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Global Biobank Week: Toward Harmonization in Biobanking.

Biobank publications - Wed, 11/22/2017 - 13:02

Global Biobank Week: Toward Harmonization in Biobanking.

Biopreserv Biobank. 2017 Nov 21;:

Authors: Henderson MK, Matharoo-Ball B, Schacter B, Kozlakidis Z, Smits E, Törnwall O, Litton JE

PMID: 29161517 [PubMed - as supplied by publisher]

Prenatal famine exposure, adulthood obesity patterns and risk of type 2 diabetes.

Biobank publications - Wed, 11/22/2017 - 13:02

Prenatal famine exposure, adulthood obesity patterns and risk of type 2 diabetes.

Int J Epidemiol. 2017 Nov 17;:

Authors: Meng R, Lv J, Yu C, Guo Y, Bian Z, Yang L, Chen Y, Zhang H, Chen X, Chen J, Chen Z, Qi L, Li L

Abstract
Background: Prenatal exposure to famine and adulthood obesity have been independently related to the risk of type 2 diabetes; however, little is known about the joint effects of these risk factors at different stages of life on adulthood diabetes risk.
Methods: The analysis included 88 830 participants of the China Kadoorie Biobank, who were born around the time of the Chinese Great Famine and without diabetes, cardiovascular diseases, or cancer at baseline. We defined famine exposure subgroups as nonexposed (born between 1 October 1962 and 30 September 964), fetal-exposed (born between 1 October 1959 and 30 September 1961) and early-childhood exposed (born between 1 October 1956 and 30 September 1958). General obesity was assessed by body mass index (BMI: overweight ≥ 24.0, obesity ≥ 28.0) and abdominal obesity assessed by waist-to-hip ratio (WHR, men/women: moderate ≥ 0.90/0.85, high ≥ 0.95/0.90).
Results: During a median 7.3 years (642 552 person-years) of follow-up, we identified 1372 incident cases of type 2 diabetes. Compared with nonexposed and early-childhood exposed participants combined as a single comparison group, fetal-exposed participants showed an increased risk of diabetes in adulthood [hazard ratio (HR) = 1.25; 95% confidence interval (CI): 1.07-1.45]. The association between general obesity and diabetes was consistent across subgroups according to famine exposure (P for interaction > 0.05). A stronger association between abdominal obesity and diabetes was observed in the fetal-exposed subgroup than in other subgroups (P for interaction = 0.025 in the whole population). This interaction was more obvious in women (P = 0.013) but not in men (P = 0.699). Compared with normal-BMI and -WHR participants, those with both general (BMI ≥ 24.0) and abdominal (WHR ≥ 0.90/0.85) obesity in adulthood had 5.32 (95% CI: 3.81-7.43)-, 3.13 (2.48-3.94)- and 4.43 (3.45-5.68)-fold higher risks if these were carried during, before and after times of famine, respectively.
Conclusions: Coexistence of prenatal experience of undernutrition and abdominal obesity in adulthood was associated with a higher risk of type 2 diabetes.

PMID: 29161448 [PubMed - as supplied by publisher]

Gallstone Disease and the Risk of Type 2 Diabetes.

Biobank publications - Wed, 11/22/2017 - 13:02

Gallstone Disease and the Risk of Type 2 Diabetes.

Sci Rep. 2017 Nov 20;7(1):15853

Authors: Lv J, Yu C, Guo Y, Bian Z, Yang L, Chen Y, Li S, Huang Y, Fu Y, He P, Tang A, Chen J, Chen Z, Qi L, Li L

Abstract
Gallstone disease (GSD) is related to several diabetes risk factors. The present study was to examine whether GSD was independently associated with type 2 diabetes in the China Kadoorie Biobank study. After excluding participants with prevalent diabetes and prior histories of cancer, heart disease, and stroke at baseline, 189,154 men and 272,059 women aged 30-79 years were eligible for analysis. The baseline prevalence of GSD was 5.7% of the included participants. During 4,138,687 person-years of follow-up (median, 9.1 years), a total of 4,735 men and 7,747 women were documented with incident type 2 diabetes. Compared with participants without GSD at baseline, the multivariate-adjusted hazard ratios (HRs) for type 2 diabetes for those with GSD were 1.09 (95% CI: 0.96-1.24; P = 0.206), 1.21 (95% CI: 1.13-1.30; P < 0.001), and 1.17 (95% CI: 1.10-1.25; P < 0.001) in men, women, and the whole cohort respectively. There was no statistically significant heterogeneity between men and women (P = 0.347 for interaction). The association between GSD and type 2 diabetes was strongest among participants who reported ≥5 years since the first diagnosis and were still on treatment at baseline (HR = 1.48; 95% CI: 1.16-1.88; P = 0.001). The present study highlights the importance of developing a novel prevention strategy to mitigate type 2 diabetes through improvement of gastrointestinal health.

PMID: 29158491 [PubMed - in process]

RNase 7 strongly promotes TLR9-mediated DNA sensing by human plasmacytoid dendritic cells.

Biobank publications - Wed, 11/22/2017 - 13:02

RNase 7 strongly promotes TLR9-mediated DNA sensing by human plasmacytoid dendritic cells.

J Invest Dermatol. 2017 Nov 17;:

Authors: Kopfnagel V, Wagenknecht S, Harder J, Hofmann K, Kleine M, Buch A, Sodeik B, Werfel T

Abstract
Plasmacytoid dendritic cells (pDCs) were described to accumulate in the skin of patients with psoriasis and to be recruited into the dermis upon allergen challenge in atopic dermatitis. Importantly, activation of pDCs in the skin has been identified as important initiator of psoriasis development. RNase 7 is one of the major antimicrobial peptides (AMP) secreted by keratinocytes and is expressed in significantly higher amounts in lesional skin of patients with atopic dermatitis or psoriasis than in healthy individuals. The skin-derived AMPs human ß-defensin 2 and LL-37 indirectly stimulate the activity of skin pDCs but to our knowledge an immunmodulatory potential of RNase 7 has not yet been reported. We show here that RNase 7 enables human pDCs to recognize self-DNA, and promotes their rapid sensing of bacterial DNA. This very fast innate immune response was sufficient to up-regulate the expression of several antiviral interferon-stimulated genes in human PBMCs, and to inhibit an infection of primary human keratinocytes with herpes simplex virus 1. Importantly, RNase 7 was a markedly stronger trigger for IFNα expression in human pDCs than the other AMPs. Our data indicate that RNase 7 exhibits potent immunomodulatory functions and supports the efficient recognition of microbial infections by human skin-infiltrating pDCs.

PMID: 29157732 [PubMed - as supplied by publisher]

Catching hidden variation: systematic correction of reference minor allele annotation in clinical variant calling.

Biobank publications - Tue, 11/21/2017 - 14:07

Catching hidden variation: systematic correction of reference minor allele annotation in clinical variant calling.

Genet Med. 2017 Oct 26;:

Authors: Barbitoff YA, Bezdvornykh IV, Polev DE, Serebryakova EA, Glotov AS, Glotov OS, Predeus AV

Abstract
PurposeWe comprehensively assessed the influence of reference minor alleles (RMAs), one of the inherent problems of the human reference genome sequence.MethodsThe variant call format (VCF) files provided by the 1000 Genomes and Exome Aggregation Consortium (ExAC) consortia were used to identify RMA sites. All coding RMA sites were checked for concordance with UniProt and the presence of same codon variants. RMA-corrected predictions of functional effect were obtained with SIFT, PolyPhen-2, and PROVEAN standalone tools and compared with dbNSFP v2.9 for consistency.ResultsWe systematically characterized the problem of RMAs and identified several possible ways in which RMA could interfere with accurate variant discovery and annotation. We have discovered a systematic bias in the automated variant effect prediction at the RMA loci, as well as widespread switching of functional consequences for variants located in the same codon as the RMA. As a convenient way to address the problem of RMAs we have developed a simple bioinformatic tool that identifies variation at RMA sites and provides correct annotations for all such substitutions. The tool is available free of charge at http://rmahunter.bioinf.me.ConclusionCorrection of RMA annotation enhances the accuracy of next-generation sequencing-based methods in clinical practice.Genetics in Medicine advance online publication, 26 October 2017; doi:10.1038/gim.2017.168.

PMID: 29155419 [PubMed - as supplied by publisher]

SIRT5 and post-translational protein modifications: A potential therapeutic target for myocardial ischemia-reperfusion injury with regard to mitochondrial dynamics and oxidative metabolism.

Biobank publications - Tue, 11/21/2017 - 14:07

SIRT5 and post-translational protein modifications: A potential therapeutic target for myocardial ischemia-reperfusion injury with regard to mitochondrial dynamics and oxidative metabolism.

Eur J Pharmacol. 2017 Nov 14;:

Authors: Zou R, Shi W, Tao J, Li H, Lin X, Yang S, Hua P

Abstract
SIRT5 is a sirtuin family member that participates in dynamic and reversible protein chemical modification after translation. It has pivotal roles in the regulation of numerous aspects of myocardial energy metabolism and cardiac functions. Recent studies suggest that down-regulation of this regulator significantly increased the extent of myocardial infarction during ischemia-reperfusion injury (IRI). Accordingly, SIRT5 is emerging as a major contributor to the pathogenesis of IRI and may possess therapeutic potential for reversing mitochondrial respiratory chain disturbances and cellular damage attributed to ischemia-reperfusion. To better understand this specific mechanism, we reviewed the structure of SIRT5, its gene distribution and the SIRT5 pathways that influence myocardial IRI associated with mitochondrial dynamics and oxidative phosphorylation.

PMID: 29154835 [PubMed - as supplied by publisher]

Association of Cerebrospinal Fluid (CSF) Insulin with Cognitive Performance and CSF Biomarkers of Alzheimer's Disease.

Biobank publications - Tue, 11/21/2017 - 14:07

Association of Cerebrospinal Fluid (CSF) Insulin with Cognitive Performance and CSF Biomarkers of Alzheimer's Disease.

J Alzheimers Dis. 2017 Nov 16;:

Authors: Geijselaers SLC, Aalten P, Ramakers IHGB, De Deyn PP, Heijboer AC, Koek HL, OldeRikkert MGM, Papma JM, Reesink FE, Smits LL, Stehouwer CDA, Teunissen CE, Verhey FRJ, van der Flier WM, Biessels GJ, Parelsnoer Institute Neurodegenerative Diseases study group

Abstract
BACKGROUND: Abnormal insulin signaling in the brain has been linked to Alzheimer's disease (AD).
OBJECTIVE: To evaluate whether cerebrospinal fluid (CSF) insulin levels are associated with cognitive performance and CSF amyloid-β and Tau. Additionally, we explore whether any such association differs by sex or APOE ɛ4 genotype.
METHODS: From 258 individuals participating in the Parelsnoer Institute Neurodegenerative Diseases, a nationwide multicenter memory clinic population, we selected 138 individuals (mean age 66±9 years, 65.2% male) diagnosed with subjective cognitive impairment (n = 45), amnestic mild cognitive impairment (n = 44), or AD (n = 49), who completed a neuropsychological assessment, including tests of global cognition and memory performance, and who underwent lumbar puncture. We measured CSF levels of insulin, amyloid-β1-42, total (t-)Tau, and phosphorylated (p-)Tau.
RESULTS: CSF insulin levels did not differ between the diagnostic groups (p = 0.136). Across the whole study population, CSF insulin was unrelated to cognitive performance and CSF biomarkers of AD, after adjustment for age, sex, body mass index, diabetes status, and clinic site (all p≥0.131). Importantly, however, we observed effect modification by sex and APOE ɛ4 genotype. Specifically, among women, higher insulin levels in the CSF were associated with worse global cognition (standardized regression coefficient -0.483; p = 0.008) and higher p-Tau levels (0.353; p = 0.040). Among non-carriers of the APOE ɛ4 allele, higher CSF insulin was associated with higher t-Tau (0.287; p = 0.008) and p-Tau (0.246; p = 0.029).
CONCLUSION: Our findings provide further evidence for a relationship between brain insulin signaling and AD pathology. It also highlights the need to consider sex and APOE ɛ4 genotype when assessing the role of insulin.

PMID: 29154275 [PubMed - as supplied by publisher]

Prognostic value of tumour-infiltrating lymphocytes in small HER2-positive breast cancer.

Biobank publications - Tue, 11/21/2017 - 14:07

Prognostic value of tumour-infiltrating lymphocytes in small HER2-positive breast cancer.

Eur J Cancer. 2017 Nov 15;87:164-171

Authors: Criscitiello C, Bagnardi V, Pruneri G, Vingiani A, Esposito A, Rotmensz N, Curigliano G

Abstract
BACKGROUND: The standard treatment for patients with small, node-negative, human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (BC) is still controversial. Our aim was to assess the prognostic role of tumour-infiltrating lymphocytes (TILs) in patients with stage pT1a-b HER2-positive BC.
PATIENTS AND METHODS: Haematoxylin and eosin slides from node-negative, pT1a-b HER2-positive BC surgical specimens were retrieved from pathology archives to assess TILs and their association with outcome.
RESULTS: TILs were evaluated in 205 patients with HER2-positive, pT1a-b tumours, who underwent breast surgery between 1997 and 2009 at the European Institute of Oncology. At a median follow-up of 11 years, we did not observe any association between the presence of TILs, either assessed as a continuous or dichotomous variable (<50 versus ≥ 50%), and outcome. Within the subgroup of patients with pT1a tumours who did not receive any adjuvant therapy (36/97 patients), the rate of disease-free survival events was lower in lymphocyte-predominant BC (LPBC) as compared with non-LPBC patients (p = 0.066).
CONCLUSIONS: TILs cannot be used as a prognostic biomarker in pT1a-b HER2-positive BC. Additional biomarkers are needed for selecting patients with stage I HER2-positive BC who candidate to adjuvant therapy de-escalation.

PMID: 29154173 [PubMed - as supplied by publisher]

Labor therapeutics and BMI as risk factors for postpartum preeclampsia: A case-control study.

Biobank publications - Tue, 11/21/2017 - 14:07

Labor therapeutics and BMI as risk factors for postpartum preeclampsia: A case-control study.

Pregnancy Hypertens. 2017 Oct;10:177-181

Authors: Skurnik G, Hurwitz S, McElrath TF, Tsen LC, Duey S, Saxena AR, Karumanchi A, Rich-Edwards JW, Seely EW

Abstract
OBJECTIVES: This study aims at identifying associations between therapeutics used during labor and the occurrence of postpartum preeclampsia (PPPE), a poorly understood entity.
STUDY DESIGN AND MAIN OUTCOME MEASURES: This is a case-control study of women who received an ICD-9 code for PPPE (cases) during the years 2009-2011, compared to women with a normotensive term pregnancy, delivery and postpartum period until discharge (controls), matched on age (±1year) and delivery date (±3months). Cases were defined as women having a normotensive term pregnancy, delivery and initial postpartum period (48h post-delivery) but developing hypertension between 48h and 6weeks postpartum. Single variable and multiple variable models were used to determine significant risk factors.
RESULTS: Forty-three women with PPPE were compared to 86 controls. Use of vasopressors and oxytocin did not differ between cases and controls, but rate of fluids administered during labor (OR=1.68 per 100cc/h; 95% CI: 1.09-2.59, p=0.02) and an elevated pre-pregnancy/first trimester BMI (OR=1.18 per kg/m(2), 95% CI: 1.07-1.3, p=0.001) were identified as significant risk factors in multivariate analysis.
CONCLUSIONS: We identified two potentially modifiable risk factors for PPPE; further studies are needed to better define the role of these two variables in the development of PPPE.

PMID: 29153674 [PubMed - in process]

Maternal serum IGF-1, IGFBP-1 and 3, and placental growth hormone at 20weeks' gestation in pregnancies complicated by preeclampsia.

Biobank publications - Tue, 11/21/2017 - 14:07

Maternal serum IGF-1, IGFBP-1 and 3, and placental growth hormone at 20weeks' gestation in pregnancies complicated by preeclampsia.

Pregnancy Hypertens. 2017 Oct;10:149-154

Authors: Liao S, Vickers MH, Taylor RS, Jones B, Fraser M, McCowan LME, Baker PN, Perry JK

Abstract
OBJECTIVE: To investigate whether maternal serum concentrations of placental growth hormone (GH-V), insulin-like growth factor (IGF) 1 and 2, and IGF binding proteins (IGFBP) 1 and 3 were altered in pregnancies complicated by later preeclampsia (PE).
STUDY DESIGN: In a nested case-control study, PE cases (n=71) and matched controls (n=71) were selected from the Screening for Pregnancy Endpoints (SCOPE) biobank in Auckland, New Zealand. Maternal serum hormone concentrations at 20weeks of gestation were determined by ELISA.
RESULTS: We found that maternal serum GH-V concentration at 20weeks of gestation was unaltered in the PE group, compared to the control group (median, 1.78ng/ml vs. 1.65ng/ml, p=0.884). Maternal IGF-1 and IGFBP-3 concentrations and the IGF-1/IGFBP-3 ratio in PE pregnancies were significantly higher than in controls (median, 253.1ng/ml vs. 204.3ng/ml, p<0.0001; 8535ng/ml vs. 7711ng/ml, p=0.0023; 0.032vs. 0.026, p<0.0001, respectively), whereas maternal IGFBP-1 concentration was significantly lower in PE pregnancies than in controls (median, 34.85ng/ml vs. 48.92ng/ml, p=0.0006).
CONCLUSION: Our findings suggest a potential role of IGFs and IGFBPs in the prediction of pregnancies complicated by PE. However, the maternal serum concentration of GH-V at 20weeks' gestation is unlikely to be useful in the early prediction of PE.

PMID: 29153669 [PubMed - in process]

Development of a population-based cancer case-control study in southern china.

Biobank publications - Tue, 11/21/2017 - 14:07
Related Articles

Development of a population-based cancer case-control study in southern china.

Oncotarget. 2017 Oct 20;8(50):87073-87085

Authors: Ye W, Chang ET, Liu Z, Liu Q, Cai Y, Zhang Z, Chen G, Huang QH, Xie SH, Cao SM, Shao JY, Jia WH, Zheng Y, Liao J, Chen Y, Lin L, Liang L, Ernberg I, Vaughan TL, Huang G, Zeng Y, Zeng YX, Adami HO

Abstract
With its population of over 1.3 billion persons, China offers abundant opportunities to discover causes of disease. However, few rigorous population-based case-control studies have as yet been conducted in mainland China. We conducted a population-based case-control study of nasopharyngeal carcinoma in Guangdong Province and Guangxi Autonomous Region. We collected questionnaires and biospecimens from incident cases recruited between March 2010 and December 2013, and population-based controls between November 2010 and November 2014. Preparatory activities prior to subject enrollment required approximately 18 months. We enrolled a total of 2554 NPC cases and 2648 controls. Among all identified cases, 83.8% participated. For the participating cases, the median time between diagnosis and interview was 2 days. Among all contacted controls, 82.7% participated. From the enrolled cases, we collected 2518 blood specimens (provided by 98.6% of eligible cases), 2350 saliva specimens (92.0%), 2514 hair specimens (98.4%), and 2507 toenail/fingernail specimens (98.2%). From the enrolled controls, we collected 2416 blood specimens (91.2%), 2505 saliva specimens (94.6%), 2517 hair specimens (95.1%), and 2514 toenail/fingernail specimens (94.9%). We demonstrate that population-based epidemiologic research can successfully be conducted in southern China. The study protocols, databases, and biobank will serve as an extraordinarily valuable resource for testing future etiologic hypotheses.

PMID: 29152064 [PubMed]

Comparison of regional fat measurements by dual-energy X-ray absorptiometry and conventional anthropometry and their association with markers of diabetes and cardiovascular disease risk.

Biobank publications - Tue, 11/21/2017 - 14:07
Related Articles

Comparison of regional fat measurements by dual-energy X-ray absorptiometry and conventional anthropometry and their association with markers of diabetes and cardiovascular disease risk.

Int J Obes (Lond). 2017 Nov 20;:

Authors: Vasan SK, Osmond C, Canoy D, Christodoulides C, Neville MJ, Di Gravio C, Fall CHD, Karpe F

Abstract
BACKGROUND/OBJECTIVE: Fat distribution is a strong and independent predictor of type 2 diabetes (T2D) and cardiovascular disease (CVD) and is usually determined using conventional anthropometry in epidemiological studies. Dual-energy X-ray absorptiometry (DXA) can measure total and regional adiposity more accurately. Nonetheless, whether DXA provides more precise estimates of cardiovascular risk in relation to total and regional adiposity is not known. We determined the strength of the associations between DXA- and conventional anthropometry determined fat distribution and T2D and CVD risk.
SUBJECTS/METHODS: Waist (WC) and hip circumference (HC) and DXA was used to measure total and regional adiposity in 4950 (2119 men) participants aged 29-55 years from the Oxford Biobank without pre-existing T2D or CVD. Cross-sectional associations were compared between WC and HC vs DXA-determined regional adiposity (all z-score normalized) with impaired fasting glucose, hypertriglyceridemia, hypertension and insulin resistance (IR).
RESULTS: Following adjustment for total adiposity, upper body adiposity measurements showed consistently increased risk of T2D and CVD risk markers except for abdominal subcutaneous fat in both sexes, and arm fat in men, which showed protective associations. Among upper adiposity depots, visceral fat mass showed stronger odds ratios (OR) ranging from 1.69-3.64 compared with WC 1.07-1.83. Among lower adiposity depots, HC showed modest protection for IR in both sexes [men: OR 0.80 (95%CI 0.67, 0.96); women: 0.69 (0.56, 0.86)] whereas gynoid fat and in particular leg fat showed consistent and strong protective effects for all outcomes in both men and women. The differential effect of body fat distribution on CVD and T2D were more pronounced at higher levels of total adiposity.
CONCLUSIONS: Compared with DXA, conventional anthropometry underestimates the associations of regional adiposity with T2D and CVD risk markers. After correcting for overall adiposity, greater subcutaneous fat mass in particular in the lower body is protective relative to greater android or VAT mass.International Journal of Obesity accepted article preview online, 20 November 2017. doi:10.1038/ijo.2017.289.

PMID: 29151596 [PubMed - as supplied by publisher]

Cancer cells induce interleukin-22 production from memory CD4(+) T cells via interleukin-1 to promote tumor growth.

Biobank publications - Sun, 11/19/2017 - 12:58
Related Articles

Cancer cells induce interleukin-22 production from memory CD4(+) T cells via interleukin-1 to promote tumor growth.

Proc Natl Acad Sci U S A. 2017 Nov 17;:

Authors: Voigt C, May P, Gottschlich A, Markota A, Wenk D, Gerlach I, Voigt S, Stathopoulos GT, Arendt KAM, Heise C, Rataj F, Janssen KP, Königshoff M, Winter H, Himsl I, Thasler WE, Schnurr M, Rothenfußer S, Endres S, Kobold S

Abstract
IL-22 has been identified as a cancer-promoting cytokine that is secreted by infiltrating immune cells in several cancer models. We hypothesized that IL-22 regulation would occur at the interface between cancer cells and immune cells. Breast and lung cancer cells of murine and human origin induced IL-22 production from memory CD4(+) T cells. In the present study, we found that IL-22 production in humans is dependent on activation of the NLRP3 inflammasome with the subsequent release of IL-1β from both myeloid and T cells. IL-1 receptor signaling via the transcription factors AhR and RORγt in T cells was necessary and sufficient for IL-22 production. In these settings, IL-1 induced IL-22 production from a mixed T helper cell population comprised of Th1, Th17, and Th22 cells, which was abrogated by the addition of anakinra. We confirmed these findings in vitro and in vivo in two murine tumor models, in primary human breast and lung cancer cells, and in deposited expression data. Relevant to ongoing clinical trials in breast cancer, we demonstrate here that the IL-1 receptor antagonist anakinra abrogates IL-22 production and reduces tumor growth in a murine breast cancer model. Thus, we describe here a previously unrecognized mechanism by which cancer cells induce IL-22 production from memory CD4(+) T cells via activation of the NLRP3 inflammasome and the release of IL-1β to promote tumor growth. These findings may provide the basis for therapeutic interventions that affect IL-22 production by targeting IL-1 activity.

PMID: 29150554 [PubMed - as supplied by publisher]

Biobanking in Israel 2016-17; expressed perceptions versus real life enrollment.

Biobank publications - Sun, 11/19/2017 - 12:58
Related Articles

Biobanking in Israel 2016-17; expressed perceptions versus real life enrollment.

BMC Med Ethics. 2017 Nov 17;18(1):63

Authors: Koren G, Beller D, Laifenfeld D, Grossman I, Shalev V

Abstract
BACKGROUND: As part of the preparations to establish a population-based biobank in a large Israeli health organization, we aimed to investigate through focus groups the knowledge, perceptions and attitudes of insured Israelis, toward biobanking, and then, after input from focus groups' participants, to empirically assess the impact of a revised recruitment process on recruitment rates.
METHODS: 1) Six Focus group discussions were conducted (n = 10 per group) with individuals who had routine blood laboratory tests taken in the last 2 years. 2) After addressing the issues raised in the focus groups and revising the recruitment process, individuals undergoing routine blood tests in phlebotomy clinics (N = 10,262) were invited to participate in the future biobank.
RESULTS: At the outset of the focus groups there was an overall positive response to the prospect of a population-based biobank. Concerns revolved around infringement on privacy, fears of the "big brother"(e.g. insurance companies), and anxiety about inequality. Reaction to the language of the informed consent document revolved around concerns over ability to maintain anonymity, to withdraw consent, involvement of commercial entities, and the general tenor of the informed consent, which was perceived as legalistic and unilateral. In general, the longer participants were exposed to discussion about the biobank, the less likely they were to consent to sign in. Overall, only 20% (12) of the 60 participants stated they would agree to sign in by the end of the 2 hour group session. The feedback obtained from the focus groups was used in the second stage ("real life") of the study. A team of recruiters received extensive training to enable fruitful discussion and a detailed explanation to questions and concerns raised during the recruitment process. During the second stage of the study, after revising the consent form and training recruiters, a 53% consent rate was observed among 10,262 participants, more than 4 fold higher than estimated at the focus group stage.
CONCLUSIONS: The qualitative focus group research helped identify important perceptions and concerns, which were subsequently addressed in the revised consent form and in the discussion the recruiters had with potential biobank donors.

PMID: 29149849 [PubMed - in process]

Taiwan Biobank: making cross-database convergence possible in the Big Data era.

Biobank publications - Sat, 11/18/2017 - 13:11

Taiwan Biobank: making cross-database convergence possible in the Big Data era.

Gigascience. 2017 Nov 15;:

Authors: Lin JC, Fan CT, Liao CC, Chen YS

Abstract
The Taiwan Biobank (TWB) is a biomedical research database of biopsy data from 200,000 participants. Access to this database has been granted to research communities taking part in the development of precision medicines; however, this has raised issues surrounding TWB's access to electronic medical records (EMR). The Personal Data Protection Act of Taiwan restricts access to EMR for purposes not covered by patients' original consent. This commentary explores possible legal solutions to help ensure that the access TWB has to EMR abides with legal obligations, and with governance frameworks associated with ethical, legal and social implications. We suggest utilizing "hash function" algorithms to create non-retrospective, anonymized data for the purpose of cross-transmission and/or linkage with EMR.

PMID: 29149267 [PubMed - as supplied by publisher]

Roles of VEGF-Flt-1 signaling in malignant behaviors of oral squamous cell carcinoma.

Biobank publications - Sat, 11/18/2017 - 13:11

Roles of VEGF-Flt-1 signaling in malignant behaviors of oral squamous cell carcinoma.

PLoS One. 2017;12(11):e0187092

Authors: Subarnbhesaj A, Miyauchi M, Chanbora C, Mikuriya A, Nguyen PT, Furusho H, Ayuningtyas NF, Fujita M, Toratani S, Takechi M, Niida S, Takata T

Abstract
BACKGROUND: Vascular endothelial growth factor (VEGF) is a highly specific signaling protein for vascular endothelial cells that plays a critical role in tumor growth and invasion through angiogenesis, and may contribute to cell migration and activation of pre-osteoclasts, osteoclasts and some tumor cells.
OBJECTIVES: We aimed to clarify the detailed roles of VEGF-Flt-1 signaling in bone invasion of oral squamous cell carcinoma (OSCC) cells.
RESULTS: Forty-two (42) of 54 cases with gingival SCC (77.8%) strongly expressed VEGF, and had a significantly increased number of Flt-1+ osteoclasts (p<0.01) and more aggressive bone invasion (p<0.05). PlGF, a ligand of Flt-1, induced osteoclastogenesis in single culture of bone marrow cells (BMCs), and inhibition of Flt-1-signaling by VEGF tyrosine kinase inhibitor and It's down stream (Akt and ERK1/2) inhibitos reduced osteoclastogenesis in PlGF-stimulated BMCs (p<0.01). In molecular level, PlGF stimulation significantly upregulated RANKL expression in Flt-1-expressing HSC2 cells via phosphorylation of Akt and ERK1/2. In the co-culture of VEGF-producing HSC2 cells and BMCs, number of TRAP-positive osteoclasts markedly increased (p<0.01). The osteoclastogenesis was significantly inhibited by RANKL-neutralizing antibody (p<0.01) as well as by VEGF tyrosine kinase inhibitor (p<0.01) and it's downstream (Akt and ERK1/2) inhibitors (p<0.01, p<0.05, respectively).
CONCLUSION: VEGF-Flt-1 signaling induces osteoclastogenesis in OSCC through two possible ways: 1) VEGF produced from OSCC cells can directly stimulate the Flt-1 pathway in preosteoclasts to induce migration to future bone resorbing area and differentiation into osteoclasts, and 2) VEGF-Flt-1 signaling upregulates RANKL expression in OSCC cells, which indirectly leads to osteoclast differentiation. Therefore, blocking of the VEGF-Flt-1 signaling may help inhibit bone invasion of OSCC.

PMID: 29149180 [PubMed - in process]

Is Your Biobank Up to Standards? A Review of the National Canadian Tissue Repository Network Required Operational Practice Standards and the Controlled Documents of a Certified Biobank.

Biobank publications - Sat, 11/18/2017 - 13:11

Is Your Biobank Up to Standards? A Review of the National Canadian Tissue Repository Network Required Operational Practice Standards and the Controlled Documents of a Certified Biobank.

Biopreserv Biobank. 2017 Nov 17;:

Authors: Hartman V, Castillo-Pelayo T, Babinszky S, Dee S, Leblanc J, Matzke L, O'Donoghue S, Carpenter J, Carter C, Rush A, Byrne J, Barnes R, Mes-Messons AM, Watson P

Abstract
Ongoing quality management is an essential part of biobank operations and the creation of high quality biospecimen resources. Adhering to the standards of a national biobanking network is a way to reduce variability between individual biobank processes, resulting in cross biobank compatibility and more consistent support for health researchers. The Canadian Tissue Repository Network (CTRNet) implemented a set of required operational practices (ROPs) in 2011 and these serve as the standards and basis for the CTRNet biobank certification program. A review of these 13 ROPs covering 314 directives was conducted after 5 years to identify areas for revision and update, leading to changes to 7/314 directives (2.3%). A review of all internal controlled documents (including policies, standard operating procedures and guides, and forms for actions and processes) used by the BC Cancer Agency's Tumor Tissue Repository (BCCA-TTR) to conform to these ROPs was then conducted. Changes were made to 20/106 (19%) of BCCA-TTR documents. We conclude that a substantial fraction of internal controlled documents require updates at regular intervals to accommodate changes in best practices. Reviewing documentation is an essential aspect of keeping up to date with best practices and ensuring the quality of biospecimens and data managed by biobanks.

PMID: 29148831 [PubMed - as supplied by publisher]

Biobanking of Fresh-Frozen Cancer Tissue: RNA Is Stable Independent of Tissue Type with Less Than 1 Hour of Cold Ischemia.

Biobank publications - Sat, 11/18/2017 - 13:11

Biobanking of Fresh-Frozen Cancer Tissue: RNA Is Stable Independent of Tissue Type with Less Than 1 Hour of Cold Ischemia.

Biopreserv Biobank. 2017 Nov 17;:

Authors: Song SY, Jun J, Park M, Park SK, Choi W, Park K, Jang KT, Lee M

Abstract
BACKGROUND: The effects of preanalytical variables in tissue processing and storage periods on RNA quality of tissues have been well documented in each type of cancer. However, few studies have been performed on a comparative assessment of the impacts across different cancer tissues, even though it is well known that RNase activity is highly variable in various tissue types and RNase-rich tissues have been found to yield low-quality RNA.
METHODS: We investigated the impacts of cold ischemia times and long-term storage on RNA integrity in various types of cancer tissue, which had been fresh-frozen and collected at the Samsung Medical Center Biobank. RNA quality was also evaluated with regard to histopathological variables. We analyzed RNA integrity number (RIN) data, which had been obtained from our quality control (QC) processes over the last 7 years. Approximately 2% of samples were randomly selected and processed to measure RIN quarterly and after 6 years of storage for QC purposes.
RESULTS: Fresh-frozen tumor tissues yielded high-quality RNA regardless of tumor type and histopathological features. Up to 1-hour cold ischemia times and up to 6-year storage times did not adversely influence RNA integrity. Only 3 samples showed RIN of <7 out of a total of 396 analyzed tumor tissues.
CONCLUSIONS: Tissue quality was not adversely affected by long-term storage or limited variations of cold ischemia times. The low-quality samples could be correlated with the structural composition or intratumoral heterogeneity of tissues. The strict application of standardized protocols for tissue collection is the key for high-quality biobanking.

PMID: 29148824 [PubMed - as supplied by publisher]

Sex hormone-binding globulin (SHBG) is a potential early diagnostic biomarker for gastric cancer.

Biobank publications - Sat, 11/18/2017 - 13:11

Sex hormone-binding globulin (SHBG) is a potential early diagnostic biomarker for gastric cancer.

Cancer Med. 2017 Nov 17;:

Authors: Cheng CW, Chang CC, Patria YN, Chang RT, Liu YR, Li FA, Shih HM, Lin CY

Abstract
The use of blood plasma biomarkers in gastric cancer (GC) management is limited due to a lack of reliable biomarkers. An LC-MS/MS assay and a bioinformatic analysis were performed to identify blood plasma biomarkers in a GC discovery cohort. The data obtained were verified and validated by western blotting and an ELISA in an independent study cohort. A label-free quantification analysis of the MS data using PEAKS7 software found that four plasma proteins of apolipoprotein C-1, gelsolin, sex hormone-binding globulin (SHBG), and complement component C4-A were significantly overexpressed in GC patients. A western blot assay of these plasma proteins showed that only SHBG was consistently overexpressed in the patient group. ELISA measurement of SHBG blood plasma levels confirmed that the patient group had significantly higher SHBG levels than the control group. SHBG levels in the patient group remained significantly higher after being stratified by gender, age, and disease stage. These findings show that LC-MS/MS is powerful and highly sensitive for plasma biomarker discovery, and SHBG could be a potential plasma biomarker for GC management.

PMID: 29148252 [PubMed - as supplied by publisher]

Abnormal brain white matter microstructure is associated with both pre-hypertension and hypertension.

Biobank publications - Sat, 11/18/2017 - 13:11

Abnormal brain white matter microstructure is associated with both pre-hypertension and hypertension.

PLoS One. 2017;12(11):e0187600

Authors: Suzuki H, Gao H, Bai W, Evangelou E, Glocker B, O'Regan DP, Elliott P, Matthews PM

Abstract
OBJECTIVES: To characterize effects of chronically elevated blood pressure on the brain, we tested for brain white matter microstructural differences associated with normotension, pre-hypertension and hypertension in recently available brain magnetic resonance imaging data from 4659 participants without known neurological or psychiatric disease (62.3±7.4 yrs, 47.0% male) in UK Biobank.
METHODS: For assessment of white matter microstructure, we used measures derived from neurite orientation dispersion and density imaging (NODDI) including the intracellular volume fraction (an estimate of neurite density) and isotropic volume fraction (an index of the relative extra-cellular water diffusion). To estimate differences associated specifically with blood pressure, we applied propensity score matching based on age, sex, educational level, body mass index, and history of smoking, diabetes mellitus and cardiovascular disease to perform separate contrasts of non-hypertensive (normotensive or pre-hypertensive, N = 2332) and hypertensive (N = 2337) individuals and of normotensive (N = 741) and pre-hypertensive (N = 1581) individuals (p<0.05 after Bonferroni correction).
RESULTS: The brain white matter intracellular volume fraction was significantly lower, and isotropic volume fraction was higher in hypertensive relative to non-hypertensive individuals (N = 1559, each). The white matter isotropic volume fraction also was higher in pre-hypertensive than in normotensive individuals (N = 694, each) in the right superior longitudinal fasciculus and the right superior thalamic radiation, where the lower intracellular volume fraction was observed in the hypertensives relative to the non-hypertensive group.
SIGNIFICANCE: Pathological processes associated with chronically elevated blood pressure are associated with imaging differences suggesting chronic alterations of white matter axonal structure that may affect cognitive functions even with pre-hypertension.

PMID: 29145428 [PubMed - in process]