Publications by authors named "Koji Fujita"

460 Publications

Long-Term Follow-Up of 12 Patients Treated with Bilateral Pallidal Stimulation for Tardive Dystonia.

Life (Basel) 2021 May 24;11(6). Epub 2021 May 24.

Department of Neurosurgery, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan.

Tardive dystonia (TD) is a side effect of prolonged dopamine receptor antagonist intake. TD can be a chronic disabling movement disorder despite medical treatment. We previously demonstrated successful outcomes in six patients with TD using deep brain stimulation (DBS); however, more patients are needed to better understand the efficacy of DBS for treating TD. We assessed the outcomes of 12 patients with TD who underwent globus pallidus internus (GPi) DBS by extending the follow-up period of previously reported patients and enrolling six additional patients. All patients were refractory to pharmacotherapy and were referred for surgical intervention by movement disorder neurologists. In all patients, DBS electrodes were implanted bilaterally within the GPi under general anesthesia. The mean ages at TD onset and surgery were 39.2 ± 12.3 years and 44.6 ± 12.3 years, respectively. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) performed the preoperative and postoperative evaluations. The average BFMDRS improvement rate at 1 month postoperatively was 75.6 ± 27.6% ( < 0.001). Ten patients were assessed in the long term (78.0 ± 50.4 months after surgery), and the long-term BFMDRS improvement was 78.0 ± 20.4%. Two patients responded poorly to DBS. Both had a longer duration from TD onset to surgery and older age at surgery. A cognitive and psychiatric decline was observed in the oldest patients, while no such decline ware observed in the younger patients. In most patients with TD, GPi-DBS could be a beneficial therapeutic option for long-term relief of TD.
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http://dx.doi.org/10.3390/life11060477DOI Listing
May 2021

Long-Term Outcomes and Evaluation of Hepatocellular Carcinoma Recurrence after Hepatitis C Virus Eradication by Direct-Acting Antiviral Treatment: All Kagawa Liver Disease Group (AKLDG) Study.

Cancers (Basel) 2021 May 8;13(9). Epub 2021 May 8.

Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan.

There are limited studies that have evaluated the long-term outcomes in patients with hepatocellular carcinoma (HCC) recurrence after direct-acting antiviral (DAA) treatment. In this retrospective study, we aimed to investigate the recurrence rates, recurrence factors, and prognosis of 130 patients who were treated with IFN-free DAA treatment after treatment for HCC. The median observation time was 41 ± 13.9 months after DAA treatment. The recurrence rates of HCC were 23.2%, 32.5%, 46.3%, and 59.4% at 6, 12, 24, and 36 months, respectively. A multivariate analysis showed that palliative treatment prior to DAA treatment (HR = 3.974, 95% CI 1.924-8.207, = 0.0006) and alpha-fetoprotein at sustained virological response 12 (HR = 1.048, 95% CI 1.016-1.077, = 0.0046) were associated with independent factors for HCC recurrence (HCC-R). The 12-, 24-, and 36-month overall survival rates were 97.6%, 94.0%, and 89.8%, respectively. The 12-, 24-, and 36-month survival rates of the non-recurrence and recurrence groups were 97.7%, 97.7%, and 94.1% and 97.6%, 92.3%, and 87.9%, respectively ( = 0.3404). The size of the main tumor lesion and the serological data were significantly improved at the time of HCC-R after DAA treatment. This study showed an improved prognosis regardless of recurrence rate, which suggests that DAA treatment in HCV patients should be considered.
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http://dx.doi.org/10.3390/cancers13092257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125844PMC
May 2021

Preoperative Radiographic Evaluation of Thoracic Flexibility and Compensation for Adult Spinal Deformity Surgery. How to Select Optimal Upper Instrumented Vertebra to Prevent Proximal Junctional Kyphosis.

Spine (Phila Pa 1976) 2021 May 21. Epub 2021 May 21.

Department of Orthopaedic Surgery, University of Yamanashi, Japan Department of Orthopaedic Surgery, Shinshu University, School of Medicine.

Study Design: Retrospective study of a cohort of consecutive patients.

Objective: (1) To clarify the usefulness and value of the difference in thoracic kyphosis (ΔTK) angle in various positions by imaging the patient standing, prone, and supine to evaluate TK flexibility and compensation, and (2) to establish optimal radiography to determine an appropriate thoracic level for upper instrumented vertebra (UIV) because a strategy to select an appropriate level to avoid proximal junctional kyphosis (PJK) remains elusive.

Summary Of Background Data: Postoperative reciprocal progression of TK is a significant risk factor for PJK. However, how to predict and prevent postoperative reciprocal progression of TK remains unclear. We hypothesized that preoperative evaluation of both TK flexibility and compensation is essential to predict PJK and determine the UIV level.

Methods: We included 144 consecutive patients with ASD, ≥2 years follow-up, and UIV Th9-11 in this retrospective cohort study. TK was measured from images with patients standing, prone, and supine. Supine ΔTK was calculated as standing TK - supine TK. Prone ΔTK was calculated as standing TK - prone TK. Receiver operating characteristic (ROC) curves were analyzed to determine the thresholds of supine ΔTK and prone ΔTK for PJK occurrence.

Results: PJK was observed in 64/144 (44%) patients 2 years postoperatively. Prone and supine ΔTKs were significantly larger in patients with PJK. A significant positive correlation between prone ΔTK and supine ΔTK was observed. When data from patients with and without PJK were plotted separately, a significantly higher proportion of patients with PJK had large prone and supine ΔTKs. The cutoff values of prone and supine ΔTKs for PJK risk were determined using ROC curve analysis.

Conclusions: Because of their significantly high risk for PJK, in patients with ASD and prone ΔTK > 11.5° and supine ΔTK > 18.5°, the upper-thoracic spine should be considered for UIV.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000004126DOI Listing
May 2021

Early effects of acotiamide or mosapride intake on gastric emptying: a randomized 3-way crossover study using the C breath test.

J Clin Biochem Nutr 2021 May 5;68(3):264-267. Epub 2021 Feb 5.

Department of Gastroenterology and Hepatology, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.

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http://dx.doi.org/10.3164/jcbn.20-162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129981PMC
May 2021

Oxygen Release and Storage Property of Fe-Al Spinel Compounds: A Three-Way Catalytic Reaction over a Supported Rh Catalyst.

ACS Appl Mater Interfaces 2021 Jun 20;13(21):24615-24623. Epub 2021 May 20.

Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Kyotodaigaku Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.

We evaluated the catalytic performance of the Rh-Fe/AlO catalyst during a three-way catalytic reaction and found, by chance, that a part of Fe species was dissolved into the γ-AlO support and worked as an oxygen storage material, which adjusts the oxygen concentration around the catalytically active sites to a suitable level for three-way catalysis. In this study, we demonstrated that the Fe-doped γ-AlO can reversibly store and release oxygen by the redox of Fe/Fe at the tetrahedral (T) site of the spinel structure without its structure deformation. The finding that a spinel-structured metal oxide, Fe-doped γ-AlO, could work as an oxygen storage material suggested a new opportunity for the development of oxygen storage materials without rare metals.
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http://dx.doi.org/10.1021/acsami.1c01486DOI Listing
June 2021

A novel COL4A1 variant associated with recurrent epistaxis and glioblastoma.

Hum Genome Var 2021 May 14;8(1):18. Epub 2021 May 14.

Department of Neurology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.

COL4A1-related disorders are characterized by a higher incidence of cerebral hemorrhage than other hereditary cerebral small vessel diseases. Accumulating data have shown broad phenotypic variations, and extracerebral hemorrhages have been linked to these disorders. Moreover, the coexistence of neural tumors has been described. Here, we report a Japanese family with a novel COL4A1 variant, including a patient with recurrent epistaxis and glioblastoma.
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http://dx.doi.org/10.1038/s41439-021-00150-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121905PMC
May 2021

Projected land ice contributions to twenty-first-century sea level rise.

Nature 2021 05 5;593(7857):74-82. Epub 2021 May 5.

Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA, USA.

The land ice contribution to global mean sea level rise has not yet been predicted using ice sheet and glacier models for the latest set of socio-economic scenarios, nor using coordinated exploration of uncertainties arising from the various computer models involved. Two recent international projects generated a large suite of projections using multiple models, but primarily used previous-generation scenarios and climate models, and could not fully explore known uncertainties. Here we estimate probability distributions for these projections under the new scenarios using statistical emulation of the ice sheet and glacier models. We find that limiting global warming to 1.5 degrees Celsius would halve the land ice contribution to twenty-first-century sea level rise, relative to current emissions pledges. The median decreases from 25 to 13 centimetres sea level equivalent (SLE) by 2100, with glaciers responsible for half the sea level contribution. The projected Antarctic contribution does not show a clear response to the emissions scenario, owing to uncertainties in the competing processes of increasing ice loss and snowfall accumulation in a warming climate. However, under risk-averse (pessimistic) assumptions, Antarctic ice loss could be five times higher, increasing the median land ice contribution to 42 centimetres SLE under current policies and pledges, with the 95th percentile projection exceeding half a metre even under 1.5 degrees Celsius warming. This would severely limit the possibility of mitigating future coastal flooding. Given this large range (between 13 centimetres SLE using the main projections under 1.5 degrees Celsius warming and 42 centimetres SLE using risk-averse projections under current pledges), adaptation planning for twenty-first-century sea level rise must account for a factor-of-three uncertainty in the land ice contribution until climate policies and the Antarctic response are further constrained.
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http://dx.doi.org/10.1038/s41586-021-03302-yDOI Listing
May 2021

Isotopic evidence for acidity-driven enhancement of sulfate formation after SO emission control.

Sci Adv 2021 May 5;7(19). Epub 2021 May 5.

Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, Yokohama 226-8502, Japan.

After the 1980s, atmospheric sulfate reduction is slower than the dramatic reductions in sulfur dioxide (SO) emissions. However, a lack of observational evidence has hindered the identification of causal feedback mechanisms. Here, we report an increase in the oxygen isotopic composition of sulfate ([Formula: see text]) in a Greenland ice core, implying an enhanced role of acidity-dependent in-cloud oxidation by ozone (up to 17 to 27%) in sulfate production since the 1960s. A global chemical transport model reproduces the magnitude of the increase in observed [Formula: see text] with a 10 to 15% enhancement in the conversion efficiency from SO to sulfate in Eastern North America and Western Europe. With an expected continued decrease in atmospheric acidity, this feedback will continue in the future and partially hinder air quality improvements.
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http://dx.doi.org/10.1126/sciadv.abd4610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099192PMC
May 2021

WAPL induces cervical intraepithelial neoplasia modulated with estrogen signaling without HPV E6/E7.

Oncogene 2021 May 4;40(21):3695-3706. Epub 2021 May 4.

Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.

Since cervical cancer still afflicts women around the world, it is necessary to understand the underlying mechanism of cervical cancer development. Infection with HPV is essential for the development of cervical intraepithelial neoplasia (CIN). In addition, estrogen receptor signaling is implicated in the development of cervical cancer. Previously, we have isolated human wings apart-like (WAPL), which is expected to cause chromosomal instability in the process of HPV-infected precancerous lesions to cervical cancer. However, the role of WAPL in the development of CIN is still unknown. In this study, in order to elucidate the role of WAPL in the early lesion, we established WAPL overexpressing mice (WAPL Tg mice) and HPV E6/E7 knock-in (KI) mice. WAPL Tg mice developed CIN lesion without HPV E6/E7. Interestingly, in WAPL Tg mice estrogen receptor 1 (ESR1) showed reduction as compared with the wild type, but cell growth factors MYC and Cyclin D1 controlled by ESR1 expressed at high levels. These results suggested that WAPL facilitates sensitivity of ESR1 mediated by some kind of molecule, and as a result, affects the expression of MYC and Cyclin D1 in cervical cancer cells. To detect such molecules, we performed microarray analysis of the uterine cervix in WAPL Tg mice, and focused MACROD1, a co-activator of ESR1. MACROD1 expression was increased in WAPL Tg mice compared with the wild type. In addition, knockdown of WAPL induced the downregulation of MACROD1, MYC, and Cyclin D1 but not ESR1 expression. Furthermore, ESR1 sensitivity assay showed lower activity in WAPL or MACROD1 downregulated cells than control cells. These data suggested that WAPL increases ESR1 sensitivity by activating MACROD1, and induces the expression of MYC and Cyclin D1. Therefore, we concluded that WAPL not only induces chromosomal instability in cervical cancer tumorigenesis, but also plays a key role in activating estrogen receptor signaling in early tumorigenesis.
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http://dx.doi.org/10.1038/s41388-021-01787-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154587PMC
May 2021

Galectin‑9 suppresses the tumor growth of colon cancer and .

Oncol Rep 2021 Jun 28;45(6). Epub 2021 Apr 28.

Department of Gastroenterology and Neurology, Kagawa University, Faculty of Medicine, Miki‑cho, Kita‑gun, Kagawa 761‑0793, Japan.

Colon cancer is the second leading cause of cancer‑related mortality worldwide, and the prognosis of advanced colon cancer has remained poor in recent years. Galectin‑9 (Gal‑9) is a tandem‑repeat type galectin that has recently been shown to exert antiproliferative effects on various types of cancer cells. The present study aimed to assess the effects of Gal‑9 on human colon and colorectal cancer cells and , as well as to evaluate the microRNAs (miRNAs/miRs) associated with the antitumor effects of Gal‑9. We examined the ability of Gal‑9 to inhibit cell proliferation via apoptosis, and the effects of Gal‑9 on cell cycle‑related molecules in various human colon and colorectal cancer cell lines. In addition, Gal‑9‑mediated changes in activated tyrosine kinase receptors and angiogenic molecules were assessed using protein array chips in colon and colorectal cancer cells. Moreover, miRNA array analysis was performed to examine Gal‑9‑induced miRNA expression profiles. We also elucidated if Gal‑9 inhibited tumor growth in a murine model. We found that Gal‑9 suppressed the cell proliferation of colon cancer cell lines and . Our data further revealed that Gal‑9 increased caspase‑cleaved keratin 18 levels in Gal‑9‑treated colon cancer cells. In addition, Gal‑9 enhanced the phosphorylation of ALK, DDR1, and EphA10 proteins. Furthermore, the miRNA expression levels, such as miR‑1246, miR‑15b‑5p, and miR‑1237, were markedly altered by Gal‑9 treatment and . In conclusion, Gal‑9 suppresses the cell proliferation of human colon cancer by inducing apoptosis, and these findings suggest that Gal‑9 can be a potential therapeutic target in the treatment of colon cancer.
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http://dx.doi.org/10.3892/or.2021.8056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072828PMC
June 2021

BRCA1 degradation in response to mitochondrial damage in breast cancer cells.

Sci Rep 2021 Apr 22;11(1):8735. Epub 2021 Apr 22.

Department of Biochemistry, Tokyo Medical University, Shinjuku, Tokyo, 160-8402, Japan.

BRCA1 is a well-studied tumor suppressor involved in the homologous repair of DNA damage, whereas PINK1, a mitochondrial serine/threonine kinase, is known to be involved in mitochondrial quality control. Genetic mutations of PINK1 and Parkin cause autosomal recessive early-onset Parkinson's disease. We found that in breast cancer cells, the mitochondrial targeting reagents, which all induce mitochondrial depolarization along with PINK1 upregulation, induced proteasomal BRCA1 degradation. This BRCA1 degradation was dependent on PINK1, and BRCA1 downregulation upon mitochondrial damage caused DNA double-strand breaks. BRCA1 degradation was mediated through the direct interaction with the E3 ligase Parkin. Strikingly, BRCA1 and PINK1/Parkin expression were inversely correlated in cancerous mammary glands from breast cancer patients. BRCA1 knockdown repressed cancer cell growth, and high BRCA1 expression predicted poor relapse-free survival in breast cancer patients. These observations indicate a novel mechanism by which mitochondrial damage is transmitted to the nucleus, leading to BRCA1 degradation.
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http://dx.doi.org/10.1038/s41598-021-87698-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062582PMC
April 2021

Human language evolution: a view from theoretical linguistics on how syntax and the lexicon first came into being.

Primates 2021 Apr 5. Epub 2021 Apr 5.

Graduate School of Human and Environmental Studies, Kyoto University, Yoshida Nihonmatsu-cho, Sakyo-ku, Kyoto, 606-8501, Japan.

Human language is a multi-componential function comprising several sub-functions each of which may have evolved in other species independently of language. Among them, two sub-functions, or modules, have been claimed to be truly unique to the humans, namely hierarchical syntax (known as "Merge" in linguistics) and the "lexicon." This kind of species-specificity stands as a hindrance to our natural understanding of human language evolution. Here we challenge this issue and advance our hypotheses on how human syntax and lexicon may have evolved from pre-existing cognitive capacities in our ancestors and other species including but not limited to nonhuman primates. Specifically, we argue that Merge evolved from motor action planning, and that the human lexicon with the distinction between lexical and functional categories evolved from its predecessors found in animal cognition through a process we call "disintegration." We build our arguments on recent developments in generative grammar but crucially depart from some of its core ideas by borrowing insights from other relevant disciplines. Most importantly, we maintain that every sub-function of human language keeps evolutionary continuity with other species' cognitive capacities and reject a saltational emergence of language in favor of its gradual evolution. By doing so, we aim to offer a firm theoretical background on which a promising scenario of language evolution can be constructed.
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http://dx.doi.org/10.1007/s10329-021-00891-0DOI Listing
April 2021

MicroRNA Interference in Hepatic Host-Pathogen Interactions.

Int J Mol Sci 2021 Mar 30;22(7). Epub 2021 Mar 30.

Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa 761-0793, Japan.

The liver is well recognized as a non-immunological visceral organ that is involved in various metabolic activities, nutrient storage, and detoxification. Recently, many studies have demonstrated that resident immune cells in the liver drive various immunological reactions by means of several molecular modulators. Understanding the mechanistic details of interactions between hepatic host immune cells, including Kupffer cells and lymphocytes, and various hepatic pathogens, especially viruses, bacteria, and parasites, is necessary. MicroRNAs (miRNAs), over 2600 of which have been discovered, are small, endogenous, interfering, noncoding RNAs that are predicted to regulate more than 15,000 genes by degrading specific messenger RNAs. Several recent studies have demonstrated that some miRNAs are associated with the immune response to pathogens in the liver. However, the details of the underlying mechanisms of miRNA interference in hepatic host-pathogen interactions still remain elusive. In this review, we summarize the relationship between the immunological interactions of various pathogens and hepatic resident immune cells, as well as the role of miRNAs in the maintenance of liver immunity against pathogens.
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http://dx.doi.org/10.3390/ijms22073554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036276PMC
March 2021

Prognosis of probable autoimmune hepatitis patients: a single-center study in Japan.

Intern Emerg Med 2021 Mar 30. Epub 2021 Mar 30.

Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan.

Autoimmune hepatitis (AIH) is an idiopathic inflammatory liver disease with genetic susceptibility and unknown environmental triggers. The gold standard for diagnosis, International Autoimmune Hepatitis Group (IAIHG) scoring system, classifies AIH as definite or probable. Conventional research on probable AIH has focused on the Caucasian population and there is little data pertaining to the Asian population. This study aimed to assess and compare the prognosis of Japanese patients with probable and definite AIH. In the current study, patients with probable and definite AIH diagnosed based on IAIHG scores between 1987 and 2018 were enrolled. As a result, 72 patients with definite AIH and 49 patients with probable AIH were evaluated. Univariate analysis revealed age, fibrosis stage 4, and the fibrosis-4 index were prognostic factors for overall survival. Multivariate analysis indicated that age and liver cirrhosis significantly affected the overall survival. When the cut off albumin-bilirubin score was set appropriately, cirrhosis was differentially diagnosed using albumin-bilirubin score with 100% sensitivity and 70.5% specificity. Classification of probable or definite disease did not alter overall survival with statistical significance. In conclusion, our findings suggest that probable AIH should be managed as definite AIH is managed in Japanese population. The albumin-bilirubin score helps identify liver cirrhosis and is a prognostic biomarker for overall survival.
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http://dx.doi.org/10.1007/s11739-021-02720-0DOI Listing
March 2021

A Screening Method Using Anomaly Detection on a Smartphone for Patients With Carpal Tunnel Syndrome: Diagnostic Case-Control Study.

JMIR Mhealth Uhealth 2021 03 14;9(3):e26320. Epub 2021 Mar 14.

Department of Functional Joint Anatomy, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Background: Carpal tunnel syndrome (CTS) is a medical condition caused by compression of the median nerve in the carpal tunnel due to aging or overuse of the hand. The symptoms include numbness of the fingers and atrophy of the thenar muscle. Thenar atrophy recovers slowly postoperatively; therefore, early diagnosis and surgery are important. While physical examinations and nerve conduction studies are used to diagnose CTS, problems with the diagnostic ability and equipment, respectively, exist. Despite research on a CTS-screening app that uses a tablet and machine learning, problems with the usage rate of tablets and data collection for machine learning remain.

Objective: To make data collection for machine learning easier and more available, we developed a screening app for CTS using a smartphone and an anomaly detection algorithm, aiming to examine our system as a useful screening tool for CTS.

Methods: In total, 36 participants were recruited, comprising 36 hands with CTS and 27 hands without CTS. Participants controlled the character in our app using their thumbs. We recorded the position of the thumbs and time; generated screening models that classified CTS and non-CTS using anomaly detection and an autoencoder; and calculated the sensitivity, specificity, and area under the curve (AUC).

Results: Participants with and without CTS were classified with 94% sensitivity, 67% specificity, and an AUC of 0.86. When dividing the data by direction, the model with data in the same direction as the thumb opposition had the highest AUC of 0.99, 92% sensitivity, and 100% specificity.

Conclusions: Our app could reveal the difficulty of thumb opposition for patients with CTS and screen for CTS with high sensitivity and specificity. The app is highly accessible because of the use of smartphones and can be easily enhanced by anomaly detection.
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http://dx.doi.org/10.2196/26320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005991PMC
March 2021

The Wakayama-Immediate Stroke Life Support Course: Achieving Successful Training on the Stroke Emergency System without using Mechanical Medical Training Simulators.

Asian J Neurosurg 2020 Oct-Dec;15(4):970-975. Epub 2020 Oct 19.

Department of Neurological Surgery, School of Medicine, Wakayama Medical University, Wakayama, Japan.

Background: The Immediate Stroke Life Support (ISLS) course run in Wakayama (Wakayama-ISLS course) is an off-the-job training course for understanding the initial treatment of acute stroke. A total of 22 Wakayama-ISLS courses have been held in Wakayama Prefecture since 2008. To begin with, the case presentation was performed using human-like, mechanical manikins for simulation training. However, as the course progressed, we found the students paying great attention to the display monitor, and less to the patients' neurological status.

Methods: From the fourth Wakayama-ISLS course onward, we conducted the group work with the facilitators pretending to be patients, i.e., without medical training manikins.

Results: When the facilitators acted as patients, the students gained a more realistic and expressive perception of neurological symptoms. As a result, they expressed a high level of satisfaction with the course in the questionnaire sent immediately afterwards, regardless of their profession or prior experience. Moreover, as we did not need to transfer medical training simulators, we were able to carry out three ISLS courses at locations some distance from Wakayama city on a low-cost basis. This also enabled the regional medical staff in rural hospitals to participate in the courses easily.

Conclusion: The Wakayama-ISLS course without medical training manikins is an entirely feasible off-the-job training course, which provides training on fast and excellent treatment of acute stroke problems based on clinical practice. The course has the potential to spread not only across Japan but throughout the world, including to developing countries, given the cost perspective.
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http://dx.doi.org/10.4103/ajns.AJNS_254_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869296PMC
October 2020

Editorial: The Biology of Language Under a Minimalist Lens: Promises, Achievements, and Limits.

Front Psychol 2021 22;12:654768. Epub 2021 Feb 22.

Linguistics Program, Department of English, Wayne State University, Detroit, MI, United States.

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http://dx.doi.org/10.3389/fpsyg.2021.654768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938305PMC
February 2021

Albumin platelet product as a novel score for liver fibrosis stage and prognosis.

Sci Rep 2021 Mar 5;11(1):5345. Epub 2021 Mar 5.

Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe Miki Kita, Kagawa, 761-0793, Japan.

Fibrosis-4 index, a conventional biomarker for liver fibrosis stage, is confounded by age and hepatitis activity grade. The current retrospective multicenter study aimed to formulate the novel indices of liver fibrosis by mathematically combining items of peripheral blood examination and to evaluate ability of prognosis prediction. After a novel index was established in a training cohort, the index was tested in a validation cohort. Briefly, a total of 426 patients were enrolled in a training cohort. Albumin and platelet most strongly correlated to fibrosis stage among blood examination. Albumin platelet product (APP) = Albumin × platelet/1000 could differentiate the four stages of liver fibrosis (p < 0.05). APP indicated fibrosis stage independent from hepatitis activity grade. A cut-off value = 4.349 diagnosed cirrhosis with area under ROC more than 0.8. Multivariate analysis revealed that smaller APP independently contributed to HCC prevalence and overall mortality. The results were validated in another 707 patients with HCV infection. In conclusion, APP was not confounded by age or hepatitis activity grade contrary to Fibrosis-4 index. APP is as simple as physicians can calculate it by pen calculation. The product serves physicians in managing patients with chronic liver disease.
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http://dx.doi.org/10.1038/s41598-021-84719-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935926PMC
March 2021

Radiological Assessment of Postoperative Paraspinal Muscle Changes After Lumbar Interbody Fusion With or Without Minimally Invasive Techniques.

Global Spine J 2021 Mar 4:2192568221994794. Epub 2021 Mar 4.

Department of Orthopaedic Surgery, University of Yamanashi, Yamanashi, Japan.

Study Design: Retrospective cohort study.

Background: Percutaneous pedicle screws (PPS) have the advantage of being able to better preserve the paraspinal muscles when compared with a traditional open approach. However, the nature of changes in postoperative paraspinal muscle after damage by lumbar fusion surgery has remained largely unknown. It is clinically important to clarify and compare changes in paraspinal muscles after the various surgeries.

Objective: (1) To determine postoperative changes of muscle density and cross-sectional area using computed tomography (CT), and (2) to compare paraspinal muscle changes after posterior lumbar interbody fusion (PLIF) with traditional open approaches and minimally invasive lateral lumbar interbody fusions (LLIF) with PPS.

Methods: We included data from 39 consecutive female patients who underwent open PLIF and 23 consecutive patients who underwent single-staged treatment with LLIF followed by posterior PPS fixation at a single level (L4-5). All patients underwent preoperative, 6 months postoperative, and 1-year postoperative CT imaging. Measurements of the cross-sectional area (CSA) and muscle densities of paraspinal muscles were obtained using regions of interest defined by manual tracing.

Results: We did not find any decrease of CSA in any paraspinal muscles. We did find a decrease of muscle density in the multifidus at 1 year after surgery in patients in the PILF group, but not in those in LLIF/PPS group.

Conclusions: One year after surgery, a significant postoperative decrease of muscle density of the multifidi was observed only in patients who underwent open PLIF, but not in those who underwent LLIF/PPS.
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http://dx.doi.org/10.1177/2192568221994794DOI Listing
March 2021

Association between microRNA-527 and glypican-3 in hepatocellular carcinoma.

Oncol Lett 2021 Mar 26;21(3):229. Epub 2021 Jan 26.

Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Miki-cho, Kagawa 761-0793, Japan.

The present study aimed to identify the specific microRNAs (miRNAs/miRs) and their corresponding target genes involved in hepatocellular carcinomas (HCCs). Microarray analysis was performed to examine the miRNA expression profiles of four paired HCC and corresponding non-cancerous (N) liver tissues using 985 miRNA probes. The Human miRNA Target database was used to identify the target genes of differentially expressed miRNAs between the HCC and N tissues. The protein expression levels of target genes in the HCC tissues and cell lines were evaluated using western blotting. miRNA-mediated suppression of target gene expression was evaluated by transiently transfecting the miRNA into the HCC cell lines. Of the 985 miRNAs evaluated, four miRNAs were differentially expressed (three upregulated and one downregulated miRNAs). Of these four miRNAs, miRNA-527 was highly downregulated in the HCC tissues. Glypican-3 (GPC-3) was predicted as a target gene of miRNA-527. Western blotting revealed that GPC-3 protein is highly expressed in the HCC tissues and HCC cell lines compared with N and normal cell lines. Transfection with miR-527 resulted in suppression of GPC-3 protein expression in the Cos7 cells. Furthermore, transfection with miR-527 also inhibited the intrinsic expression of GPC-3 in the Huh-7 cell line. This indicated that miR-527 in the HCC tissues may be an important novel miRNA that targets the GPC-3 gene expression. GPC-3, whose expression is regulated by miR-527, may be involved in the development and progression of HCC.
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http://dx.doi.org/10.3892/ol.2021.12490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856685PMC
March 2021

Risk Factors and Assessment Using an Endoscopic Scoring System for Postoperative Respiratory Complications after Anterior Cervical Decompression and Fusion Surgery.

Spine Surg Relat Res 2021 31;5(1):10-15. Epub 2020 Aug 31.

Department of Orthopaedic Surgery, University of Yamanashi, Yamanashi, Japan.

Introduction: Postoperative respiratory complications (PRC) are one of the most serious complications. Potentially life-threatening accidents can occur after an anterior cervical discectomy and fusion (ADF), such as airway obstruction and aspiration pneumonia. Despite numerous studies, preoperative predictive and preventive methodology has yet to be established. As reported in our previous study, the evaluation of preoperative dysphagia using the eating assessment tool (EAT-10) and a flexible endoscopic evaluation of swallowing (FEES) is useful for predicting the incidence and risk factors of dysphagia after ADF.

Methods: This prospective study comprised 60 consecutive patients who underwent ADF. An otolaryngologist and a speech-language-hearing therapist preoperatively and 1 week postoperatively evaluated dysphagia using EAT-10 and Hyodo-Komagane (H-K) scores during FEES. Patient demographics, comorbidities, and pre- and postoperative dysphagia were compared between patients with and without PRC.

Results: Seven of 60 (11.6%) patients had preoperative dysphagia diagnosed using the H-K score. A significant positive correlation existed between the pre- and postoperative H-K scores. Of all 60 cases, eight (13.3%) had PRC. Among them, two required reintubation due to airway obstruction and six had aspiration pneumonia. The PRC(+) group was significantly older and more prone to diabetes and asthma. The preoperative H-K score of the PRC(+) group was significantly higher than that of the PRC(-) group. Postoperatively, but not preoperatively, EAT-10 was significantly higher in the PRC(+) group.

Conclusions: Preoperative dysphagia may potentially exacerbate postoperative dysphagia after ADF. A preoperative evaluation of dysphagia using the H-K score during FEES is a useful method for predicting and reducing the risk of PRC. Level of Evidence: 3.
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http://dx.doi.org/10.22603/ssrr.2020-0104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870322PMC
August 2020

Marked Changes in Serum Amyloid A Distribution and High-Density Lipoprotein Structure during Acute Inflammation.

Biomed Res Int 2021 27;2021:9241259. Epub 2021 Jan 27.

Analytical Laboratory Chemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.

High-density lipoprotein- (HDL-) cholesterol measurements are generally used in the diagnosis of cardiovascular diseases. However, HDL is a complicated heterogeneous lipoprotein, and furthermore, it can be converted into dysfunctional forms during pathological conditions including inflammation. Therefore, qualitative analysis of pathophysiologically diversified HDL forms is important. A recent study demonstrated that serum amyloid A (SAA) can remodel HDL and induce atherosclerosis not only over long periods of time, such as during chronic inflammation, but also over shorter periods. However, few studies have investigated rapid HDL remodeling. In this study, we analyzed HDL samples from patients undergoing orthopedic surgery inducing acute inflammation. We enrolled 13 otherwise healthy patients who underwent orthopedic surgery. Plasma samples were obtained on preoperative day and postoperative days (POD) 1-7. SAA, apolipoprotein A-I (apoA-I), and apolipoprotein A-II (apoA-II) levels in the isolated HDL were determined. HDL particle size, surface charge, and SAA and apoA-I distributions were also analyzed. In every patient, plasma SAA levels peaked on POD3. Consistently, the HDL apoA-I : apoA-II ratio markedly decreased at this timepoint. Native-polyacrylamide gel electrophoresis and high-performance liquid chromatography revealed the loss of small HDL particles during acute inflammation. Furthermore, HDL had a decreased negative surface charge on POD3 compared to the other timepoints. All changes observed were SAA-dependent. SAA-dependent rapid changes in HDL size and surface charge were observed after orthopedic surgery. These changes might affect the atheroprotective functions of HDL, and its analysis can be available for the qualitative HDL assessment.
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http://dx.doi.org/10.1155/2021/9241259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861920PMC
May 2021

MicroRNAs in the Pathogenesis of Hepatocellular Carcinoma: A Review.

Cancers (Basel) 2021 Jan 29;13(3). Epub 2021 Jan 29.

Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan.

Hepatocellular carcinoma (HCC) is the seventh most frequent cancer and the fourth leading cause of cancer mortality worldwide. Despite substantial advances in therapeutic strategies, the prognosis of late-stage HCC remains dismal because of the high recurrence rate. A better understanding of the etiology of HCC is therefore necessary to improve outcomes. MicroRNAs (miRNAs) are small, endogenous, noncoding, single-stranded RNAs that modulate the expression of their target genes at the posttranscriptional and translational levels. Aberrant expression of miRNAs has frequently been detected in cancer-associated genomic regions or fragile sites in various human cancers and has been observed in both HCC cells and tissues. The precise patterns of aberrant miRNA expression differ depending on disease etiology, including various causes of hepatocarcinogenesis, such as viral hepatitis, alcoholic liver disease, or nonalcoholic steatohepatitis. However, little is known about the underlying mechanisms and the association of miRNAs with the pathogenesis of HCC of various etiologies. In the present review, we summarize the key mechanisms of miRNAs in the pathogenesis of HCC and emphasize their potential utility as valuable diagnostic and prognostic biomarkers, as well as innovative therapeutic targets, in HCC diagnosis and treatment.
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http://dx.doi.org/10.3390/cancers13030514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866004PMC
January 2021

Effect of pegylated interferon alfa-2a in HBeAg-negative chronic hepatitis B during and 48 weeks after off-treatment follow-up: the limitation of pre-treatment HBsAg load for the seroclearance of HBsAg.

Intern Emerg Med 2021 Jan 27. Epub 2021 Jan 27.

Department of Gastroenterology and Neurology, Kagawa University Hospital, Ikenobe Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.

Hepatitis B virus (HBV) infection is a major public health problem worldwide. The study aimed to evaluate the efficacy of pegylated interferon (Peg-IFN) alfa-2a treatment for seroclearance of HBs antigen (HBsAg) in HBe antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. This retrospective study investigated 16 HBeAg-negative CHB patients who received Peg-IFN alfa-2a weekly for 48 weeks. Thereafter, the patients were followed-up for 48 weeks after the end of therapy. The following criteria were also used for inclusion: HBV-DNA < 5.0 log copies/mL and without nucleot(s)ide analogs. Four HBsAg-positive cases became HBsAg negative. The HBsAg levels of the 4 patients who achieved HBsAg seroclearance were lower significantly than that of the non-seroclearance group (p = 0.007). The mean HBsAg levels in these 4 cases were 68 IU/mL, while the mean HBsAg levels in the non-seroclearance group were 2,114 IU/mL. The mean HBV-DNA levels in the 4 HBsAg seroclearance cases were 2.8 log copies/mL as compared to 3.6 log copies/mL in HBsAg-non-seroclearance cases (p = 0.01). Cases that are HBeAg negative, with HBV-DNA levels < 5 log copies/mL, and HBsAg titers < 120 IU/mL cases may achieve HBsAg clearance with Peg-IFN therapy.
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http://dx.doi.org/10.1007/s11739-020-02622-7DOI Listing
January 2021

Blood-brain barrier permeability in Parkinson's disease patients with and without dyskinesia.

J Neurol 2021 Jun 27;268(6):2246-2255. Epub 2021 Jan 27.

Center for Neurosciences, The Feinstein Institutes for Medical Research, 350 Community Drive, Manhasset, NY, 11030, USA.

Objective: Recent studies on a rodent model of Parkinson's disease (PD) have raised the possibility of increased blood-brain barrier (BBB) permeability, demonstrated by histology, autoradiography, and positron emission tomography (PET). However, in human PD patients, in vivo evidence of increased BBB permeability is lacking. We examined the hypothesis that levodopa treatment increases BBB permeability in human subjects with PD, particularly in those with levodopa-induced dyskinesia (LID).

Methods: We used rubidium-82 (Rb) and PET to quantify BBB influx in vivo in 19 PD patients, including eight with LID, and 12 age- and sex-matched healthy subjects. All subjects underwent baseline Rb scans. Seventeen chronically levodopa-treated patients were additionally rescanned during intravenous levodopa infusion. Influx rate constant, K, by compartmental modeling or net influx transport, K, by graphical approach could not be estimated reliably. However, V, the "apparent volume of distribution" based on the Rb concentration in brain tissue and blood, was estimated with good stability as a local measure of the volume of distribution.

Results: Rubidium influx into brain tissue was undetectable in PD patients with or without LID, scanned on and off drug. No significant differences in regional V were observed for PD patients with or without LID relative to healthy subjects, except in left thalamus. Moreover, changes in V measured off- and on-levodopa infusion were also not significant for dyskinetic and non-dyskinetic subjects.

Conclusion: Rb PET did not reveal significant changes in BBB permeability in PD patients.
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http://dx.doi.org/10.1007/s00415-021-10411-1DOI Listing
June 2021

Aspirin inhibits cholangiocarcinoma cell proliferation via cell cycle arrest in vitro and in vivo.

Int J Oncol 2021 02 30;58(2):199-210. Epub 2020 Dec 30.

Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kida, Kagawa 761‑0793, Japan.

Cholangiocarcinoma is the most common biliary duct malignancy and the second most common primary liver cancer, accounting for 10‑20% of hepatic malignancies. With high mortality and poor prognosis, the 5‑year survival rate of cholangiocarcinoma is only 10%. A previous study demonstrated a significant association between aspirin use and a decreased risk of cholangiocarcinoma. However, the effect of aspirin on cholangiocarcinoma remains unknown. Therefore, the aim of the present study was to investigate the effects of aspirin on cholangiocarcinoma in vitro and in vivo. Three cholangiocarcinoma cell lines were used to analyze the effect of aspirin on cell proliferation, cell cycle progression, apoptosis, and the regulation of microRNAs. MicroRNAs are known to regulate the development and progression of various types of cancer. An HuCCT‑1 xenograft model was used for the in vivo study. It was determined that aspirin inhibited the proliferation of human cholangiocarcinoma cells (except TKKK cells). Aspirin induced cell cycle arrest in the G0/G1 phase and regulated cell‑cycle related proteins in cholangiocarcinoma cells (HuCCT‑1 cells) but did not induce apoptosis. The expression of miR‑340‑5p was significantly upregulated after treatment, and overexpression of miR‑340‑5p inhibited the proliferation of HuCCT‑1 cells and decreased the levels of cyclin D1. TKKK cells had low miR‑340‑5p expression, which may explain why aspirin had no effect on their proliferation. In vivo, aspirin reduced the growth of xenografted tumors. In conclusion, the present study indicated that aspirin partially inhibited cholangiocarcinoma cell proliferation and tumor growth by inducing G0/G1 phase cell cycle arrest, potentially through the miR‑340‑5p/cyclin D1 axis.
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http://dx.doi.org/10.3892/ijo.2020.5165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864011PMC
February 2021

Wafer paper and ring-mounted polyglycolic acid sheet method for shielding artificial gastric floor.

Minim Invasive Ther Allied Technol 2021 Jan 19:1-13. Epub 2021 Jan 19.

Departments of Gastroenterology and Neurology, Kagawa University, Kita, Japan.

Background: The management of postoperative bleeding, after gastric endoscopic submucosal dissection (ESD), has become particularly important because of the recent increase in antithrombotic use. Endoscopic shielding with polyglycolic acid (PGA) sheets has been shown to be effective. However, shrinkage and early displacement of the sheet remain challenges. This study aimed to determine the efficacy and safety of our developed method, named wafer paper and ring-mounted PGA sheet (WaRP).

Material And Methods: Twenty-four patients with antithrombotic uptake who underwent the WaRP method following gastric ESD were retrospectively examined. This involved the delivery of a PGA sheet wrapped in wafer paper with ring-thread, and its fixation on the gastric floor using hemoclips. The primary outcome was the technical success rate of the WaRP, and several secondary outcomes were evaluated.

Results: The technical success rate of WaRP was 100%. The procedure lasted a mean of 10.5 min (SD 6.7 min). The prevalence of complete retention at follow-up endoscopy was 83.3% (20/24). There were no WaRP-associated complications, but post-ESD hemorrhage occurred in two patients undergoing hemodialysis (8.3%).

Conclusions: The WaRP method is a simple and reliable means of PGA sheet delivery and placement that reduces the incidence of post-ESD hemorrhage.
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http://dx.doi.org/10.1080/13645706.2020.1871370DOI Listing
January 2021

Peg-IFNα-2a Contributed to HBs Antigen Seroclearance in a Patient with Chronic Hepatitis B Administered Nucleic Acid Analogs: A Three-year Follow-up.

Intern Med 2021 Jan 15. Epub 2021 Jan 15.

Department of Gastroenterology and Neurology, Kagawa University School of Medicine/Graduate School of Medicine, Japan.

We treated a 51-year-old Japanese man with chronic hepatitis B (viral load 7.6 LC/mL, genotype C). HBV DNA and HBe antigen were undetectable during the administration of the nucleic acid analogs (NUCs) lamivudine and adefovir, although the concentration of HBs antigen (HBsAg) was 851.2 IU/mL. The HBsAg levels were reduced 150-fold when Peg-IFNα-2a was administered weekly for 48 weeks and did not increase during the rest period. Therefore, Peg-IFNα-2a was administered twice each week. During this time, HBsAg reached undetectable concentrations, and HBs antibody was detected and continued to be detectable during the three-year follow-up. These unprecedented findings suggest that IFN may contribute to the seroclearance of HBsAg in patients treated with NUCs.
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http://dx.doi.org/10.2169/internalmedicine.5783-20DOI Listing
January 2021

Reversible mixed perfusion on I-IMP SPECT in anti-AMPA receptor encephalitis: A case report.

J Neurol Sci 2021 Feb 4;421:117306. Epub 2021 Jan 4.

Department of Neurology, Tokushima University Graduate School of Biomedical Sciences, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.

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http://dx.doi.org/10.1016/j.jns.2020.117306DOI Listing
February 2021

Understanding the susceptibility to lateral condyle fracture by analyzing unaffected Baumann's angle in children with distal humeral fracture.

J Orthop Sci 2021 Jan 7. Epub 2021 Jan 7.

Department of Functional Joint Anatomy, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.

Background: Previous studies have shown that posttraumatic cubitus varus deformity in children is somehow related to subsequent humeral lateral condyle fracture. Moreover, we had previously encountered an exactly similar case. In this study, we aim to understand whether there is a morphological difference between pediatric supracondylar and lateral condyle fracture of the humerus by comparing Baumann's angle of the unaffected elbow.

Methods: We conducted a retrospective evaluation of 40 cases of supracondylar fractures (36 boys, 4 girls) and 20 cases of lateral condyle fractures (16 boys, 4 girls) at a single facility between January 2014 and December 2018. The unaffected Baumann's angles and lateral capitellohumeral angles of both groups were measured by two orthopedic surgeons and analyzed using Welch's t-test. The effect size was also calculated using Cohen's d, and intraclass correlation coefficients were applied for intra-rater and inter-rater reliability.

Results: The average age of patients in the supracondylar fracture group was 6.78 years and that in the lateral condyle fracture group was 5.70 years. No significant differences were observed between gender and fracture type, between laterality and fracture type, and in the lateral capitellohumeral angles between the groups. Baumann's angle was significantly less in the lateral condyle fracture group (17.27° ± 4.68°) than in the supracondylar fracture group (20.28° ± 3.10°) as analyzed by Welch's t-test (p = 0.015). The effect size was 0.76. Each of the intra-rater reliabilities were 0.97 and 0.96, whereas the inter-rater reliability was 0.75.

Conclusions: A significant morphological difference was found between the supracondylar fracture group and the lateral condyle fracture group. The loss of Baumann's angle which tends to occur after the healing of supracondylar fracture may increase the susceptibility to lateral condyle fracture. Orthopedic surgeons should repair and fix supracondylar fractures appropriately to avoid an ipsilateral second fracture, such as lateral condyle fracture.
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http://dx.doi.org/10.1016/j.jos.2020.12.002DOI Listing
January 2021