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BackgroundMepolizumab (MPZ) has demonstrated efficacy in clinical trials for eosinophilic granulomatosis with polyangiitis (EGPA); however, few studies compare the disease course between patients treated with MPZ (MPZ group) and those who were not treated with MPZ (non-MPZ group) in real-world settings.ObjectivesThis study aimed to compare the disease course and outcomes between the two groups and assess the long-term efficacy of MPZ in a multicenter cohort in Japan. Methods: We enrolled 113 EGPA patients registered in the cohort until June 2023. Data on clinical characteristics, disease activity, organ damage, treatments, and outcomes were retrospectively collected. To minimize potential confounding factors, we conducted propensity score matching (PSM).ResultsAfter PSM, 37 pairs of matched patients were identified. Clinical characteristics, including age at disease onset, sex, disease duration at last observation, antineutrophil cytoplasmic antibody positivity at disease onset, Birmingham Vasculitis Activity Score (BVAS) at disease onset, and Five-factor score at disease onset, were comparable between the groups. The median BVAS at the last observation was 0 in both groups; however, more cases in the non-MPZ group exhibited elevated BVAS, resulting in a significantly higher BVAS in the non-MPZ group at the last observation (median; MPZ group: 0, non-MPZ group: 0, p=0.028). The MPZ group had significantly lower glucocorticoid (GC) doses at the last observation (median; MPZ group: 4 mg/day, non-MPZ group: 5 mg/day, p=0.011), with a higher proportion achieving a GC dose ≤ 4 mg/day at the last observation (MPZ group: 51.4%, non-MPZ group: 24.2%, p=0.027). Three models of multivariable logistic regression analyses were performed to identify factors associated with GC doses ≤ 4 mg/day at the last observation. In all models, achieving a GC dose ≤ 4 mg/day was positively associated with MPZ administration and inversely associated with asthma at disease onset. Finally, we evaluated the survival rates between the groups, and the 5-year survival rates were significantly higher in the MPZ group compared to the non-MPZ group (MPZ group: 100%, non-MPZ group: 81.3%, p=0.012).ConclusionMepolizumab not only contributes to disease activity control but also reduces the GC dose, which may lead to improved survival in EGPA patients.

Abstract Background Antipsychotics with dopamine (D2) receptor antagonism can be effective for emesis in cancer patients. Extrapyramidal symptoms (EPS) induced by typical antipsychotics can be exacerbated by other D2 receptor antagonists. We describe a case of persistent EPS induced by long‐term, intermittent administration of low‐dose olanzapine along with metoclopramide for emesis. Case Presentation A 59‐year‐old pancreatic cancer patient underwent chemotherapy for 7 months. He was referred to the psychiatry department because of restlessness and insomnia. Although he did not have obvious depressive symptoms, he was anxious about the cancer treatment. For chemotherapy‐induced nausea, he had been prescribed 5 mg of olanzapine intermittently for 7 months. He had last used the drug 9 days before presenting it to us. Additionally, he received metoclopramide and palonosetron as antiemetics. We considered akathisia and cancer‐related anxiety/agitation as possible causes of restlessness and insomnia, and prescribed clonazepam. However, his symptoms worsened, resulting in hospitalization. We reconsidered his symptoms as cancer‐related anxiety/agitation and prescribed quetiapine. Although it was effective, he had tremors and was assessed by a neurologist. Considering the clinical manifestations of rigidity, postural reflex disorder, and a mask‐like face, we suspected drug‐induced parkinsonism and replaced quetiapine with biperiden on the next day, leading to his discharge after 2 weeks. He did not have symptom recurrence even after discontinuation of biperiden. Conclusions Long‐term, intermittent administration of low‐dose antipsychotics with other antiemetics having D2 receptor antagonism can cause prolonged EPS. Especially in cancer patients, who often require polypharmacy, clinicians should consider exacerbated adverse effects due to drug interactions.

Abstract Background Good’s syndrome (GS) is characterized by immunodeficiency, and can lead to severe infection, which is the most significant complication. Although Mycobacterium rarely causes infection in patients with GS, disseminated nontuberculous mycobacterial (NTM) infection frequently occurs in GS patients that are also positive for the human immunodeficiency virus (HIV) or anti-interferon (IFN)-γ autoantibodies. Here, we report a rare case of GS with NTM without HIV or IFN-γ autoantibodies. Case presentation A 57-year-old Japanese male with GS and myasthenia gravis (treated with prednisolone and tacrolimus) was diagnosed with disseminated NTM infection caused by Mycobacterium abscessus subsp. massiliense. He presented with fever and back pain. Blood, lumbar tissue, urine, stool, and sputum cultures tested positive for M. abscessus. Bacteremia, spondylitis, intestinal lumber abscess, and lung infection were confirmed by bacteriological examination and diagnostic imaging; urinary and intestinal tract infections were suspected by bacteriological examination but not confirmed by imaging. Despite multidrug combination therapy, including azithromycin, imipenem/cilastatin, levofloxacin, minocycline, linezolid, and sitafloxacin, the patient ultimately died of the infection. The patient tested negative for HIV and anti-IFN-γ autoantibodies. Conclusions Since myasthenia gravis symptoms interfere with therapy, patients with GS and their physicians should carefully consider the antibacterial treatment options against disseminated NTM.

Abstract11 AbbreviationsBDI, Beck Depression Inventory; CFS, Chalder Fatigue Scale; EDSS, Expanded Disability Status Scale; HC, Health control subjects; MMSE, Mini-Mental State ExaminationMS, Multiple sclerosis; PASAT, Paced Auditory Serial Addition Test; QoL, Quality-of-lifeSD, Standard deviation; SDMT, Symbol Digit Modalities Test; VC, Visual cancellation;: Background: Depression and fatigue are debilitating symptoms in multiple sclerosis (MS), which affect cognitive function. This study investigated the association between depression and fatigue, and whether depression or fatigue influences cognition in MS patients. Methods: Twenty MS patients were included. The severity of fatigue was assessed using the Chalder Fatigue Scale (CFS), which classified CFS_Physical and CFS_Mental fatigue and MMSE. Depression was assessed using the Beck Depression Inventory (BDI). Attention deficit was evaluated using several tasks. The CFS scores, the BDI scores and performance during the attention tasks were compared between MS patients and healthy control subjects (HCs). Correlations between CFS sub-scores, BDI values, and participants’ attention performance were also investigated. Results: The total CFS, BDI, and MMSE scores were significantly worse in MS patients compared to HCs (p

Both amyloid plaques and neurofibrillary tangles are pathological hallmarks in the brains of patients with Alzheimer’s disease (AD). However, the constituents of these hallmarks, amyloid beta (Aβ) 40, Aβ42, and total Tau (t-Tau), have been detected in the blood of cognitively normal subjects by using an immunomagnetic reduction (IMR) assay. Whether these levels are age-dependent is not known, and their interrelation remains undefined. We determined the levels of these biomarkers in cognitively normal subjects of different age groups. A total of 391 cognitively normal subjects aged 23–91 were enrolled from hospitals in Asia, Europe, and North America. Healthy cognition was evaluated by NIA-AA guidelines to exclude subjects with mild cognitive impairment (MCI) and AD and by cognitive assessment using the Mini Mental State Examination and Clinical Dementia Rating (CDR). We examined the effect of age on plasma levels of Aβ40, Aβ42, and t-Tau and the relationship between these biomarkers during aging. Additionally, we explored age-related reference intervals for each biomarker. Plasma t-Tau and Aβ42 levels had modest but significant correlations with chronological age (r = 0.127, p = 0.0120 for t-Tau; r = −0.126, p = 0.0128 for Aβ42), ranging from ages 23 to 91. Significant positive correlations were detected between Aβ42 and t-Tau in the groups aged 50 years and older, with Rho values ranging from 0.249 to 0.474. Significant negative correlations were detected between Aβ40 and t-Tau from age 40 to 91 (r ranged from −0.293 to −0.582) and between Aβ40 and Aβ42 in the age groups of 30–39 (r = −0.562, p = 0.0235), 50–59 (r = −0.261, p = 0.0142), 60–69 (r = −0.303, p = 0.0004), and 80–91 (r = 0.459, p = 0.0083). We also provided age-related reference intervals for each biomarker. In this multicenter study, age had weak but significant effects on the levels of Aβ42 and t-Tau in plasma. However, the age group defined by decade revealed the emergence of a relationship between Aβ40, Aβ42, and t-Tau in the 6th and 7th decades. Validation of our findings in a large-scale and longitudinal study is warranted.

Purpose: While amyloid-β deposition in the cerebral cortex for Alzheimer's disease (AD) is often evaluated by amyloid positron emission tomography (PET), amyloid-β-related iron can be detected using phase difference enhanced (PADRE) imaging; however, no study has validated the association between PADRE imaging and amyloid PET. This study investigated whether the degree of hypointense areas on PADRE imaging correlated with the uptake of amyloid PET. Methods: PADRE imaging and amyloid PET were performed in 8 patients with AD and 10 age-matched normal controls. ROIs in the cuneus, precuneus, superior frontal gyrus (SFG), and superior temporal gyrus (STG) were automatically segmented. The degree of hypointense areas on PADRE imaging in each ROI was evaluated using 4-point scaling of visual assessment or volumetric semiquantitative assessment (the percentage of hypointense volume within each ROI). The mean standardized uptake value ratio (SUVR) of amyloid PET in each ROI was also calculated. The Spearman's correlation coefficient between the 4-point scale of PADRE imaging and SUVR of amyloid PET or between the semiquantitative hypointense volume percentage and SUVR in each ROI was evaluated. Results: In the precuneus, a significant positive correlation was identified between the 4-point scale of PADRE imaging and SUVR of amyloid PET (Rs = 0.5; P = 0.034) in all subjects. In the cuneus, a significant positive correlation was identified between the semiquantitative volume percentage of PADRE imaging and SUVR of amyloid PET (Rs = 0.55; P = 0.02) in all subjects. Conclusion: Amyloid-β-enhancing PADRE imaging can be used to predict the SUVR of amyloid PET, especially in the cuneus and precuneus, and may have the potential to be used for diagnosing AD by detecting amyloid deposition. [ABSTRACT FROM AUTHOR]

The present paper proposes a new approach for detecting music boundaries, such as the boundary between music pieces or the boundary between a music piece and a speech section for automatic segmentation of musical video data and retrieval of a designated music piece. The proposed approach is able to capture each music piece using acoustic similarity defined for short-term segments in the music piece. The short segmental acoustic similarity is obtained by means of a new algorithm called segmental continuous dynamic programming, or segmental CDP. The location of each music piece and its music boundaries are then identified by referring to multiple similar segments and their location information, avoiding oversegmentation within a music piece. The performance of the proposed method is evaluated for music boundary detection using actual music datasets. The present paper demonstrates that the proposed method enables accurate detection of music boundaries for both the evaluation data and a real broadcasted music program.

A class of games for finding a leader among a group of candidates is studied in detail. This class covers games based on coin tossing and rock-paper-scissors as special cases and its complexity exhibits similar stochastic behaviors: either of logarithmic mean and bounded variance or of exponential mean and exponential variance. Many applications are also discussed. [ABSTRACT FROM AUTHOR]

Background and objective: Loss of intermediolateral nucleus (IML) neurons is considered to play a major role in orthostatic hypotension (OH) of multiple system atrophy (MSA). In Parkinson disease (PD) and dementia with Lewy bodies (DLB), autonomic phenomena such as OH are common and attributed to dysfunction of sympathetic, parasympathetic, and visceral autonomic neurons. However, apart from MSA, fewreports have focused on the neuropathologic aspects in PD and DLB. Here we assessed IML degeneration as well as the fine myelinated fibers (FFs; maximum diameter less than 3 m) considered to be preganglionic sympathetic nerve fibers derived from IML neurons in PD, DLB, MSA, and age-matched normal controls (NC). Methods: We counted IML neurons and measured the diameter and number of myelinated fibers of the ventral root at the level of the 12th thoracic segment. Results: Compared to NC, number of IML neurons and density of FF were significantly reduced in PD (53% and 67%), DLB (47% and 71%) and MSA (27% and 42%). Compared to combined group of PD and DLB without OH (OH-), IML neurons in combined group of PD and DLB with OH (OH+) were significantly reduced (77%). Compared to NC, FF densities in OH-, OH+ were significantly reduced (74% and 59%). The mean ratio of small to large myelinated fibers in OH+ (1.18), but not that in OH- (1.58), was significantly lower than that in NC (3.17). Conclusions: We present neuropathological evidence that IML neurons and FFs in the ventral root are reduced in PD and DLB and that the reduction was more severe in the combined group of OH+ than in OH-. [ABSTRACT FROM AUTHOR]

This paper studies a special type of binomial splitting process. Such a process can be used to model a high dimensional corner parking problem as well as determining the depth of random PATRICIA (practical algorithm to retrieve information coded in alphanumeric) tries, which are a special class of digital tree data structures. The latter also has natural interpretations in terms of distinct values in independent and identically distributed geometric random variables and the occupancy problem in urn models. The corresponding distribution is marked by a logarithmic mean and a bounded variance, which is oscillating, if the binomial parameter p is not equal to 1/2, and asymptotic to one in the unbiased case. Also, the limiting distribution does not exist as a result of the periodic fluctuations. [ABSTRACT FROM AUTHOR]

Cathepsin L remained with the actomyosin (AM) fraction which was extracted from walleye pollock surimi after three repeats of washing followed by one cycle of dilution–precipitation. The main peak of cathepsin L separated from the peak of AM by Sepharose 6B gel filtration chromatography. This result suggests that cathepsin L is not associated with AM in AM solution, and the enzyme might have interaction with AM in washed meat. In the presence of 0.3–1.0 M NaCl, the activity of cathepsin L was much higher in acidic condition (pH 5.5). In neutral condition (pH 7.0), the activity of cathepsin L still has about 85% that of at pH 5.5 in 0.6 M NaCl. This indicates that the enzyme contributes to the gel deterioration of surimi even at neutral conditions. The activity of cathepsin L in walleye pollock surimi was not affected by a serine-type protease inhibitor, but was inhibited by a cysteine-type protease inhibitor, suggesting that cathepsin L is not activated by trypsin-type serine protease. PRACTICAL APPLICATIONS Walleye pollock is one of the most popular material fish used in the surimi production. But the gel strength of the kamaboko made from this fish was much low because of the modori phenomena which was believed to be due to the hydrolysis of myofibrillar components by proteinases contained in the surimi. In this study, cathepsin L was confirmed to be still remained in actomyosin fractions after conventional treatments. The activity of cathepsin L at neutral condition in the presence of 0.3–1.0 M NaCl was much higher than that at acidic condition, indicating the potential hydrolytic ability of capthepsin L in walleye Pollock surimi. [ABSTRACT FROM AUTHOR]

Abstract This paper proposes a new, efficient algorithm for extracting similar sections between two time sequence data sets. The algorithm, called Relay Continuous Dynamic Programming (Relay CDP), realizes fast matching between arbitrary sections in the reference pattern and the input pattern and enables the extraction of similar sections in a frame synchronous manner. In addition, Relay CDP is extended to two types of applications that handle spoken documents. The first application is the extraction of repeated utterances in a presentation or a news speech because repeated utterances are assumed to be important parts of the speech. These repeated utterances can be regarded as labels for information retrieval. The second application is flexible spoken document retrieval. A phonetic model is introduced to cope with the speech of different speakers. The new algorithm allows a user to query by natural utterance and searches spoken documents for any partial matches to the query utterance. We present herein a detailed explanation of Relay CDP and the experimental results for the extraction of similar sections and report results for two applications using Relay CDP. [ABSTRACT FROM AUTHOR]

[18F][3-(3-(3-Fluoropropyl)thio)-1,2,5-thiadiazol-4-yl]-1,2,5,6-tetrahydro-1-methylpyridine ([18F]FP-TZTP) is an M2 selective muscarinic agonist that may allow noninvasive studies of Alzheimer's disease with PET. 3-(3-(Propylthio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine (P-TZTP), a nonfluorinated analog of FP-TZTP, and unlabeled FP-TZTP inhibited [18F]FP-TZTP binding in vivo. Because muscarinic action of the loading dose of P-TZTP administered might have had pharmacological effects, the apparent inhibition might have resulted from reduced delivery rather than competition with receptor-binding. Therefore, we examined the effects of P-TZTP or FP-TZTP administration on cerebral blood flow (CBF) measured by the [14C]iodoantipyrine method and laser-Doppler flowmetry in rats. Statistically significant synchronous decreases in both CBF and mean arterial blood pressure (MABP) were observed within the first minute following administration. The decreases in both CBF and MABP were prevented by pretreatment with atropine methyl bromide (M-At), a peripheral muscarinic antagonist, and coadministration of M-At with either FP-TZTP or P-TZTP resulted in the same degree of inhibition of cerebral [18F]FP-TZTP-uptake 30 min after administration as observed without M-At. Also, with programmed infusions designed to produce constant arterial concentrations of [18F]FP-TZTP and FP-TZTP, which avoid changes in CBF, significant inhibition of [18F]FP-TZTP-binding by FP-TZTP was observed. These results indicate that inhibition of [18F]FP-TZTP-binding in the brain by P-TZTP or FP-TZTP in vivo occurs independently of their effects on CBF. The methods employed here may also be of interest to evaluate physiological effects of blocking agents utilized to validate other radiopharmaceuticals. Synapse 50:151–163, 2003. Published 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The eigenfunction expansion by Gegenbauer polynomials for the diffusion on a hypersphere is transformed into the diffusion for the Wright–Fisher model with a particular mutation rate. We use the Ito calculus considering stochastic differential equations. The expansion gives a simple interpretation of the Griffiths eigenfunction expansion for the Wright–Fisher model. Our representation is useful to simulate the Wright–Fisher model as well as Brownian motion on a hypersphere. [ABSTRACT FROM AUTHOR]