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  1. Reza F, Churei H, Takahashi H, Iwasaki N, Ueno T
    Dent Traumatol, 2014 Jun;30(3):193-7.
    PMID: 24102720 DOI: 10.1111/edt.12068
    Several methods have been used to measure the impact force absorption capacities of mouthguard materials; however, the relationships among these measurement systems have not been clearly determined. The purpose of the present study was to evaluate the impact force-absorbing capability of materials using a drop-ball system with film sensors and load cells to clarify the relationship between these two sensor systems.
  2. Arai YT, Takahashi H, Kameoka Y, Shiino T, Wimalaratne O, Lodmell DL
    Acta Virol., 2001;45(5-6):327-33.
    PMID: 12083333
    Thirty-four suspected rabid brain samples from 2 humans, 24 dogs, 4 cats, 2 mongooses, I jackal and I water buffalo were collected in 1995-1996 in Sri Lanka. Total RNA was extracted directly from brain suspensions and examined using a one-step reverse transcription-polymerase chain reaction (RT-PCR) for the rabies virus nucleoprotein (N) gene. Twenty-eight samples were found positive for the virus N gene by RT-PCR and also for the virus antigens by fluorescent antibody (FA) test. Rabies virus isolates obtained from different animal species in different regions of Sri Lanka were genetically homogenous. Sequences of 203 nucleotides (nt)-long RT-PCR products obtained from 16 of 27 samples were found identical. Sequences of 1350 nt of N genes of 14 RT-PCR products were determined. The Sri Lanka isolates under study formed a specific cluster that included also an earlier isolate from India but did not include the known isolates from China, Thailand, Malaysia, Israel, Iran, Oman, Saudi Arabia, Russia, Nepal, Philippines, Japan and from several other countries. These results suggest that one type of rabies virus is circulating among human, dog, cat, mongoose, jackal and water buffalo living near Colombo City and in other five remote regions in Sri Lanka.
  3. Gan HM, Takahashi H, Hammer MP, Tan MH, Lee YP, Voss JM, et al.
    Mitochondrial DNA B Resour, 2017 Feb 06;2(1):73-75.
    PMID: 33473721 DOI: 10.1080/23802359.2017.1285206
    The complete mitochondrial genomes of four fish species of the commercially important family Latidae were sequenced using the Illumina MiSeq, thereby significantly increasing the mitogenomic resources for the family. Whole mitogenome-based phylogenetic analysis supports the monophyly of the genus Lates and more generally the family Latidae. The mitogenome sequences from this study will be useful for future assessments of the diversity within and between Lates species and studies of phylogenetic relationships within the diverse and taxonomically challenging perciform fishes.
  4. Nakamura Y, Ise K, McNamara KM, Azmahani A, Sato S, Fujishima F, et al.
    Hum Pathol, 2019 02;84:124-132.
    PMID: 30290162 DOI: 10.1016/j.humpath.2018.09.011
    The expression statuses of sex steroid receptors and sex steroid-synthesizing/metabolizing enzymes have been reported in primary prostate cancer lesions, but that in metastatic lymph nodes has remained unknown. Therefore, in this study, we immunolocalized these proteins in primary tumors and paired metastatic lymph nodes of prostate cancer and correlated the findings with clinicopathological factors of individual patients. The expression statuses of AR and ER β was significantly increased in metastatic lymph nodes compared with primary lesions, whereas that of 17βHSD1, 17βHSD2, 17βHSD5, and STS immunoreactivity was decreased in metastatic lymph nodes. In metastatic lymph nodes, the status of 5α2 was significantly correlated with that of AR. In addition, 17βHSD5-, 5α1-, STS-, and EST-positive cases were significantly associated with Gleason score (GS) status (GS > 8 versus GS < 7) in metastatic lymph nodes. Results of our present study did demonstrate that in situ androgen and estrogen metabolism and action play roles in pathophysiology of prostate cancer in metastatic lymph nodes, but these steroidogenic effects could be different from those in primary lesions.
  5. Mazlan D, Krishnan S, Din MFM, Tokoro C, Khalid NHA, Ibrahim IS, et al.
    Sci Rep, 2020 04 14;10(1):6412.
    PMID: 32286486 DOI: 10.1038/s41598-020-63575-7
    This paper aims to examine the effect of cellulose nanocrystals (CNCs) derived from oil palm empty fruit bunch fiber (EFB) incorporating cement mortar on its structural performances. Cellulose nanocrystals (CNCs) were extracted from α-cellulose extracted from EFB using an acid hydrolysis process with a concentration of acid used was 64% w/v under the temperature of 45 °C for 60 minutes. The Cellulose nanocrystals (CNCs) were mixed into the cement mortar ranging from 0 to 0.8% w/w and its mechanical properties were determined. The developed CNCs mortar was characterized for their compressive and flexural properties as well as microstructure. The influence of CNCs concentration, curing method, dispersion of CNCs on mortar's mechanical performance was thoroughly examined to find out the optimum condition. Overall results revealed that an addition of 0.4% cellulose nanocrystals has shown to increase the compressive and flexural strength to 46% and 20%, respectively cured under the wrapping method. The hydration of cementitious composites also improved significantly with the addition of CNCs by the formation of highly crystalline of portlandite observed under the XRD test. This present work demonstrates the importance of palm oil empty fruit bunch waste as a sustainable resource of cellulose nanocrystals admixture to achieve structural strength of cement mortar and promotes green technologies in construction.
  6. Uni S, Fukuda M, Otsuka Y, Hiramatsu N, Yokobayashi K, Takahashi H, et al.
    Parasit Vectors, 2015;8:59.
    PMID: 25623081 DOI: 10.1186/s13071-015-0655-2
    Zoonotic infections with Onchocerca species are uncommon, and to date only 25 clinical cases have been reported worldwide. In Japan, five previous zoonotic infections were concentrated in Oita, Kyushu (the southern island), with one previous case in Hiroshima in the western part of Honshu (the main island). The causative agent in Japan was identified as Onchocerca dewittei japonica Uni, Bain & Takaoka, 2001 from Japanese wild boars (Sus scrofa leucomystax Temminck, 1842). Here we report two infections caused by a female and male O. dewittei japonica, respectively, among residents of Hiroshima and Shimane Prefectures in the western part of Honshu.
  7. Lim WH, Tay P, Ng CH, Tan DJH, Ong C, Koh JH, et al.
    Aliment Pharmacol Ther, 2024 Mar;59(6):730-741.
    PMID: 38303565 DOI: 10.1111/apt.17888
    BACKGROUND: Although alcohol abstinence may be an effective intervention for alcohol-associated cirrhosis, its association with prognosis has not been systematically assessed or quantified.

    AIMS: To determine the prevalence of alcohol abstinence, factors associated with alcohol abstinence and the impact of abstinence on morbidity and overall survival in people with alcohol-associated cirrhosis.

    METHODS: We searched Medline and Embase from inception to 15 April 2023 for prospective and retrospective cohort studies describing alcohol abstinence in people with known alcohol-associated cirrhosis. Meta-analysis of proportions for pooled estimates was performed. The method of inverse variance, employing a random-effects model, was used to pool the hazard ratio (HR) comparing outcomes of abstinent against non-abstinent individuals with alcohol-associated cirrhosis.

    RESULTS: We included 19 studies involving 18,833 people with alcohol-associated cirrhosis. The prevalence of alcohol abstinence was 53.8% (CI: 44.6%-62.7%). Over a mean follow-up duration of 48.6 months, individuals who continued to consume alcohol had significantly lower overall survival compared to those who were abstinent (HR: 0.611, 95% CI: 0.506-0.738). These findings remained consistent in sensitivity/subgroup analysis for the presence of decompensation, study design and studies that assessed abstinence throughout follow-up. Alcohol abstinence was associated with a significantly lower risk of hepatic decompensation (HR: 0.612, 95% CI: 0.473-0.792).

    CONCLUSIONS: Alcohol abstinence is associated with substantial improvement in overall survival in alcohol-associated cirrhosis. However, only half of the individuals with known alcohol-associated cirrhosis are abstinent.

  8. Younossi ZM, Ong JP, Takahashi H, Yilmaz Y, Eguchi Y, El Kassas M, et al.
    PMID: 34229038 DOI: 10.1016/j.cgh.2021.06.048
    BACKGROUND & AIMS: Despite rapidly increasing NAFLD prevalence, providers' knowledge may be limited. We assessed NAFLD knowledge and associated factors among physicians of different specialties globally.

    APPROACH & RESULTS: NAFLD knowledge surveys containing 54 and 59 questions covering three domains (Epidemiology/Pathogenesis, Diagnostics, and Treatment) were completed electronically by hepatologists, gastroenterologists (GEs), endocrinologists (ENDOs) and primary care physicians (PCPs) from 40 countries comprising 5 Global Burden of Disease (GBD) super-regions. Over 24 months, 2202 surveys were completed (488 hepatologists, 758 GEs, 148 ENDOs, and 808 PCPs; 50% High-Income GBD super-region, 27% from North Africa and Middle East, 12% Southeast Asia, and 5% South Asian and Latin America). Hepatologists saw the greatest number of NAFLD patients annually: median (IQR) 150 (60-300) vs. 100 (35-200) for GEs, 100 (30-200) for ENDOs, and 10 (4-50) for PCPs (all p<0.0001). The primary sources of NAFLD knowledge acquisition for hepatologists were international conferences (33% vs. 8-26%) and practice guidelines for others (39-44%). Internet was the second most common source of NAFLD knowledge for PCPs (28%). NAFLD knowledge scores were higher for hepatologists than GEs: Epidemiology 62% vs. 53%, Diagnostics 80% vs. 73%, Treatment 61% vs. 58% (p<0.0001) and ENDOs scores were higher than PCPs: Epidemiology 70% vs. 60%, Diagnostics 71% vs. 64%, Treatment 79% vs. 68% (p<0.0001). Being a hepatologist or ENDO was associated with higher knowledge scores than GE or PCP, respectively (p<0.05). Higher NAFLD knowledge scores were independently associated with greater number of NAFLD patients seen (p<0.05).

    CONCLUSION: Despite the growing burden of NAFLD, significant knowledge gap remains for identification, diagnosis and management of NAFLD.

  9. Itai T, Hamanaka K, Sasaki K, Wagner M, Kotzaeridou U, Brösse I, et al.
    Hum Mutat, 2021 01;42(1):66-76.
    PMID: 33131106 DOI: 10.1002/humu.24130
    We report heterozygous CELF2 (NM_006561.3) variants in five unrelated individuals: Individuals 1-4 exhibited developmental and epileptic encephalopathy (DEE) and Individual 5 had intellectual disability and autistic features. CELF2 encodes a nucleocytoplasmic shuttling RNA-binding protein that has multiple roles in RNA processing and is involved in the embryonic development of the central nervous system and heart. Whole-exome sequencing identified the following CELF2 variants: two missense variants [c.1558C>T:p.(Pro520Ser) in unrelated Individuals 1 and 2, and c.1516C>G:p.(Arg506Gly) in Individual 3], one frameshift variant in Individual 4 that removed the last amino acid of CELF2 c.1562dup:p.(Tyr521Ter), possibly resulting in escape from nonsense-mediated mRNA decay (NMD), and one canonical splice site variant, c.272-1G>C in Individual 5, also probably leading to NMD. The identified variants in Individuals 1, 2, 4, and 5 were de novo, while the variant in Individual 3 was inherited from her mosaic mother. Notably, all identified variants, except for c.272-1G>C, were clustered within 20 amino acid residues of the C-terminus, which might be a nuclear localization signal. We demonstrated the extranuclear mislocalization of mutant CELF2 protein in cells transfected with mutant CELF2 complementary DNA plasmids. Our findings indicate that CELF2 variants that disrupt its nuclear localization are associated with DEE.
  10. Tan DJH, Ng CH, Muthiah M, Yong JN, Chee D, Teng M, et al.
    Metabolism, 2024 Mar;152:155744.
    PMID: 38029839 DOI: 10.1016/j.metabol.2023.155744
    BACKGROUND: High body mass index (BMI) is a major risk factor for cancer development, but its impact on the global burden of cancer remains unclear.

    METHODS: We estimated global and regional temporal trends in the burden of cancer attributable to high BMI, and the contributions of various cancer types using the framework of the Global Burden of Disease Study.

    RESULTS: From 2010 to 2019, there was a 35 % increase in deaths and a 34 % increase in disability-adjusted life-years from cancers attributable to high BMI. The age-standardized death rates for cancer attributable to high BMI increased over the study period (annual percentage change [APC] +0.48 %, 95 % CI 0.22 to 0.74 %). The greatest number of deaths from cancer attributable to high BMI occurred in Europe, but the fastest-growing age-standardized death rates and disability-adjusted life-years occurred in Southeast Asia. Liver cancer was the fastest-growing cause of cancer mortality (APC: 1.37 %, 95 % CI 1.25 to 1.49 %) attributable to high BMI.

    CONCLUSION: The global burden of cancer-related deaths attributable to high BMI has increased substantially from 2010 to 2019. The greatest increase in age-standardized death rates occurred in Southeast Asia, and liver cancer is the fastest-growing cause of cancer mortality attributable to high BMI. Urgent and sustained measures are required at a global and regional level to reverse these trends and slow the growing burden of cancer attributed to high BMI.

  11. Younossi ZM, Alqahtani SA, Alswat K, Yilmaz Y, Keklikkiran C, Funuyet-Salas J, et al.
    J Hepatol, 2024 Mar;80(3):419-430.
    PMID: 37984709 DOI: 10.1016/j.jhep.2023.11.004
    BACKGROUND & AIMS: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers.

    METHODS: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey.

    RESULTS: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%).

    CONCLUSIONS: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties.

    IMPACT AND IMPLICATIONS: Over the past decades, efforts have been made to change the nomenclature of nonalcoholic fatty liver disease (NAFLD) to better align with its underlying pathogenetic pathways and remove any potential stigma associated with the name. Given the paucity of data related to stigma in NAFLD, we undertook this global comprehensive survey to assess stigma in NAFLD among patients and providers from around the world. We found there is a disconnect between physicians and patients related to stigma and related nomenclature. With this knowledge, educational programs can be developed to better target stigma in NAFLD among all stakeholders and to provide a better opportunity for the new nomenclature to address the issues of stigma.

  12. Younossi ZM, AlQahtani SA, Funuyet-Salas J, Romero-Gómez M, Yilmaz Y, Keklikkiran C, et al.
    JHEP Rep, 2024 Jul;6(7):101066.
    PMID: 39022387 DOI: 10.1016/j.jhepr.2024.101066
    BACKGROUND & AIMS: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL.

    METHODS: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination.

    RESULTS: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest independent predictor of lower HRQL scores (beta from -5% to -8% of score range size, p <0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncomfortable with the term "fatty liver disease" with lower Emotional Health scores (all p <0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients' self-blame for their liver disease.

    CONCLUSIONS: Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD.

    IMPACT AND IMPLICATIONS: Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se, is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers' perception may not adequately reflect patients' perspective and experience with the disease.

  13. Wijedasa LS, Jauhiainen J, Könönen M, Lampela M, Vasander H, Leblanc MC, et al.
    Glob Chang Biol, 2017 03;23(3):977-982.
    PMID: 27670948 DOI: 10.1111/gcb.13516
  14. Ji F, Tran S, Ogawa E, Huang CF, Suzuki T, Wong YJ, et al.
    J Clin Transl Hepatol, 2024 Jul 28;12(7):646-658.
    PMID: 38993510 DOI: 10.14218/JCTH.2024.00089
    BACKGROUND AND AIMS: As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6.

    METHODS: We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014-07/01/2021.

    RESULTS: The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12.

    CONCLUSIONS: In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (>91%).

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