Diffusion magnetic resonance imaging-based surrogate marker in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is the most prevalent type of motor neuron disease (MND) and is diagnosed with a delay from the first appearance of symptoms. Surrogate markers that may be used to detect pathological changes before a significant neuronal loss occurs and allow for early intervention with disease-modifying therapy techniques are desperately needed. Using water molecules that diffuse within the tissue and experience displacement on the micron scale, diffusion magnetic resonance imaging (MRI) is a promising technique that can be used to infer microstructural characteristics of the brain, such as microstructural integrity and complexity, axonal density, order, and myelination. Diffusion tensor imaging (DTI) is the primary diffusion MRI technique used to evaluate the pathogenesis of ALS. Neurite orientation dispersion and density imaging (NODDI), diffusion kurtosis imaging (DKI), and free water elimination DTI (FWE-DTI) are only a few of the approaches that have been developed to overcome the shortcomings of the diffusion tensor technique. This article provides a summary of these methods and their potential as surrogate markers for detecting the onset of ALS at an early stage

Boosting for Bounding the Worst-class Error

This paper tackles the problem of the worst-class error rate, instead of the standard error rate averaged over all classes. For example, a three-class classification task with class-wise error rates of 10\%, 10\%, and 40\% has a worst-class error rate of 40\%, whereas the average is 20\% under the class-balanced condition. The worst-class error is important in many applications. For example, in a medical image classification task, it would not be acceptable for the malignant tumor class to have a 40\% error rate, while the benign and healthy classes have 10\% error rates.We propose a boosting algorithm that guarantees an upper bound of the worst-class training error and derive its generalization bound. Experimental results show that the algorithm lowers worst-class test error rates while avoiding overfitting to the training set

STABILITY CRITERIA FOR THE SYSTEM OF DELAY DIFFERENTIAL EQUATIONS AND ITS APPLICATIONS

In this paper, we consider the asymptotic stability for the system of linear delay differential equations. Because of the complicated interactions induced by the delay effects of the system, there are few results of the asymptotic stability for the system of the delay differential equations with multiple delays. Given this fact, we propose the new stability conditions for the system and apply these conditions to some mathematical models for the population dynamics and neural network system described by the system of delay differential equations

A study on EMI noise source modeling with voltage source in synchronous DC-DC buck converter

Y. Saito, T. Ibuchi, T. Funaki, K. Kawai and T. Tsuda, "A study on EMI noise source modeling with voltage source in synchronous DC-DC buck converter," 2020 IEEE 11th International Symposium on Power Electronics for Distributed Generation Systems (PEDG), Dubrovnik, Croatia, 2020, pp. 470-475, doi: 10.1109/PEDG48541.2020.9244423

Association Between Aldosterone and Hypertension Among Patients With Overt and Subclinical Hypercortisolism

INTRODUCTION: Hypertension is one of the most common clinical features of patients with overt and subclinical hypercortisolism. Although previous studies have shown the coexistence of autonomous cortisol and aldosterone secretion, it is unclear whether aldosterone plays a role in hypertension among patients with hypercortisolism. Therefore, we examined the associations of plasma aldosterone concentrations (PACs) with hypertension among patients with overt and subclinical hypercortisolism. METHODS: This single-center retrospective cohort study included patients with adrenal tumor and serum cortisol levels after 1-mg dexamethasone suppression test >1.8 µg/dL (50 nmol/L). Using multivariable regression models adjusting for baseline characteristics, we investigated the association of PACs with systolic blood pressure and postoperative improvement of hypertension after the adrenalectomy. RESULTS: Among 89 patients enrolled in this study (median age, 51 years), 21 showed clinical signs of Cushing syndrome (overt hypercortisolism) and 68 did not show clinical presentations (subclinical hypercortisolism). We found that higher PACs were significantly associated with elevated systolic blood pressure among patients with subclinical hypercortisolism (adjusted difference [95% CI] = +0.59 [0.19-0.99], P = 0.008) but not among those with overt hypercortisolism. Among 33 patients with subclinical hypercortisolism and hypertension who underwent adrenalectomy, the postoperative improvement of hypertension was significantly associated with higher PACs at baseline (adjusted risk difference [95% CI] = +1.45% [0.35-2.55], P = 0.01). CONCLUSION: These findings indicate that aldosterone may contribute to hypertension among patients with subclinical hypercortisolism. Further multi-institutional and population-based studies are required to validate our findings and examine the clinical effectiveness of the intervention targeting aldosterone for such patients

Radiological characteristics and diagnostic impact of duplicated right adrenal veins on adrenal venous sampling in primary aldosteronism

PURPOSEWe aimed to analyze the prevalence and radiological characteristics of duplicated right adrenal veins (DRAVs) and evaluate the diagnostic impact of adrenal venous sampling (AVS) in primary aldosteronism.METHODSDRAVs were retrospectively identified among patients who underwent segmental AVS between April 2017 and March 2020. DRAVs were defined as main or accessory according to the drainage area. The diameter, position, hormone levels, and treatment plan based on AVS were compared between main and accessory RAVs, using the Wilcoxon rank-sum test.RESULTSFourteen of 432 patients (3.2%) were diagnosed with DRAVs. On venography, the mean diameters of the main and accessory side were 3±0.63 mm and 2.1±0.41 mm, respectively, and were significantly different (p < 0.001). The mean relative position in craniocaudal direction of main and accessory veins from the adrenal caudal edge on computed tomography was 65.5%±16.0%, and 48.1%±16.8%, respectively, which was significantly different (p = 0.007). The left–right positions and hormone levels were not significantly different. Based on conventional AVS, the treatment plan between DRAVs was not changed in six of eight patients, but changed from surgery to medication in two patients with right aldosterone-producing adenoma (APA)/microadenoma based on segmental AVS findings.CONCLUSIONDRAVs, in which the main RAV was thicker and more cranially located than the accessory RAV were rare. Depending on blood sampled from either of DRAVs, the diagnosis made through conventional AVS might change treatment approach from surgery to medication, especially with right APA. Hence, their identification is important to make an accurate subtyping by AVS

Structural basis of enzyme activity regulation by the propeptide of l-lysine α-oxidase precursor from Trichoderma viride

Harmuful proteins are usually synthesized as inactive precursors and are activated by proteolytic processing. l-Amino acid oxidase (LAAO) is a flavoenzyme that catalyzes the oxidative deamination of l-amino acid to produce a 2-oxo acid with ammonia and highly toxic hydrogen peroxide and, therefore, is expressed as a precursor. The LAAO precursor shows significant variation in size and the cleavage pattern for activation. However, the molecular mechanism of how the propeptide suppresses the enzyme activity remains unclear except for deaminating/decarboxylating Pseudomonasl-phenylalanine oxidase (PAO), which has a short N-terminal propeptide composed of 14 residues. Here we show the inactivation mechanism of the l-lysine oxidase (LysOX) precursor (prLysOX), which has a long N-terminal propeptide composed of 77 residues, based on the crystal structure at 1.97 Å resolution. The propeptide of prLysOX indirectly changes the active site structure to inhibit the enzyme activity. prLysOX retains weak enzymatic activity with strict specificity for l-lysine and shows raised activity in acidic conditions. The structures of prLysOX crystals that soaked in a solution with various concentrations of l-lysine have revealed that prLysOX can adopt two conformations; one is the inhibitory form, and the other is very similar to mature LysOX. The propeptide region of the latter form is disordered, and l-lysine is bound to the latter form. These results indicate that prLysOX uses a different strategy from PAO to suppress the enzyme activity and suggest that prLysOX can be activated quickly in response to the environmental change without proteolytic processing

Characterization of candidate intermediates in the Black Box of the ecdysone biosynthetic pathway in Drosophila melanogaster: Evaluation of molting activities on ecdysteroid-defective larvae

Early steps of the biosynthetic pathway of the insect steroid hormone ecdysone remains the “Black Box” wherein the characteristic ecdysteroid skeleton is built. 7-Dehydrocholesterol (7dC) is the precursor of uncharacterized intermediates in the Black Box. The oxidation step at C-3 has been hypothesized during conversion from 7dC to 3-oxo-2, 22, 25-trideoxyecdysone, yet 3-dehydroecdysone is undetectable in some insect species. Therefore, we first confirmed that the oxidation at C-3 occurs in the fruitfly, Drosophila melanogaster using deuterium-labeled cholesterol. We next investigated the molting activities of candidate intermediates, including oxidative products of 7dC, by feeding-rescue experiments for Drosophila larvae in which an expression level of a biosynthetic enzyme was knocked down by the RNAi technique. We found that the administration of cholesta-4, 7-dien-3-one (3-oxo-Δ4, 7C) could overcome the molting arrest of ecdysteroid-defective larvae in which the expression level of neverland was reduced. However, feeding 3-oxo-Δ4, 7C to larvae in which the expression levels of shroud and Cyp6t3 were reduced inhibited molting at the first instar stage, suggesting that this steroid could be converted into an ecdysteroid-antagonist in loss of function studies of these biosynthetic enzymes. Administration of the highly conjugated cholesta-4, 6, 8(14)-trien-3-one, oxidized from 3-oxo-Δ4, 7C, did not trigger molting of ecdysteroid-defective larvae. These results suggest that an oxidative product derived from 7dC is converted into ecdysteroids without the formation of this stable conjugated compound. We further found that the 14α-hydroxyl moiety of Δ4-steroids is required to overcome the molting arrest of larvae in loss of function studies of Neverland, Shroud, CYP6T3 or Spookier, suggesting that oxidation at C-14 is indispensable for conversion of these Δ4-steroids into ecdysteroids via 5β-reduction

Thermal Reformation of Polystyrene Using Metal Oxide as Redox Catalyst

While plastic has been regarded as a useful and cost-effective material, there is growing global concern about its disposal. Chemical recycling presents a promising solution to this issue. This study explores the utilization of vanadium oxide as a redox catalyst to effectively decompose polystyrene into industrially useful CO. By heating polystyrene with V2O5 under an inert gas atmosphere, CO was successfully produced accompanied with CO2 as the primary by-product. Adding 5 wt% iron to V2O5 improved the selectivity of CO production without compromising gas yield. X-ray diffraction analysis indicated that V2O5 acted as an oxygen source and turned into V2O4 and V6O13 after the reaction. This process enables polymer reformation at lower temperatures than conventional methods, making it an energy-efficient chemical recycling strategy. Additionally, V2O4 and V6O13 generated during the process were easily oxidized to V2O5 through heating under atmospheric conditions. As both polymer reformation and oxidation are exothermic reactions, the proposed reaction scheme can be used as a thermally efficient chemical recycling process