2,121 research outputs found
Inherently Interpretable Multi-Label Classification Using Class-Specific Counterfactuals
Interpretability is essential for machine learning algorithms in high-stakes
application fields such as medical image analysis. However, high-performing
black-box neural networks do not provide explanations for their predictions,
which can lead to mistrust and suboptimal human-ML collaboration. Post-hoc
explanation techniques, which are widely used in practice, have been shown to
suffer from severe conceptual problems. Furthermore, as we show in this paper,
current explanation techniques do not perform adequately in the multi-label
scenario, in which multiple medical findings may co-occur in a single image. We
propose Attri-Net, an inherently interpretable model for multi-label
classification. Attri-Net is a powerful classifier that provides transparent,
trustworthy, and human-understandable explanations. The model first generates
class-specific attribution maps based on counterfactuals to identify which
image regions correspond to certain medical findings. Then a simple logistic
regression classifier is used to make predictions based solely on these
attribution maps. We compare Attri-Net to five post-hoc explanation techniques
and one inherently interpretable classifier on three chest X-ray datasets. We
find that Attri-Net produces high-quality multi-label explanations consistent
with clinical knowledge and has comparable classification performance to
state-of-the-art classification models.Comment: Accepted to MIDL 202
Differential effects of anti-Nogo-A antibody treatment and treadmill training in rats with incomplete spinal cord injury
Locomotor training on treadmills can improve recovery of stepping in spinal cord injured animals and patients. Likewise, lesioned rats treated with antibodies against the myelin associated neurite growth inhibitory protein, Nogo-A, showed increased regeneration, neuronal reorganization and behavioural improvements. A detailed kinematic analysis showed that the hindlimb kinematic patterns that developed in anti-Nogo-A antibody treated versus treadmill trained spinal cord injured rats were significantly different. The synchronous combined treatment group did not show synergistic effects. This lack of synergistic effects could not be explained by an increase in pain perception, sprouting of calcitonin gene-related peptide (CGRP) positive fibres or by interference of locomotor training with anti-Nogo-A antibody induced regeneration and sprouting of descending fibre tracts. The differential mechanisms leading to behavioural recovery during task-specific training and in regeneration or plasticity enhancing therapies have to be taken into account in designing combinatorial therapies so that their potential positive interactive effects can be fully expresse
High resolution MRI for quantitative assessment of inferior alveolar nerve impairment in course of mandible fractures: an imaging feasibility study
The purpose of this study was to evaluate a magnetic resonance imaging (MRI) protocol for direct visualization of the inferior alveolar nerve in the setting of mandibular fractures. Fifteen patients suffering from unilateral mandible fractures involving the inferior alveolar nerve (15 affected IAN and 15 unaffected IAN from contralateral side) were examined on a 3 T scanner (Elition, Philips Healthcare, Best, the Netherlands) and compared with 15 healthy volunteers (30 IAN in total). The sequence protocol consisted of a 3D STIR, 3D DESS and 3D T1 FFE sequence. Apparent nerve-muscle contrast-to-noise ratio (aNMCNR), apparent signal-to-noise ratio (aSNR), nerve diameter and fracture dislocation were evaluated by two radiologists and correlated with nerve impairment. Furthermore, dislocation as depicted by MRI was compared to computed tomography (CT) images. Patients with clinically evident nerve impairment showed a significant increase of aNMCNR, aSNR and nerve diameter compared to healthy controls and to the contralateral side (p < 0.05). Furthermore, the T1 FFE sequence allowed dislocation depiction comparable to CT. This prospective study provides a rapid imaging protocol using the 3D STIR and 3D T1 FFE sequence that can directly assess both mandible fractures and IAN damage. In patients with hypoesthesia following mandibular fractures, increased aNMCN R, aSNR and nerve diameter on MRI imaging may help identify patients with a risk of prolonged or permanent hypoesthesia at an early time
Climatological Study of the Short-Term Variation of the 0 C, -10 C, and -20 C Altitude Levels over the Florida Spaceport
For evaluation of the potential of cloud electrification, it is necessary to know the altitude of the 0, -10 and -20 degree Celsius levels. Cape Canaveral Air Force Station has recorded balloon launch data back to 1989. In support of rocket launches, often multiple balloons are launched within minutes of each other in the 4-6 hours leading up to launch. In the past, temperature data from sondes was typically available every hour or so through the launch countdown, allowing for frequent updates of these critical temperature thresholds. Recently, launch customers are relying on Jimsphere and wind profiler data that do not have a thermodynamic component in the latter 4-6 hours of a countdown. This study compares the altitude differences of the 0, -10 and -20 degree Celsius levels from consecutive balloon pairs not to exceed 6 hours apart. The analysis uses 9685 soundings from 1989 to 2013. Approximately 5 of the time the altitude of the temperature level in question (0, -10, -20 degrees C), varies by more than 500 feet (operationally significant threshold) within 6 hours. This study analyzes the altitude variability as a function of several meteorological parameters, such as change in sonde type, dew point depression, and solar zenith angle. Additionally, the study concludes with impacts to launch operations
CD4\u3csup\u3e+\u3c/sup\u3e T cells in the lungs of acute sarcoidosis patients recognize an Aspergillus nidulans epitope
Löfgrenâs syndrome (LS) is an acute form of sarcoidosis characterized by a genetic association with HLA-DRB1*03 (HLA-DR3) and an accumulation of CD4+ T cells of unknown specificity in the bronchoalveolar lavage (BAL). Here, we screened related LS-specific TCRs for antigen specificity and identified a peptide derived from NAD-dependent histone deacetylase hst4 (NDPD) of Aspergillus nidulans that stimulated these CD4+ T cells in an HLA-DR3ârestricted manner. Using ELISPOT analysis, a greater number of IFN-Îłâ and IL-2âsecreting T cells in the BAL of DR3+ LS subjects compared with DR3+ control subjects was observed in response to the NDPD peptide. Finally, increased IgG antibody responses to A. nidulans NDPD were detected in the serum of DR3+ LS subjects. Thus, our findings identify a ligand for CD4+ T cells derived from the lungs of LS patients and suggest a role of A. nidulans in the etiology of LS
Identification of beryllium-dependent peptides recognized by CD4+ T cells in chronic beryllium disease
Chronic beryllium disease (CBD) is a granulomatous disorder characterized by an influx of beryllium (Be)-specific CD4+ T cells into the lung. The vast majority of these T cells recognize Be in an HLA-DPârestricted manner, and peptide is required for T cell recognition. However, the peptides that stimulate Be-specific T cells are unknown. Using positional scanning libraries and fibroblasts expressing HLA-DP2, the most prevalent HLA-DP molecule linked to disease, we identified mimotopes and endogenous self-peptides that bind to MHCII and Be, forming a complex recognized by pathogenic CD4+ T cells in CBD. These peptides possess aspartic and glutamic acid residues at p4 and p7, respectively, that surround the putative Be-binding site and cooperate with HLA-DP2 in Be coordination. Endogenous plexin A peptides and proteins, which share the core motif and are expressed in lung, also stimulate these TCRs. Be-loaded HLA-DP2âmimotope and HLA-DP2âplexin A4 tetramers detected high frequencies of CD4+ T cells specific for these ligands in all HLA-DP2+ CBD patients tested. Thus, our findings identify the first ligand for a CD4+ T cell involved in metal-induced hypersensitivity and suggest a unique role of these peptides in metal ion coordination and the generation of a common antigen specificity in CBD
A Polymorphism of Bactericidal/Permeability-Increasing Protein Affects Its Neutralization Efficiency towards Lipopolysaccharide
Gram-negative sepsis driven by lipopolysaccharide (LPS) has detrimental outcomes, especially in neonates. The neutrophil-derived bactericidal/permeability-increasing protein (BPI) potently neutralizes LPS. Interestingly, polymorphism of the BPI gene at position 645 (rs4358188) corresponds to a favorable survival rate of these patients in the presence of at least one allele 645 A as opposed to 645 G. When we exploited the existing X-ray crystal structure, the corresponding amino acid at position 216 was revealed as surface exposed and proximal to the lipid-binding pocket in the N-terminal domain of BPI. Our further analysis predicted a shift in surface electrostatics by a positively charged lysine (BPI216K) exchanging a negatively charged glutamic acid (BPI216E). To investigate differences in interaction with LPS, we expressed both BPI variants recombinantly. The amino acid exchange neither affected affinity towards LPS nor altered bactericidal activity. However, when stimulating human peripheral blood mononuclear cells, BPI216K exhibited a superior LPS-neutralizing capacity (IC50 12.0 ± 2.5 pM) as compared to BPI216E (IC50 152.9 ± 113.4 pM, p = 0.0081) in respect to IL-6 secretion. In conclusion, we provide a functional correlate to a favorable outcome of sepsis in the presence of BPI216K
Nanoscale mapping and spectroscopy of non-radiative hyperbolic modes in hexagonal boron nitride nanostructures
The inherent crystal anisotropy of hexagonal boron nitride (hBN) sustains
naturally hyperbolic phonon polaritons, i.e. polaritons that can propagate with
very large wavevectors within the material volume, thereby enabling optical
confinement to exceedingly small dimensions. Indeed, previous research has
shown that nanometer-scale truncated nanocone hBN cavities, with deep
subwavelength dimensions, support three-dimensionally confined optical modes in
the mid-infrared. Due to optical selection rules, only a few of many such modes
predicted theoretically have been observed experimentally via far-field
reflection and scattering-type scanning near-field optical microscopy. The
Photothermal induced resonance (PTIR) technique probes optical and vibrational
resonances overcoming weak far-field emission by leveraging an atomic force
microscope (AFM) probe to transduce local sample expansion due to light
absorption. Here we show that PTIR enables the direct observation of previously
unobserved, dark hyperbolic modes of hBN nanostructures. Leveraging these
optical modes could yield a new degree of control over the electromagnetic
near-field concentration, polarization and angular momentum in nanophotonic
applications.Comment: 14 pages with references, 4 figure
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