Developing New Image Registration Techniques and 3D Displays for Neuroimaging and Neurosurgery

poster abstractImage guided surgery requires that the pre-operative data used for planning the surgery should be aligned with the patient during surgery. For this surgical application a fast, effective volume registration algorithm is needed. In addition, such an algorithm can also be used to develop surgical training presentations. This research extends existing methods and techniques to improve convergence and speed of execution. The aim is to find the most promising speed improvements while maintaining accuracy to best fit the neurosurgery application. In the recent phase, we focus on algorithm speed up by translating the registration algorithm from Matlab into Java. Medical image volumes acquired fromMRI scans and a depth map from the video data provided by Indiana University School of Medicine were used as testing images. Accuracy of the results from the translated algorithm is compared against the ground truth evaluated with mean squared error metrics. Algorithm execution time with and without the code translation is measured on standard personal computer (PC) hardware. The 3D registered model is developed by the Informatics students to show the results of the speed improvements from the remaining students’ work. Additionally, the surgical and preoperative data overlay will be presented in a 3D movie. Our past testing indicates that an intelligent subset of the data points that are needed for registration improved the speed significantly but was still time taking. Preliminary results show that even though image registration in real-time is a challenging task for real time neurosurgery applications, intelligent preprocessing provides a promising solution. Final results will be available at poster presentation

Protein subcellular localization prediction based on compartment-specific features and structure conservation

BACKGROUND: Protein subcellular localization is crucial for genome annotation, protein function prediction, and drug discovery. Determination of subcellular localization using experimental approaches is time-consuming; thus, computational approaches become highly desirable. Extensive studies of localization prediction have led to the development of several methods including composition-based and homology-based methods. However, their performance might be significantly degraded if homologous sequences are not detected. Moreover, methods that integrate various features could suffer from the problem of low coverage in high-throughput proteomic analyses due to the lack of information to characterize unknown proteins. RESULTS: We propose a hybrid prediction method for Gram-negative bacteria that combines a one-versus-one support vector machines (SVM) model and a structural homology approach. The SVM model comprises a number of binary classifiers, in which biological features derived from Gram-negative bacteria translocation pathways are incorporated. In the structural homology approach, we employ secondary structure alignment for structural similarity comparison and assign the known localization of the top-ranked protein as the predicted localization of a query protein. The hybrid method achieves overall accuracy of 93.7% and 93.2% using ten-fold cross-validation on the benchmark data sets. In the assessment of the evaluation data sets, our method also attains accurate prediction accuracy of 84.0%, especially when testing on sequences with a low level of homology to the training data. A three-way data split procedure is also incorporated to prevent overestimation of the predictive performance. In addition, we show that the prediction accuracy should be approximately 85% for non-redundant data sets of sequence identity less than 30%. CONCLUSION: Our results demonstrate that biological features derived from Gram-negative bacteria translocation pathways yield a significant improvement. The biological features are interpretable and can be applied in advanced analyses and experimental designs. Moreover, the overall accuracy of combining the structural homology approach is further improved, which suggests that structural conservation could be a useful indicator for inferring localization in addition to sequence homology. The proposed method can be used in large-scale analyses of proteomes

Minimal clinically important difference of the EORTC QLQ-CIPN20 for worsening peripheral neuropathy in patients receiving neurotoxic chemotherapy.

Context/objectivesThis is the first study to determine the minimal clinically important difference (MCID) of the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale (EORTC QLQ-CIPN20), a validated instrument designed to elicit cancer patients' experience of symptoms and functional limitations related to chemotherapy-induced peripheral neuropathy.MethodsCancer patients receiving neurotoxic chemotherapy completed EORTC QLQ-CIPN20 and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity [FACT/GOG-NTX] at baseline, second cycle of chemotherapy (T2, n = 287), and 12 months after chemotherapy (T3, n = 191). Anchor-based approach used the validated FACT/GOG-NTX neurotoxicity (Ntx) subscale to identify optimal MCID cutoff for deterioration. Distribution-based approach used one-third standard deviation (SD), half SD, and one standard error of measurement of the total EORTC QLQ-CIPN20 score.ResultsThere was a moderate correlation between the change scores of the Ntx subscale and sensory and motor subscales of QLQ-CIPN20 (T2: r = - 0.722, p < 0.001 and r = - 0.518, p < 0.001, respectively; T3: r = - 0.699; p < 0.001 and r = - 0.523, p < 0.001, respectively). The correlation between the change scores of the Ntx subscale and the QLQ-CIPN20 autonomic subscale was poor (T2: r = - 0.354, p < 0.001; T3: r = 0.286, p < 0.001). Based on the MCID derived using distribution-based method, the MCID for the QLQ-CIPN20 sensory subscale was 2.5-5.9 (6.9% to 16.4% of the subdomain score) and for motor subscale was 2.6-5.0 (8.1%-15.6% of the subdomain score).ConclusionThe MCID for the EORTC QLQ-CIPN20 established using distribution-based approaches was 2.5-5.9 for the sensory subscale and 2.6-5.0 for the motor subscale. When noted in assessments even with small change in scores, clinicians can be alerted for appropriate intervention

Psychosocial, behavioral, and supportive interventions for pediatric, adolescent, and young adult cancer survivors: a systematic review and meta-analysis

Background Pediatric, adolescent, and young adult (PAYA) cancer survivors suffer from multiple domains of adverse psychosocial and behavioral outcomes during and after their cancer treatment. This study conducted a systematic review and metaanalysis of psychosocial, behavioral, and supportive interventions for PAYA cancer survivors. Methods We searched 11 electronic databases, 4 professional websites, and manual search of reference lists in existing reviews. We selected randomized controlled trials and controlled trials without randomization focusing on PAYA cancer survivors across six outcome domains. Results We included 61 studies (4,402 participants) published between 1987 and 2020. Overall risk of bias across studies was low. We identified an overall moderate and statistically significant treatment effect size for PAYA cancer survivors across six outcome domains. Conclusion psychosocial, behavioral, and supportive interventions were overall effective for PAYA cancer survivors. However, interventions were not effective for certain outcome domains, and less effective among AYA versus pediatric cancer survivors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167608/1/Zhang_et al. CROH.pdfDescription of Zhang_et al. CROH.pdf : Main articleSEL

Regulation of virulence gene expression resulting from Streptococcus pneumoniae and nontypeable Haemophilus influenzae interactions in chronic disease

Chronic rhinosinusitis (CRS) is a common inflammatory disease of the sinonasal cavity mediated, in part, by polymicrobial communities of bacteria. Recent molecular studies have confirmed the importance of Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi) in CRS. Here, we hypothesize that interaction between S. pneumoniae and NTHi mixed-species communities cause a change in bacterial virulence gene expression. We examined CRS as a model human disease to validate these polymicrobial interactions. Clinical strains of S. pneumoniae and NTHi were grown in mono- and coculture in a standard biofilm assay. Reverse transcriptase real-time PCR (RTqPCR) was used to measure gene expression of key virulence factors. To validate these results, we investigated the presence of the bacterial RNA transcripts in excised human tissue from patients with CRS. Consequences of physical or chemical interactions between microbes were also investigated. Transcription of NTHi type IV pili was only expressed in co-culture in vitro, and expression could be detected ex vivo in diseased tissue. S. pneumoniae pyruvate oxidase was up-regulated in co-culture, while pneumolysin and pneumococcal adherence factor A were down-regulated. These results were confirmed in excised human CRS tissue. Gene expression was differentially regulated by physical contact and secreted factors. Overall, these data suggest that interactions between H. influenzae and S. pneumoniae involve physical and chemical mechanisms that influence virulence gene expression of mixed-species biofilm communities present in chronically diseased human tissue. These results extend previous studies of population-level virulence and provide novel insight into the importance of S. pneumoniae and NTHi in CRS

2MASSJ035523.51+113337.4: A Young, Dusty, Nearby, Isolated Brown Dwarf Resembling A Giant Exoplanet

We present parallax and proper motion measurements, near-infrared spectra, and WISE photometry for the low surface gravity L5gamma dwarf 2MASSJ035523.37+113343.7 (2M0355). We use these data to evaluate photometric, spectral, and kinematic signatures of youth as 2M0355 is the reddest isolated L dwarf yet classified. We confirm its low-gravity spectral morphology and find a strong resemblance to the sharp triangular shaped $H$-band spectrum of the 10 Myr planetary-mass object 2M1207b. We find that 2M0355 is underluminous compared to a normal field L5 dwarf in the optical and MKO J,H, and K bands and transitions to being overluminous from 3-12 microns, indicating that enhanced photospheric dust shifts flux to longer wavelengths for young, low-gravity objects, creating a red spectral energy distribution. Investigating the near-infrared color magnitude diagram for brown dwarfs confirms that 2M0355 is redder and underluminous compared to the known brown dwarf population, similar to the peculiarities of directly imaged exoplanets 2M1207b and HR8799bcd. We calculate UVW space velocities and find that the motion of 2M0355 is consistent with young disk objects (< 2-3 Gyr) and it shows a high likelihood of membership in the AB Doradus association.Comment: 23 pages, 10 figures, 5 Tables, Submitted to AJ 13 May 201

Total Synthesis and Evaluation of c26-Hydroxyepothilone D Derivatives for Photoaffinity Labeling of β-Tubulin

Three photaffinity labeled derivatives of epothilone D were prepared by total synthesis, using efficient novel asymmetric synthesis methods for the preparation of two important synthetic building blocks. The key step for the asymmetric synthesis of (S,E)-3-(tert-butyldimethylsilyloxy)-4-methyl-5-(2-methylthiazol-4-yl)pent-4-enal involved a ketone reduction with (R)-Me-CBS-oxazaborolidine. For the synthesis of (5S)-5,7-di-[(tert-butyldimethylsilyl)oxy]-4,4-dimethylheptan-3-one an asymmetric Noyori reduction of a β-ketoester was employed. The C26 hydroxyepothilone D derivative was constructed following a well-established total synthesis strategy and the photoaffinity labels were attached to the C26 hydroxyl group. The photoaffinity analogues were tested in a tubulin assembly assay and for cytotoxicity against MCF-7 and HCT-116 cancer cell lines. The 3- and 4-azidobenzoic acid analogues were found to be as active as epothilone B in a tubulin assembly assay, but demonstrated significantly reduced cellular cytotoxicity compared to epothilone B. The benzophenone analogue was inactive in both assays. Docking and scoring studies were conducted that suggested that the azide analogues can bind to the epothilone binding site, but that the benzophenone analogue undergoes a sterically driven ligand rearrangement that interrupts all hydrogen bonding and therefore protein binding. Photoaffinity labeling studies with the 3-azidobenzoic acid derivative did not identify any covalently labeled peptide fragments, suggesting that the phenylazido side chain was predominantly solvent-exposed in the bound conformation

Total synthesis and evaluation of 22-(3-azidobenzoyloxy)methyl epothilone C for photoaffinity labeling of β-tubulin

The total synthesis of 22-(3-azidobenzoyloxy)methyl epothilone C is described as a potential photoaffinity probe to elucidate the β-tubulin binding site. A sequential Suzuki-aldol-Yamaguchi macrolactonization strategy was utilized employing a novel derivatized C1–C6 fragment. The C22-functionalized analog exhibited good activity in microtubule assembly assays, but cytotoxicity was significantly reduced. Molecular modeling simulations indicated that excessive steric bulk in the C22 position is accommodated by the large hydrophobic pocket of the binding site. Photoaffinity labeling studies were inconclusive suggesting non-specific labeling

Discoveries from a Near-infrared Proper Motion Survey using Multi-epoch 2MASS Data

We have conducted a 4030-square-deg near-infrared proper motion survey using multi-epoch data from the Two Micron All-Sky Survey (2MASS). We find 2778 proper motion candidates, 647 of which are not listed in SIMBAD. After comparison to DSS images, we find that 107 of our proper motion candidates lack counterparts at B-, R-, and I-bands and are thus 2MASS-only detections. We present results of spectroscopic follow-up of 188 targets that include the infrared-only sources along with selected optical-counterpart sources with faint reduced proper motions or interesting colors. We also establish a set of near-infrared spectroscopic standards with which to anchor near-infrared classifications for our objects. Among the discoveries are six young field brown dwarfs, five "red L" dwarfs, three L-type subdwarfs, twelve M-type subdwarfs, eight "blue L" dwarfs, and several T dwarfs. We further refine the definitions of these exotic classes to aid future identification of similar objects. We examine their kinematics and find that both the "blue L" and "red L" dwarfs appear to be drawn from a relatively old population. This survey provides a glimpse of the kinds of research that will be possible through time-domain infrared projects such as the UKIDSS Large Area Survey, various VISTA surveys, and WISE, and also through z- or y-band enabled, multi-epoch surveys such as Pan-STARRS and LSST.Comment: To appear in the September 2010 issue of The Astrophysical Journal, Supplement Serie