The "Peeking" Effect in Supervised Feature Selection on Diffusion Tensor Imaging Data

We read with great interest the article by Haller et al[1][1] in the February 2013 issue of the American Journal of Neuroradiology . The authors used whole-brain diffusion tensor imaging–derived fractional anisotropy (FA) data, skeletonized through use of the standard tract-based spatia

Fractal Analysis of MRI Data at 7 T: How Much Complex Is the Cerebral Cortex?

The human brain is a highly complex structure, which can be only partially described by conventional metrics derived from magnetic resonance imaging (MRI), such as volume, cortical thickness, and gyrification index. In the last years, the fractal dimension (FD) - a useful quantitative index of fractal geometry - has proven to well express the morphological complexity of the cerebral cortex. However, this complexity is likely higher than that we can observe using MRI scanners with 1.5 T or 3 T field strength. Ultrahigh-field MRI (UHF-MRI) improves imaging of smaller anatomical brain structures by exploring down to a submillimetric spatial resolution with higher signal-to-noise and contrast-to-noise ratios. Accordingly, we hypothesized that UHF-MRI might reveal a higher level of the structural complexity of the cerebral cortex. In this study, using an improved box-counting algorithm, we estimated the FD of the cerebral cortex in six public or private T1-weighted MRI datasets of young healthy subjects (for a total of 87 subjects), acquired at different field strengths (1.5 T, 3 T, and 7 T). Our results showed, for the first time, that MRI-derived FD values of the cerebral cortex imaged at 7 T were significantly higher than those observed at lower field strengths. UHF-MRI provides an anatomical definition not achievable at lower field strengths and can improve unveiling the real structural complexity of the human brain

In vitro evidences of different fibroblast morpho-functional responses to red, near-infrared and violet-blue photobiomodulation: Clues for addressingwound healing

Although photobiomodulation (PBM) has proven promising to treat wounds, the lack of univocal guidelines and of a thorough understanding of light–tissue interactions hampers its mainstream adoption for wound healing promotion. This study compared murine and human fibroblast responses to PBM by red (635 ± 5 nm), near-infrared (NIR, 808 ± 1 nm), and violet-blue (405 ± 5 nm) light (0.4 J/cm2 energy density, 13 mW/cm2 power density). Cell viability was not altered by PBM treatments. Light and confocal laser scanning microscopy and biochemical analyses showed, in red PBM irradiated cells: F-actin assembly reduction, up-regulated expression of Ki67 proliferation marker and of vinculin in focal adhesions, type-1 collagen down-regulation, matrix metalloproteinase-2 and metalloproteinase-9 expression/functionality increase concomitant to their inhibitors (TIMP-1 and TIMP-2) decrease. Violet-blue and even more NIR PBM stimulated collagen expression/deposition and, likely, cell differentiation towards (proto)myofibroblast phenotype. Indeed, these cells exhibited a higher polygonal surface area, stress fiber-like structures, increased vinculin- and phospho-focal adhesion kinase-rich clusters and α-smooth muscle actin. This study may provide the experimental groundwork to support red, NIR, and violet-blue PBM as potential options to promote proliferative and matrix remodeling/maturation phases of wound healing, targeting fibroblasts, and to suggest the use of combined PBM treatments in the wound management setting

Fast storage of photons in cavity-assisted quantum memories

Ideal photonic quantum memories can store arbitrary pulses of light with unit efficiency. This requires operating in the adiabatic regime, where pulses have a duration much longer than the bandwidth of the memory. In the non-adiabatic regime of short pulses, memories are therefore imperfect, and information is always lost. We theoretically investigate the bandwidth limitations for setups based on individual atoms, or ensembles thereof, confined inside optical cavities. We identify an effective strategy for optimizing the efficiencies of the storage and retrieval process regardless of the duration of the pulses. Our protocol is derived almost completely analytically and attains efficiencies better than or comparable to those obtained by numerical optimization. Furthermore, our results provide an improved understanding of the performance of quantum memories in several regimes. When considering pulses defined on an infinite time interval, the shapes can be divided into two categories, depending on their asymptotic behaviours. If the intensity of the pulse increases with time slower than or as an exponential function, then the storage efficiency is only limited by the pulse width. For pulses defined on a finite interval, on the other hand, the efficiency is determined by the shape at the beginning of the storage or, correspondingly, at the end of the retrieval process.Comment: 21 pages, 8 figures, all kinds of feedback welcom

Validation of a lab-on-chip assay for measuring sorafenib effectiveness on hcc cell proliferation

Hepatocellular carcinoma (HCC) is a highly lethal cancer, and although a few drugs are available for treatment, therapeutic effectiveness is still unsatisfactory. New drugs are urgently needed for hepatocellular carcinoma (HCC) patients. In this context, reliable preclinical assays are of paramount importance to screen the effectiveness of new drugs and, in particular, measure their effects on HCC cell proliferation. However, cell proliferation measurement is a time-consuming and operator-dependent procedure. The aim of this study was to validate an engineered miniaturized on-chip platform for real-time, non-destructive cell proliferation assays and drug screening. The effectiveness of Sorafenib, the first-line drug mainly used for patients with advanced HCC, was tested in parallel, comparing the gold standard 96-well-plate assay and our new lab-on-chip platform. Results from the lab-on-chip are consistent in intra-assay replicates and comparable to the output of standard crystal violet proliferation assays for assessing Sorafenib effectiveness on HCC cell proliferation. The miniaturized platform presents several advantages in terms of lesser reagents consumption, operator time, and costs, as well as overcoming a number of technical and operator-dependent pitfalls. Moreover, the number of cells required is lower, a relevant issue when primary cell cultures are used. In conclusion, the availability of inexpensive on-chip assays can speed up drug development, especially by using patient-derived samples to take into account disease heterogeneity and patient-specific characteristics

AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease

<p>Abstract</p> <p>Background</p> <p>The incidence and mortality of hepatocellular cancer (HCC) complicating alcoholic and non-alcoholic fatty liver diseases (ALD and NAFLD) is rising in western societies. Despite knowing the at risk populations for HCC development, the lack of sensitive and specific means of surveillance hampers disease detection at curable stages. The most widely used serum HCC marker is alpha-fetoprotein (AFP), while PIVKA-II, glypican-3 (GP3) and Squamous Cell Carcinoma Antigen -1 (SCCA-1) have been proposed as new biomarkers. Assessment of these HCC biomarkers has largely been performed in patients with viral hepatitis. We conducted a cross sectional study assessing the value of these serum proteins, as well a novel candidate biomarker -follistatin – in patients with HCC arising on a background of ALD or NAFLD.</p> <p>Methods</p> <p>Pre-treatment serum samples from 50 patients with HCC arising on a background of ALD (n = 31) or NAFLD (n = 19) were assessed by specific ELISA assay for PIVKAII, Glypican-3, SCCA-1 and Follistatin. Results were compared and contrasted with a control patient group with biopsy proven steatohepatitis-related cirrhosis (n = 41). The diagnostic accuracy of each of the candidate biomarkers was evaluated using receiver operating characteristic (ROC) curve analysis, reporting the area under the curve (AUC) and its 95% confidence interval (CI). Performance was compared to that of the established biomarker, AFP.</p> <p>Results</p> <p>Serum levels of all proteins were assessed by specific ELISA assays. GP3, SCCA-1 and follistatin had no HCC surveillance benefit in these patients. AFP and PIVKAII were superior to the other markers, particularly in combination.</p> <p>Conclusion</p> <p>We conclude that while novel means of surveillance are urgently required, the combination of AFP and PIVKAII for HCC is an improvement on AFP alone in ALD/NAFLD patients. Furthermore, our data in this homogenous subset of patients- particularly that confirming no role for SCCA-1 – suggests that the choice of optimal biomarkers for HCC surveillance may be determined by the aetiology of underlying chronic liver disease.</p

Serum levels of tumour associated glycoprotein (TAG 72) in patients with gynaecological malignancies.

Serum levels of TAG 72 were measured in 726 serum samples from patients with benign and malignant gynaecological conditions in order to evaluate the clinical usefulness of TAG 72 alone or in combination with other tumour markers. Sixty-six per cent of patients with ovarian cancer showed abnormal concentrations of TAG 72 antigen. A good correlation was also found between serial TAG 72 values and the clinical course of disease during chemotherapy and follow-up. In cervical and endometrial cancer abnormal TAG 72 values occurred in 23% and 14% of cases, while none of the patients with breast cancer had abnormal TAG 72 levels. Among patients with benign disease only one out of 12 patients (8%) with benign ovarian tumours and one of 15 patients with uterine fibromyomatosis (7%) showed high TAG 72 serum levels. However, the determination of TAG 72 did not increase the sensitivity of CA 125 and squamous cell carcinoma antigen (SCC), in ovarian and cervical cancer, respectively. The systemic administration of recombinant interferon alpha-2b to 15 patients with ovarian cancer and different basal levels of TAG 72 did not increase serum levels of the antigen

Evaluation of vision in gnathological and orthodontic patients with temporomandibular disorders: a prospective experimental observational cohort study

Objectives: Temporomandibular disorders (TMDs), orthodontic diseases, and vision dysfunctions seem to be strictly related. The purpose of this study was to prove the relationship, to evaluate the prevalence and the distribution of vision defects in dysfunctional and orthodontic patients, and to establish the type of the relationship. Materials and Methods: A total of 100 patients with TMDs were selected and studied through epidemiological analyses of the following factors: gnathological parameters (temporomandibular joint pathologies according to Diagnostic Criteria for Temporomandibular Disorders); occlusal and skeletal parameters (overjet, overbite, dental class, transversal discrepancies, and mandibular asymmetry); and orthoptic parameters (refractive defects and oculomotor diseases). A prospective experimental observational cohort study was conducted. A comparison with the average frequency of vision defects of the Italian population was performed. The prevalence of vision defects was evaluated. All gnathological and orthodontic parameters were associated with the orthoptic ones. A descriptive and statistical analysis of the data was carried out with the Statistical Package for the Social Sciences software; z test (P 0.05), frequency analysis (frequency 50%), chi-square test, and Student's t test (P 0.05) were performed. The scientific consistency was evaluated by using the scientific criteria of Bradford Hill. Results: The comparison with the Italian population showed a higher frequency of refractive defects in the study sample (P 0.001). The most frequent vision defects were phorias (92%) and tropia (3%). The increased frequency of ocular convergence reduction in the presence of disc displacement with reduction was significant (n = 28; 60%; P 0.05). In the presence of asymmetry, low frequencies of astigmatism (n = 18; 30%) were observed compared to its absence (n = 22; 54%) (P 0.05) and high frequencies of motor ocular deviations (n = 59; 100%) were observed compared to its absence (n = 36; 88%) (P 0.05). In the presence of headache, low frequencies of emmetropia (n = 13; 22%) and higher frequencies of hyperopia (n = 18; 30%) were observed (P 0.05). Two of five scientific criteria of Bradford Hill were met. Conclusion: It seems to emerge a possible positive relationship between TMD and vision defects. In particular, the most interesting associations were found between functional or skeletal orthognathic alterations and oculomotor dysfunctions. However, it was not possible to establish the type of relationship

Regional Analysis of the Magnetization Transfer Ratio of the Brain in Mild Alzheimer Disease and Amnestic Mild Cognitive Impairment

BACKGROUND AND PURPOSE: Manually drawn VOI-based analysis shows a decrease in magnetization transfer ratio in the hippocampus of patients with Alzheimer disease. We investigated with whole-brain voxelwise analysis the regional changes of the magnetization transfer ratio in patients with mild Alzheimer disease and patients with amnestic mild cognitive impairment. MATERIALS AND METHODS: Twenty patients with mild Alzheimer disease, 27 patients with amnestic mild cognitive impairment, and 30 healthy elderly control subjects were examined with high-resolution T1WI and 3-mm-thick magnetization transfer images. Whole-brain voxelwise analysis of magnetization transfer ratio maps was performed by use of Statistical Parametric Mapping 8 software and was supplemented by the analysis of the magnetization transfer ratio in FreeSurfer parcellation-derived VOIs. RESULTS: Voxelwise analysis showed 2 clusters of significantly decreased magnetization transfer ratio in the left hippocampus and amygdala and in the left posterior mesial temporal cortex (fusiform gyrus) of patients with Alzheimer disease as compared with control subjects but no difference between patients with amnestic mild cognitive impairment and either patients with Alzheimer disease or control subjects. VOI analysis showed that the magnetization transfer ratio in the hippocampus and amygdala was significantly lower (bilaterally) in patients with Alzheimer disease when compared with control subjects (ANOVA with Bonferroni correction, at P < .05). Mean magnetization transfer ratio values in the hippocampus and amygdala in patients with amnestic mild cognitive impairment were between those of healthy control subjects and those of patients with mild Alzheimer disease. Support vector machine-based classification demonstrated improved classification performance after inclusion of magnetization transfer ratio-related features, especially between patients with Alzheimer disease versus healthy subjects. CONCLUSIONS: Bilateral but asymmetric decrease of magnetization transfer ratio reflecting microstructural changes of the residual GM is present not only in the hippocampus but also in the amygdala in patients with mild Alzheimer disease