibited lower IC50 values within the low-risk group, whereas Lapatinib demonstrated greater efficacy among the high-risk group. Moreover, 10 potential therapeutic agents and their targets were predicted for high-risk patients. RT-qPCR validation confirmed the robustness of the model. CONCLUSIONS: We successfully verified a new model of molecular markers of MDSCs-related lncRNAs, offering critical insights for predicting outcomes and guiding therapeutic decisions in BRCA cases.

Bioinformatics↗

Integrating a MRI scanner with a 6 MV radiotherapy accelerator: dose deposition in a transverse magnetic field.

Integrating magnetic resonance imaging (MRI) functionality with a radiotherapy accelerator can facilitate on-line, soft-tissue based, position verification. A technical feasibility study, in collaboration with Elekta Oncology Systems and Philips Medical Systems, led to the preliminary design specifications of a MRI accelerator. Basically the design is a 6 MV accelerator rotating around a 1.5 T MRI system. Several technical issues and the clinical rational are currently under investigation. The aim of this paper is to determine the impact of the transverse 1.5 T magnetic field on the dose deposition. Monte Carlo simulations were used to calculate the dose deposition kernel in the presence of 1.5 T. This kernel in turn was used to determine the dose deposition for larger fields. Also simulations and measurements were done in the presence of 1.1 T. The pencil beam dose deposition is asymmetric. For larger fields the asymmetry persists but decreases. For the latter the distance to dose maximum is reduced by approximately 5 mm, the penumbra is increased by approximately 1 mm, and the 50% isodose line is shifted approximately 1 mm. The dose deposition in the presence of 1.5 T is affected, but the effect can be taken into account in a conventional treatment planning procedure. The impact of the altered dose deposition for clinical IMRT treatments is the topic of further research.

Computer Simulation↗

A Grangeat-type half-scan algorithm for cone-beam CT.

Modern CT and micro-CT scanners are rapidly moving from fan-beam toward cone-beam geometry. Half-scan CT algorithms are advantageous in terms of temporal resolution, and widely used in fan-beam and cone-beam geometry. While existing half-scan algorithms for cone-beam CT are in the Feldkamp framework, in this paper we compensate missing data explicitly in the Grangeat framework, and formulate a half-scan algorithm in the circular scanning case. The half-scan spans 180 degrees plus two cone angles that guarantee sufficient data for reconstruction of the midplane defined by the source trajectory. The smooth half-scan weighting functions are designed for the suppression of data inconsistency. Numerical simulation results are reported for verification of our formulas and programs. This Grangeat-type half-scan algorithm produces excellent image quality, without off-mid-plane artifacts associated with Feldkamp-type half-scan algorithms. The Grangeat-type half-scan algorithm seems promising for quantitative and dynamic biomedical applications of CT and micro-CT.

Algorithms↗

Optimization of metal/phosphor screens for on-line portal imaging.

Studies were conducted to determine the optimal metal/phosphor screen for on-line video verification of radiation treatment portals. Screens were evaluated for luminance and spatial resolution as a function of composition and thickness at 6- and 23-MV x-ray energies. A new video technique was used to determine modulation transfer functions. Gd2O2S was found to be the most efficient (brightest) phosphor for this application. Luminance was found to vary linearly with phosphor thickness up to a thickness of 500 mg/cm2. Metal plates made of iron, brass, copper, lead, and sintered tungsten of various thicknesses were also tested for luminance and resolution with Gd2O2S phosphor. Brightness peaked at about 2-mm thickness for most metals. Significant contributions to the brightness were found to come from x rays interacting with the phosphor itself.

Evaluation Studies as Topic↗

Microarray and real-time PCR analysis of adrenal gland gene expression in the 7-day-old rat: effects of hypoxia from birth.

We hypothesize that changes in adrenal gene expression mediate the increased plasma corticosterone and steroidogenesis in rat pups exposed to hypoxia from birth. In the current study, rat pups (with their dams) were exposed to hypoxia from birth and compared with pups from normoxic dams fed ad libitum or pair fed to match the decreased maternal food intake that occurs during hypoxia. Microarray analysis was performed, followed by verification with real-time PCR. Furthermore, the expression of selected genes involved in adrenal function was analyzed by real-time PCR, regardless of microarray results. Hypoxia increased plasma ACTH and corticosterone, while food restriction had no effect. Microarray revealed that many of the genes affected by hypoxia encode proteins that require molecular oxygen (monooxygenases, oxidoreductases, and electron transport), whereas only a few genes known to be involved in adrenal steroidogenesis were affected. Interestingly, the expression of genes involved in mitochondrial function and intermediary metabolism was increased by hypoxia. Real-time PCR detected a small but significant increase in the expression of Cyp21a1 mRNA in the hypoxic adrenal. When decreased maternal food intake was controlled for, the effects of hypoxia were more pronounced, in that real-time PCR detected significant increases in the expression of Star (244%), Cyp21a1 (208%), and Ldlr (233%). The present study revealed that increased plasma corticosterone in rat pups was due to hypoxia per se, and not as a result of decreased food intake by the hypoxic dam. Furthermore, hypoxia induced changes in gene expression that account for more productive and efficient steroidogenesis.

Adrenal Glands↗

[The laboratory diagnosis of von Willebrand's disease (author's transl)].

This investigation was undertaken in order to determine the most suitable methods for diagnosing von Willebrand's disease (v. W. d.), with particular reference to "mild" cases. 50 healthy persons, 21 patients with "severe" v.W.d. (verified according to all hitherto-established criteria) and 39 persons suffering from "mild" v.W.d. were examined. Even though - as far as the latter group is concerned - some of the characteristic laboratory findings were absent, the fact that these persons are related to the patients with "severe" v.W.d. made verification of the diagnosis nevertheless possible. In the group with "mild" v.W.d. 85% had decreased functional factor VIII activity and 82% showed reduced platelet adhesiveness; a prolonged bleeding time according to Borchgrevink was recorded in 72% of the cases and 64% had pathological values for the Ristocetin-induced platelet aggregation were pathological in less than 50% of the group. There was a close relation between the diagnostic significance and reproducibility of the various methods; in regard to the group of patients with "mild" v.W.d., the methods yielding the greatest number of pathological findings (functional factor VIII and platelet adhesiveness) were the ones with the lowest variation coefficients, i.e. 3.1 and 2.1%, respectively. The consideration of a time-dependent rise in the aggregation capability of washed platelets with Ristocetin was of decisive importance in the reproducibility of the rather sophisticated technique of determining the Ristocetin cofactor. The addition of EDTA largely inhabited this effect. Even in the group of patients with "severe" v.W.d., part of the findings obtained with screening tests of the intrinsic coagulation system remained within the normal range. There was no statistical correlation between the individual laboratory findings in the group of healthy persons. In the group with "mild" v.W.d., there was a significant correlation between platelet adhesiveness and Ristocetin-induced platelet aggregation on the one hand, and platelet adhesiveness and the Ristocetin cofactor on the other. In addition, a verified correlation was found to exist between Ristocetin-induced platelet aggregation and Ristocetin cofactor and between functional factor VIII and factor VIII-related antigen. In the group of "severe" v.W.d., only platelet adhesiveness and functional factor VIII were not significantly correlated, whilst all other correlations were of statistical significance. Further problems involved in the diagnosis of v.W.d., such as the variablility of laboratory findings, the existence of subgroups, as well as the difficulties involved in the statistical evaluation of individual cases suffering from v.W.d. are discussed.

Factor VIII↗

[Diagnostic criteria for idiopathic Parkinson's disease].

Clinical diagnosis of parkinsonian syndrome is reasonably easy, but the distinction between idiopathic Parkinson's disease (IPD) and other parkinsonian syndromes (Secondary parkinsonisms and "Parkinsons plus") may be very difficult particularly in early cases. A correct diagnosis is not only important for counselling and management of patients but also in conducting pharmacological and epidemiological studies. A critical analysis of the diagnosis criteria of IPD, based on the pathological verification, is discussed from recent data of literature. Without any validated and available criteria from functional imaging or molecular biology, the most effective diagnostic criteria remain on the clinical range; the five most effective criteria are resting tremor, rigidity, bradykinesia, asymmetry at onset and marked levoDOPA responsiveness. The diagnosis of IPD should be periodically reassessed along the course of its natural history.

Humans↗

Implementation framework for digital signatures for electronic data interchange in healthcare.

This paper aims to propose an action plan for the deployment of the use of digital signatures in Belgian healthcare. This action plan is the result of a number of technical, legal and organisational requirements. It starts by establishing the functional components that are needed to set up a framework for the deployment of digital signatures. The main components should implement an infrastructure for: --the creation of digital signatures; --the verification of digital signatures; --the certification of signature keys; --the certification of attributes; --the handling of revocation. The tasks in the action plan are the logical consequence of all the functions that need to be addressed. The objective of this report is to list what has to be done and how it can be done in the context of healthcare, rather to state who will perform the functions required.

Belgium↗

[Religiousness of patients with diagnosis of schizophrenia. Wide-ranging studies].

AIMS: (1) The correlations between: (1.1) various aspects of religiousness and (1.2) age, anxiety-state, anxiety-trait, locus of control, and, in the group of patients with shizophrenia: span of treatment, rate of therapy, ego psychopathology, paranoid and depression dimensions, self-rating of state of self-feeling, state of feeling of illness, and quality of life and (2) the comparison of various aspects of religiousness of patients with schizophrenia and healthy people were studied. METHODS: The Scale of Christian Religiousness, Individual Religiousness Scale, Intrinsic, Extrinsic and Quest Religious Orientation Scales, Scale of Fundamentalism, State-Trait Anxiety Inventory, Rotter's questionnaire of locus of control, Scharfetter's questionnaire of ego psychopathology, Paranoid-Depresivity Scale-abridgment, Frankfurt Self-feeling Scale-abridgment, visual analogy of self-feeling, visual analogy of feeling of illness, and questionnaire of quality of life (WHOQOL-BREF) were used in the study. 91 adults both of sexes, 60 patients with a diagnosis of schizophrenia according to ICD-10 and DCR-10 in the diagnostic group and 31 healthy persons were studied. RESULTS: It was noticed that: (1) various correlations are manifested between religiousness and psychopathology of patients with schizophrenia; (2) patients diagnosed as having schizophrenia have a significantly higher level of extrinsic religiousness and fundamentalism than healthy individuals; (3) many results pointed out in the bibliography had no verification in these studies. CONCLUSIONS: Intrinsic, extrinsic, quest, and orthodox religiousness and fundamentalism realize significant functions in psychopathology of schizophrenia disorder. The knowledge about religiousness of schizophrenia patients can be important for diagnostic and therapeutic processes of the disorder.

Adult↗

[The relationship between the sympathetic nerves and immunocytes in the spleen].

Ever since Galen, the ancient Greek physician, said "Melancholic women develop disease more than sanguine women," it has been said that the mental condition affects the physical condition. However, there is hardly any scientific verification. About half a century ago, Selye (1936) proposed a relationship between stress and immune function, and it is becoming increasingly clear that the nervous system and immune system interact with each other. Also researchers have strongly hoped to demonstrate the existence of specific pathways by which immunocytes can be directly regulated by the nervous elements instead of by the humoral influence of immunomodulators. In this study, the author showed by electron microscopic observation how the immunocytes in the guinea pig spleen are directly innervated. The sustentacular supporting element of the guinea pig spleen is the connective tissue system which includes the capsulo-trabecular, peri-vascular and reticular systems. The latter system is composed of the outer sheath of the reticular cell or its cellular processes which have abundant microfilaments and the inner minute connective tissue space in which lamina densa-like material, collagenous fibrils, elastic fibers and nervous elements are present. The sympathetic adrenergic nerves for the spleen enter the organ, and scatter around the arterial walls. All components of the connective tissue system are continuous with each other, and the nervous elements appearing in the reticular system are the elongated ones from other connective tissue systems, especially peri-vascular connective tissue. Thus, the adrenergic nerves are more abundant in the white pulp, into which the central artery penetrates, than in the red pulp which arterioles or capillaries pass through. The minute connective tissue space of the reticular system may be called the noradrenalin (NA) canal because catecholamine released from the naked adrenergic nerve terminals in this tissue diffuses and is stored in this enclosed space. The reticular system in the spleen divides the parenchyma into small non-endothelial vascular spaces owing to its meshwork, and free mobile immunocytes, such as T-cells, B-cells and macrophages, stagnate in these spaces. This stagnation of the mobile immunocytes and the presence of the adrenergic nerves in the NA canals provide the chance for the immunocytes and nerves to meet each other in the following fashion; the reticular cell sheaths show the exposed phenomena owing to the contraction of the microfilament-rich reticular cell processes, caused by noradrenalin in the NA canal, and the nervous elements in the NA canals can face the nonendothelial vascular spaces where mobile immunocytes pass freely.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Comparison of acute alprazolam (0.25, 0.50 and 1.0 mg) effects versus those of lorazepam 2 mg and placebo on memory in healthy volunteers using laboratory and telephone tests.

This study was designed to confirm the hypothetical dose-dependent effect of alprazolam on memory and to compare its effects on tests measuring different aspects of cognitive and psychomotor functioning. A secondary purpose was to compare the sensitivity of newly developed telephone tests with a standard laboratory test of memory. Twenty healthy male volunteers (aged 18-35 years) participated in a five-way double-blind crossover design. Treatments were single oral doses of alprazolam (0.25, 0.5 and 1.0 mg), placebo and lorazepam 2.0 mg. The latter was included as an internal control for demonstrating sensitivity of the method. Lorazepam significantly impaired all performance measures except two: verbal fluency and accuracy of music recognition were insensitive to drug effects. Alprazolam had clear dose-dependent effects on different aspects of memory: 0.25 mg did not affect any parameter; 0.5 mg impaired performance in a Word Learning Test and a Spatial Memory Test and also psychomotor performance; 1.0 mg additionally impaired Syntactic Reasoning, Semantic Verification, and Critical Flicker Fusion performance. Alprazolam's effects were not selective for any of the cognitive functions as measured in this study. The telephone tests were clearly less sensitive than the standard test, though sufficient for showing significant effects of alprazolam 1 mg and lorazepam 2 mg.

Adolescent↗

Pediatric otolaryngological relations of velopharyngeal insufficiency.

On the basis of his examinations, the author presents data and gives his opinion on the classification, etiopathogenesis, diagnostics, phonosurgery, and therapy of the otological complications of velopharyngeal insufficiency (VPI). VPI may be organic or functional, produced by congenital or acquired causes, due to paresis or local disorders, but most frequently occurs as a result of cleft palate. Usually, diagnosis is evident; however, the verification of the milder cases of anatomic disproportion and/or muscular dysfunction is sometimes difficult. For the examination of dubious cases the author suggests, apart from the well-known methods (auditive evaluation, function tests, nasopharyngoscopy, velopharyngometry, supersound, X-ray, manometric measurements, speech intelligibility tests, acoustic analyses, etc.), electrophysiological and enzyme-histochemical measurements. Careful examination is most important, also on account of the possible indication of phonosurgery. An operation is to be proposed when a progressive neuro-myogenic process can thus be excluded, or when logopedic treatment is hopeless. The author has done 500 flap operations (as well as 2500 cleft palate and cleft lip ones) in the course of 30 years with a 98% result of anatomical healing. According to the pathological situation he employed 10 variants of the operation. As a result, hyperrhinophony ceased or became minimal in 90% of the cases; speech intelligibility was judged good or excellent in 74%. Functional effects can be influenced by the following: the width of the flap, the functional ability of the pharyngeal muscles, the cause of VPI, the patient's age, and the state of ears and hearing. In case of VPI otological and audiological examinations are routinely required. The author considers adenoidectomy and grommet-insertion to be alternative methods. One of the most important factors in achieving good results is teamwork, which the author discusses on the basis of the model developed at the Heim Pál Hospital for Sick Children, Budapest.

Adolescent↗

Taxol biosynthesis: molecular cloning of a benzoyl-CoA:taxane 2alpha-O-benzoyltransferase cDNA from taxus and functional expression in Escherichia coli.

A cDNA clone encoding a taxane 2alpha-O-benzoyltransferase has been isolated from Taxus cuspidata. The recombinant enzyme catalyzes the conversion of 2-debenzoyl-7,13-diacetylbaccatin III, a semisynthetic substrate, to 7,13-diacetylbaccatin III, and thus appears to function in a late-stage acylation step of the Taxol biosynthetic pathway. By employing a homology-based PCR cloning strategy for generating acyltransferase oligodeoxynucleotide probes, several gene fragments were amplified and used to screen a cDNA library constructed from mRNA isolated from methyl jasmonate-induced Taxus cells, from which several full-length acyltransferases were obtained and individually expressed in Escherichia coli. The functionally expressed benzoyltransferase was confirmed by radio-HPLC, (1)H-NMR, and combined HPLC-MS verification of the product, 7, 13-diacetylbaccatin III, derived from 2-debenzoyl-7, 13-diacetylbaccatin III and benzoyl-CoA as cosubstrates in the corresponding cell-free extract. The full-length cDNA has an open reading frame of 1,320 base pairs and encodes a protein of 440 residues with a molecular weight of 50,089. The recombinant benzoyltransferase has a pH optimum of 8.0, K(m) values of 0.64 mM and 0.30 mM for the taxoid substrate and benzoyl-CoA, respectively, and is apparently regiospecific for acylation of the 2alpha-hydroxyl group of the functionalized taxane nucleus. This enzyme may be used to improve the production yields of Taxol and for the semisynthesis of drug analogs bearing modified aroyl groups at the C2 position.

Acyltransferases↗

Computer verification of fluence map for intensity modulated radiation therapy.

In a treatment planning system for intensity modulated radiation therapy (IMRT), the time sequence of multileaf collimator (MLC) settings are derived from an optimal fluence map as a postoptimization process using a software module called a "leaf sequencer." The dosimetric accuracy of the dynamic delivery depends on the functionality of the module and it is important to verify independently the correctness of the leaf sequences for each field of a patient treatment. This verification is unique to the IMRT treatment and has been done using radiographic film, electronic portal imaging device (EPID) or electronic imaging system (BIS). The measurement tests both the leaf sequencer and the dynamic multileaf collimator (MLC) delivery system, providing a reliable assurance of clinical IMRT treatment. However, this process is labor intensive and time consuming. In this paper, we propose to separate quality assurance (QA) of the leaf sequencer from the dynamic MLC delivery system. We describe a simple computer algorithm for the verification of the leaf sequences. The software reads in the leaf sequences and simulates the motion of the MLC leaves. The generated fluence map is then compared quantitatively with the reference map from the treatment planning system. A set of pre-defined QA indices is introduced to measure the "closeness" between the computed and the reference maps. The approach has been used to validate the CORVUS (NOMOS Co., Sewickley, PA) treatment plans. The results indicate that the proposed approach is robust and suitable to support the complex IMRT QA process.

Algorithms↗

Pricing health services: verification of a monopoly pricing model for dentistry.

A model of monopoly with constant marginal costs is used to derive a price function for dental services. The implications of the model are tested using data on individual practitioners from a national survey. The implications of the model are met by the data, providing strong evidence of the appropriateness of the monopoly model to analyses of the market for dental services. The empirical evidence also provides substantial information on the determinants of dental fees.

Dentists↗

Intracranial neurosurgery guided by functional imaging.

Neurosurgery on eloquent cortex entails important risks of functional deficits complicating aggressive lesion resection. In this study, advanced biomagnetic functional imaging of somatosensory and motor cortex combined with surface rendered magnetic resonance imaging displays including vascular anatomy were used in conjunction with a new nonintrusive intraoperative guided instrumentation system to resect a tumor in eloquent cortex. Intraoperative verification of the accuracy of pre-operative motor localization demonstrated highly accurate results comparing direct stimulation and noninvasive presurgical mapping. The applicability of surface rendered combined functional and anatomic maps of cortex is directly evident on comparison of preoperative computer images and intraoperative pictures. This combination of new technologies has a significant potential for reduced risk and improved outcome in neurosurgery of eloquent cortex.

Brain Mapping↗