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Background With the goal of realizing genome-based personalized healthcare, we have developed a biobank that integrates personal health, genome, and omics data along with biospecimens donated by volunteers of 150,000. Such a large-scale of data integration involves obvious risks of privacy violation. The research use of personal genome and health information is a topic of global discussion with regard to the protection of privacy while promoting scientific advancement. The present paper reports on our plans, current attempts, and accomplishments in addressing security problems involved in data sharing to ensure donor privacy while promoting scientific advancement. Methods Biospecimens and data have been collected in prospective cohort studies with the comprehensive agreement. The sample size of 150,000 participants was required for multiple researches including genome-wide screening of gene by environment interactions, haplotype phasing, and parametric linkage analysis. Results We established the T ohoku M edical M egabank (TMM) data sharing policy: a privacy protection rule that requires physical, personnel, and technological safeguards against privacy violation regarding the use and sharing of data. The proposed policy refers to that of NCBI and that of the Sanger Institute. The proposed policy classifies shared data according to the strength of re-identification risks. Local committees organized by TMM evaluate re-identification risk and assign a security category to a dataset. Every dataset is stored in an assigned segment of a supercomputer in accordance with its security category. A security manager should be designated to handle all security problems at individual data use locations. The proposed policy requires closed networks and IP-VPN remote connections. Conclusion The mission of the biobank is to distribute biological resources most productively. This mission motivated us to collect biospecimens and health data and simultaneously analyze genome/omics data in-house. The biobank also has the mission of improving the quality and quantity of the contents of the biobank. This motivated us to request users to share the results of their research as feedback to the biobank. The TMM data sharing policy has tackled every security problem originating with the missions. We believe our current implementation to be the best way to protect privacy in data sharing. Electronic supplementary material The online version of this article (doi:10.1186/s12911-017-0494-5) contains supplementary material, which is available to authorized users.

PurposeA prospective cohort study for pregnant women, the Maternity Log study, was designed to construct a time-course high-resolution reference catalogue of bioinformatic data in pregnancy and explore the associations between genomic and environmental factors and the onset of pregnancy complications, such as hypertensive disorders of pregnancy, gestational diabetes mellitus and preterm labour, using continuous lifestyle monitoring combined with multiomics data on the genome, transcriptome, proteome, metabolome and microbiome.ParticipantsPregnant women were recruited at the timing of first routine antenatal visits at Tohoku University Hospital, Sendai, Japan, between September 2015 and November 2016. Of the eligible women who were invited, 65.4% agreed to participate, and a total of 302 women were enrolled. The inclusion criteria were age ≥20 years and the ability to access the internet using a smartphone in the Japanese language.Findings to dateStudy participants uploaded daily general health information including quality of sleep, condition of bowel movements and the presence of nausea, pain and uterine contractions. Participants also collected physiological data, such as body weight, blood pressure, heart rate and body temperature, using multiple home healthcare devices. The mean upload rate for each lifelog item was ranging from 67.4% (fetal movement) to 85.3% (physical activity), and the total number of data points was over 6 million. Biospecimens, including maternal plasma, serum, urine, saliva, dental plaque and cord blood, were collected for multiomics analysis.Future plansLifelog and multiomics data will be used to construct a time-course high-resolution reference catalogue of pregnancy. The reference catalogue will allow us to discover relationships among multidimensional phenotypes and novel risk markers in pregnancy for the future personalised early prediction of pregnancy complications.

Perduram por quase um século as contribuições teórico­-políticas de Antonio Gramsci, em especial no sentido das definições e das interpretações em torno da noção de hegemonia – combinação de relações de poderes que se sustenta fundamentalmente no consentimento de oprimidos perante opressores. Com base em reflexões sobre a obra gramsciana que consideram a matriz abissal fundada na coisificação de povos racializados/subalternizados, são problematizados os potenciais enfrentamentos da hegemonia capitalista – a qual se vale também da dominação via coerção colonial, desde a sua formação histórica até à contemporaneidade. Daí os aportes de movimentos indígenas no Brasil e na Bolívia que, com seus atos de desobediências político­-epistêmicas em eventos públicos ou posicionamentos políticos, podem ser entendidos como aprendizagens contra­-hegemônicas, em consonância com as epistemologias do Sul. The theoretical and political contributions from Antonio Gramsci last for nearly a century, in particular his definitions and understanding of the broad notion of hegemony – the combination of power relationships whose preferential locus is called civil society and which is sustained fundamentally via the consent of the oppressed with respect to their oppressors. Based on the reflections on Gramsci’s work which consider the abyssal matrix as anchored in the thingification of racialized/subordinate peoples, the potential avenues for confronting the capitalist hegemony are problematicized, which, from its historical inception to the present day, has unyieldingly taken advantage of objectifying colonial power of domination by coercion. Hence the impact achieved by the indigenous movements in Brazil and Bolivia, felt in terms of the anti­-hegemonic learning present in the public acts and manifestations of political and epistemological disobedience, in harmony with the epistemologies of the South. Il y a presque un siècle que perdurent les contributions théorico­-politiques de Antonio Gramsci, en particulier dans le sens des définitions et des compréhensions tournant autour de la notion d’hégémonie – conjugaison de relations de pouvoir qui repose fondamentalement sur le consentement des opprimés envers les oppresseurs. Sur la base de réflexions partant de l’œuvre de Gramsci qui considèrent la matrice abyssale comme ancrée dans la chosification de peuples racialisés/subalternisés, les voies de confrontation à l’hégémonie capitaliste se problématisent, hégémonie qui puise aussi de la domination par la coercition coloniale, depuis sa formation jusqu’à la contemporanéité. D’où les apports de mouvements indigènes au Brésil et en Bolivie qui, par leurs actes de désobéissance politico­-épistémiques menées dans des évènements publics ou positionnements politiques, peuvent être perçus comme apprentissages contre­-hégémoniques, en consonance avec les épistémologies du Sud.

In patients with nonalcoholic steatohepatitis (NASH), the prevalence of cirrhosis is higher among women than men, and hepatocellular carcinoma (HCC) develops mainly in the cirrhotic stage among women. However, the long-term outcomes in female patients with NASH have not been fully elucidated, and age, gender and BMI were not simultaneously adjusted in previous studies on the prognosis of NASH. To elucidate the outcomes in female patients with NASH, we prospectively compared NASH patients with advanced fibrosis (advanced NASH) with hepatitis C virus-related advanced fibrosis (advanced CHC) patients and NASH patients with mild fibrosis (mild NASH) using study cohorts that were adjusted for body mass index (BMI) in addition to age. The median follow-up period was 92.5 months. Liver-related complication-free survival was significantly reduced in the advanced NASH group compared to the mild NASH group. No liver-related complications developed in the mild NASH group. The overall survival, liver-related complication- and cardiovascular/cerebrovascular disease-free survival were not significantly different between the advanced NASH and CHC groups. Female patients with NASH and advanced fibrosis may have a less favorable prognosis for liver-related complications than the matched cohorts with NASH and mild fibrosis, but may have a similar prognosis to the matched cohorts with CHC.

We devised an extended 72-wk peginterferon-α-2a/ribavirin therapy regimen for the retreatment of highly intractable cases, i.e., 48-wk peginterferon-α-2b/ribavirin therapy-intractable cases. Although 2 cases achieved a rapid virological response to 72-wk peginterferon-α-2a/ribavirin therapy, 1 case failed to achieve a sustained virological response. Although the reason for this difference in the effectiveness of 72-wk peginterferon-α-2a/ribavirin therapy between the cases was unclear, the rebound phenomenon of serum transaminase after 48-wk peginterferon-α-2b/ribavirin therapy and the resultant lower viral load compared to that before 48-wk peginterferon-α-2b/ribavirin therapy might have influenced the treatment outcome. Thus, it may be beneficial to consider the rebound phenomenon of serum transaminase and the changes in viral load resulting from previous interferon-based therapy and then cautiously determine the indication and the timing of the administration of 72-wk peginterferon-α-2a/ribavirin in highly intractable cases. Further studies should be performed to confirm this strategy.

The role that transforming growth factor-α (TGF-α) has in chronic pancreatitis and pancreatic cancer has not been fully elucidated. We evaluated the effects of TGF-α on the human pancreatic stellate cell (PSC) line RLT-PSC and primary human PSCs, and the expression levels of TGF-α and metalloproteinase-1 (MMP-1) in human chronic pancreatitis and pancreatic cancer tissues. TGF-α stimulated the proliferation and migration of PSCs. Although the mRNA expression levels of tissue inhibitor of metalloproteinase-1 and α1(I) collagen were unchanged, the mRNA expression levels of MMP-1 increased concomitant with increases in MMP-1 protein levels and collagenase activity. TGF-α-stimulated migration of RLT-PSC cells was partially blocked by tissue inhibitor of metalloproteinase-1 protein and MMP-1 small interfering RNA. MMP-1 was also observed to stimulate the migration of PSCs. TGF-α-induced MMP-1 expression was completely blocked by gefitinib in PSCs. The Ras-ERK and PI3/Akt pathways appear to be involved in the activation of MMP-1 in PSCs. Immunohistochemical analyses showed that MMP-1 expression was significantly increased in the pancreatic interstitial tissues in case of chronic pancreatitis or pancreatic cancer compared with those in case of normal pancreas. In conclusion, TGF-α increased proliferation and migration of PSCs. TGF-α-induced migration of cells may be partly due to upregulation of MMP-1. TGF-α and MMP-1 upregulation may contribute to the pathogenesis of chronic pancreatitis and pancreatic cancer.

A S L D A b st ra ct s were included in the study. Hemoglobin less than 14.0g/dl at W1 and W2 of treatment was associated with subsequent decrease in ribavirin dose (p = 0.0005 and 0.0002, respectively), and addition of erythropoietin (p = 0.0145 and 0.0001, respectively). Drop in hemoglobin of.2g/dl from baseline atW2was also significantly associated with addition of erythropoietin (p = 0.0005). Hemoglobin at W1 or W2 was not associated with requirement for blood transfusion or with extended rapid virological response (eRVR), end of therapy response (ETR) or sustained virological response (with 4, 12 and 24 week follow-up; SVR4, SVR12 and SVR24 respectively). Undetectable viral load at W2 was associated with eRVR (p = 0.0025), ETR (p = 0.027), SVR4 (p = 0.037) and SVR12 (p = 0.0007). Undetectable viral load at W1 was not significantly associated with eRVR (p = 0.08), ETR or SVR4, SVR12 and SVR24. Conclusions In patients being treated with P, R, PI for CHC, undetectable viral load at W2 is associated with eRVR, ETR, SVR4 and SVR12. Early anemia (at W1 or W2) is associated with subsequent ribavirin dose reduction and addition of erythropoietin. Early monitoring of hemoglobin at W1 and W2 and of HCV RNA at W2may be helpful in patient management.

Background: Hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) has been increasingly reported as the concept of NASH has received wide acceptance among clinicians in the intervening years. Moreover incidence of NASH itself is expected to increase reflecting age of gluttony. However it does not make sense from a cost-effectiveness point of view to screen HCC frequently in all patients with NASH because patients with NASH make up around 1% in overall Japanese population. Aim: This study was designed to assess risk factors for HCC in patients with NASH to develop effective screening methods. Patients and Methods: Our study included all the patients who were consecutively diagnosed at Gunma University Graduate School of Medicine and its affiliated hospitals as having NASH between 2000 and 2006, were followed up for at least 24 months. We evaluated incidence of HCC to date. We compared clinicopathological features (physical findings, laboratory findings, histological features and complications) between patients with HCC (HCC group) and patients without HCC (non-HCC group). The criteria for the diagnosis of NASH were compatible liver histology. We confirmed the diagnosis of HCC by ultrasonographic scanguided tumor biopsy except the treatment-resistant ascites or absence of informed consent in which an angiography or computed tomography showed typical characteristics of HCC. Results: The overall sample included 79 patients (26 men and 53 women, median age 63 years). The follow-up period ranged from 30 to 138 months with an average of 52 months. Fourteen patients (9 men and 5 women, median age 63 years) developed HCC. As for histological stage due to Blunt's classification, 1 and 16 had stage 1, 2 and 23 had stage 2, 3 and 12 had stage 3, and 8 and 14 had stage 4 in HCC group and non-HCC group, respectively. All cases accompanied either obesity or diabetes mellitus. Univariate analysis showed age, sex, histological stage, prothrombin time, serum total cholesterol level, and serum uremic acid level were significant different between HCC group and non-HCC group. Multiple logistic analysis showed male sex (odds ratio: 44.09, 95% Confidence interval: 3.564-545.4, p=0.032) and elder age (odds ratio: 1.134, 95% Confidence interval: 1.0181.265, p=0.029) were significant risk factors for HCC in patients with NASH. Conclusions: Though preliminary results, male sex and elder age were significant risk factors for HCC in patients with NASH and these patients have to be regularly monitored for early detection of HCC. At the same time, we should increase the sample size and follow-up periods and confirm our hypothesis in the near future.