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Prostaglandin-endoperoxide synthase-2 ( PTGS2 ) plays a pivotal role in inflammation and carcinogenesis in human breast cancer. Our aim of the study is to find the prognostic value of PTGS2 in breast cancer. We conducted a multiomic analysis to determine whether PTGS2 functions as a prognostic biomarker in human breast cancer. We explored PTGS2 mRNA expressions using different public bioinformatics portals. Oncomine, Serial Analysis of Gene Expression (SAGE), GEPIA, ULCAN, PrognoScan database, Kaplan-Meier Plotter, bc-GenExMiner, USC XENA, and Cytoscape/STRING DB were used to identify the prognostic roles of PTGS2 in breast cancer. Based on the clinicopathological analysis, decreased PTGS2 expressions correlated positively with older age, lymph node status, the human epidermal growth factor receptor 2 (HER2) status ( P

The objective of this prospective study was to evaluate whether magnetic resonance imaging (MRI) is equivalent to lateral cephalometric radiographs (LCR, "gold standard") in cephalometric analysis.The applied MRI technique was optimized for short scanning time, high resolution, high contrast and geometric accuracy. Prior to orthodontic treatment, 20 patients (mean age ± SD, 13.95 years ± 5.34) received MRI and LCR. MRI datasets were postprocessed into lateral cephalograms. Cephalometric analysis was performed twice by two independent observers for both modalities with an interval of 4 weeks. Eight bilateral and 10 midsagittal landmarks were identified, and 24 widely used measurements (14 angles, 10 distances) were calculated. Statistical analysis was performed by using intraclass correlation coefficient (ICC), Bland-Altman analysis and two one-sided tests (TOST) within the predefined equivalence margin of ± 2°/mm.Geometric accuracy of the MRI technique was confirmed by phantom measurements. Mean intraobserver ICC were 0.977/0.975 for MRI and 0.975/0.961 for LCR. Average interobserver ICC were 0.980 for MRI and 0.929 for LCR. Bland-Altman analysis showed high levels of agreement between the two modalities, bias range (mean ± SD) was -0.66 to 0.61 mm (0.06 ± 0.44) for distances and -1.33 to 1.14° (0.06 ± 0.71) for angles. Except for the interincisal angle (p = 0.17) all measurements were statistically equivalent (p < 0.05).This study demonstrates feasibility of orthodontic treatment planning without radiation exposure based on MRI. High-resolution isotropic MRI datasets can be transformed into lateral cephalograms allowing reliable measurements as applied in orthodontic routine with high concordance to the corresponding measurements on LCR.

Pandemic and seasonal influenza viruses cause considerable morbidity and mortality in the general human population. Protection from severe disease may result from vaccines that activate antigen-presenting DC for effective stimulation of influenza-specific memory T cells. Special attention is paid to vaccine-induced CD8+ T-cell responses, because they are mainly directed against conserved internal influenza proteins thereby presumably mediating cross-protection against circulating seasonal as well as emerging pandemic virus strains. Our study showed that influenza whole virus vaccines of major seasonal A and B strains activated DC more efficiently than those of pandemic swine-origin H1N1 and pandemic-like avian H5N1 strains. In contrast, influenza split virus vaccines had a low ability to activate DC, regardless which strain was investigated. We also observed that whole virus vaccines stimulated virus-specific CD8+ memory T cells much stronger compared to split virus counterparts, whereas both vaccine formats activated CD4+ Th cell responses similarly. Moreover, our data showed that whole virus vaccine material is delivered into the cytosolic pathway of DC for effective activation of virus-specific CD8+ T cells. We conclude that vaccines against seasonal and pandemic (-like) influenza strains that aim to stimulate cross-reacting CD8+ T cells should include whole virus rather than split virus formulations.

ObjectiveClinical assessment of consciousness relies on behavioural assessments, which have several limitations. Hence, disorder of consciousness (DOC) patients are often misdiagnosed. In this work, we aimed to compare the repetitive assessment of consciousness performed with a clinical behavioural and a Brain-Computer Interface (BCI) approach.Materials and methodsFor 7 weeks, sixteen DOC patients participated in weekly evaluations using both the Coma Recovery Scale-Revised (CRS-R) and a vibrotactile P300 BCI paradigm. To use the BCI, patients had to perform an active mental task that required detecting specific stimuli while ignoring other stimuli. We analysed the reliability and the efficacy in the detection of command following resulting from the two methodologies.ResultsOver repetitive administrations, the BCI paradigm detected command following before the CRS-R in seven patients. Four clinically unresponsive patients consistently showed command following during the BCI assessments.ConclusionBrain-Computer Interface active paradigms might contribute to the evaluation of the level of consciousness, increasing the diagnostic precision of the clinical bedside approach.SignificanceThe integration of different diagnostic methods leads to a better knowledge and care for the DOC.

Persons diagnosed with disorders of consciousness (DOC) typically suffer from motor and cognitive disabilities. Recent research has shown that non-invasive brain-computer interface (BCI) technology could help assess these patients’ cognitive functions and command following abilities. 20 DOC patients participated in the study and performed 10 vibro-tactile P300 BCI sessions over 10 days with 8–12 runs each day. Vibrotactile tactors were placed on the each patient’s left and right wrists and one foot. Patients were instructed, via earbuds, to concentrate and silently count vibrotactile pulses on either their left or right wrist that presented a target stimulus and to ignore the others. Changes of the BCI classification accuracy were investigated over the 10 days. In addition, the Coma Recovery Scale-Revised (CRS-R) score was measured before and after the 10 vibro-tactile P300 sessions. In the first run, 10 patients had a classification accuracy above chance level (>12.5%). In the best run, every patient reached an accuracy ≥60%. The grand average accuracy in the first session for all patients was 40%. In the best session, the grand average accuracy was 88% and the median accuracy across all sessions was 21%. The CRS-R scores compared before and after 10 VT3 sessions for all 20 patients, are showing significant improvement (p = 0.024). Twelve of the twenty patients showed an improvement of 1 to 7 points in the CRS-R score after the VT3 BCI sessions (mean: 2.6). Six patients did not show a change of the CRS-R and two patients showed a decline in the score by 1 point. Every patient achieved at least 60% accuracy at least once, which indicates successful command following. This shows the importance of repeated measures when DOC patients are assessed. The improvement of the CRS-R score after the 10 VT3 sessions is an important issue for future experiments to test the possible therapeutic applications of vibro-tactile and related BCIs with a larger patient group.

In circuit motorsport, race strategy helps to finish the race in the best possible position by optimally determining the pit stops. Depending on the racing series, pit stops are needed to replace worn-out tires, refuel the car, change drivers, or repair the car. Assuming a race without opponents and considering only tire degradation, the optimal race strategy can be determined by solving a quadratic optimization problem, as shown in the paper. In high-class motorsport, however, this simplified approach is not sufficient. There, comprehensive race simulations are used to evaluate the outcome of different strategic options. The published race simulations require the user to specify the expected strategies of all race participants manually. In such simulations, it is therefore desirable to automate the strategy decisions, for better handling and greater realism. It is against this background that we present a virtual strategy engineer (VSE) based on two artificial neural networks. Since our research is focused on the Formula 1 racing series, the VSE decides whether a driver should make a pit stop and which tire compound to fit. Its training is based on timing data of the six seasons from 2014 to 2019. The results show that the VSE makes reasonable decisions and reacts to the particular race situation. The integration of the VSE into a race simulation is presented, and the effects are analyzed in an example race.

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Applying an optimal race strategy is a decisive factor in achieving the best possible result in a motorsport race. This mainly implies timing the pit stops perfectly and choosing the optimal tire compounds. Strategy engineers use race simulations to assess the effects of different strategic decisions (e.g., early vs. late pit stop) on the race result before and during a race. However, in reality, races rarely run as planned and are often decided by random events, for example, accidents that cause safety car phases. Besides, the course of a race is affected by many smaller probabilistic influences, for example, variability in the lap times. Consequently, these events and influences should be modeled within the race simulation if real races are to be simulated, and a robust race strategy is to be determined. Therefore, this paper presents how state of the art and new approaches can be combined to modeling the most important probabilistic influences on motorsport races—accidents and failures, full course yellow and safety car phases, the drivers’ starting performance, and variability in lap times and pit stop durations. The modeling is done using customized probability distributions as well as a novel “ghost” car approach, which allows the realistic consideration of the effect of safety cars within the race simulation. The interaction of all influences is evaluated based on the Monte Carlo method. The results demonstrate the validity of the models and show how Monte Carlo simulation enables assessing the robustness of race strategies. Knowing the robustness improves the basis for a reasonable determination of race strategies by strategy engineers.

Patients with locked-in syndrome (LIS) are typically unable to move or communicate and can be misdiagnosed as patients with disorders of consciousness (DOC). Behavioral assessment scales are limited in their ability to detect signs of consciousness in this population. Recent research has shown that brain-computer interface (BCI) technology could supplement behavioral scales and allows to establish communication with these severely disabled patients. In this study, we compared the vibro-tactile P300 based BCI performance in two groups of patients with LIS of different etiologies: stroke (n = 6) and amyotrophic lateral sclerosis (ALS) (n = 9). Two vibro-tactile paradigms were administered to the patients to assess conscious function and command following. The first paradigm is called vibrotactile evoked potentials (EPs) with two tactors (VT2), where two stimulators were placed on the patient’s left and right wrist, respectively. The patients were asked to count the rare stimuli presented to one wrist to elicit a P300 complex to target stimuli only. In the second paradigm, namely vibrotactile EPs with three tactors (VT3), two stimulators were placed on the wrists as done in VT2, and one additional stimulator was placed on his/her back. The task was to count the rare stimuli presented to one wrist, to elicit the event-related potentials (ERPs). The VT3 paradigm could also be used for communication. For this purpose, the patient had to count the stimuli presented to the left hand to answer “yes” and to count the stimuli presented to the right hand to answer “no.” All patients except one performed above chance level in at least one run in the VT2 paradigm. In the VT3 paradigm, all 6 stroke patients and 8/9 ALS patients showed at least one run above chance. Overall, patients achieved higher accuracies in VT2 than VT3. LIS patients due to ALS exhibited higher accuracies that LIS patients due to stroke, in both the VT2 and VT3 paradigms. These initial data suggest that controlling this type of BCI requires specific cognitive abilities that may be impaired in certain sub-groups of severely motor-impaired patients. Future studies on a larger cohort of patients are needed to better identify and understand the underlying cortical mechanisms of these differences.

Persons diagnosed with disorders of consciousness (DOC) typically suffer from motor disablities, and thus assessing their spared cognitive abilities can be difficult. Recent research from several groups has shown that non-invasive brain-computer interface (BCI) technology can provide assessments of these patients' cognitive function that can supplement information provided through conventional behavioral assessment methods. In rare cases, BCIs may provide a binary communication mechanism. Here, we present results from a vibrotactile BCI assessment aiming at detecting command-following and communication in 12 unresponsive wakefulness syndrome (UWS) patients. Two different paradigms were administered at least once for every patient: (i) VT2 with two vibro-tactile stimulators fixed on the patient's left and right wrists and (ii) VT3 with three vibro-tactile stimulators fixed on both wrists and on the back. The patients were instructed to mentally count either the stimuli on the left or right wrist, which may elicit a robust P300 for the target wrist only. The EEG data from −100 to +600 ms around each stimulus were extracted and sub-divided into 8 data segments. This data was classified with linear discriminant analysis (using a 10 × 10 cross validation) and used to calibrate a BCI to assess command following and YES/NO communication abilities. The grand average VT2 accuracy across all patients was 38.3%, and the VT3 accuracy was 26.3%. Two patients achieved VT3 accuracy ≥80% and went through communication testing. One of these patients answered 4 out of 5 questions correctly in session 1, whereas the other patient answered 6/10 and 7/10 questions correctly in sessions 2 and 4. In 6 other patients, the VT2 or VT3 accuracy was above the significance threshold of 23% for at least one run, while in 4 patients, the accuracy was always below this threshold. The study highlights the importance of repeating EEG assessments to increase the chance of detecting command-following in patients with severe brain injury. Furthermore, the study shows that BCI technology can test command following in chronic UWS patients and can allow some of these patients to answer YES/NO questions.

Many patients with locked-in syndrome (LIS) or complete locked-in syndrome (CLIS) also need brain-computer interface (BCI) platforms that do not rely on visual stimuli and are easy to use. We investigate command following and communication functions of mindBEAGLE with 9 LIS, 3 CLIS patients and three healthy controls. This tests were done with vibro-tactile stimulation with 2 or 3 stimulators (VT2 and VT3 mode) and with motor imagery (MI) paradigms. In VT2 the stimulators are fixed on the left and right wrist and the participant has the task to count the stimuli on the target hand in order to elicit a P300 response. In VT3 mode an additional stimulator is placed as a distractor on the shoulder and the participant is counting stimuli either on the right or left hand. In motor imagery mode the participant is instructed to imagine left or right hand movement. VT3 and MI also allow the participant to answer yes and no questions. Healthy controls achieved a mean assessment accuracy of 100% in VT2, 93% in VT3, and 73% in MI modes. They were able to communicate with VT3 (86.7%) and MI (83.3%) after 2 training runs. The patients achieved a mean accuracy of 76.6% in VT2, 63.1% in VT3, and 58.2% in MI modes after 1–2 training runs. 9 out of 12 LIS patients could communicate by using the vibro-tactile P300 paradigms (answered on average 8 out of 10 questions correctly) and 3 out of 12 could communicate with the motor imagery paradigm (answered correctly 4,7 out of 5 questions). 2 out of the 3 CLIS patients could use the system to communicate with VT3 (90 and 70% accuracy). The results show that paradigms based on non-visual evoked potentials and motor imagery can be effective for these users. It is also the first study that showed EEG-based BCI communication with CLIS patients and was able to bring 9 out of 12 patients to communicate with higher accuracies than reported before. More importantly this was achieved within less than 15–20 min.