Deep Learning-Based Software Improves Clinicians' Detection Sensitivity of Aneurysms on Brain TOF-MRA.

BACKGROUND AND PURPOSE: The detection of cerebral aneurysms on MRA is a challenging task. Recent studies have used deep learning-based software for automated detection of aneurysms on MRA and have reported high performance. The purpose of this study was to evaluate the incremental value of using deep learning-based software for the detection of aneurysms on MRA by 2 radiologists, a neurosurgeon, and a neurologist. MATERIALS AND METHODS: TOF-MRA examinations of intracranial aneurysms were retrospectively extracted. Four physicians interpreted the MRA blindly. After a washout period, they interpreted MRA again using the software. Sensitivity and specificity per patient, sensitivity per lesion, and the number of false-positives per case were measured. Diagnostic performances, including subgroup analysis of lesions, were compared. Logistic regression with a generalized estimating equation was used. RESULTS: A total of 332 patients were evaluated; 135 patients had positive findings with 169 lesions. With software assistance, patient-based sensitivity was statistically improved after the washout period (73.5% versus 86.5%, P < .001). The neurosurgeon and neurologist showed a significant increase in patient-based sensitivity with software assistance (74.8% versus 85.2%, P = .03, and 56.3% versus 84.4%, P < .001, respectively), while the number of false-positive cases did not increase significantly (23 versus 30, P = .20, and 22 versus 24, P = .75, respectively). CONCLUSIONS: Software-aided reading showed significant incremental value in the sensitivity of clinicians in the detection of aneurysms on MRA without a significant increase in false-positive findings, especially for the neurosurgeon and neurologist. Software-aided reading showed equivocal value for the radiologist.

Disrupted Functional and Structural Connectivity in Angelman Syndrome.

BACKGROUND AND PURPOSE: This work investigated alterations in functional connectivity (FC) and associated structures in patients with Angelman syndrome (AS) by using integrated quantitative imaging analysis and connectivity measures. MATERIALS AND METHODS: We obtained 3T brain MR imaging, including resting-state functional MR imaging, diffusion tensor imaging, and 3D T1-weighted imaging from children with AS (n = 14) and age- and sex-matched controls (n = 28). The brains of patients with AS were analyzed by measuring FC, white matter microstructural analysis, cortical thickness, and brain volumes; these were compared with brains of controls. RESULTS: Interregional FC analysis revealed significantly reduced intra- and interhemispheric FC, especially in the basal ganglia and thalamus, in patients with AS. Significant reductions in fractional anisotropy were found in the corpus callosum, cingulum, posterior limb of the internal capsules, and arcuate fasciculus in patients with AS. Quantitative structural analysis also showed gray matter volume loss of the basal ganglia and diffuse WM volume reduction in AS compared with the control group. CONCLUSIONS: This integrated quantitative MR imaging analysis demonstrated poor functional and structural connectivity, as well as brain volume reduction, in children with AS, which may explain the motor and language dysfunction observed in this well-characterized neurobehavioral phenotype.

Observations of the Interaction and Transport of Fine Mode Aerosols with Cloud and/or Fog in Northeast Asia from Aerosol Robotic Network (AERONET) and Satellite Remote Sensing.

Analysis of sun photometer measured and satellite retrieved aerosol optical depth (AOD) data has shown that major aerosol pollution events with very high fine mode AOD (>1.0 in mid-visible) in the China/Korea/Japan region are often observed to be associated with significant cloud cover. This makes remote sensing of these events difficult even for high temporal resolution sun photometer measurements. Possible physical mechanisms for these events that have high AOD include a combination of aerosol humidification, cloud processing, and meteorological co-variation with atmospheric stability and convergence. The new development of Aerosol Robotic network (AERONET) Version 3 Level 2 AOD with improved cloud screening algorithms now allow for unprecedented ability to monitor these extreme fine mode pollution events. Further, the Spectral Deconvolution Algorithm (SDA) applied to Level 1 data (L1; no cloud screening) provides an even more comprehensive assessment of fine mode AOD than L2 in current and previous data versions. Studying the 2012 winter-summer period, comparisons of AERONET L1 SDA daily average fine mode AOD data showed that Moderate Resolution Imaging Spectroradiometer (MODIS) satellite remote sensing of AOD often did not retrieve and/or identify some of the highest fine mode AOD events in this region. Also, compared to models that include data assimilation of satellite retrieved AOD, the L1 SDA fine mode AOD was significantly higher in magnitude, particularly for the highest AOD events that were often associated with significant cloudiness.

Neuroprotective Effects of Endurance Exercise Against High-Fat Diet-Induced Hippocampal Neuroinflammation.

Obesity contributes to systemic inflammation, which is associated with the varied pathogenesis of neurodegenerative diseases. Growing evidence has demonstrated that endurance exercise (EE) mitigates obesity-induced brain inflammation. However, exercise-mediated anti-inflammatory mechanisms remain largely unknown. We investigated how treadmill exercise (TE) reverses obesity-induced brain inflammation, mainly focusing on toll-like receptor-4 (TLR-4)-dependent neuroinflammation in the obese rat brain after 20 weeks of a high-fat diet (HFD). TE in HFD-fed rats resulted in a significant lowering in the homeostasis model assessment of insulin resistance index, the area under the curve for glucose and abdominal visceral fat, and also improved working memory ability in a passive avoidance task relative to sedentary behaviour in HFD-fed rats, with the exception of body weight. More importantly, TE revoked the increase in HFD-induced proinflammatory cytokines (tumour necrosis factor α and interleukin-1ß) and cyclooxygenase-2, which is in parallel with a reduction in TLR-4 and its downstream proteins, myeloid differentiation 88 and tumour necrosis factor receptor associated factor 6, and phosphorylation of transforming growth factor ß-activated kinase 1, IkBα and nuclear factor-κB. Moreover, TE reduced an indicator of microglia activation, ionised calcium-binding adapter molecule-1, and also decreased glial fibrillary acidic protein, an indicator of gliosis formed by activated astrocytes in the cerebral cortex and the hippocampal dentate gyrus, compared to HFD-fed sedentary rats. Finally, EE up-regulated the expression of anti-apoptotic protein, Bcl-2, and suppressed the expression of pro-apoptotic protein, Bax, in the hippocampus compared to HFD-fed sedentary rats. Taken together, these data suggest that TE may exert neuroprotective effects as a result of mitigating the production of proinflammatory cytokines by inhibiting the TLR4 signalling pathways. The results of the present study suggest that the unique combination of the beneficial effects of TE on the restoration of the blood profile and the anti-inflammatory and anti-apoptotic effects on cognitive function should inspire further investigations into its therapeutic potential for metabolic disorders and neurodegenerative diseases.

miR-125b transcriptionally increased by Nrf2 inhibits AhR repressor, which protects kidney from cisplatin-induced injury.

MicroRNAs (miRNAs) have a role in the cellular defense mechanism. Nuclear factor erythroid-2-related factor 2 (Nrf2) increases antioxidant enzyme capacity. However, miRNA transcriptionally controlled by Nrf2 had been uncharacterized. Here we report that miR-125b is transactivated by Nrf2 and inhibits aryl hydrocarbon receptor (AhR) repressor (AhRR). Bioinformatic approaches enabled us to extract six candidate miRNAs. Of them, only miR-125b was increased in the kidney of mice treated with oltipraz. Nrf2 overexpression enhanced primary, precursor and mature miR-125b levels. Functional assays revealed MIR125B1 is a bona fide target gene of Nrf2. Oltipraz treatment protected the kidney from cisplatin toxicity with increase of miR-125b. Consistently, Nrf2 knockout abrogated an adaptive increase of miR-125b elicited by cisplatin, augmenting kidney injury. An integrative network of miRNA and messenger RNA changes enabled us to predict miR-125b as an inhibitor of AhRR for the control of AhR activity and cell survival. In our molecular study, miR-125b inhibited AhRR and thereby activated AhR, leading to the induction of mdm2. Consistently, p53 activation by cisplatin was diminished by either miR-125b or oltipraz treatment. The results of experiments using miR-125b mimic or small interfering RNA of AhRR verified the role of miR-125b in AhRR regulation for kidney protection. In conclusion, miR-125b is transcriptionally activated by Nrf2 and serves as an inhibitor of AhRR, which contributes to protecting kidney from acute injury.

Thermal characterization of polyamide 11/nanographene platelet nanocomposites.

The objective of this study is to evaluate thermal properties of polyamide 11 (PA11)/nanographene platelet (NGP) nanocomposites. Samples were prepared using 1 wt%, 3 wt%, and 5 wt% of NGPs. Isopropyl alcohol (IPA) was used as a solvent to assist in dispersion of the NGPs within the PA11 powder. The NGPs were hand mixed evenly into the PA11 powder using a wooden dowel. Morphological characterization of the PA11/NGP nanocomposite was conducted using scanning electron microscopy. Thermal characterization of nanocomposites includes thermogravimetric analysis, differential scanning calorimetry and thermomechanical analysis. Results indicate that the addition of NGPs shows an initial increase in thermal stability and crystallization temperature (T(c)) along with a decrease in glass transition temperature (T(g)) and no improvement in coefficient of thermal expansion (alpha). These results are attributed to improved interfacial adhesion between NGPs and PA11, restricting polymer chain mobility.

Digital tomosynthesis of the chest: utility for detection of lung metastasis in patients with colorectal cancer.

AIM: To evaluate the performance of digital tomosynthesis (DT) of the chest for detection of lung nodules in patients with colorectal cancer (CRC). MATERIALS AND METHODS: The institutional review board approved this study, and all patients provided informed consent. A commercial caesium iodide/amorphous silicon (CsI/a-Si) flat-panel detector system was used to verify the performance of the DT and chest radiography (XR) methods. DT was performed in 142 patients with CRC. All 142 patients underwent chest computed tomography (CT) within a week of DT. As a reference standard, two radiologists reviewed the chest CT in consensus and recorded the presence of pulmonary nodules. Another two radiologists independently observed the DT images and recorded the presence of pulmonary nodules. The status of all lung nodules was assessed either histologically or by follow-up over a period of 1 year. The nodules were classified into metastasis, benign, and uncertain. Statistical analysis of the results was performed. RESULTS: Two hundred and thirty-seven nodules from 142 patients were found at CT. These included 71 proven metastases and 126 benign nodules; 40 nodules were uncertain. Observers detected 83% of all lung nodules and 93% of proven metastases using DT. Among 237 nodules, 147 nodules were larger than 4mm in diameter on the CT images. Observers detected 87% of lung nodules that were larger than 4mm. CONCLUSION: Despite a reasonably low radiation dose, DT is a sensitive method, and is comparable to chest CT for the detection of lung nodules, particularly metastatic lung nodules in patients with CRC.

Suppressing harmonic vibrations of a miniature cryogenic cooler using an adaptive tunable vibration absorber based on magneto-rheological elastomers.

This paper presents dynamic performances of an adaptive tunable vibration absorber (TVA) designed to suppress the main harmonic disturbance of a miniature linear cryogenic cooler, which is being used in space applications such as an observation satellite. The adaptive TVA employs a magneto-rheological elastomer (MRE) for a variable stiffness element. This study first investigates the shear modulus change of MRE samples with respect to the magnetic flux density, which varies through the alignment of particle chains. The MRE with the maximal shear modulus change is mounted for the TVA on a prototype cooler, which emulates the characteristics of a miniature cryogenic cooler. Using the test setup, a series of vibration tests are performed to evaluate the performance and efficacy of the MRE TVA and its re-tuning ability. The experimental results show that the MRE TVA is able to robustly suppress the vibration of the cooler even when the frequency of resonant vibration is changed up to 87% from its initial frequency.

A dual-design expandable colorectal stent for malignant colorectal obstruction: results of a multicenter study.

BACKGROUND AND STUDY AIMS: It is known that metal stent placement is safe, easy, and effective for the treatment of malignant colorectal obstruction, but these stents are associated with delayed complications of tumor ingrowth and stent migration. The aim of this study was to prospectively investigate the technical feasibility, clinical effectiveness, and safety of a dual-design colorectal stent (consisting of an outer stent and an inner bare nitinol stent) in patients with malignant colorectal obstruction. PATIENTS AND METHODS: Placement of the dual stent using a 4.5-mm stent delivery system was attempted in 151 patients with malignant colorectal obstruction, either before surgery (n = 50) or for palliation (n = 101). Multivariate logistic regression analysis was used to identify risk factors associated with complications. RESULTS: Stent placement was technically successful in 145/151 patients (96%). Of the patients who had a technically successful placement, bowel obstruction resolved within 2 days after stent placement in 48/50 (96%) of the patients in the bridge-to-surgery group and in 87/95 (92%) of the patients in the palliative group. Perforation occurred in 16 patients, incomplete stent expansion in eight patients, stent migration in four patients, tumor overgrowth in five patients, severe rectal pain in five patients, and bleeding in eight patients. Complete obstruction was the only significant risk factor for perforation (odds ratio 6.88, 95% CI 2.04-23.17, P = 0.002). In the palliative group, the median survival was 152.0 days and the mean survival was 263.8 days. CONCLUSIONS: The dual stent with a 4.5-mm stent delivery system is easy to insert, safe, and reasonably effective for the palliative treatment of malignant colorectal obstruction. However, a great deal of care is needed in its deployment because of the high rate of perforation.

Quantifying the dispersion of mixture microstructures.

A general method to quantify the inclusion dispersion of mixture microstructures has been developed. The dispersion quantity, D, is defined as the probability of inclusion particle free-path spacing falling into a certain range of the mean spacing mu, according to the particle spacing data frequency distribution. Two quantities, D(0.1) and D(0.2), are proposed, which are the probabilities of the particle free-path spacing falling into the ranges of mu+/- 0.1 mu and mu+/- 0.2 mu, respectively. Both normal and lognormal distributions are discussed, and in both cases, the quantities D(0.1) and D(0.2) are specified as monotonous increasing functions of mu/sigma, where mu and sigma; are the mean particle free-path spacing and standard deviation, respectively. Examples of composite are presented to quantify the dispersion of foreign reinforcements based on the proposed method.

Effect of AP-1 decoy using hemagglutinating virus of Japan-liposome on the intimal hyperplasia of the autogenous vein graft in mongrel dogs.

Intimal hyperplasia is the leading cause of late vein graft failure. Smooth muscle cell proliferation and migration is the underlying mechanism. Pharmacological approaches to prolong vein graft patency have produced limited results. AP-1 proteins play a role in the expression of many genes involved in cellular proliferation and cell cycle progression. Previously we reported inhibition of vascular smooth muscle cell migration, proliferation, and intimal hyperplasia in the balloon-injured rat carotid artery using an AP-1 decoy with HVJ-liposomes. In this report, we evaluated the effect of the AP-1 decoy on intimal hyperplasia in a large animal model. The jugular vein was transfected with hemagglutinating virus of Japan-liposomes containing the AP-1 decoy or scrambled oligonucleotides. An interposition graft was performed with the pretreated jugular vein between the transected femoral arteries. The graft was harvested at 16 weeks after the procedure. The intimal area was compared: the intimal area of the AP-1 decoy-treated versus control group was 47.3 +/- 15.2 versus 102.3 +/- 15.9 (P < .05), respectively. In conclusion, AP-1 decoy using HVJ-liposomes effectively prevented intimal hyperplasia of an autogenous vein graft in mongrel dogs.

Relationship between sonographic and pathologic findings in epidermal inclusion cysts.

PURPOSE: We evaluated the sonographic findings in epidermal inclusion cysts and related them to the pathologic findings. METHODS: We retrospectively reviewed the sonograms and pathology specimens of 24 patients with pathologically proven epidermal inclusion cysts. We evaluated the lesions for shape, size, internal echogenicity, posterior sound enhancement, and presence of color Doppler signals. We classified the masses into 5 sonographic types according to their internal echogenicity. The relationship between the sonographic types and the pathologic findings was examined. RESULTS: The masses were ovoid or spherical in 17 cases (71%), lobulated in 5 (21%), and tubular in 2 (8%). The longest diameter ranged from 1 to 6 cm (mean, 3.1 cm). Twenty-three cases (96%) were associated with posterior sound enhancement. Color Doppler signals were absent in 20 cases, but some vascularity was noted in 4 ruptured epidermal cysts, in areas of granulation tissue. The most common sonographic type was a hypoechoic lesion with scattered echogenic reflectors (10 cases). Sonographic findings were related to the lamellation of keratin debris and the granulation tissue secondary to rupture. Most cases with a lobulated configuration (4 of 5) or color Doppler signals (4 of 4) were ruptured cysts. CONCLUSIONS: Epidermal inclusion cysts most often appeared sonographically as a hypoechoic mass containing variable echogenic foci without color Doppler signals. Ruptured epidermal cysts, however, may have lobulated contours and show color Doppler signals, mimicking a solid mass.

Detection of circulating tumor cells in patients with gastrointestinal tract cancer using RT-PCR and its clinical implications.

To investigate the relationship between the presence of circulating tumor cells in different stages of gastrointestinal tract cancer and the subsequent relapse or distant metastasis, circulating levels of CEA mRNA was serially examined at an interval of 10.6+/-4.5 or 13.7+/-3.0 months in gastric or colorectal cancer patients, respectively. CEA mRNA was measured by means of RT-PCR amplification as an indicator for micrometastatic malignant cells. Seven of twenty-nine respectable gastric cancer patients (24.1%) [EGC: 2/9 (22.2%), AGC IIIa: 1/5 (20.0%), AGC IIIb: 4/15 (26.6%)] were positive for CEA mRNA on the initial test and 10 of 29 patients (34.4%) [EGC: 2/ 9 (22.2%), AGC IIIa: 1/5 (20.0%), AGC IIIb: 7/15 (46.7%)] were positive on a follow-up test. Only in AGC IIIb, the positive rate for CEA mRNA increased about twice and 6 of 7 positive cases (85.7%) relapsed within 2.6+/-2.4 months after the follow-up test. In colorectal cancer, 4 of 19 patients (21.1%) [B2: 1/6 (16.7%), C2: 3/13 (23.0%)] were positive on the initial test and 10 of 19 patients (52.6%) [B2: 4/6 (66.7%), C2: 6/13 (46.2%)] were positive on a follow-up test showing an increase in positive rates during a follow-up, however, no significant correlation between CEA mRNA positivity and subsequent relapse was demonstrated. These results suggest that an early tumor cell dissemination may occur in gastrointestinal tract cancer without subsequent relapse, however, the serial regular examination of CEA mRNA level may contribute to predicting a subsequent relapse in AGC IIIb in gastric cancer.

Bacterial biofilm formation under microgravity conditions.

Although biofilm formation is widely documented on Earth, it has not been demonstrated in the absence of gravity. To explore this possibility, Pseudomonas aeruginosa, suspended in sterile buffer, was flown in a commercial payload on space shuttle flight STS-95. During earth orbit, biofilm formation was induced by exposing the bacteria to sterile media through a 0.2-microm (pore size) polycarbonate membrane. Examination of these membranes by confocal microscopy revealed biofilms to be present and that these biofilms could persist in spite of vigorous agitation. These results represent the first report of biofilm formation under microgravity conditions.

The malonate decarboxylase operon of Acinetobacter calcoaceticus KCCM 40902 is regulated by malonate and the transcriptional repressor MdcY.

A regulatory gene-like open reading frame oriented oppositely to mdcL, coined mdcY, was found upstream from the structural genes of the mdcLMACDEGBH operon in Acinetobacter calcoaceticus KCCM 40902. To elucidate the function of this gene, mdcY was expressed in Escherichia coli, and the MdcY protein was purified to homogeneity. Its DNA binding activity and binding site were examined by gel retardation and footprinting assays in vitro and by site-directed mutagenesis of the binding sites in vivo. The regulator bound target DNA regardless of the presence of malonate, and the binding site was found centered at -65 relative to the mdcL transcriptional start site and contains a 12-bp palindromic structure (5'-ATTGTA/TACAAT-3'). Using a promoter fusion to the reporter gene luc, we found that the promoter P(mdcY) is negatively regulated by MdcY independent of malonate. However, the promoter P(mdcL) recovered its activity in the presence of malonate. When mdcY was introduced into A. calcoaceticus KCCM 40902 in which the gene is inactivated by an IS3 family element, malonate decarboxylase was significantly repressed in cultures growing in acetate, succinate, or Luria-Bertani medium. However, in cells growing in malonate, malonate decarboxylase was induced, indicating that MdcY is a transcriptional repressor and that malonate or a product resulting from malonate metabolism should be the intracellular inducer of the mdc operon.

Functional evaluation of the genes involved in malonate decarboxylation by Acinetobacter calcoaceticus.

The genomic locus containing the potential repressor gene mdcY (inactivated by a putative IS3 element) and the mdcLMACDEGBH genes from Acinetobacter calcoaceticus was cloned and sequenced. In order to evaluate the biochemical function of the protein components, the genes were expressed independently and their activities predicted by database analysis. The mdcA gene product, the alpha subunit, was found to be malonate/acetyl-CoA transferase and the mdcD gene product, the beta subunit, was found to be malonyl-CoA decarboxylase. The mdcE gene product, the gamma subunit, may play a role in subunit interaction to form a stable complex or as a codecarboxylase. The mdcC gene product, the delta subunit, was an acyl-carrier protein, which has a unique CoA-like prosthetic group. Various combinations of malonate decarboxylase subunits allowed us to estimate their contribution to malonyl-CoA decarboxylase activity. The prosthetic group was identified as carboxymethylated 2'-(5"-phosphoribosyl)-3'-dephospho-CoA by mass spectrometry. The mdcH gene product was determined to have malonyl-CoA/dephospho-CoA acyltransferase activity. Using database analysis mdcLM, mdcG, mdcB and mdcI were estimated to be the genes for a malonate transporter, a holo-acyl carrier synthase, protein for the formation of precursor of the prosthetic group and a regulatory protein, respectively. From the data shown above we propose a metabolic pathway for malonate in A. calcoaceticus.

Stereochemical course of biotin-independent malonate decarboxylase catalysis.

Malonate decarboxylases, which catalyze the conversion of malonate to acetate, can be classified into biotin-dependent and biotin-independent enzymes. In order to reveal the stereochemical course of the reactions catalyzed by the biotin-independent enzymes from Acinetobacter calcoaceticus and Pseudomonas fluorescens, a chiral substrate, malonate carrying (13)C in one carboxyl group and (3)H at one of the methylene positions, was prepared and used in the reactions catalyzed by these two enzymes. The decarboxylation of (R)-[1-(13)C(1), 2-(3)H]malonate in (2)H(2)O gave a pseudo-racemate of chiral acetate which was converted via acetyl-CoA into malate with malate synthase. From the relative proportions of the isotopomers of malate present, determined by (3)H NMR analysis, it was concluded that in the decarboxylation of malonate by these two biotin-independent enzymes COOH is replaced by H with retention of configuration. The same stereochemical outcome had been previously observed for the reaction catalyzed by the biotin-dependent malonate decarboxylase from Malonomonas rubra (J. Micklefield et al. J. Am. Chem. Soc. 117, 1153-1154, 1995).

Recombinant human growth hormone and Gitelman's syndrome.

Gitelman's syndrome is a primary renal tubular disorder with hypokalemic metabolic alkalosis, hypocalciuria, and magnesium deficiency. Short stature is one of clinical manifestations in children. The pathogenesis of short stature in Gitelman's syndrome is not known. To evaluate whether growth hormone (GH) is deficient and whether recombinant human GH (rhGH) improves growth rate, rhGH therapy was tried in a child with Gitelman's syndrome. Both height and body weight were less than the third percentile. Laboratory and radiologic findings suggested GH deficiency. During the first 6 months, rhGH therapy with potassium supplement markedly elevated growth rate from 3.8 cm/yr to 12.0 cm/yr. After cessation of rhGH, height increment markedly decreased to the pretreatment level of 3.6 cm/yr during the second 6 months. Additionally, hypomagnesemia was corrected after rhGH therapy. Accordingly, GH deficiency may contribute to short stature in children with Gitelman's syndrome, and rhGH therapy would be an excellent adjunctive treatment for short children with Gitelman's syndrome whose condition is resistant to conventional therapies in terms of growth.

Ileal obstruction caused by idiopathic sclerosing encapsulating peritonitis.

A 26-year-old woman presented with epigastric pain, vomiting, and a palpable mass in the right lower abdomen. Ultrasonography showed a high echogenic mass associated with a small amount of ascites in the right lower abdomen. Computed tomography demonstrated entrapped ileal loops within a thin-walled fibrous capsule. A thin fibrous sac encasing the terminal ileum was detected on laparotomy and confirmed as idiopathic sclerosing encapsulating peritonitis.