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After a long period of scepticism, more and more publications describe basic research but also practical approaches to howabstract data can be presented in immersive environments for effective and efficient data understanding. Central aspects of thisimportant research question in immersive analytics research are concerned with the use of 3D for visualization, the embeddingin the immersive space, the combination with spatial data, suitable interaction paradigms and the evaluation of use cases.We provide a characterization that facilitates the comparison and categorization of published works and present a survey ofpublications that gives an overview of the state of the art, current trends, and gaps and challenges in current research. published

The treatment of malignant tumors localized in the upper thoracic cavity and involving the spine at the cervico-thoracic junction (CTJ) is challenging. We report on three patients with malignant tumors invading the thoracic inlet and the spine at the CTJ. All three patients underwent radical tumor resection and 360° spine fusion following the posterior pedicle screw instrumentation and anterior vertebrectomy combined with implantation of an expandable titanium cage. Postoperatively, a mild paresis with hypesthesia of the ipsilateral arm occurred in one patient because of brachial plexus involvement. Two patients were still alive at last follow-up after 83 and 143 months, the third patient succumbed to tumor progression 13 months after extended salvage surgery. We display the possibilities of extended ‘salvage’ therapy in well-selected patients that were deemed hopeless regarding neurological function, biomechanical stability and tumor control after multiple courses of combined radio-chemotherapy.

The exploration of new materials has provided new insights into the progressive use of living biological materials in everyday designs. Living biological materials are expected to have the potential to overcome the depletion of non-renewable resources. Through bio-design and biophilic design in the urban environment, designers apply living systems as appropriate solutions to everyday designs. This paper aims to classify the biological materials and the sense of ownership towards biological materials embedded in products in terms of a) Function, b) Aesthetic and Semantic, and c) Emotion and Experience. A survey was conducted from 173 respondents through an online questionnaire. Keywords: biological materials; biophilic design; product designs; purposes and ownership eISSN: 2398-4287© 2020. The Authors. Published for AMER ABRA cE-Bs by e-International Publishing House, Ltd., UK. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer–review under responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians) and cE-Bs (Centre for Environment-Behaviour Studies), Faculty of Architecture, Planning & Surveying, Universiti Teknologi MARA, Malaysia. DOI: https://doi.org/10.21834/ebpj.v5i15.2479

Bioinformatics applies computer science approaches to the analysis of biological data. It is widely known for its genomics-based analysis approaches that have supported, for example, the 1000 Genomes Project. In addition, bioinformatics relates to many other areas, such as analysis of microscopic images (e.g., organelle localization), molecular modelling (e.g., proteins, biological membranes), and visualization of biological networks (e.g., protein–protein interaction networks, metabolism). Design is a highly interdisciplinary field that incorporates aspects such as aesthetic, economic, functional, philosophical, and/or socio-political considerations into the creative process and is usually determined by context. While visualization plays a critical role in bioinformatics, as reflected in a number of conferences and workshops in the field, design in bioinformatics-related research contexts in particular is not as well studied. With this special issue in conjunction with an international workshop, we aim to bring together bioinformaticians from different fields with designers, design researchers, and medical and scientific illustrators to discuss future challenges in the context of bioinformatics and design.

The reconstruction of frontobasal defects following oncologic resections of paranasal and anterior skull base malignancies remains challenging. Ineffective reconstruction could lead to cerebrospinal fluid leak, meningitis, and tension pneumocephalus. Aim of this investigation was to analyse postoperative complication rates with or without bone graft for anterior skull base reconstruction. In this retrospective study, we included patients following resection of paranasal and/or anterior skull base malignancies between October 2013 and November 2020. Complications were analysed with regards to the type of skull base reconstruction. Ten patients were identified (2 female, 8 male, age (median, SD) 65±14.8 years (range 38 – 81). There were eight cases of paranasal sinus and nasal cavity carcinomas and two cases of olfactory neuroblastomas. Overall survival was 20±25.1 months (range: 5-72), progression free survival was 17.0±20.3 months (range: 4-72). Bone skull base reconstruction using a split graft was performed in three cases. Postoperative complications requiring surgical intervention were seen in 33% (one tension pneumocephalus) of cases in the bone reconstruction group and 57% (three patients with cerebrospinal fluid leak, one infection) in the non-bone reconstruction group. Additional bone reconstruction of the anterior skull base seems to lower the CSF leakage rate due to the additional abutment following resection of paranasal and anterior skullbase malignancies.

This special issue of the Journal of Integrative Bioinformatics contains updated specifications of COMBINE standards in systems and synthetic biology. The 2021 special issue presents four updates of standards: Synthetic Biology Open Language Visual Version 2.3, Synthetic Biology Open Language Visual Version 3.0, Simulation Experiment Description Markup Language Level 1 Version 4, and OMEX Metadata specification Version 1.2. This document can also be consulted to identify the latest specifications of all COMBINE standards.

Purpose External beam radiotherapy (EBRT) is the predominant method for localized brain radiotherapy (LBRT) after resection of brain metastases (BM). Intraoperative radiotherapy (IORT) with 50kV x-rays is an alternative way to irradiate the resection cavity focally after BM surgery with the option to shorten the overall treatment time and limit normal tissue irradiation.Methods We retrospectively analyzed the outcomes of all patients who underwent neurosurgical resection of BM and 50kV x-ray IORT between 2013 and 2020 at Augsburg University Medical Center.Results We identified 40 patients with 44 resected BM treated with 50kV x-ray IORT. Median diameter of the resected metastases was 2.8 cm (range 1.5–5.9 cm). Median applied dose was 20 Gy. All patients received standardized follow-up (FU) including 3-monthly MRI of the brain. Mean FU was 14.4 months, with a median MRI FU for patients alive of 12.2 months. Median overall survival (OS) of all treated patients was 26.4 months (estimated 1-year OS 61.6%). The observed local control (LC) rate of the resection cavity was 88.6% (estimated 1-year LC 84.3%). Distant brain control (DC) was 47.5% (estimated 1-year DC 33.5%). Only 25% of all patients needed WBI in the further course of disease. The observed radionecrosis rate was 2.5%.Conclusion IORT with 50kV x-rays is a safe and appealing way to apply LBRT after neurosurgical resection of BM with low toxicity and excellent LC. Close MRI FU is paramount to detect distant brain failure (DBF) early.

Biophilia, biophilic design, bio-inspired and bio-design are design genres that adopted nature and biological elements as part of design processes. With the spread use of natural elements in design nowadays, from the analogical approach to the application of the biological materials in design brought up a different connotation towards the diverse use of nature in everyday life. This paper discusses the background knowledge of Biophilia, biophilic design, bio-inspired and bio-design and the application of biological materials in urban environments, especially for home. As part of a larger project on the application of biological materials in everyday products, this study investigates the emotional design and perception, while identifying the purposes of biological materials which incorporated into designs or systems. Data from 158 potential consumers were collected in an online survey specifically designed for this study, differentiating between design and non-design participants. Interesting findings are that more than 65% of non-design respondents are not aware of the terms biophilia and biophilic design, but they are familiar with the terms bio-inspired and bio-design. On the other hand, the potential consumers which are from non-design and design background as well agreed that having biological materials indoors, can a) help to release stress, b) create awareness of nature and ecological impact, c) can foster a sense of care, and d) can be educational.

This special issue of the Journal of Integrative Bioinformatics presents papers related to the 10th COMBINE meeting together with the annual update of COMBINE standards in systems and synthetic biology.

OBJECTIVEThere is no established method of noninvasive intracranial pressure (NI-ICP) monitoring that can serve as an alternative to the gold standards of invasive monitoring with external ventricular drainage or intraparenchymal monitoring. In this study a new method of NI-ICP monitoring performed using algorithms to determine ICP based on acoustic properties of the brain was applied in patients undergoing invasive ICP (I-ICP) monitoring, and the results were analyzed.METHODSIn patients with traumatic brain injury and subarachnoid hemorrhage who were undergoing treatment in a neurocritical intensive care unit, the authors recorded ICP using the gold standard method of invasive external ventricular drainage or intraparenchymal monitoring. In addition, the authors simultaneously measured the ICP noninvasively with a device (the HS-1000) that uses advanced signal analysis algorithms for acoustic signals propagating through the cranium. To assess the accuracy of the NI-ICP method, data obtained using both I-ICP and NI-ICP monitoring methods were analyzed with MATLAB to determine the statistical significance of the differences between the ICP measurements obtained using NI-ICP and I-ICP monitoring.RESULTSData were collected in 14 patients, yielding 2543 data points of continuous parallel ICP values in recordings obtained from I-ICP and NI-ICP. Each of the 2 methods yielded the same number of data points. For measurements at the ≥ 17–mm Hg cutoff, which was arbitrarily chosen for this preliminary analysis, the sensitivity and specificity for the NI-ICP monitoring were found to be 0.7541 and 0.8887, respectively. Linear regression analysis indicated that there was a strong positive relationship between the measurements. Differential pressure between NI-ICP and I-ICP was within ± 3 mm Hg in 63% of data-paired readings and within ± 5 mm Hg in 85% of data-paired readings. The receiver operating characteristic–area under the curve analysis revealed that the area under the curve was 0.895, corresponding to the overall performance of NI-ICP monitoring in comparison with I-ICP monitoring.CONCLUSIONSThis study provides the first clinical data on the accuracy of the HS-1000 NI-ICP monitor, which uses advanced signal analysis algorithms to evaluate properties of acoustic signals traveling through the brain in patients undergoing I-ICP monitoring. The findings of this study highlight the capability of this NI-ICP device to accurately measure ICP noninvasively. Further studies should focus on clinical validation for elevated ICP values.

Objective Tissue oxygen tension is an important parameter for brain tissue viability and its noninvasive intraoperative monitoring in the whole brain is of highly clinical relevance. The purpose of this study was the introduction of a multiparametric quantitative blood oxygenation dependent magnetic resonance imaging (MRI) approach for intraoperative examination of oxygen metabolism during the resection of brain lesions. Methods Sixteen patients suffering from brain lesions were examined intraoperatively twice (before craniotomy and after gross-total resection) via the quantitative blood oxygenation dependent technique and a 1.5-Tesla MRI scanner, which is installed in an operating room. The MRI protocol included T2*- and T2 mapping and dynamic susceptibility weighted perfusion. Data analysis was performed with a custom-made, in-house MatLab software for calculation of maps of oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) as well as of cerebral blood volume and cerebral blood flow. Results Perilesional edema showed a significant increase in both perfusion (cerebral blood volume +21%, cerebral blood flow +13%) and oxygen metabolism (OEF +32%, CMRO 2 +16%) after resection of the lesions. In perilesional nonedematous tissue only, however, oxygen metabolism (OEF +19%, CMRO 2 +11%) was significantly increased, but not perfusion. No changes were found in normal brain. Fortunately, no neurovascular adverse events were observed. Conclusions This approach for intraoperative examination of oxygen metabolism in the whole brain is a new application of intraoperative MRI additionally to resection control (residual tumor detection) and updating of neuronavigation (brain shift detection). It may help to detect neurovascular adverse events early during surgery.

For more than one decade, CELLmicrocosmos tools are being developed. Here, we discus some of the technical and administrative hurdles to keep a software suite running so many years. The tools were being developed during a number of student projects and theses, whereas main developers refactored and maintained the code over the years. The focus of this publication is laid on two Java-based Open Source Software frameworks. Firstly, the CellExplorer with the PathwayIntegration combines the mesoscopic and the functional level by mapping biological networks onto cell components using database integration. Secondly, the MembraneEditor enables users to generate membranes of different lipid and protein compositions using the PDB format. Technicalities will be discussed as well as the historical development of these tools with a special focus on group-based development. In this way, university-associated developers of Integrative Bioinformatics applications should be inspired to go similar ways. All tools discussed in this publication can be downloaded and installed from https://www.CELLmicrocosmos.org.

Objective Intrathecal (IT) opioid pumps are one therapeutic cornerstone of refractory nonmalignant pain syndromes. The aim of this study was to evaluate the efficacy of and surgical and pharmacological complications of IT pumps beyond a time span of 10 years. Methods In this retrospective single-center cohort study, 27 patients (14 female, 13 male, age 64.0 ± 8.9 [median, 1 SD] years) were identified. Pain intensity using the numeric rating scale (NRS), pain and IT pump characteristics, and complications were analyzed. The German Pain Questionnaire was used to investigate the physical and mental health status. Results Overall time of IT therapy from first implantation to last follow-up was 20.4 ± 6.0 years. Time to implantation of the second pump (n = 18) was 10.0 ± 5.3 years, and between the second and third pump (n = 6) 6.5 ± 2.7 years; 2 patients received their fourth pump 6 years later. The NRS score was 9.0 ± 0.9 before implantation, 7.0 ± 1.8 1 year after implantation, and 4.0 ± 2.3 at the last follow-up. IT drug dose remained stable after 3 years. Opioid intoxications occurred in 3 patients (10%). One patient (3%) underwent revision surgery due to a catheter infection. Drug side effects occurred in 4 patients (14%). Our patient group had pain-related restrictions in physical activities with menial impact regarding mental and emotional stress. Conclusion Even after a time span of over 15 years and several exchanges of pump systems, pain intensity was still reduced. After 3 years, IT drug dose remained unchanged with low side-effect and complication rates.

Understanding the movement of animals is important for a wide range of scientific interests including migration, disease spread, collective movement behaviour and analysing motion in relation to dynamic changes of the environment such as wind and thermal lifts. Particularly, the three-dimensional (3D) spatial–temporal nature of bird movement data, which is widely available with high temporal and spatial resolution at large volumes, presents a natural option to explore the potential of immersive analytics (IA). We investigate the requirements and benefits of a wide range of immersive environments for explorative visualization and analytics of 3D movement data, in particular regarding design considerations for such 3D immersive environments, and present prototypes for IA solutions. Tailored to biologists studying bird movement data, the immersive solutions enable geo-locational time-series data to be investigated interactively, thus enabling experts to visually explore interesting angles of a flock and its behaviour in the context of the environment. The 3D virtual world presents the audience with engaging and interactive content, allowing users to ‘fly with the flock’, with the potential to ascertain an intuitive overview of often complex datasets, and to provide the opportunity thereby to formulate and at least qualitatively assess hypotheses. This work also contributes to ongoing research efforts to promote better understanding of bird migration and the associated environmental factors at the global scale, thereby providing a visual vehicle for driving public awareness of environmental issues and bird migration patterns.

Objective. Resection remains the most important form of treatment for patients with intracranial malignancies. The advantages of surgical resection must be balanced with the risk of surgery. Intraoperative neuromonitoring (IOM) is utilized to improve safety and enlarge the resection extent. However, comparative data on the use if IOM is scarce. Methods. Retrospective analysis of patients following resection of motor eloquent lesions between June 2018 and June 2020 was performed. A comparative analysis of the extend of resection; neurological squeal were compared between resections with or without IOM. Results. 66 patients (31 female, 35 male, age median, SD 62+/− 11,2) were identified. IOM was performed in 34 (51%) cases. 46% were female with a median age of 62 (range 31–82). There were no differences in baseline patient“s characteristics between both groups. 14% and 3% had a temporary neurological deterioration in the IOM and non-IOM group (P = 0,198), respectively. 3% and 15% had a permanent neurological in the IOM and non-IOM group, respectively (P = 0.100). 65% and 35% of resections were total and subtotal in both the IOM and non-IOM group (P = 0.027), respectively. Conclusion. IOM is associated with lower rates of new postoperative neurological deterioration with the same rate resection quality following resection of motor eloquent lesions.

The CELLmicrocosmos 4.2 PathwayIntegration (CmPI) is a tool which provides hybrid-dimensional visualization and analysis of intracellular protein and gene localizations in the context of a virtual 3D environment. This tool is developed based on Java/Java3D/JOGL and provides a standalone application compatible to all relevant operating systems. However, it requires Java and the local installation of the software. Here we present the prototype of an alternative web-based visualization approach, using Three.js and D3.js. In this way it is possible to visualize and explore CmPI-generated localization scenarios including networks mapped to 3D cell components by just providing a URL to a collaboration partner. This publication describes the integration of the different technologies - Three.js, D3.js and PHP - as well as an application case: a localization scenario of the citrate cycle. The CmPI web viewer is available at: http://CmPIweb.CELLmicrocosmos.org., Journal of Integrative Bioinformatics - JIB

Objective Various complex techniques for depth electrode insertion in refractory epilepsy using preoperative imaging have been investigated. We evaluated a simple, accurate, cost-effective, and timesaving method using intraoperative magnetic resonance imaging (MRI). Methods A neuronavigation-guided insertion tube attached to bone facilitated the placement of stereotactic percutaneous drill holes, bolt implantation, and frameless stereotactic insertion of depth electrodes. Image registration was carried out by head coil fiducials with trajectory planning and intraoperative electrode correction. Results In 6 patients with refractory epilepsy (3 women and 3 men; mean age, 30.0 years; range, 20–37 years), 58 depth electrodes (9–11 per patient) were placed. The mean length of the inserted electrodes was 37.3 mm ± 8.8 (mean ± SD) (range, 22.1–84.4 mm). The overall target point accuracy was 3.2 mm ± 2.2 (range, 0–8.6 mm), which was significantly different from the overall entry point accuracy of 1.4 mm ± 1.2 ( P Conclusions Our frameless technique of depth electrode insertion using intraoperative MRI guidance is an accurate, reliable, cost-effective, and timesaving method for stereo-electroencephalography.

Standards are essential to the advancement of science and technology. In systems and synthetic biology, numerous standards and associated tools have been developed over the last 16 years. This special issue of the Journal of Integrative Bioinformatics aims to support the exchange, distribution and archiving of these standards, as well as to provide centralised and easily citable access to them., Journal of Integrative Bioinformatics - JIB

Stereoscopic photography has a long history which started just a few years after the first known photo was taken: 1849 Sir David Brewster introduced the first binocular camera. Whereas mobile photography is omnipresent because of the wide distribution of smart phones, stereoscopic photography is only used by a very small set of enthusiasts or professional (stereo) photographers. One important aspect of professional stereoscopic photography is that the required technology is usually quite expensive. Here, we present an alternative approach, uniting easily affordable vintage analogue SLR cameras with smart phone technology to measure and predict the stereo base/camera separation as well as the focal distance to zero parallax. For this purpose, the StereoCompass app was developed which is utilizing a number of smart phone sensors, combined with a Google Maps-based distance measure- ment. Three application cases including red/cyan anaglyph stereo photographs are shown. More information and the app can be found at: http://stereocompass.i2d.uk

Multidrug‐resistant Acinetobacter baumannii is a top‐priority pathogen globally and polymyxins are a last‐line therapy. Polymyxin dependence in A. baumannii (i.e., nonculturable on agar without polymyxins) is a unique and highly‐resistant phenotype with a significant potential to cause treatment failure in patients. The present study discovers that a polymyxin‐dependent A. baumannii strain possesses mutations in both lpxC (lipopolysaccharide biosynthesis) and katG (reactive oxygen species scavenging) genes. Correlative multiomics analyses show a significantly remodeled cell envelope and remarkably abundant phosphatidylglycerol in the outer membrane (OM). Molecular dynamics simulations and quantitative membrane lipidomics reveal that polymyxin‐dependent growth emerges only when the lipopolysaccharide‐deficient OM distinctively remodels with ≥ 35% phosphatidylglycerol, and with “patch” binding on the OM by the rigid polymyxin molecules containing strong intramolecular hydrogen bonding. Rather than damaging the OM, polymyxins bind to the phosphatidylglycerol‐rich OM and strengthen the membrane integrity, thereby protecting bacteria from external reactive oxygen species. Dependent growth is observed exclusively with polymyxin analogues, indicating a critical role of the specific amino acid sequence of polymyxins in forming unique structures for patch‐binding to bacterial OM. Polymyxin dependence is a novel antibiotic resistance mechanism and the current findings highlight the risk of ‘invisible’ polymyxin‐dependent isolates in the evolution of resistance., Herein, a mechanism of polymyxin‐dependent resistance in Acinetobacter baumannii is demonstrated. This unique dependence emerges only when i) the phosphatidylglycerol proportion in bacterial outer membrane increases to ≈35% and above, and ii) with ‘patch’ binding on the outer membrane by the rigid polymyxin molecules containing strong intramolecular hydrogen bonding, whereby polymyxin molecules enhance the membrane stability.

Chlamydomonas reinhardtii cells have been in the focus of research for more than a decade, in particular due to its use as alternative source for energy production. However, the molecular processes in these cells are still not completely known, and 3D visualisations may help to understand these complex interactions and processes. In previous work, we presented the stereoscopic 3D (S3D) visualisation of a complete Chlamydomonas reinhardtii cell created with the 3D modelling framework Blender. This animation contained already a scene showing an illustrative membrane model of the thylakoid membrane. During discussion with domain experts, shortcomings of the visualisation for several detailed analysis questions have been identified and it was decided to redefine it.A new modelling and visualisation pipeline based on a Membrane Packing Algorithm was developed, which can be configured via a user interface, enabling the composition of membranes employing published material. An expert user study was conducted to evaluate this new approach, with half the participants having a biology and the other half having an informatics background. The new and old Chlamydomonas thylakoid membrane models were presented on a S3D back projection system. The evaluation results reveal that the majority of participants preferred the new, more realistic membrane visualisation. However, the opinion varied with the expertise, leading to valuable conclusions for future visualisations. Interestingly, the S3D presentation of molecular structures lead to a positive change in opinion regarding S3D technology.

Although large-scale stereoscopic 3D environments like CAVEs are a favorable location for group presentations, the perspective projection and stereoscopic optimization usually follows a navigator-centric approach. Therefore, these presentations are usually accompanied by strong side-effects, such as motion sickness which is often caused by a disturbed stereoscopic vision. The reason is that the stereoscopic visualization is usually optimized for the only head-tracked person in the CAVE – the navigator – ignoring the needs of the real target group – the audience. To overcome this misconception, this work proposes an alternative to the head tracking-based stereoscopic effect optimization. By using an interactive virtual overview map in 3D, the pre-tour and on-tour configuration of the stereoscopic effect is provided, partly utilizing our previously published interactive projection plane approach. This Stereoscopic Space Map is visualized by the zSpace 200®, whereas the virtual world is shown on a panoramic 330° CAVE2TM. A pilot expert study with eight participants was conducted using pre-configured tours through 3D models. The comparison of the manual and automatic stereoscopic adjustment showed that the proposed approach is an appropriate alternative to the nowadays commonly used head tracking-based stereoscopic adjustment.

The incidence of epilepsy in older adults is growing, as does the incidence of comorbidities. Therefore, when it comes to epilepsy surgery in medically intractable epilepsy, age is often seen as a limiting factor. To investigate the outcome after epilepsy surgery in a population of older adults, we compared the benefit for patients aged 50-59 years with those aged 60 years and older in respect of efficacy and safety.Patients aged ≥50 years with medically intractable epilepsy who underwent epilepsy surgery from 1990 to 2013 were selected from the database of a German epilepsy center. All of them received a standardised and detailed presurgical diagnostic evaluation. Follow-up included at least four scheduled visits with EEG, MRI and neuropsychological testing. Outcome was assessed using the Engel outcome scale.79 patients aged between 50 and 67 years were followed-up for a median of 4.7 years (2-16 years). 68% of patients were free of disabling seizures (Engel class I, ≥60 years: 75%) and 58% were seizure-free (Engel class IA, ≥60 years: 70%). 90% of our patients suffered from temporal lobe epilepsy (TLE), 9% from frontal lobe epilepsy (FLE) and one occipital lobe epilepsy (OLE). After surgery, 9% discontinued or tapered their medication. Permanent surgical complications occurred in 10% of cases and transient neurological deficits were seen in 11%. Older patients had a higher risk for postoperative hygroma (≥60 years 15%; 60 years 8%) and were more prone to postoperative memory deficits (≥60 years 45%), especially after resection of the dominant temporal lobe. Verbal and figural memory testing did not differ significantly between the groups.The results support the view that in selected older patients, epilepsy surgery shows equal or even higher success rates as compared to younger patients. However, patients of older age may be at greater risk for postoperative hygroma and memory deficits, especially after dominant temporal lobe resections.

Focal cortical dysplasia (FCD) is one important cause of drug-resistant epilepsy potentially curable by epilepsy surgery. We investigated the options of using neuronavigation and intraoperative magnetic-resonance tomographical imaging (MRI) to avoid residual epileptogenic tissue during resection of patients with FCD II to improve seizure outcome.Altogether, 24 patients with FCD II diagnosed by MRI (16 female, 8 male; mean age 34 ± 10 years) suffered from drug-resistant electroclinical and focal epilepsy for a mean of 20.7 ± 5 years. Surgery was performed with preoperative stereoelectroencephalography (in 15 patients), neuronavigation, and intraoperative 1.5T-iopMRI in all 24 investigated patients.In 75% of patients (18/24), a complete resection was performed. In 89% (16/18) of completely resected patients, we documented an Engel I seizure outcome after a mean follow-up of 42 months. All incompletely resected patients had a worse outcome (Engel II-III, P0.0002). Patients with FCD IIB had also significant better seizure outcome compared with patients diagnosed as having FCD IIA (82% vs. 28%, P0.02). In 46% (11/24) of patients, intraoperative second-look surgeries due to residual lesions detected during the intraoperative MRI were performed. In these 11 patients, there were significant more completely seizure free patients (73% vs. 38% Engel IA), compared with 13 patients who finished surgery after the first intraoperative MRI (P0.05).Excellent seizure outcome after surgery of patients with FCD II positively correlated with the amount of resection, histologic subtype, and the use of intraoperative MRI, especially when intraoperative second-look surgeries were performed.

Background Intraoperative monitoring of cerebral microcirculation in patients with subarachnoid hemorrhage (SAH) may predict the postoperative neurologic outcome. In this pilot study, we examined the value of a novel noninvasive real-time measurement technique for detecting changes in local microcirculation. Methods We used the O2C (Oxygen to see) laser-Doppler spectrophotometry system in 14 patients with Hunt & Hess grade 2–5 SAH who underwent microsurgical cerebral aneurysm clipping. A subdural probe recorded capillary venous oxygenation (SO2), relative hemoglobin concentration, blood cell velocity, and blood flow at a tissue depth of 7 mm. Data were recorded immediately before dural closure. We also recorded somatosensory evoked potentials (SEPs) with median and tibial nerve stimulation. Results were compared with neurologic performance, as measured on the modified Rankin Scale, at the day of discharge from the hospital and 12 months thereafter. Results Patient functional outcomes after discharge and 12 months were correlated with pathological decreased flow and increased SO2 values. In 6 of 8 patients, microcirculatory monitoring parameters indicated ischemia during surgery, as shown by electrophysiological SEP changes and infarction detected on the postoperative computed tomography (CT) scan. Pathological SEP results correlated closely with infarct demarcation as seen on CT. Conclusions Our results indicate the potential benefit of intraoperative combined laser-Doppler flowmetry and spectrophotometry for predicting postoperative clinical outcomes in this small patient sample. Larger-cohort testing is needed to verify our findings and show the possible merits of this novel method.

Design Engineering is an innovative field that usually combines a number of disciplines, such as material science, mechanics, electronics, and/or biochemistry, etc. New immersive technologies, such as Virtual Reality (VR) and Augmented Reality (AR), are currently in the process of being widely adapted in various engineering fields. It is a proven fact that the modeling of spatial structures is supported by immersive exploration. But the field of Design Engineering reaches beyond standard engineering tasks. With this review paper we want to achieve the following: define the term “Immersive Design Engineering”, discuss a number of recent immersive technologies in this context, and provide an inspiring overview of work that belongs to, or is related to the field of Immersive Design Engineering. Finally, the paper concludes with definitions of research questions as well as a number of suggestions for future developments.

This work presents DaTo, a semi-automatically generated world atlas of biological databases and tools. It extracts raw information from all PubMed articles which contain exact URLs in their abstract section, followed by a manual curation of the abstract and the URL accessibility. DaTo features a user-friendly query interface, providing extensible URL-related annotations, such as the status, the location and the country of the URL. A graphical interaction network browser has also been integrated into the DaTo web interface to facilitate exploration of the relationship between different tools and databases with respect to their ontology-based semantic similarity. Using DaTo, the geographical locations, the health statuses, as well as the journal associations were evaluated with respect to the historical development of bioinformatics tools and databases over the last 20 years. We hope it will inspire the biological community to gain a systematic insight into bioinformatics resources. DaTo is accessible via http://bis.zju.edu.cn/DaTo/., Journal of Integrative Bioinformatics - JIB

Background Monitoring of cortical cerebral perfusion is essential, especially in neurovascular surgery. Study Aims To test a novel noninvasive laser-Doppler flowmetry and spectrophotometry device for feasibility during elective cerebral aneurysm surgery. Material and Methods In this prospective single-institution nonrandomized trial, we studied local cerebral microcirculation using the noninvasive laser-Doppler spectrophotometer "Oxygen-to-see" (O2C) in 20 consecutive patients (15 female, 5 male; median age: 60.5 ± 11.7 years) who were operated on for incidental cerebral aneurysms. Capillary-venous oxygenation (oxygen saturation ["SO2"]), postcapillary venous filling pressures (relative hemoglobin content ["rHb"]), blood cell velocity ("velo"), and blood flow ("flow") were measured in 7-mm tissue depth using a subdural fiberoptic probe. Results Representative recordings were acquired immediately after dural opening over a median time span of 88 ± 21.8 seconds (range: 60-128 seconds) before surgical manipulation. Baseline values (median ± 2 standard deviations) of brain perfusion as measured with the O2C device were SO2, 39 ± 16.6%; rHb, 53 ± 18.6 arbitrary units (AU); velo, 60 ± 20.4 AU; and flow, 311 ± 72.8 AU. Placement of the self-retaining retractor led to a decrease in SO2 of 17% ± 29% (p

published

Background Especially in hidden lesions causing drug-resistant frontal lobe epilepsy (FLE), the localization of the epileptic zone EZ can be a challenge. Magnetoencephalography (MEG) can raise the chances for localization of the (EZ) in combination with electroencephalography (EEG). We investigated the impact of MEG-guided epilepsy surgery with the aid of neuronavigation and intraoperative MR imaging (iopMRI) on seizure outcome of FLE patients. Methods Twenty-eight patients (15 females, 13 males; mean age 31.0 ± 11.1 years) underwent surgery in our department. All patients underwent presurgical MEG monitoring (two-sensor Magnes II or whole head WH3600 MEG system; 4-D Neuroimaging, San Diego, CA, USA). Of those, six patients (group 1) with MRI-negative FLE were operated on before 2002 with intraoperative electrocorticography (ECoG) and invasive EEG mapping only. Eleven patients with MRI-negative FLE (group 2) and eleven with lesional FLE (group 3) underwent surgery using 1.5 T-iopMRI and neuronavigation, including intraoperative visualization of the MEG localizations in 22 and functional MR imaging (for motor and speech areas) as well as DTI fiber tracking (for language and pyramidal tracts) in 13 patients. Results In the first group, complete resection of the defined EZ including the MEG localization according to the latest postoperative MRI was achieved in four out of six patients. Groups two and three had complete removal of the MEG localizations in 20/22 (91%, 10 of 11 each). Intraoperative MRI revealed incomplete resection of the MEG localizations of four patients (12%; two in both groups), leading to successful re-resection. Transient and permanent neurological deficits alike occurred in 7.1%, surgery-associated complications in 11% of all patients. In the first group, excellent seizure outcome (Engel Class IA) was achieved in three (50%), in the second in 7 patients (61%) and third group in 8 patients (64%, two iopMRI-based re-resections). Mean follow-up was 70.3 months (from 12 to 284 months). Conclusion In our series, MEG-guided resection using neuronavigation and iopMR imaging led to promising seizure control rates. Even in non-lesional FLE, seizure control rates and the probability of complete resection of the MEG localizations was similar to lesional FLE using multimodal navigation.

The integration of 2D visualization and navigation techniques has reached a state where the potential for improvements is relatively low. With 3D-stereoscopy-compatible technology now commonplace not only in research but also in many households, the need for better 3D visualization and navigation techniques has increased. Nevertheless, for the representation of many abstract data such as networks, 2D visualization remains the primary choice. But often such abstract data is associated with spatial data, thereby increasing the need for combining both 2D and 3D visualization and navigation techniques. Here, we discuss a new hybrid-dimensional approach integrating 2D and 3D (stereoscopic) visualization as well as navigation into a semi-immersive virtual environment. This approach is compared to classical 6DOF navigation techniques. Three scientific as well as educational applications are presented: an educational car model, a plant simulation data exploration, and a cellular model with network exploration, each of these combining spatial with associated abstract data. The software is available at: http://Cm4.CELLmicrocosmos.org

BACKGROUND We investigated mechanical pull-out behavior and tightening torque of a novel dual-core pedicle "6T screw" (6T). The aim of this study was to test if these changes in screw geometry are increasing the strength of the pedicle screw fixation after repeated insertion. METHODS Three different types of pedicle screws were inserted in rigid foam blocks. Tightening torque and pull-out strength were measured during two repetitive insertions of a standard 6.5×45-mm conical screw. The third insertion into the pilot hole was performed using either standard 6.5×45-mm or 7.2×45-mm conical screws or the novel 6.5×45-mm (6T) screw. Additionally, we performed a surface analysis to investigate the bone/screw interface. RESULTS The maximal tightening torque at the third insertion of the novel 6T screw was 194% higher compared to the standard 6.5×45-mm conical screw and 135% higher compared to the standard 7.2×45-mm conical screw. The pull-out strength of the 6T screw showed no significant changes, and surface analysis revealed a compression of the screw-foam interface due to the different internal diameters. CONCLUSIONS The modified geometrical design of the 6T screw seems to have no statistically significant effect on the pull-out strength, although it achieved a higher tightening torque. This might be due to the different pitch angle cutting a new thread into the material and also to the enlarged inner diameter.

Despite advances in multimodal treatments, malignant gliomas remain characterized by a short survival time. Surgical treatment is accepted to be the first line of therapy, with recent studies revealing that maximal possible tumor reduction exerts significant impact on patient outcome. Consideration of tumor localization in relation to functionally eloquent brain areas has been gaining increasing importance. Despite existing assessment methods, the availability of a simple but reliable preoperative grading based on functional data would therefore prove to be indispensable for the prediction of postoperative outcome and hence for overall survival in glioma patients. We performed a clinical investigation comprising 322 patients with gliomas and developed a novel classification system of preoperative tumor status, which considers tumor operability based on two graduations (Friedlein Grading - FG): FGA with lesions at safe distance to eloquent regions which can be completely resected and FGB referring to tumors which can only be partially resected or biopsied. Investigation of outcome revealed that FGA were characterized by a significantly longer overall survival time compared to FGB. We offer the opportunity to classify brain tumors in a dependable and reproducible manner. The FGA/B grading method provides high prognostic value with respect to overall survival time in relation to the extent of location-dependent tumor resection.

OBJECT Cerebral gangliogliomas (GGs) are highly associated with intractable epilepsy. Incomplete resection due to proximity to eloquent brain regions or misinterpretation of the resection amount is a strong negative predictor for local tumor recurrence and persisting seizures. A potential method for dealing with this obstacle could be the application of intraoperative high-field MRI (iopMRI) combined with neuronavigation. METHODS Sixty-nine patients (31 female, 38 male; median age 28.5 ± 15.4 years) suffering from cerebral GGs were included in this retrospective study. Five patients received surgery twice in the observation period. In 48 of the 69 patients, 1.5-T iopMRI combined with neuronavigational guidance was used. Lesions close to eloquent brain areas were resected with the implementation of preoperative diffusion tensor imaging tractography and blood oxygenation level–dependent functional MRI (15 patients). RESULTS Overall, complete resection was accomplished in 60 of 69 surgical procedures (87%). Two patients underwent biopsy only, and in 7 patients, subtotal resection was accomplished because of proximity to critical brain areas. Excluding the 2 biopsies, complete resection using neuronavigation/iopMRI was documented in 33 of 46 cases (72%) by intraoperative imaging. Remnant tumor mass was identified intraoperatively in 13 of 46 patients (28%). After intraoperative second-look surgery, the authors improved the total resection rate by 9 patients (up to 91% [42 of 46]). Of 21 patients undergoing conventional surgery, 14 (67%) had complete resection without the use of iopMRI. Regarding epilepsy outcome, 42 of 60 patients with seizures (70%) became completely seizure free (Engel Class IA) after a median follow-up time of 55.5 ± 36.2 months. Neurological deficits were found temporarily in 1 (1.4%) patient and permanently in 4 (5.8%) patients. CONCLUSIONS Using iopMRI combined with neuronavigation in cerebral GG surgery, the authors raised the rate of complete resection in this series by 19%. Given the fact that total resection is a strong predictor of long-term seizure control, this technique may contribute to improved seizure outcome and reduced neurological morbidity.

Object The authors performed a retrospective study to assess the impact of functional neuronavigation and intraoperative MRI (iMRI) on surgery of extratemporal epileptogenic lesions on postsurgical morbidity and seizure control. Methods Twenty-five patients (14 females and 11 males) underwent extratemporal resections for drug-resistant epilepsy close to speech/motor brain areas or adjacent to white matter tracts. The mean age at surgery was 34 years (range 12–67 years). The preoperative mean disease duration was 13.2 years. To avoid awake craniotomy, cortical motor-sensory representation was mapped during preoperative evaluation in 14 patients and speech representation was mapped in 15 patients using functional MRI. In addition, visualization of the pyramidal tract was performed in 11 patients, of the arcuate fascicle in 7 patients, and of the visual tract in 6 patients using diffusion tensor imaging. The mean minimum distance of tailored resection between the eloquent brain areas was 5.6 mm. During surgery, blood oxygen level–dependent imaging and diffusion tensor imaging data were integrated into neuronavigation and displayed through the operating microscope. The postoperative mean follow-up was 44.2 months. Results In 20% of these patients, further intraoperative resection was performed because of intraoperatively documented residual lesions according to iMRI findings. At the end of resection, the final iMRI scans confirmed achievement of total resection of the putative epileptogenic lesion in all patients. Postoperatively, transient complications and permanent complications were observed in 20% and 12% of patients, respectively. Favorable postoperative seizure control (Engel Classes I and II) was achieved in 84% and seizure freedom in 72% of these consecutive surgical patients. Conclusions By using functional neuronavigation and iMRI for treatment of epileptogenic brain lesions, the authors achieved a maximum extent of resection despite the lesions' proximity to eloquent brain cortex and fiber tracts in all cases. The authors' results underline possible benefits of this technique leading to a favorable seizure outcome with acceptable neurological deficit rates in difficult-to-treat extratemporal epilepsy.

The CELLmicrocosmos PathwayIntegration (CmPI) was developed to support and visualize the subcellular localization prediction of protein-related data such as protein-interaction networks. From the start it was possible to manually analyze the localizations by using an interactive table. It was, however, quite complicated to compare and analyze the different localization results derived from data integration as well as text-mining-based databases. The current software release provides a new interactive visual workflow, the Subcellular Localization Charts. As an application case, a MUPP1-related protein-protein interaction network is localized and semi-automatically analyzed. It will be shown that the workflow was dramatically improved and simplified. In addition, it is now possible to use custom protein-related data by using the SBML format and get a view of predicted protein localizations mapped onto a virtual cell model.

POEMS syndrome includes the clinical features of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. A severe complication of patients with this syndrome is ischemic stroke, which has been described only occasionally despite the hematologic abnormalities that may be associated with the disease. In the literature, only eight patients have been reported as suffering from multiple or recurrent strokes until now. We present a 54-year-old woman from Sri Lanka with POEMS syndrome who experienced recurrent ischemic strokes followed by an acute abdomen and global heart failure. On the basis of a literature review, we discuss current therapeutic approaches and their possible side effects.