HYL1-CLEAVAGE SUBTILASE 1 (HCS1) suppresses miRNA biogenesis in response to light-to-dark transition.

The core plant microprocessor consists of DICER-LIKE 1 (DCL1), SERRATE (SE), and HYPONASTIC LEAVES 1 (HYL1) and plays a pivotal role in microRNA (miRNA) biogenesis. However, the proteolytic regulation of each component remains elusive. Here, we show that HYL1-CLEAVAGE SUBTILASE 1 (HCS1) is a cytoplasmic protease for HYL1-destabilization. HCS1-excessiveness reduces HYL1 that disrupts miRNA biogenesis, while HCS1-deficiency accumulates HYL1. Consistently, we identified the HYL1K154A mutant that is insensitive to the proteolytic activity of HCS1, confirming the importance of HCS1 in HYL1 proteostasis. Moreover, HCS1-activity is regulated by light/dark transition. Under light, cytoplasmic CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) E3 ligase suppresses HCS1-activity. COP1 sterically inhibits HCS1 by obstructing HYL1 access into the catalytic sites of HCS1. In contrast, darkness unshackles HCS1-activity for HYL1-destabilization due to nuclear COP1 relocation. Overall, the COP1-HYL1-HCS1 network may integrate two essential cellular pathways: the miRNA-biogenetic pathway and light signaling pathway.

Impact of COVID-19 Infection and Its Association With Previous Vaccination in Patients With Myasthenia Gravis in Korea: A Multicenter Retrospective Study.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. METHODS: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. RESULTS: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. CONCLUSION: This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.

A disproportionality analysis for the association of central nervous system demyelinating diseases with COVID-19 vaccination using the World Health Organization pharmacovigilance database.

BACKGROUND: Limited information is available on associations between COVID-19 vaccines and central nervous system (CNS) demyelinating diseases. OBJECTIVES: We investigated potential safety signals for CNS demyelinating diseases related to COVID-19 vaccines using the World Health Organization pharmacovigilance database. METHODS: Disproportionality analyses of CNS demyelinating disease following COVID-19 vaccination were performed by calculating the information component (IC) or the reporting odds ratio (ROR) compared with those for the entire database and for all other viral vaccines. RESULTS: We identified 715 cases of optic neuritis, 515 of myelitis, 220 of acute disseminated encephalomyelitis (ADEM), and 2840 total CNS demyelinating events adverse drug reactions from July 2020 through February 2022. For mRNA-based and ChAdOx1 nCoV-19 vaccines, there were no potential safety signals of disproportionality for optic neuritis (IC025 = -0.93, ROR025 = 0.38; IC025 = -1.76, ROR025 = 0.26), myelitis (IC025 = -0.69, ROR025 = 0.50; IC025 = -0.63, ROR025 = 0.53), ADEM (IC025 = -1.05, ROR025 = 0.33; IC025 = -1.76, ROR025 = 0.20), or overall CNS demyelinating disease events (IC025 = -0.66, ROR025 = 0.52; IC025 = -1.31, ROR025 = 0.34) compared with other viral vaccines. CONCLUSION: As with other viral vaccines, our disproportionality analyses indicate that the risk of COVID-19 vaccine-associated CNS demyelinating disease was low.

Associations of neuralgic amyotrophy with COVID-19 vaccination: Disproportionality analysis using the World Health Organization pharmacovigilance database.

INTRODUCTION/AIMS: There are limited studies on the association of COVID-19 vaccination with neuralgic amyotrophy (NA). Therefore, we evaluated the association between COVID-19 vaccination and the occurrence of NA. METHODS: We explored unexpected safety signals for NA related to COVID-19 vaccination through disproportionality analysis using VigiBase, the World Health Organization's pharmacovigilance database. RESULTS: On October 15, 2021, 335 cases of NA were identified in the database. The median time to onset of NA after vaccination was around 2 weeks. A significant signal of disproportionality of NA was observed for the ChAdOx1 nCoV-19 vaccine (AstraZeneca) (information component [IC]025  = 0.33, reporting odds ratio [ROR]025  = 1.30) and two mRNA-based COVID-19 vaccines (BNT162b2 [Pfizer and BioNTech] and mRNA-1273 [Moderna]) (IC025  = 1.74, ROR025  = 3.82) compared with the entire database. However, when compared with influenza vaccines, we did not detect any signal of disproportionality of NA for both the ChAdOx1 nCoV-19 vaccine (IC025  = -2.71, ROR025  = 0.05) and mRNA-based COVID-19 vaccines (IC025  = -1.38, ROR025  = 0.13). DISCUSSION: A weak association was observed between NA and COVID-19 vaccines. However, the risk did not surpass that of influenza vaccines.

Associations of Guillain-Barré syndrome with coronavirus disease 2019 vaccination: Disproportionality analysis using the World Health Organization pharmacovigilance database.

Vaccinations against the severe acute respiratory syndrome coronavirus 2 which causes COVID-19 have been administered worldwide. We aimed to investigate associations of COVID-19 vaccination with the occurrence of Guillain-Barré syndrome (GBS). We explored potential safety signals regarding the development of GBS using disproportionality analyses to compare COVID-19 vaccination with all adverse drug reaction (ADR) reports and influenza vaccines reported to VigiBase. As of October 15, 2021, a total of 2163 cases (0.13%) of GBS and its variants (including 46 cases of Miller-Fisher syndrome and 13 cases of Bickerstaff's encephalitis) were identified in entire ADR database after vaccination with the ChAdOx1 nCoV-19 (AstraZeneca, Cambridge, UK) or the two messenger RNA-based COVID-19 (BNT162b2; Pfizer and BioNTech) or mRNA-1273; Moderna) vaccines. The median time to onset of GBS after vaccination was around 2 weeks. The ChAdOx1 nCoV-19 and two messenger RNA-based COVID-19 vaccines demonstrated a higher risk for GBS against entire database (information component [IC]025  = 1.73 reporting odds ratio [ROR]025  = 3.51; IC025  = 1.07, ROR025  = 2.22, respectively). When compared with influenza vaccines, neither the ChAdOx1 nCoV-19 nor mRNA-based vaccines were found to be associated with greater risks of GBS (IC025  = -1.84, ROR025  = 0.11; IC025  = -1.86, ROR025  = 0.06, respectively). Although potential safety signals associated with GBS COVID-19 vaccines have been identified, the risk of GBS from COVID-19 vaccines were low and did not surpass those of influenza vaccines; however, because of the heterogeneity of the sources of information in the WHO pharmacovigilance database, further epidemiological studies are warranted to confirm these observations.

Miller Fisher syndrome following COVID-19 vaccines: A scoping review.

BACKGROUND AND PURPOSE: Miller Fisher syndrome (MFS), a variant of Guillain-Barré Syndrome (GBS), could be underestimated in evaluations of its adverse events (AEs) following COVID-19 vaccination. We aimed to identify and characterize MFS following COVID-19 vaccination. MATERIALS AND METHODS: Relevant studies reported on during the COVID-19 pandemic were identified in the MEDLINE, Embase, and other databases. RESULTS: Nine cases of MFS following COVID-19 vaccination from various regions were included. Unlike MFS following COVID-19 infection, patients with MFS following COVID-19 vaccination frequently presented with anti-GQ1b antibody positivity (44%, 4/9). Unlike GBS following COVID-19 vaccination, only two of nine (22%) cases of MFS following COVID-19 vaccination had developed after viral-vector-related vaccine administration. CONCLUSIONS: Miller Fisher syndrome following COVID-19 vaccination seems to have a different pathophysiology from MFS following COVID-19 infection and GBS following COVID-19 vaccination. This neurological syndrome with a rare incidence and difficulty in diagnosis should be considered an AE of COVID-19 vaccination.

Prevalence and incidence of neuromyelitis optica spectrum disorder and multiple sclerosis in Korea.

BACKGROUND: The epidemiology of neuromyelitis optica spectrum disorder and multiple sclerosis varies depending on the region and ethnicity. OBJECTIVE: To estimate the prevalence and incidence of neuromyelitis optica spectrum disorder and multiple sclerosis in Korea during 2010-2016. METHODS: We analyzed the National Health Insurance research database, which contains single-payer health insurance data collected in Korea. Neuromyelitis optica spectrum disorder was defined based on the 2006 Wingerchuk criteria (for 2010-2015), and the 2015 International Panel for Neuromyelitis Optica Diagnosis criteria (for 2016). Multiple sclerosis was defined by the 2005 International Panel criteria for multiple sclerosis. RESULTS: In 2016, the age-standardized prevalence per 100,000 persons was 2.56 (95% confidence interval: 2.43-2.7) for neuromyelitis optica spectrum disorder and 3.23 (95% confidence interval: 3.08-3.39) for multiple sclerosis. The age-standardized incidence of neuromyelitis optica spectrum disorder and multiple sclerosis were 0.73 (95% confidence interval: 0.66-0.8) and 0.50 (95% confidence interval: 0.44-0.56) per 100,000 persons in 2016. The prevalence of neuromyelitis optica spectrum disorder and multiple sclerosis have increased over time during 2010-2016 (18.5% and 5.4% annually; both p-trend < 0.001). The incidence of neuromyelitis optica spectrum disorder increased annually (10.0%, p-trend < 0.001), while the incidence of multiple sclerosis remained stable. CONCLUSION: While the prevalence of neuromyelitis optica spectrum disorder and multiple sclerosis are comparable in Korea, the incidence of neuromyelitis optica spectrum disorder is higher than that of multiple sclerosis. Both the prevalence and incidence of neuromyelitis optica spectrum disorder are rapidly increasing in Korea.

Efficacy of an RNA-based multigene assay with core needle biopsy samples for risk evaluation in hormone-positive early breast cancer.

BACKGROUND: Gene expression profiling provides key information for prognosis of breast cancer to establish treatment strategy. However, the genetic assessment should be available before induction of treatment to be useful for clinical practice. To evaluate the reliability of using needle biopsy samples for gene assays, we compared gene-expression profiling results between core needle biopsy (CNB) samples and surgical specimens in breast cancer. METHODS: Thirty-one paired, formalin-fixed, paraffin-embedded CNB and surgical specimen samples were selected from patients with hormone receptor-positive breast cancer. Total RNA was extracted from the samples and the risk classifications based on GenesWell BCT scores were compared. RESULTS: The BCT scores correlated between CNB samples and surgical specimens of hormone receptor-positive breast cancer (Pearson r = 0.66). The overall concordance rate of risk classification (high/low risk) was 83.9%. However, when the breast cancer does not contain intratumoral microcalcification, the concordance rate increased as 92.0%. And, when the breast cancer formed a solitary nodule (non-multifocal), the concordance rate increased up to 95.8%. CONCLUSION: Risk classification using the GenesWell BCT multigene kit with CNB samples could be considered reliable, when the breast cancer is a solitary nodule without intratumoral microcalcification. Such genetic profiling results should be helpful for establishing a treatment plan for hormone receptor-positive breast cancer before treatment induction.

Physical Activity Protects Against the Risk of Erosive Esophagitis on the Basis of Body Mass Index.

GOAL: To determine whether physical activity lowers the risk for erosive esophagitis on the basis of body mass index (BMI). BACKGROUND: Although previous studies have shown that physical activity is closely associated with erosive esophagitis, these data may be confounded by obesity. STUDY: In this retrospective study, we included 182,409 patients who underwent an upper endoscopy and were diagnosed with erosive esophagitis. The impact of the amount and intensity of physical activity on the risk for erosive esophagitis was analyzed based on BMI groups. Subjects were classified into three BMI groups with equal numbers in each group. RESULTS: Overall, 10.3% (n=18,859) of patients were diagnosed with erosive esophagitis. After adjusting for confounding factors, a greater amount of exercise [lower tertile: odd ratio (OR), 0.86; 95% confidence interval (CI), 0.77-0.96; middle tertile: OR, 0.91; 95%, CI 0.84-1.00; upper tertile: OR, 0.79; 95% CI, 0.73-0.85) and increased exercise intensity (lower tertile, moderate: OR, 0.61; 95% CI, 0.52-0.71; vigorous: OR, 0.51; 95% CI, 0.44-0.58; middle tertile, moderate: OR, 0.62; 95% CI, 0.55-0.70; vigorous: OR, 0.58; 95% CI, 0.51-0.65; upper tertile, moderate: OR, 0.58; 95% CI, 0.53-0.65; vigorous: OR, 0.58; 95% CI, 0.53-0.64) was associated with a decreased risk for erosive esophagitis in all 3 BMI groups. In addition, we observed that increased physical activity intensity notably decreased the risk for erosive esophagitis in subjects performing lesser physical activity, but slightly decreased the risk for erosive esophagitis in subjects performing more physical activity. CONCLUSION: Physical activity is inversely associated with erosive esophagitis.

Only estrogen receptor "positive" is not enough to predict the prognosis of breast cancer.

PURPOSE: Beginning in 2018, biomarkers including estrogen receptor (ER) status were incorporated in the 8th AJCC staging system. ER expression levels were not considered in these changes. We hypothesized that the levels of ER expression could affect the prognosis of breast cancer. METHODS: A retrospective review was conducted to identify all female patients with invasive breast cancer between 2003 and 2012. ER negative (group I), weakly ER-positive (group II), and strongly ER-positive (group III) were defined as Allred total scores of 0-2, 3-5, and 6-8, respectively. We examined a multigene panel, designated the BCT score, which is a newly developed prognostic model for predicting the risk of a distant metastasis. RESULTS: Among the 4949 patients enrolled in this study, 1310 (26.5%), 361 (7.3%), and 3277 (66.2%) were categorized as group I, II, and III, respectively. Median F/U duration was 57.8 months. Compared to group III, patients in group II were younger, had larger tumors, and were also more likely to have PR-negative tumors, HER-2 amplification, high Ki-67, and high nuclear grade. Between group II and III, there was a significant difference in OS (P = 0.0764, 0.909, and 0.010, respectively). After adjusting for additional factors that may affect OS, the HR for OS showed higher in group II than in group III. The baseline median BCT score indicated that lower ER expression was associated with significantly higher BCT score (P < 0.0001) and significantly more likely to have high risk group (P < 0.0001) relative to higher levels of ER expression group. CONCLUSION: ER expression levels affect the prognosis of breast cancer. The risk for patients with weakly ER-positive breast cancer should not be underestimated.

Identification of risk factors for sessile and traditional serrated adenomas of the colon by using big data analysis.

BACKGROUND AND AIM: Little is known about the risk factors associated with serrated polyps, because the early studies, which occurred before the new World Health Organization classification was introduced, included mixtures of serrated polyps. This study aimed to evaluate the risk factors associated with the presence of sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs) using big data analytics. METHODS: Using a case-control design, we evaluated the risk factors associated with the presence of SSAs and TSAs. Subjects who underwent colonoscopies from 2002 to 2012 as part of the comprehensive health screening programs undertaken at the Samsung Medical Center, Korea, participated in this study. RESULTS: Of the 48 677 individuals who underwent colonoscopies, 183 (0.4%) had SSAs and 212 (0.4%) had TSAs. The multivariate analysis determined that being aged ≥ 50 years (odds ratio [OR] 1.91, 95% confidential interval [CI] 1.27-2.90, P = 0.002) and a history of colorectal cancer among first-degree relatives (OR 3.14, 95% CI 1.57-6.27, P = 0.001) were significant risk factors associated with the presence of SSAs and that being aged ≥ 50 years (OR 2.61, 95% CI 1.79-3.80, P < 0.001), obesity (OR 1.63, 95% CI 1.12-2.36, P = 0.010), and a higher triglyceride level (OR 1.63, 95% CI 1.12-2.36, P = 0.010) were independent risk factors associated with the presence of TSAs. CONCLUSIONS: We used big data analytics to determine the risk factors associated with the presence of specific polyp subgroups, and individuals who have these risk factors should be carefully scrutinized for the presence of SSAs or TSAs during screening colonoscopies.

Searching the Footprints of Pioneers on Neurology: A Bibliometric Analysis.

BACKGROUND: We identify the most cited articles that have influenced the clinical practices of neurologists. METHODS: We first analyzed the top 100 cited articles published in 50 neurology journals with high impact factors. We collected all of the original articles on clinical neurology published in all 554 medical journals. The Institute for Scientific Information Web of Science search tools were used to identify the top 100 cited articles in the database of Journal Citation Reports since 1950, which were then manually reviewed to discover their contents. RESULTS: In the first part of analysis, the top 100 cited articles were all published in 17 journals, with 26 articles published in Neurology. The most frequent topic subject of neurodegeneration appeared in 40 articles. The second part of the analysis revealed that the top 100 cited articles were also all published in 17 journals, with 30 articles published in New England Journal of Medicine. In contrast to the first part of the analysis, stroke was the most frequent topic subject (in 38 articles). CONCLUSIONS: Our bibliometric analysis has yielded 2 detailed lists of the top 100 cited articles that were listed separately using different methods. This approach can provide information about the trends and academic achievements in the field of clinical neurology.

Citation Classics in Stroke: The Top-100 Cited Articles on Hemorrhagic Stroke.

BACKGROUND: Stroke is a disastrous disease and a major health burden worldwide, especially in Korea. Hemorrhagic stroke (HS) accounts for approximately 20% of all the types of strokes. It is important to be able to evaluate stroke diagnoses and evolving treatments. OBJECTIVE: We aimed to identify the top-100 cited articles and assess a paradigm shift that occurred in the field of HS. METHODS: We searched all articles that had been cited more than 100 times using the Web of Science citation search tool during January 2016. Among a total of 2,651 articles, we identified the top-100 cited articles on HS. RESULTS: The number of citations for the articles analyzed in this study ranged from 1,746 to 211, and the number of annual citations ranged from 125.6 to 5.5. Most of the articles that were published in Stroke (35%) and Journal of Neurosurgery (22%), originated in the United States (n = 56), were original articles (64%), and dealt with the natural history or etiology (n = 37) and vasospasm in subarachnoid hemorrhage (n = 8). CONCLUSIONS: We analyzed the top-100 cited articles in the field of HS based on citation rates. The results provide a unique perspective on historical and academic developments in this field.

Top-100 cited articles on Guillain-Barré syndrome: a bibliometric analysis.

Since the first description of Guillain-Barré syndrome (GBS) 100 years ago, the concept of this syndrome has changed remarkably. The purpose of our study was to identify and characterize the most-cited articles that have contributed to advancing the understanding of GBS. Based on the database of Journal Citation Reports, we selected 554 journals that were considered as potential sources of reports on studies related to clinical neurology and general medicine. The Web of Science search tools were used to identify the most-cited articles relevant to GBS or other variants in the selected journals. Of the selected articles, 18 were review articles and the remainder were original articles or included only a few case series. Among the original articles, 13 described basic research associated with immunological pathogenesis involving anti-ganglioside antibodies. Most of the original studies (42/64, 66%) published after 1990 evaluated anti-ganglioside antibodies that mediated axonal GBS or Miller Fisher syndrome, with only a small number of the papers involving electrodiagnostic medicine (n = 4). Our bibliometric analysis has yielded a detailed list of the top-100 cited articles in the field of GBS.

MiR 21-5p as a predictor of recurrence in young gastric cancer patients.

BACKGROUND AND AIM: It is generally assumed that gastric cancer (GC) in young patients has different clinicopathologic characteristics than that of elderly patients. Although recurrence is an important factor in determining prognosis, traditional clinicopathological factors are sometimes inadequate for predicting recurrence in individuals. Therefore, we aimed to identify miRNAs with the potential to predict recurrence in young patients. METHODS: Young patients (age <40 years) undergoing gastrectomy for potentially curable GC (stage III) at Asan Medical Center participated in this study. A total of 50 GC patients with (n = 28) and without (n = 22) GC recurrence were selected for analysis. miRNA microarrays were analyzed to screen tissue samples (n = 7), and we validated the selected miRNAs by quantitative PCR in validation samples (n = 43). RESULTS: Two miRNAs (hsa-miR-21-5p and hsa-miR-451a) identified in the microarray analysis were evaluated in the validation samples. Among the validation samples containing intratumoral stroma ≥ 70 (n = 35), hsa-miR-21-5p was more highly expressed in the recurrence group than in the nonrecurrence group (fold change 1.82, P = 0.03). In the validation samples with intratumoral stroma ≥ 70, the ΔCt of hsa-miR-21-5p, which was >3.35, had a sensitivity and specificity of 86.7% and 65.5%, respectively, for predicting recurrence, with an area under the ROC curve of 0.723. CONCLUSIONS: miR-21-5p may be useful as a predictor of recurrence in young GC patients whose tumors contain a high proportion of intratumoral stroma. The combination of this miRNA with conventional clinicopathological factors should allow patient prognoses to be more accurately predicted.

Prevalence and Risk Factors of Respiratory Viral Infections in Exacerbations of Chronic Obstructive Pulmonary Disease.

Exacerbations of chronic obstructive pulmonary disease (COPD) lead to high morbidity and mortality. Respiratory virus infection is considered as one of the important causes of COPD exacerbations. The aim of this study was to assess the prevalence of respiratory virus infection in COPD exacerbations and to find the factors associated with susceptibility to viral infections. Furthermore, we tried to examine if COPD exacerbations caused by viral infections have more severe clinical outcomes in comparison with those with non-viral causes. We enrolled the patients with acute exacerbations of COPD who were hospitalized in a university hospital, over a 2-year period. Nasopharyngeal swabs were taken and viruses were identified by multiplex polymerase chain reaction. A total of 278 episodes of COPD exacerbations were recorded in 213 patients with COPD (number of females = 73). Among the COPD exacerbations, viral infection was detected in 78 episodes (28.1%) from 67 subjects. The most common virus was rhinovirus (38.8%), followed by respiratory syncytial virus, coronavirus, influenza A, parainfluenza, adenovirus and metapneumovirus. In multivariate regression analysis adjusting for sex, age, BMI, lung function and history of exacerbations, female subjects were found to be significantly associated with viral infections in COPD exacerbations (Odds ratio 2.58, 95%CI 1.25-5.31, P = 0.010). The severity of COPD exacerbations were not different between positive and negative viral detections. In conclusion, the prevalence of viral infection was 28.1% in the hospitalized patients with COPD exacerbations. Moreover, female subjects are at significantly higher risk for viral infections in COPD exacerbations.

Motor unit number index (MUNIX) in the orbicularis oculi muscle of healthy subjects.

INTRODUCTION: The motor unit number index (MUNIX) refers to an electrophysiological method that measures the number of motor units in the surface electromyographic interference pattern (SIP) recorded during graded muscle contractions. MUNIX studies of limb muscles have been conducted, but MUNIX studies of bulbo-facial muscles have not been reported. METHODS: We assessed bilateral orbicularis oculi muscles using MUNIX, and the reference values and reproducibility of MUNIX and motor unit size index (MUSIX) were investigated in healthy subjects. RESULTS: In this study, MUNIX was applied successfully to the orbicularis oculi muscles and showed good reproducibility. The correlation coefficients for MUNIX and MUSIX were 0.803 and 0.592, respectively, and the coefficients of variation were 20.9% and 8.5%, respectively. CONCLUSIONS: The MUNIX procedure for the orbicularis oculi muscle would be a useful tool for evaluating bulbar symptoms, especially in amyotrophic lateral sclerosis.

Pattern difference of dissociated hand muscle atrophy in amyotrophic lateral sclerosis and variants.

INTRODUCTION: Split hand is considered to be a specific feature of amyotrophic lateral sclerosis (ALS). METHODS: We evaluated the pattern difference of intrinsic hand muscles of upper limb-onset ALS (UL-ALS), upper limb-onset progressive muscular atrophy (UL-PMA), brachial amyotrophic diplegia (BAD), and Hirayama disease (HD) by measuring objective electrophysiological markers. RESULTS: The abductor digiti minimi (ADM)/abductor pollicis brevis (APB) compound muscle action potential (CMAP) amplitude ratio was significantly higher in UL-ALS than other variants, but a considerable proportion of UL-ALS cases had an amplitude ratio in the range of other variants. Absent APB CMAP and abnormally high ADM/APB CMAP amplitude ratio (≥4) occurred only with UL-ALS. Conversely, an absent ADM CMAP was identified only in UL-PMA and BAD. CONCLUSIONS: The absolute ADM/APB CMAP amplitude ratio was not specific for ALS; however, several findings from simple electrophysiological measurements may help predict prognosis in patients with motor neuron diseases and may be early diagnostic markers for ALS.

Evaluation of alpha-fetoprotein as a screening marker for hepatocellular carcinoma in hepatitis prevalent areas.

The objective of this study was to establish modified cutoff values of serum alpha-fetoprotein (AFP) according to hepatitis status. While AFP is used as a serum marker in the diagnosis or monitoring of hepatocellular carcinoma (HCC), its use as a screening method to the general population is controversial. We evaluated its screening performance in a hepatitis prevalent East Asian population, and suggest different cutoff values according to the individual's hepatitis status. We evaluated the performance of AFP as a screening test in 48,123 consecutive Koreans during the period from March, 2012 to August, 2013 who underwent routine health checks at a single institution. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated with fixed cutoff and with modified cutoffs according the individual's hepatitis status. A total of 24 out of 48,123 subject (0.05%) were newly diagnosed with HCC after screening. Among the 1,874 subject with positive hepatitis B virus surface antigen (HBsAg), 17 (0.91%) developed HCC, compared with two out of 393 (0.51%) individuals with hepatitis C virus antibody (anti-HCV). Five out of 45,855 (0.01%) subject with neither HBsAg nor anti-HCV developed HCC. Compared to the performance of a fixed cutoff, specificity, PPV, and NPV improved without sacrificing sensitivity when applying modified cutoff. In conclusion, our findings suggest that AFP with modified cutoffs according to the individual's hepatitis status might be a useful screening marker for HCC in hepatitis prevalent areas.