Long-range fiber-based laser Doppler vibrometer using Faraday rotator for polarization-rotation compensation.

In this paper, we report a method for extending distance of an optical fiber-based laser Doppler vibrometer system. This method uses a Faraday rotator (FR) to compensate polarization rotation in an installed long-range optical fiber. The construction of the proposed system is simple and achieved only by adding the FR to the sensing head unit, leading to stable and highly reliable vibration measurement even by using a long-range optical fiber exceeding kilometer. Experiments by using 100-m and 10-km long standard single mode fibers with emulated polarization rotation verified advantages of the proposed method; the system performances retained almost the same values even when the polarization state of reflected light was randomly rotated in installed optical fibers.

In-hospital recurrence and functional outcome between ischemic stroke caused by intracranial arterial dissection and intracranial atherosclerosis: Retrospective cohort study of the nationwide multicenter registry.

BACKGROUND: Intracranial arterial dissection (ICAD) and intracranial atherosclerotic stenosis (ICAS) are often difficult to differentiate, and studies on their background factors and prognosis are scarce. Information on prognosis, including recurrence, is necessary for stroke care, and clarification of epidemiological and clinical differences between the two diseases is important for appropriately handling their heterogeneity. This study aimed to determine the association of ICAD and ICAS with in-hospital recurrence and prognosis and compare their background and clinical findings. METHODS: In this multicenter cohort study, we retrospectively analyzed data from the Saiseikai Stroke Database. Adults with ischemic stroke caused by ICAD or ICAS were included in this study. Patients' backgrounds and clinical findings were compared between the ICAD and ICAS groups. The outcome showed an association of ICAD with in-hospital recurrence of ischemic stroke and poor functional outcome relative to ICAS. Multivariable logistic regression analyses were performed to calculate the adjusted odds ratios (ORs) for ICAD with 95% confidence intervals (CIs) for each outcome. RESULTS: Among 15,622 patients registered in the Saiseikai Stroke Database, 2,020 were enrolled (ICAD group: 89; ICAS group: 1,931). In the ICAD group, 65.2% of the patients were aged <64 years. Vascular lesion location was more common in ICAD with the vertebral artery [42 (47.2%)], anterior cerebral artery [20 (22.5%)], and middle cerebral artery (MCA) [16 (18.0%)], and in ICAS with MCA 1046 (52.3%). Multivariable logistic regression analyses of the association between ICAD and in-hospital recurrence and poor functional outcome yielded a crude OR (95% CI) of 3.26 (1.06-9.97) and 0.97 (0.54-1.74), respectively, relative to ICAS. CONCLUSION: ICAD was associated with a higher in-hospital recurrence than ICAS; however, there was no significant difference in prognosis between the two groups. Differences in background characteristics and vessel lesions may be of interest in these two diseases.

DARE: Distill and Reinforce Ensemble Neural Networks for Climate-Domain Processing.

Natural-language processing is well positioned to help stakeholders study the dynamics of ambiguous Climate Change-related (CC) information. Recently, deep neural networks have achieved good results on a variety of NLP tasks depending on high-quality training data and complex and exquisite frameworks. This raises two dilemmas: (1) the networks are highly reliant on powerful hardware devices and processing is time-consuming, which is not only inconducive to execution on edge devices but also leads to resource consumption. (2) Obtaining large-scale effective annotated data is difficult and laborious, especially when it comes to a special domain such as CC. In this paper, we propose a CC-domain-adapted BERT distillation and reinforcement ensemble (DARE) model for tackling the problems above. Specifically, we propose a novel data-augmentation strategy which is a Generator-Reinforced Selector collaboration network for countering the dilemma of CC-related data scarcity. Extensive experimental results demonstrate that our proposed method outperforms baselines with a maximum of 26.83% on SoTA and 50.65× inference time speed-up. Furthermore, as a remedy for the lack of CC-related analysis in the NLP community, we also provide some interpretable conclusions for this global concern.

Case Report: Shortest Course of Pediatric Paroxysmal Hemicrania.

Paroxysmal hemicrania (PH) is a rare primary headache disorder, especially among children. We describe herein a case with the shortest course of pediatric PH among previously reported cases, and the first case report of Japanese pediatric PH. An 11-year-old boy was referred to our clinic by his primary care physician for a headache evaluation. He had been complaining of severe, sharp, pulsating headache for 5 days. Attacks were restricted to the left side with a duration ranging from 2 to 20 minutes, 20-30 times a day. Attacks were associated with left autonomic symptoms (conjunctival injection, lacrimation, nasal congestion, eyelid edema, and ptosis). Two days after we prescribed indomethacin at 0.9 mg/kg/day, the patient was headache free. He stopped taking indomethacin 14 days after consultation because of drug eruptions. As of the time of writing, more than 1 year later, he has experienced no recurrence of headache. This case indicates the importance of improving awareness among general doctors regarding PH in children, and of conducting further investigations about low-dose, short-term indomethacin treatment.

Intravenous immunoglobulin preparation prevents the production of pro-inflammatory cytokines by modulating NFκB and MAPKs pathways in the human monocytic THP-1 cells stimulated with procalcitonin.

OBJECTIVE: In the previous investigations, we showed that intravenous immunoglobulin (IVIG) prevented cytokine release in procalcitonin (PCT)-stimulated monocytic cells. The aim of the present study was to investigate the underlying mechanisms of inhibition of IVIG on cytokine production in PCT-stimulated THP-1 cells. METHODS: THP-1 cells treated with phorbol myristate acetate were stimulated with PCT. The protein levels of pro-inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and high-mobility group box 1 (HMGB1)] in the culture supernatants were determined using enzyme-linked immunosorbent assay kits. The mRNA level of TNF-α was determined by reverse transcription-polymerase chain reaction. The phosphorylations of nuclear factor kappa B (NFκB) and the mitogen-activated protein kinases (MAPKs) were determined by Western blotting. RESULTS: IVIG reduced mRNA expression and protein production of TNF-α in PCT-stimulated THP-1 cells. Not only IVIG but also both the Fc fragment and the F(ab')2 fragment inhibited PCT-induced TNF-α, IL-6, and HMGB1 production. Furthermore, IVIG and its fragments suppressed PCT-induced phosphorylations of NFκB, p38 MAPK, and c-Jun N-terminal kinase. CONCLUSIONS: Our results indicate that IVIG prevents PCT-induced cytokine production mediated by not only the Fab region but also the Fc region. The activity of IVIG and its fragments might be regulated by inhibiting NFκB and MAPKs pathways in THP-1 cells.

Regional Disparities in Hyperacute Treatment and Functional Outcomes after Acute Ischemic Stroke in Japan.

AIM: This study investigated the impact of rurality on acute ischemic stroke (AIS) outcomes, emphasizing the hyperacute phase, in which immediate care is crucial. METHODS: This retrospective cohort study analyzed data from a large Japanese hospital network covering AIS patients from 2013-2021, was analyzed. The focus was on patients admitted within 4.5 h of the onset, using the Rurality Index for Japan (RIJ) to categorize patients into rural or urban groups. This study examined treatment methods (intravenous thrombolysis [IVT] and mechanical thrombectomy [MT]) and functional outcomes measured using the modified Rankin Scale (mRS), where scores of 3-6 indicated poor outcomes. Multilevel logistic regression was used to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for poor outcomes baSed on rurality. The study also evaluated the population-attributable fraction (PAF) to estimate potential outcome improvements in urban settings. RESULTS: Of 27,691 patients, 17,516 were included in the total cohort and 4,954 in the hyperacute cohort. Urban patients constituted 73.7% (12,902), with higher IVT (5.2%) and MT (3.6%) rates than rural patients (4.1% IVT, 2.0% MT). Poor mRS outcomes were more common in rural areas than in urban areas, with adjusted ORs of 1.30 (1.18-1.43) in the total cohort and 1.43 (1.19-1.70) in the hyperacute cohort. The PAF for poor outcomes due to rural residency was 14.8% (0.5%-31.0%). CONCLUSION: This study demonstrated a notable association between rurality and poorer AIS outcomes in Japan, particularly in the hyperacute phase.

Hashimoto's encephalopathy as a treatable adult-onset cerebellar ataxia mimicking spinocerebellar degeneration.

BACKGROUND: Hashimoto's encephalopathy (HE) presents with a variety of neurologic and neuropsychiatric features. In this study, we investigated the clinical and immunological profiles of the cerebellar ataxic form of HE. METHODS: The clinical features, treatments, laboratory features, brain imaging, and serum anti-NH(2)-terminal of α-enolase autoantibodies (anti-NAE Abs), a useful diagnostic marker for HE, were investigated in 13 patients who presented with sporadic adult-onset cerebellar ataxia and fulfilled the HE diagnostic criteria (antithyroid Abs and responsiveness to immunotherapy). RESULTS: All of the patients presented with truncal ataxia, but nystagmus was uncommon (17%). Eight patients had an insidious onset that mimicked spinocerebellar degeneration (SCD), but brain imaging showed little or no cerebellar atrophy in all of the patients. Those patients with serum anti-NAE Abs (n = 8) did not have nystagmus and tended to respond better to immunotherapy than the anti-NAE Ab-negative patients. CONCLUSION: The present study suggests that insidious adult-onset and truncal ataxia are common in the cerebellar ataxic form of HE, which mimics SCD, but that nystagmus and severe cerebellar atrophy are uncommon. Antithyroid and anti-NAE Abs may be useful for diagnosing cerebellar ataxic HE.

Zinc Administration Favorably Affects Prophylactic Therapy-refractory Migraine Attacks: A Case Series.

Notably, certain nutrients are effective in preventing migraine. Nonetheless, zinc replacement therapy for migraine treatment has yet to be explored. We herein report four patients with migraine who were refractory to prophylactic therapy and whose headache frequency and severity improved with zinc supplementation. Zinc administration may be an option for treating patients with prophylaxis-refractory migraine. Further investigation is required to determine the efficacy of zinc replacement therapy as a treatment option for migraine.

Intravenous immunoglobulin prevents release of proinflammatory cytokines in human monocytic cells stimulated with procalcitonin.

OBJECTIVE: The aim of this study was to investigate whether the stimulation of monocytic cells with procalcitonin (PCT) results in the release of proinflammatory cytokines. The effects of intravenous immunoglobulin (IVIG) on the production of cytokines from the cells stimulated with PCT were also studied. MATERIALS AND METHODS: Cultured monocytic cells [THP-1 cells treated with phorbol myristate acetate or peripheral blood mononuclear cells (PBMCs)] were stimulated with PCT. The protein levels of proinflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and high mobility group box-1] in the culture supernatants were determined by ELISA kits. The concentration of PCT-specific IgG antibody in IVIG was measured using a specific ELISA. RESULTS: PCT induced the release of cytokines from THP-1 cells in a time- and dose-dependent manner. IVIG inhibited the release of cytokines from the cells stimulated with PCT. It was confirmed that IVIG also inhibited TNF-α release in the same dose range for PBMCs stimulated with PCT. The presence of PCT-specific IgG antibody was detected in the tested IVIG, which might be one of the mechanisms. CONCLUSIONS: PCT induced the release of proinflammatory cytokines from THP-1 cells and PBMCs. The function of PCT was prevented by the presence of IVIG.

Ubiquitination and downregulation of ErbB2 and estrogen receptor-alpha by kinase inhibitor MP-412 in human breast cancer cells.

ErbB2 has been proven to be an important target for breast cancer therapy. MP-412 is a dual ErbB2 and epidermal growth factor receptor tyrosine kinase inhibitor belonging to an irreversible-type anilinoquinazoline derivative. We demonstrate herein that along with the kinase inhibition, MP-412 has the ability to induce ubiquitination, internalization, and degradation of ErbB2 in several human breast cancer cell lines at concentrations relatively higher than those required for kinase inhibition. Another irreversible inhibitor, CI-1033, showed similar activity, while the reversible compounds were ineffective, suggesting a crucial role of covalent bonding functionality in these effects. In MCF7 cells, MP-412 depleted not only ErbB2 but also estrogen receptor (ER)-α, and to some extent, affected Raf-1, while MP-412 activated Hsp70 expression. Moreover, we observed that MP-412 increased immunocomplexing of Hsp70 with ErbB2 and ER-α, with simultaneous induction of ubiquitination of these client proteins. Furthermore, in combination with proteasome inhibitor, MP-412 resulted in the noticeable accumulation of ErbB2 and ER-α in the detergent insoluble fraction of cell lysates. These results suggest that MP-412 acts as an inhibitor of Hsp90 function, whereas MP-412 did not bind directly to ATP-binding site of Hsp90, unlike geldanamycin. We also found that new protein synthesis was involved in the activity of MP-412 on Hsp90 modulation. Since downregulation of ErbB2 and ER-α by accelerating the ubiquitin-proteolysis system will become an attractive approach for breast cancer therapy, we expect MP-412 to be a lead compound for the drug design and the development of such agents.

Acute central nervous system vasculitis as a manifestation of neurosarcoidosis: A case report and literature review.

Neurosarcoidosis (NS) affects various sites of the central nervous system, including the cranial nerve, meninges, brain parenchyma, hypothalamus, and pituitary gland. NS rarely causes intracerebral vasculitis and subsequent strokes, or cerebral infarction and hemorrhage, which are associated with high mortality. Herein, we report a 71-year-old woman's case of stroke associated with NS, which showed aggressive cerebral vasculitis with brain herniation; it was resolved with corticosteroid therapy after accurate histopathological diagnosis. This case highlights the necessity of expecting NS to sometimes follow an aggressive course, presenting with vasculitis. Most patients with NS satisfactorily respond to corticosteroids, but this is not always the case. In cases of unfamiliar ischemic or hemorrhagic lesions, the possibility of NS must be considered.

[A comparative study of three cases of neuronal intranuclear inclusion disease (NIID)].

All three patients were men in their 70s. All cases were solitary onset and the chief complaint was gait disturbance. All patients had miosis and limb and trunk ataxia, MMSE score was declined in two patients, and FAB score was declined in all patients. Head MRI showed leukoencephalopathy, cerebellar atrophy, and DWI high intensity signal in corticomedullary junction. However, two of the three patients were not followed up without further examination. Skin biopsies in all cases showed ubiquitin-positive and p62-positive intranuclear inclusions. Genetic testing showed CGG repeat expansion of NOTCH2NLC. The diagnosis of neuronal intranuclear inclusion disease (NIID) was made based on the above findings in all cases. Most patients are diagnosed with NIID due to memory loss, but sometimes they are diagnosed due to gait disturbance with ataxia. It is important to proceed with the diagnosis by skin biopsy and genetic diagnosis based on the characteristic MRI findings of the head.

Adult Krabbe Disease That Was Successfully Treated with Intravenous Immunoglobulin.

Krabbe disease involves the accumulation of neurotoxic metabolites due to lysosomal galactocerebrosidase enzyme deficiency, which results in widespread demyelination of central and peripheral nerves. Generally, Krabbe disease presents as spastic paraplegia with a slow progressive course; however, some cases may show clinical symptoms similar to those of chronic inflammatory demyelinating polyneuropathy (CIDP). No previously reported studies have investigated the efficacy of intravenous immunoglobulin (IVIg) for treating Krabbe disease, and reporting a case involving IVIg treatment may be informative in the clinical setting. A 14-year-old girl who developed Guillain-Barré syndrome-like limb weakness was administered IVIg, and her limb weakness improved. At 16 years old, she developed abnormal sensory perception and weakness of both upper limbs. A nerve conduction study revealed demyelination, which led us to suspect CIDP. IVIg was administered, and her symptoms gradually improved. A nerve biopsy, enzyme activity, and genetic test results indicated adult Krabbe disease. In some cases, IVIg may be an effective treatment for Krabbe disease.

[A case of myasthenia gravis developed during pembrolizumab administration, suggesting an excitation-contraction connection disorder].

The patient was a 50-year-old woman. Pembrolizumab was started for bladder cancer recurrence. From the day after the second administration, ptosis, diplopia, restriction of eye movement, muscle weakness, fatigue resistance, increase in serum creatine kinase (CK) level, and muscle pain were observed. Tests for anti-acetylcholine receptor (AChR) antibody and anti-muscle specific kinase (MuSK) antibody were negative. Electrophysiological examination of the neuromuscular junction showed negative results, and electromyography revealed no myogenic changes. We considered that the immune checkpoint inhibitor caused neuromuscular damage. The patient's symptoms were gradually improved by immunotherapy, such as steroid and plasma exchange. In this case, tests for the anti-titin antibody, an anti-striational antibody, were positive. We considered that myasthenia gravis-like symptoms and serum CK level elevation might have been caused by impairment of excitation-contraction coupling, and not the neuromuscular junction.

Effect of Lomerizine Hydrochloride on Preventing Strokes in Patients With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an orphan disease clinically characterized by migraine, recurrent strokes, and dementia. Currently, there are no disease-modifying therapies, and it is difficult to prevent cerebral ischemic events in CADASIL patients by conventional antithrombotic medication. We hypothesized that an antimigraine agent, lomerizine hydrochloride, may prevent strokes in CADASIL patients, based on its effect on increasing cerebral blood flow. SUBJECTS AND METHODS: This was an open-labeled clinical trial in which 30 adult CADASIL patients received lomerizine at 10 mg/d. Numbers of symptomatic strokes during the 2 years after the start of lomerizine administration were compared with those in the 2 years before its initiation. The effect of lomerizine on preventing strokes was evaluated based on the incidence rate ratio (IR) calculated with the Mantel-Haenszel method. RESULTS: When including all 30 patients (analysis 1), the IR was less than 1 (0.46; 95% confidence interval [CI], 0.19-1.12) but did not reach significance. To evaluate the effect of lomerizine on secondary prevention, subgroups of 15 patients with stroke episodes occurring any time before lomerizine administration (analysis 2) and 10 patients with stroke episodes during the 2 years before lomerizine administration (analysis 3) were analyzed. The IR values were 0.33 (95% CI, 0.12-0.94) in analysis 2 and 0.17 (95% CI, 0.04-0.67) in analysis 3. CONCLUSIONS: Our results suggest the effect of lomerizine on preventing secondary stroke in CADASIL patients.

Antitumor activity of a dual epidermal growth factor receptor and ErbB2 kinase inhibitor MP-412 (AV-412) in mouse xenograft models.

Although epidermal growth factor receptor (EGFR) kinase inhibitors are effective for the treatment of non-small cell lung cancer (NSCLC), the emergence of mutations resistant to these inhibitors, such as T790M, has become a clinical problem. Recently, ErbB2 mutations have also been identified in a small number of NSCLC patients. Therefore, novel therapies to overcome these mutations are desirable. We describe the antitumor activity of MP-412 (AV-412), a dual EGFR/ErbB2 kinase inhibitor, against three lung cancer models with EGFR and ErbB2 mutations and also against various human xenografts with overexpression of these receptors. MP-412 inhibited phosphorylation of EGFR and its downstream signaling in NCI-H1650 and NCI-H1975 cell lines, which harbor the E746-A750 deletion and L858R + T790M point mutations, respectively, in EGFR. MP-412 inhibited the growth of these cell lines in vitro and in vivo, whereas the precedent kinase inhibitors lapatinib, erlotinib, and gefitinib were ineffective against NCI-H1975 cells in vivo. Furthermore, MP-412 inhibited ErbB2 signaling in the NCI-H1781 cell line, which harbors the G776V,C insertion in ErbB2, and correlated with its antiproliferation activity. When its antitumor spectrum was further explored in several cancer types overexpressing EGFR or ErbB2, MP-412 showed potent activity in KPL-4 and DU145 xenografts, in which lapatinib was ineffective. MP-412 also inhibited tumor models in which conventional chemotherapies were less effective. These results suggest that MP-412 is a potent dual inhibitor with the potential for treating solid cancers that overexpress EGFR or ErbB2, including NSCLC cells harboring mutations resistant to the first generation of kinase inhibitors.

Monitoring technique for waveform distortion of 160 Gb/s signal by prescaled-clock tone detection using EA modulator.

In order to monitor quality of ultra high bit-rate optical signals in a future optical network, such as 160 Gb/s, a simple monitoring technique is required. Therefore, a novel waveform monitoring technique by prescaled-clock tone detection was proposed in a previous report. In this paper, detailed principle of the proposed technique was explained. The monitoring technique is based on an asynchronous beat signal generation using an elecro-absorption modulator (EAM) and is able to separately observe waveform distortion caused by accumulated chromatic dispersion (CD), polarization mode dispersion (PMD) and optical signal-to-noise ratio (OSNR) degradation. The verification of concepts was performed by experiments, in which 1 GHz pre-scaled signals were employed to monitor distortion of OTDM 160 Gb/s carrier suppressed return-to-zero (CS-RZ) signals. Furthermore, applicability to Q factor estimation was verified by an experiment. In addition, an observation of 160 Gb/s signal by the proposed monitor was demonstrated over 120 minutes using an installed fiber in JGNII testbed.

[Effects of voriconazole and vascular lesions in invasion of aspergillosis into the central nerve system].

We report 2 patients showing invasion of aspergillosis into the central nerve system (CNS). Patient 1, an 81-year-old woman, underwent surgery for sphenoidal sinusitis. She developed cerebral infarction with unconsciousness on 12th postoperative day. CSF examination demonstrated pleocytosis with increased protein and aspergillus antigen. She was diagnosed as having invasion of aspergillosis into the CNS, and was treated with voriconazole. Her clinical manifestations and CSF findings markedly improved. However, the effects of voriconazole gradually attenuated and she demonstrated recurrence of the cerebral infarction. After 2 months, she died of systemic aspergillosis and sepsis. Autopsy studies. Severe atherosclerotic changes with calcification were demonstrated in the bilateral carotid and basilar arteries, and many aspergillus were clustered in the vessel walls. Granulomatous inflammatory lesions with aspergillus were also demonstrated in the area surrounding the chiasm. There were no massive infarcts or bleeding in the brain, but multiple small infarcts were present. Patinet 2, a 64-year-old man, showing bilateral visual loss, was receiving treatment with corticosteroids under a diagnosis of optic neuritis. Two weeks later, he developed cerebral infarction. CSF examination showed pleocytosis with increased protein and aspergillus antigen. He was diagnosed as having invasive aspergillosis from the sphenoidal sinusitis into the CNS. He was treated with voriconazole, and unconsciousness and CSF findings improved transiently. However, he developed a recurrence of the brain infarction and pneumonia and finally died 6 months later. Treatment by voriconazole was definitely effective in both patients, but both patients died of recurrent cerebral infarction, possibly due to resistance for voriconazole, or developing multicellular filamentous biofilms. Voriconazole is recommended as the first choice of antifungal agents for aspergillosis. Aspergillus infection is strongly invasive into arterial vessels. It is important to consider the possible occurrence of cerebrovascular disease when treating invasion of aspergillosis into the CNS.

Cerebral Toxoplasmosis Diagnosed by Nested-polymerase Chain Reaction in a Patient with Rheumatoid Arthritis.

A 65-year-old woman with rheumatoid arthritis (RA) visited our hospital because of right facial sensory hypoesthesia. Cerebral toxoplasmosis was suspected on brain magnetic resonance imaging. We discontinued methotrexate for RA and started a sulfamethoxazole/trimethoprim (ST) mixture. Although ST treatment was interrupted because of adverse reactions, her prognosis was favorable. The Toxoplasma 18S rDNA gene was detected by nested-polymerase chain reaction (PCR) from blood and cerebrospinal fluid. Detecting the Toxoplasma 18S rDNA gene by nested-PCR is useful for the diagnosis and safer than a brain biopsy. In addition, the discontinuation of immunosuppressants may be recommended in patients compromised by those immunosuppressants.

Unusual Clinical Sequelae of Kawasaki Disease-Symptomatic Extracranial Internal Carotid Stenosis in Young Adult.

BACKGROUND: Kawasaki disease (KD) is an acute systemic vasculitis that primarily affects the coronary artery, but it does not commonly affect the carotid artery. Cerebral infarction (CI) with internal carotid artery stenosis (ICS) in patients with KD has not been reported until now. We report a patient with CI as a remote-phase complication of KD. CASE PRESENTATION: A 32-year-old man presented with impaired consciousness. Magnetic resonance imaging and digital subtraction angiography confirmed CI and ICS. He successfully underwent carotid endarterectomy. The resected plaque had pathologic findings of KD, which suggested that the internal carotid artery suffered from chronic inflammation. CONCLUSION: KD in childhood may cause symptomatic ICS as a sequela of a remote phase.