Motivation: Microarray classification typically possesses two striking attributes: (1) classifier design and error estimation are based on remarkably small samples and (2) cross-validation error ...estimation is employed in the majority of the papers. Thus, it is necessary to have a quantifiable understanding of the behavior of cross-validation in the context of very small samples. Results: An extensive simulation study has been performed comparing cross-validation, resubstitution and bootstrap estimation for three popular classification rules—linear discriminant analysis, 3-nearest-neighbor and decision trees (CART)—using both synthetic and real breast-cancer patient data. Comparison is via the distribution of differences between the estimated and true errors. Various statistics for the deviation distribution have been computed: mean (for estimator bias), variance (for estimator precision), root-mean square error (for composition of bias and variance) and quartile ranges, including outlier behavior. In general, while cross-validation error estimation is much less biased than resubstitution, it displays excessive variance, which makes individual estimates unreliable for small samples. Bootstrap methods provide improved performance relative to variance, but at a high computational cost and often with increased bias (albeit, much less than with resubstitution). Availability and Supplementary information: A companion web site can be accessed at the URL http://ee.tamu.edu/~edward/cv_paper. The companion web site contains: (1) the complete set of tables and plots regarding the simulation study; (2) additional figures; (3) a compilation of references for microarray classification studies and (4) the source code used, with full documentation and examples.
Distinct regions of the cerebellum connect to separate regions of the cerebral cortex forming a complex topography. Although cerebellar organization has been examined in group-averaged data, study of ...individuals provides an opportunity to discover features that emerge at a higher spatial resolution. Here, functional connectivity MRI was used to examine the cerebellum of two intensively sampled individuals (each scanned 31 times). Connectivity to somatomotor cortex showed the expected crossed laterality and topography of the body maps. A surprising discovery was connectivity to the primary visual cortex along the vermis with evidence for representation of the central field. Within the hemispheres, each individual displayed a hierarchical progression from the inverted anterior lobe somatomotor map through to higher-order association zones. The hierarchy ended at Crus I/II and then progressed in reverse order through to the upright somatomotor map in the posterior lobe. Evidence for a third set of networks was found in the most posterior extent of the cerebellum. Detailed analysis of the higher-order association networks revealed robust representations of two distinct networks linked to the default network, multiple networks linked to cognitive control, as well as a separate representation of a language network. Although idiosyncratic spatial details emerged between subjects, each network could be detected in both individuals, and seed regions placed within the cerebellum recapitulated the full extent of the spatially specific cerebral networks. The observation of multiple networks in juxtaposed regions at the Crus I/II apex confirms the importance of this zone to higher-order cognitive function and reveals new organizational details.
Stable, within-individual maps of cerebellar organization reveal orderly macroscale representations of the cerebral cortex with local juxtaposed zones representing distinct networks. In addition, individuals reveal idiosyncratic organizational features.
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Hydrogels are extensively used in the biomedical field, as drug delivery systems, wound dressings, contact lenses or as scaffolds for tissue engineering. Due to their polymeric nature ...and the presence of high amounts of water in their structure, hydrogels generally present high sensitivity to terminal sterilization. The establishment of an efficient sterilization protocol that does not compromise the functional properties of the hydrogels is one of the challenges faced by researchers when developing a hydrogel for a specific application. Yet, until very recently this aspect was largely ignored in the literature. The present paper reviews the state of literature concerning hydrogels sterilization, compiling the main findings. Conventional terminal sterilization methods (heat sterilization, radiation sterilization, and gas sterilization) as well as emerging sterilization techniques (ozone, supercritical carbon dioxide) are covered. Considerations about aseptic processing are also included. Additionally, and as a framework, hydrogels’ polymeric materials, types of networks, and main biomedical applications are summarily described.
The posteromedial cortex (PMC) is known to be a core node of the default mode network. Given its anatomical location and blood supply pattern, the effects of targeted disruption of this part of the ...brain are largely unknown. Here, we report a rare case of a patient (S19_137) with confirmed seizures originating within the PMC. Intracranial recordings confirmed the onset of seizures in the right dorsal posterior cingulate cortex, adjacent to the marginal sulcus, likely corresponding to Brodmann area 31. Upon the onset of seizures, the patient reported a reproducible sense of self-dissociation-a condition he described as a distorted awareness of the position of his body in space and feeling as if he had temporarily become an outside observer to his own thoughts, his "me" having become a separate entity that was listening to different parts of his brain speak to each other. Importantly, 50-Hz electrical stimulation of the seizure zone and a homotopical region within the contralateral PMC induced a subjectively similar state, reproducibly. We supplement our clinical findings with the definition of the patient's network anatomy at sites of interest using cortico-cortical-evoked potentials, experimental and resting-state electrophysiological connectivity, and individual-level functional imaging. This rare case of patient S19_137 highlights the potential causal importance of the PMC for integrating self-referential information and provides clues for future mechanistic studies of self-dissociation in neuropsychiatric populations.
Introduction
The differential diagnosis between Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD) is often challenging and detrimental to early and timely treatment. ...Co-current and overlapping symptoms contribute to erode differential diagnostic accuracy, based mainly on clinical assessment supported by standardized instruments and reports from parents and teachers. The microbiota was recently considered a valuable resource in the search for biological markers in neurodevelopmental disorders.
Objectives
Our objective was to examine the published literature in order to clarify the role of the microbiome as a possible differential biomarker between ASD and ADHD.
Methods
Five hundred and sixteen articles were reviewed in order to contextualize the role of Gut- Brain Axis in neurodevelopment and neurodevelopmental disorders, the microbiome as a biomarker and ultimately to unravel microbiome abnormalities reported in patients diagnosed with ASD and/or ADHD.
Results
Although gut microbiome appears to be involved in the pathogenesis of ASD with several reports identifying changes in gut populations and functions, a “microbial signature” is still not reached. In ADHD patients, research confirms that the composition and predicted functions of gut microbiome are also altered, but identically controversial results were found.
Conclusions
Future studies are needed to confirm the relationship between the composition and function of the microbiome and the occurrence or presentation of each of the disorders. A specific signature of the microbiota could then constitute itself as a differential biomarker in ASD and ADHD.
Snake venom L-amino acid oxidases (LAAOs) are flavoproteins, which perform diverse biological activities in the victim such as edema, myotoxicity and cytotoxicity, contributing to the development of ...clinical symptoms of envenomation. LAAO cytotoxicity has been described, but the temporal cascade of events leading to cell death has not been explored so far. This study evaluates the involvement of LAAO in dermonecrosis in mice and its cytotoxic effects in normal human keratinocytes, the major cell type in the epidermis, a tissue that undergoes extensive necrosis at the snakebite site. Pharmacological inhibition by the antioxidant NAC (N-acetyl cysteine) prevented B. atrox venom-induced necrosis. Consistent with the potential role of oxidative stress in wounding, treatment with purified LAAO decreased keratinocyte viability with an Effective Concentration (EC
) of 5.1 μg/mL. Cytotoxicity caused by LAAO was mediated by H
O
and treated cells underwent autophagy, followed by apoptosis and necrosis. LAAO induced morphological alterations that precede cell death. Our results show the chronological events leading to cell death and the temporal resolution from autophagy, apoptosis and necrosis as distinct mechanisms triggered by LAAO. Fluorescently-labelled LAAO was efficiently and rapidly internalized by keratinocytes, suggesting that catalysis of intracellular substrates may contribute to LAAO toxicity. A better understanding of LAAO cytotoxicity and its mechanism of action will help to identify potential therapeutic strategies to ameliorate localized snake envenomation symptoms.
Interactions between the Salience Network (SN) and the Default Mode Network (DMN) are thought to be important for cognitive control. However, evidence for a causal relationship between the networks ...is limited. Previously, we have reported that traumatic damage to white matter tracts within the SN predicts abnormal DMN function. Here we investigate the effect of this damage on network interactions that accompany changing motor control. We initially used fMRI of the Stop Signal Task to study response inhibition in humans. In healthy subjects, functional connectivity (FC) between the right anterior insula (rAI), a key node of the SN, and the DMN transiently increased during stopping. This change in FC was not seen in a group of traumatic brain injury (TBI) patients with impaired cognitive control. Furthermore, the amount of SN tract damage negatively correlated with FC between the networks. We confirmed these findings in a second group of TBI patients. Here, switching rather than inhibiting a motor response: (1) was accompanied by a similar increase in network FC in healthy controls; (2) was not seen in TBI patients; and (3) tract damage after TBI again correlated with FC breakdown. This shows that coupling between the rAI and DMN increases with cognitive control and that damage within the SN impairs this dynamic network interaction. This work provides compelling evidence for a model of cognitive control where the SN is involved in the attentional capture of salient external stimuli and signals the DMN to reduce its activity when attention is externally focused.
We aimed to evaluate the impact of 2 visual diagnostic strategies for assessing secondary caries and managing permanent posterior restorations on long-term survival. We conducted a diagnostic ...cluster-randomized clinical trial with 2 parallel groups using different diagnostic strategies: (C+AS) based on caries assessment, marginal adaptation, and marginal staining aspects of the FDI (World Dental Federation) criteria and (C) based on caries assessment using the Caries Associated with Restorations or Sealants (CARS) criteria described by the International Caries Detection and Assessment System (ICDAS). The treatment for the restoration was conducted based on the decision made following the allocated diagnostic strategy. The restorations were then clinically reevaluated for up to 71 mo. The primary outcome was restoration failure (including tooth-level failure: pain, endodontic treatment, and extraction). Cox regression analyses with shared frailty were conducted in the intention-to-treat population, and hazard ratios (HRs) and 95% confidence intervals (95% CIs) were derived. We included 727 restorations from 185 participants and reassessed 502 (69.1%) restorations during follow-up. The evaluations occurred between 6 and 71 mo. At baseline, C led to almost 4 times fewer interventions compared with the C+AS strategy. A total of 371 restorations were assessed in the C group, from which 31 (8.4%) were repaired or replaced. In contrast, the C+AS group had 356 restorations assessed, from which 113 (31.7%) were repaired or replaced. During follow-up, 34 (9.2%) failures were detected in the restorations allocated to the C group and 30 (8.4%) allocated to the C+AS group in the intention-to-treat population, with no significant difference between the groups (HR = 0.83; 95% CI = 0.51 to 1.38; P = 0.435, C+AS as reference). In conclusion, a diagnostic strategy focusing on marginal defects results in more initial interventions but does not improve longevity over the caries-focused strategy, suggesting the need for more conservative approaches.
Reactive waste dumps with sulfide minerals promote acid mine drainage (AMD), which results in water and soil contamination by metals and metalloids. In these systems, contamination is regulated by ...many factors, such as mineralogical composition of soil and the presence of sorption sites on specific mineral phases. So, the present study dedicates itself to understanding the distribution of trace elements in different size fractions (<2-mm and <2-μm fractions) of mining soils and to evaluate the relationship between chemical and mineralogical composition. Cerdeirinha and Penedono, located in Portugal, were the waste dumps under study. The results revealed that the two waste dumps have high degree of contamination by metals and arsenic and that these elements are concentrated in the clay size fraction. Hence, the higher degree of contamination by toxic elements, especially arsenic in Penedono as well as the role of clay minerals, jarosite, and goethite in retaining trace elements has management implications. Such information must be carefully thought in the rehabilitation projects to be planned for both waste dumps.
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