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Rapid diagnosis of human T-cell lymphotropic virus (HTLV) type-I and -II infections are essential for timely and cost-effective disease interventions. MP Diagnostics ASSURE HTLV-I/II Rapid Test was developed for the rapid detection of anti-HTLV-I/II antibodies in patients' serum, plasma, and whole blood specimens. ASSURE HTLV-I/II Rapid Test employed MP Biomedicals' proprietary HTLV-I/II Trifusion recombinant antigen conjugated with gold nanoparticles and HTLV-I / HTLV-II recombinant antigens immobilized on the nitrocellulose membrane to detect total HTLV-I and HTLV-II antibodies. The overall performance of the ASSURE HTLV-I/II Rapid Test was found to be 99.42% sensitivity (95% Confidence Interval, 98.32–99.88%) and 100% specificity (95% Confidence Interval, 99.58–100.00%) in the tested clinical samples, including a total of 518 HTLV-I/II positive specimens (396 HTLV-I infection, 97 HTLV-II infection and 25 HTLV-I/II dual infection) and 872 HTLV negative clinical specimens consisting of 691 healthy donor samples, 116 potentially cross-reactive samples, and 65 samples with interfering substances. The ASSURE HTLV-I/II Rapid Test can effectively be deployed as a screening tool in any prevalence studies, blood banks or organ transplant centres. [ABSTRACT FROM AUTHOR]

Background: The tumour microenvironment (TME) consists of tumour-supportive immune cells, endothelial cells, and fibroblasts. PhenoCycler, a high-plex single cell spatial biology imaging platform, is used to characterize the complexity of the TME. Researchers worldwide harvest and bank tissues from mouse models which are employed to model a plethora of human disease. With the explosion of interest in spatial biology, these panoplies of archival tissues provide a valuable resource to answer new questions. Here, we describe our protocols for developing tunable PhenoCycler multiplexed imaging panels and describe our open-source data analysis pipeline. Using these protocols, we used PhenoCycler to spatially resolve the TME of 8 routinely employed pre-clinical models of lymphoma, breast cancer, and melanoma preserved as FFPE. Results: Our data reveal distinct TMEs in the different cancer models that were imaged and show that cell-cell contacts differ depending on the tumour type examined. For instance, we found that the immune infiltration in a murine model of melanoma is altered in cellular organization in melanomas that become resistant to αPD-1 therapy, with depletions in a number of cell-cell interactions. Conclusions: This work presents a valuable resource study seamlessly adaptable to any field of research involving murine models. The methodology described allows researchers to address newly formed hypotheses using archival materials, bypassing the new to perform new mouse studies. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC), which is featured with high morbidity and mortality worldwide, is a primary malignant tumor of the liver. Recently, there is a wealth of supporting evidence revealing that NK cell-related immune traits are strongly associated with the development of HCC, but the causality between them has not been proven. Methods: Two-sample Mendelian randomization (MR) study was performed to probe the causal correlation between NK cell-related immune traits and HCC. Genetic variations in NK cell-related immune traits were extracted from recent genome-wide association studies (GWAS) of individuals with European blood lineage. HCC data were derived from the UK Biobank Consortium's GWAS summary count data, including a total of 372,184 female and male subjects, with 168 cases and 372,016 controls, all of whom are of European ancestry. Sensitivity analysis was mainly used for heterogeneity and pleiotropy testing. Results: Our research indicated the causality between NK cell-related immune traits and HCC. Importantly, CD8+NKT cells had protective causal effects on HCC (OR = 0.9996;95%CI,0.9993–0.9999; P = 0.0489). CD16−CD56 caused similar effects on NK cells (OR = 0.9997;95%CI,0.9996–0.9999; P = 0.0117) as CD8+NKT cells. Intercepts from Egger showed no pleiotropy and confounding factors. Furthermore, insufficient evidence was found to support the existence of heterogeneity by Cochran's Q test. Conclusion: MR analysis suggested that low CD8+NKT cells and CD16−CD56 expression on NK cells were linked with a higher risk of HCC. [ABSTRACT FROM AUTHOR]

The goal of the AIDS and Cancer Specimen Resource (ACSR) is to play a major role in the advancement of HIV/AIDS cancer-related research/treatment by providing richly annotated biospecimens and data to researchers at no cost. The ACSR acquires, stores, and equitably distributes these samples and associated clinical data to investigators conducting HIV/AIDS-related research, at no costs. Currently, it is the only biorepository of human biospecimens from people with HIV and cancer available to eligible researchers globally who are studying HIV associated malignancies. This review describes the history and organizational structure of the ACSR, its types of specimens in its inventory, and the process of requesting specimens. In addition, the review provides an overview of research that was performed over the last 5 years with its support and gives a summary of important new findings acquired by this research into the development of cancers in people with HIV, including both Aids-related and non-Aids-related malignancies. [ABSTRACT FROM AUTHOR]

Background: Obesity is associated with type 2 diabetes mellitus and chronic low-grade inflammation. Although chronic inflammatory conditions and diabetes are associated with anaemia, less is known about associations of obesity and body shape, independent of each other, with erythrocyte and reticulocyte parameters. Methods: We investigated the associations of body mass index (BMI) and the allometric body shape index (ABSI) and hip index (HI), which are uncorrelated with BMI, with erythrocyte and reticulocyte parameters (all continuous, on a standard deviation (SD) scale) in UK Biobank participants without known metabolic, endocrine, or major inflammatory conditions (glycated haemoglobin HbA1c < 48 mmol/mol, C-reactive protein CRP < 10 mg/L). We examined erythrocyte count, total reticulocyte count and percent, immature reticulocyte count and fraction (IRF), haemoglobin, haematocrit, mean corpuscular haemoglobin mass (MCH) and concentration (MCHC), mean corpuscular and reticulocyte volumes (MCV, MRV), and red cell distribution width (RDW) in multivariable linear regression models. We additionally defined body shape phenotypes with dichotomised ABSI (≥ 73 women; ≥ 80 men) and HI (≥ 64 women; ≥ 49 men), including "pear" (small-ABSI-large-HI) and "apple" (large-ABSI-small-HI), and examined these in groups according to BMI (18.5–25 normal weight; 25–30 overweight; 30–45 kg/m2 obese). Results: In 105,853 women and 100,854 men, BMI and ABSI were associated positively with haemoglobin, haematocrit, and erythrocyte count, and more strongly with total reticulocyte count and percent, immature reticulocyte count and IRF. HI was associated inversely with all, but least with IRF. Associations were comparable in women and men. In groups according to obesity and body shape, erythrocyte count was ~ 0.6 SD higher for obese-"apple" compared to normal-weight-"pear" phenotype (SD = 0.31*1012/L women, SD = 0.34*1012/L men), total reticulocyte count was ~ 1.1 SD higher (SD = 21.1*109/L women, SD = 23.6*109/L men), immature reticulocyte count was ~ 1.2 SD higher (SD = 7.9*109/L women, SD = 8.8*109/L men), total reticulocyte percent was ~ 1.0 SD higher (SD = 0.48% women and men), and IFR was over 0.7 SD higher (SD = 5.7% women and men). BMI but not ABSI or HI was associated more weakly inversely with MCV, MRV, and MCH, but positively with MCHC in men and RDW in women. Conclusions: In obesity uncomplicated with diabetes, larger BMI and ABSI are associated with increased erythropoiesis and reticulocyte immaturity. [ABSTRACT FROM AUTHOR]

Background: The identification of reproducible subtypes within autistic populations is a priority research area in the context of neurodevelopment, to pave the way for identification of biomarkers and targeted treatment recommendations. Few previous studies have considered medical comorbidity alongside behavioural, cognitive, and psychiatric data in subgrouping analyses. This study sought to determine whether differing behavioural, cognitive, medical, and psychiatric profiles could be used to distinguish subgroups of children on the autism spectrum in the Australian Autism Biobank (AAB). Methods: Latent profile analysis was used to identify subgroups of children on the autism spectrum within the AAB (n = 1151), utilising data on social communication profiles and restricted, repetitive, and stereotyped behaviours (RRBs), in addition to their cognitive, medical, and psychiatric profiles. Results: Our study identified four subgroups of children on the autism spectrum with differing profiles of autism traits and associated comorbidities. Two subgroups had more severe clinical and cognitive phenotype, suggesting higher support needs. For the 'Higher Support Needs with Prominent Language and Cognitive Challenges' subgroup, social communication, language and cognitive challenges were prominent, with prominent sensory seeking behaviours. The 'Higher Support Needs with Prominent Medical and Psychiatric and Comorbidity' subgroup had the highest mean scores of challenges relating to social communication and RRBs, with the highest probability of medical and psychiatric comorbidity, and cognitive scores similar to the overall group mean. Individuals within the 'Moderate Support Needs with Emotional Challenges' subgroup, had moderate mean scores of core traits of autism, and the highest probability of depression and/or suicidality. A fourth subgroup contained individuals with fewer challenges across domains (the 'Fewer Support Needs Group'). Limitations: Data utilised to identify subgroups within this study was cross-sectional as longitudinal data was not available. Conclusions: Our findings support the holistic appraisal of support needs for children on the autism spectrum, with assessment of the impact of co-occurring medical and psychiatric conditions in addition to core autism traits, adaptive functioning, and cognitive functioning. Replication of our analysis in other cohorts of children on the autism spectrum is warranted, to assess whether the subgroup structure we identified is applicable in a broader context beyond our specific dataset. [ABSTRACT FROM AUTHOR]

Background: Biobanks/biorepositories are created to collect biospecimens for therapeutic and research uses. The success of the banking concept depends predominantly on the public's understanding and desire to contribute, which triggers several social, cultural, and ethical implications. The aim of this study is (1) to assess the willingness among adults attending outpatient clinics at King Abdulaziz Medical City to donate dental tissue samples to a biorepository for research purposes, (2) to identify the significant predictors for positive attitudes and willingness to donate dental bio-specimens. Methodology: This is a cross-sectional study that targeted 401 adult outpatients attending King Abdulaziz Medical City in Riyadh, Saudi Arabia. The questionnaire focused on three main parts: demographic and personal characteristics, and previous experience regarding biorepositories (part I), knowledge about dental biorepositories (part II), and willingness and attitudes towards donating dental biospecimens (part III). Data collected were analyzed using the statistical program SAS (version 9.4) with 0.05 level of significance to determine the willingness of donating tissue to biobanks for biomedical research purposes, measure knowledge and attitude about biobanking, find the association between the assessed variables, and identify significant predictors of positive attitude to donate dental biospecimens. Results: 66% of the participants were willing to donate dental biospecimens, however only 33.9% showed good level of knowledge. Despite the notable lack of knowledge, 54% respondents had favorable attitude towards donating dental biospecimens, and only 17% were negative while the remaining 29% were neutral. Previous involvement in medical research, previous blood testing or donation, female gender, higher education level, employment in a medical facility, and higher monthly income variables were found to be significantly associated with higher willingness to donate dental biospecimens. Conclusion: Although the majority of the participants exhibited lack of knowledge about dental biorepositories, they showed high willingness and good attitude towards donating dental biospecimens. This favorable attitude is, in turn, encouraging for the future establishment of dental biorepositories in Saudi Arabia. Six factors were significantly associated with the willingness to donate dental biospecimens, out of these, female gender, previous blood testing/donation, previous involvement in medical research were found to be strong predictors. [ABSTRACT FROM AUTHOR]

Background: The genetic architecture underlying Familial Hypercholesterolemia (FH) in Middle Eastern Arabs is yet to be fully described, and approaches to assess this from population-wide biobanks are important for public health planning and personalized medicine.Methods: We evaluate the pilot phase cohort (n = 6,140 adults) of the Qatar Biobank (QBB) for FH using the Dutch Lipid Clinic Network (DLCN) criteria, followed by an in-depth characterization of all genetic alleles in known dominant (LDLR, APOB, and PCSK9) and recessive (LDLRAP1, ABCG5, ABCG8, and LIPA) FH-causing genes derived from whole-genome sequencing (WGS). We also investigate the utility of a globally established 12-SNP polygenic risk score to predict FH individuals in this cohort with Arab ancestry.Results: Using DLCN criteria, we identify eight (0.1%) 'definite', 41 (0.7%) 'probable' and 334 (5.4%) 'possible' FH individuals, estimating a prevalence of 'definite or probable' FH in the Qatari cohort of ~ 1:125. We identify ten previously known pathogenic single-nucleotide variants (SNVs) and 14 putatively novel SNVs, as well as one novel copy number variant in PCSK9. Further, despite the modest sample size, we identify one homozygote for a known pathogenic variant (ABCG8, p. Gly574Arg, global MAF = 4.49E-05) associated with Sitosterolemia 2. Finally, calculation of polygenic risk scores found that individuals with 'definite or probable' FH have a significantly higher LDL-C SNP score than 'unlikely' individuals (p = 0.0003), demonstrating its utility in Arab populations.Conclusion: We design and implement a standardized approach to phenotyping a population biobank for FH risk followed by systematically identifying known variants and assessing putative novel variants contributing to FH burden in Qatar. Our results motivate similar studies in population-level biobanks - especially those with globally under-represented ancestries - and highlight the importance of genetic screening programs for early detection and management of individuals with high FH risk in health systems. [ABSTRACT FROM AUTHOR]

Background: Grip strength is a widely used and well-validated measure of overall health that is increasingly understood to index risk for psychiatric illness and neurodegeneration in older adults. However, existing work has not examined how grip strength relates to a comprehensive set of mental health outcomes, which can detect early signs of cognitive decline. Furthermore, whether brain structure mediates associations between grip strength and cognition remains unknown.Methods: Based on cross-sectional and longitudinal data from over 40,000 participants in the UK Biobank, this study investigated the behavioral and neural correlates of handgrip strength using a linear mixed effect model and mediation analysis.Results: In cross-sectional analysis, we found that greater grip strength was associated with better cognitive functioning, higher life satisfaction, greater subjective well-being, and reduced depression and anxiety symptoms while controlling for numerous demographic, anthropometric, and socioeconomic confounders. Further, grip strength of females showed stronger associations with most behavioral outcomes than males. In longitudinal analysis, baseline grip strength was related to cognitive performance at ~9 years follow-up, while the reverse effect was much weaker. Further, baseline neuroticism, health, and financial satisfaction were longitudinally associated with subsequent grip strength. The results revealed widespread associations between stronger grip strength and increased grey matter volume, especially in subcortical regions and temporal cortices. Moreover, grey matter volume of these regions also correlated with better mental health and considerably mediated their relationship with grip strength.Conclusions: Overall, using the largest population-scale neuroimaging dataset currently available, our findings provide the most well-powered characterization of interplay between grip strength, mental health, and brain structure, which may facilitate the discovery of possible interventions to mitigate cognitive decline during aging. [ABSTRACT FROM AUTHOR]

Aim: The initial cases of COVID-19 appeared in December 2019 and Spain was one of the most affected countries during the first wave (March to June). Since then, HIV HGM BioBank has been restructured as an established Paediatrics and Adults HIV_COVID-19 BioBank that aims at the long-term storage of samples obtained from not only HIV-1, but also from COVID-19 patients and HIV-1_COVID-19 coinfected patients. Methods: HIV HGM BioBank holds high quality biological samples from newborns, children, adolescents and adults with their associated clinical data. Research groups trying to establish large networks focused on research on specific clinical problems in epidemiology, biology, routes of transmission and therapies, are potential users of the clinical samples and of associated data of HIV-1_COVID-19 HGM BioBank. Results: The HIV HGM BioBank is an academic and ethical enterprise complying with all the legal regulatory rules to provide service to the society. HIV_COVID-19 HGM BioBank has been repurposed to offer an important resource for global research of COVID-19 in newborns, children, adolescents, adults and elders to study the biological effect of the pandemic. Conclusion: Herein, we present a description of how HIV HGM BioBank has rapidly become an indispensable structure in modern biomedical research, including COVID-19 research. Keypoints: Biobanks are essential platforms for the development of personalized medicine, even more so in pediatric diseases, including those of infectious origin. The possibility of having collections of excellent quality and with all the ethical and legal requirements is even more relevant in pandemic situations. [ABSTRACT FROM AUTHOR]

Background: Limited research has been conducted on explanations and understandings of biobanking for future genomic research in African contexts with low literacy and limited healthcare access. We report on the findings of a sub-study on participant understanding embedded in a multi-disease community health screening and biobank platform study known as 'Vukuzazi' in rural KwaZulu-Natal, South Africa.Methods: Semi-structured interviews were conducted with research participants who had been invited to take part in the Vukuzazi study, including both participants and non-participants, and research staff that worked on the study. The interviews were transcribed, and themes were identified from the interview transcripts, manually coded, and thematically analysed.Results: Thirty-nine individuals were interviewed. We found that the research team explained biobanking and future genomic research by describing how hereditary characteristics create similarities among individuals. However, recollection and understanding of this explanation seven months after participation was variable. The large volume of information about the Vukuzazi study objectives and procedures presented a challenge to participant recall. By the time of interviews, some participants recalled rudimentary facts about the genetic aspects of the study, but many expressed little to no interest in genetics and biobanking.Conclusion: Participant's understanding of information related to genetics and biobanking provided during the consent process is affected by the volume of information as well as participant's interest (or lack thereof) in the subject matter being discussed. We recommend that future studies undertaking biobanking and genomic research treat explanations of this kind of research to participants as an on-going process of communication between researchers, participants and the community and that explanatory imagery and video graphic storytelling should be incorporated into theses explanations as these have previously been found to facilitate understanding among those with low literacy levels. Studies should also avoid having broader research objectives as this can divert participant's interest and therefore understanding of why their samples are being collected. [ABSTRACT FROM AUTHOR]

Background: With the increasing demand for corneas, eye banks must optimize the tissue donation, collection, and selection process. This retrospective monocentric study analyzed the approval rates for corneal donation and the origin of and reasons for discarding donor corneas from 2010 to 2019.Methods: Data included the number of deceased, approval or rejection by the family for corneal donation and contraindications. Corneal grafts were included from all deceased persons who were full-body and multi-organ donors at the Saarland University Medical Center (UKS) and from external institutions. Additional analyzed parameters included endothelial cell count (ECC), blood sample serology for infections, and conjunctival swab testing .Results: A total of 1748 corneoscleral buttons were harvested from 10,265 deceased persons (17% with no contraindication) at the UKS between 2010 and 2019, with a consent rate of 23.3%. The number of keratoplasties increased from 136 in 2010 (15% of the deceased, total = 925) to 251 in 2019 (21%, total = 1214). Both the general and department-specific data showed similar percentages for corneal donation over the years, with intensive care and palliative units recently providing the most corneas. The increase in the number of corneas processed by the cornea bank over the years (368 in 2010 compared with 857 in 2019) was linked both to a better internal supply in 2010 (262, 71.2% of the total) compared with 2019 (519, 60.6%) and to an external supply by reinforcement of cooperation with external hospitals, including Luxembourg in 2010 (106, 28.8% of the total) compared with 2019 (338, 39.4%). A total of 195 of 377 corneas (52%) were discarded in 2009 compared with 260 out of 715 (36%) in 2019. The main reasons for discarding were low ECC (36% of discarded corneas in 2009; 11% in 2019), positive conjunctival swab (11% in 2009; 13% in 2019), and blood sample serology (6% in 2009 and in 2019).Conclusion: Despite an increasing number of donors, the demand for corneas is still rising. Improved cooperation with internal departments and with external clinics has led to an increasing number of explanted corneas. The main reason for discarding corneas was low ECC, followed by a positive conjunctival swab for fungal or bacterial contamination and serology. Increased donation rates and continued improvements in collection and selection processes are necessary to cover the high demand for corneas. [ABSTRACT FROM AUTHOR]

Accurate and scalable quantification of amyloid-β (Aβ) pathology is crucial for deeper disease phenotyping and furthering research in Alzheimer Disease (AD). This multidisciplinary study addresses the current limitations on neuropathology by leveraging a machine learning (ML) pipeline to perform a granular quantification of Aβ deposits and assess their distribution in the temporal lobe. Utilizing 131 whole-slide-images from consecutive autopsied cases at the University of California Davis Alzheimer Disease Research Center, our objectives were threefold: (1) Validate an automatic workflow for Aβ deposit quantification in white matter (WM) and gray matter (GM); (2) define the distributions of different Aβ deposit types in GM and WM, and (3) investigate correlates of Aβ deposits with dementia status and the presence of mixed pathology. Our methodology highlights the robustness and efficacy of the ML pipeline, demonstrating proficiency akin to experts' evaluations. We provide comprehensive insights into the quantification and distribution of Aβ deposits in the temporal GM and WM revealing a progressive increase in tandem with the severity of established diagnostic criteria (NIA-AA). We also present correlations of Aβ load with clinical diagnosis as well as presence/absence of mixed pathology. This study introduces a reproducible workflow, showcasing the practical use of ML approaches in the field of neuropathology, and use of the output data for correlative analyses. Acknowledging limitations, such as potential biases in the ML model and current ML classifications, we propose avenues for future research to refine and expand the methodology. We hope to contribute to the broader landscape of neuropathology advancements, ML applications, and precision medicine, paving the way for deep phenotyping of AD brain cases and establishing a foundation for further advancements in neuropathological research., (© 2024. The Author(s).)

Background: Chronic inflammatory diseases are linked to an increased risk of stroke events. The white blood cell (WBC) count is a common marker of the inflammatory response. However, it is unclear whether the WBC count, its subpopulations and their dynamic changes are related to the risk of fatal stroke in relatively healthy elderly population.Methods: In total, 27,811 participants without a stroke history at baseline were included and followed up for a mean of 11.5 (standard deviation = 2.3) years. After review of available records, 503 stroke deaths (ischaemic 227, haemorrhagic 172 and unclassified 104) were recorded. Cox proportional hazards regression was used to assess the associations between the WBC count, its subpopulations and their dynamic changes (two-phase examination from baseline to the 1st follow-up) and the risk of fatal all stroke, fatal ischaemic stroke and fatal haemorrhagic stroke.Results: (i) Regarding the WBC count in relation to the risk of fatal stroke, restricted cubic splines showed an atypically U-curved association between the WBC count and the risk of fatal all stroke occurrence. Compared with those in the lowest WBC count quartile (< 5.3*10^9/L), the participants with the highest WBC count (> 7.2*10^9/L) had a 53 and 67% increased risk for fatal all stroke (adjusted hazard ratio [aHR] = 1.53, 95% confidence interval (CI) 1.16-2.02, P = 0.003) and fatal haemorrhagic stroke (aHR = 1.67, 95% CI 1.10-2.67, P = 0.03), respectively; compared with those in the lowest quartile (< 3.0*10^9/L), the participants with the highest NEUT count (> 4.5*10^9/L) had a 45 and 65% increased risk for fatal all stroke (aHR = 1.45, 95% CI 1.10-1.89, P = 0.008) and fatal ischaemic stroke (aHR = 1.65, 95%CI 1.10-2.47 P = 0.02), respectively. With the additional adjustment for C-reactive protein, the same results as those for all stroke and ischaemic stroke, but not haemorrhagic stroke, were obtained for the WBC count (4 ~ 10*10^9/L) and the NEUT count (the NEUT counts in the top 1% and bottom 1% at baseline were excluded). (ii) Regarding dynamic changes in the WBC count in relation to the risk of fatal stroke, compared with the stable group (- 25% ~ 25%, dynamic changes from two phases of examination (baseline, from September 1st, 2003 to February 28th, 2008; 1st follow-up, from March 31st 2008 to December 31st 2012)), the groups with a 25% increase in the WBC count and NEUT count respectively had a 60% (aHR = 1.60, 95% CI 1.07-2.40, P = 0.02) and 45% (aHR = 1.45, 95% CI1.02-2.05, P = 0.04) increased risk of fatal all stroke occurrence.Conclusions: The WBC count, especially the NEUT count, was associated with an increased risk of fatal all stroke occurrence. Longitudinal changes in the WBC count and NEUT count increase in excess of 25% were also associated with an increased risk of fatal all stroke occurrence in the elderly population. [ABSTRACT FROM AUTHOR]

Background: Current physical activity guidelines do not distinguish between activity accumulated in different behavioural domains but some studies suggest that occupational physical activity (OPA) may not confer health benefits and could even be detrimental. The purpose of this study was to investigate associations between OPA and mortality outcomes. Methods: From baseline (2006–2010), 460,901 UK Biobank participants (aged 40–69 years) were followed for a median 12.0 (IQR: 11.3–12.7) years. OPA was categorised by cross-tabulating degree of manual work and walking/standing work amongst those in paid employment (n = 267,765), and combined with categories of occupational status for those not in paid employment (n = 193,136). Cox proportional hazards models were used to estimate sex-stratified hazard ratios (HR) and 95% confidence intervals (CI) for mortality from all causes, CVD, and cancer by occupational group, and for working hours/week and non-occupational physical activity stratified by occupational group. Models included adjustment for age and a range of lifestyle, socio-economic and health-related covariates. Results: During 5,449,989 person-years of follow-up, 28,740 deaths occurred. Compared to those reporting no heavy manual or walking/standing work (e.g. sedentary office workers) and adjusting for covariates, retirement was associated with lower mortality in women (HR = 0.62, CI: 0.53–0.72) and men (HR = 0.80, CI: 0.71–0.90), whereas unemployment was associated with higher mortality in men only (HR = 1.24, CI: 1.07–1.45). Within the working population, there was no evidence of differences in all-cause, CVD or cancer mortality by OPA group when comparing those reporting higher levels of OPA to the lowest OPA reference group for both women and men. Working < 35 h/week versus 35–40 h/week was associated with lower mortality in women (HR = 0.85, CI: 0.79–0.92) and men (HR = 0.83, CI: 0.78–0.89), with no interaction by OPA. Non-occupational physical activity was associated with lower mortality in working women (HR = 0.89 per 5 kJ/day/kg, CI: 0.84–0.95) and men (HR = 0.87 per 5 kJ/day/kg, CI: 0.84–0.91), with no interaction by OPA group. Conclusions: Jobs classified as higher levels of OPA may not be as active as reported, or the types of physical activity performed in those jobs are not health-enhancing. Irrespective of OPA category or employment status, non-occupational physical activity appears to provide health benefits. [ABSTRACT FROM AUTHOR]

Background: Emergent large vessel occlusion (ELVO) strokes are devastating ischemic vascular events for which novel treatment options are needed. Using vascular cell adhesion molecule 1 (VCAM1) as a prototype, the objective of this study was to identify proteomic biomarkers and network signaling functions that are potential therapeutic targets for adjuvant treatment for mechanical thrombectomy.Methods: The blood and clot thrombectomy and collaboration (BACTRAC) study is a continually enrolling tissue bank and registry from stroke patients undergoing mechanical thrombectomy. Plasma proteins from intracranial (distal to clot) and systemic arterial blood (carotid) were analyzed by Olink Proteomics for N=42 subjects. Statistical analysis of plasma proteomics used independent sample t tests, correlations, linear regression, and robust regression models to determine network signaling and predictors of clinical outcomes. Data and network analyses were performed using IBM SPSS Statistics, SAS v 9.4, and STRING V11.Results: Increased systemic (p<0.001) and intracranial (p=0.013) levels of VCAM1 were associated with the presence of hypertension. Intracranial VCAM1 was positively correlated to both infarct volume (p=0.032; r=0.34) and edema volume (p=0.026; r=0.35). The %∆ in NIHSS from admittance to discharge was found to be significantly correlated to both systemic (p=0.013; r = -0.409) and intracranial (p=0.011; r = -0.421) VCAM1 levels indicating elevated levels of systemic and intracranial VCAM1 are associated with reduced improvement of stroke severity based on NIHSS from admittance to discharge. STRING-generated analyses identified biologic functional descriptions as well as function-associated proteins from the predictive models of infarct and edema volume.Conclusions: The current study provides novel data on systemic and intracranial VCAM1 in relation to stroke comorbidities, stroke severity, functional outcomes, and the role VCAM1 plays in complex protein-protein signaling pathways. These data will allow future studies to develop predictive biomarkers and proteomic targets for drug development to improve our ability to treat a devastating pathology. [ABSTRACT FROM AUTHOR]

A consensus meeting was held in Toronto on February 9–10, 2020 to discuss ways to improve cornea donation and transplantation access in Canada. The meeting brought together eye and tissue bank representatives, health authority and hospital leadership, transplant ophthalmologists, organ donation organizations, transplant recipients, donor families and several national organizations. Through facilitated discussions in multidisciplinary, gender-balanced, and geographically balanced small groups, participants identified opportunities for improvement in the Canadian cornea donation and transplantation system. Discussion occurred around broad themes of donor tissue demand, supply, access, utilization, interprovincial sharing and cost recovery, interprovincial knowledge sharing and research. This event marked the first time in 10 years in which the Canadian cornea transplantation community came together. [ABSTRACT FROM AUTHOR]

Umbilical cord-derived mesenchymal stem/stromal cells (UC-MSCs) emerge as a perspective for therapeutic use in immune and inflammatory diseases. Indeed, immunomodulatory and anti-inflammatory properties, associated to fewer ethical, availability, and safety issues, position UC-MSCs as a promising active substance to develop medicinal products. Since 2007, UC-MSC-based products are classified as advanced therapy medicinal products (ATMP) according to the European Regulation 1394/2007/EC. This new regulatory status required a total adaptation of stakeholders wishing to develop UC-MSC-based ATMPs. Cell production in tissue and cell banks has been replaced by the manufacturing of a medicine, in authorized establishments, according to the good manufacturing practices (GMP) specific to ATMPs. After a brief description of UC-MSCs, we described in this review their recent use in a large panel of immune and inflammatory pathologies, including early and late phase clinical trials. Despite the use of the same product, we noticed an important heterogeneity in terms of indication, posology and study design. Then, we discussed regulatory and manufacturing challenges for stakeholders, especially in terms of process harmonization and cells characterization. Our aim was to point that despite MSCs use for several decades, the development of an UC-MSC-based ATMP remains at this day a real challenge for both academic institutions and pharmaceutical companies. [ABSTRACT FROM AUTHOR]

Background: Explanted corneae are highly needed for the surgical management of patients with severe corneal diseases. The aim of this study was to determine whether the body donors from the Institute of Anatomy are a suitable source of donor corneae.Methods: At the Institute of Anatomy at Saarland University Medical Center in Homburg, corneae are prelevated from body donors who had consented to the removal of tissues for transplantation purposes during their lifetime. Following the report of death, the LIONS Eye Bank is informed and the contraindications of corneal explantation are clarified. Obtaining a blood sample within 24 h postmortem is mandatory.Results: The Institute of Anatomy had 150 body donors in the time period from January 2018 to June 2019. Out of these, 68 (45.3%) were reported to the Eye Bank. The age of the donors (median 82 years (range: 57-96)) is not critical since the quality of the corneae depends on the number of endothelial cells (mean: 2109 ± 67 cells/mm2 (range: 511-2944 cells/mm2)). Contraindications were present in 19 (12.6%) cases. The corneae were extracted from 49 (32.7%) body donors. Out of these 98 corneae, 46 (46.9%) were successfully transplanted. Of all non-transplanted corneae, 6 (6.1%) were microbiologically contaminated, 10 (10.2%) had a positive serology, 22 (22.5%) had an endothelial cell count < 2000 cells/mm2 and 6 (6.1%) are at time of this analysis still in culture medium. The non-transplanted tissues were used for research.Conclusions: Explanted corneae from the Institute of Anatomy are a valuable option in obtaining grafts for corneal transplantation, which is why we are working toward on expanding cooperation with this department. [ABSTRACT FROM AUTHOR]

Preliminary reports suggest that the Coronavirus Disease 2019 (COVID− 19) pandemic has led to disproportionate morbidity and mortality among historically disadvantaged populations. We investigate the racial and socioeconomic associations of COVID− 19 hospitalization among 418,794 participants of the UK Biobank, of whom 549 (0.13%) had been hospitalized. Both Black participants (odds ratio 3.7; 95%CI 2.5–5.3) and Asian participants (odds ratio 2.2; 95%CI 1.5–3.2) were at substantially increased risk as compared to White participants. We further observed a striking gradient in COVID− 19 hospitalization rates according to the Townsend Deprivation Index − a composite measure of socioeconomic deprivation − and household income. Adjusting for socioeconomic factors and cardiorespiratory comorbidities led to only modest attenuation of the increased risk in Black participants, adjusted odds ratio 2.4 (95%CI 1.5–3.7). These observations confirm and extend earlier preliminary and lay press reports of higher morbidity in non-White individuals in the context of a large population of participants in a national biobank. The extent to which this increased risk relates to variation in pre-existing comorbidities, differences in testing or hospitalization patterns, or additional disparities in social determinants of health warrants further study. [ABSTRACT FROM AUTHOR]

Background: UK Biobank is a large prospective cohort study containing accelerometer-based physical activity data with strong validity collected from 100,000 participants approximately 5 years after baseline. In contrast, the main cohort has multiple self-reported physical behaviours from > 500,000 participants with longer follow-up time, offering several epidemiological advantages. However, questionnaire methods typically suffer from greater measurement error, and at present there is no tested method for combining these diverse self-reported data to more comprehensively assess the overall dose of physical activity. This study aimed to use the accelerometry sub-cohort to calibrate the self-reported behavioural variables to produce a harmonised estimate of physical activity energy expenditure, and subsequently examine its reliability, validity, and associations with disease outcomes. Methods: We calibrated 14 self-reported behavioural variables from the UK Biobank main cohort using the wrist accelerometry sub-cohort (n = 93,425), and used published equations to estimate physical activity energy expenditure (PAEESR). For comparison, we estimated physical activity based on the scoring criteria of the International Physical Activity Questionnaire, and by summing variables for occupational and leisure-time physical activity with no calibration. Test-retest reliability was assessed using data from the UK Biobank repeat assessment (n = 18,905) collected a mean of 4.3 years after baseline. Validity was assessed in an independent validation study (n = 98) with estimates based on doubly labelled water (PAEEDLW). In the main UK Biobank cohort (n = 374,352), Cox regression was used to estimate associations between PAEESR and fatal and non-fatal outcomes including all-cause, cardiovascular diseases, respiratory diseases, and cancers. Results: PAEESR explained 27% variance in gold-standard PAEEDLW estimates, with no mean bias. However, error was strongly correlated with PAEEDLW (r = −.98; p < 0.001), and PAEESR had narrower range than the criterion. Test-retest reliability (Λ =.67) and relative validity (Spearman =.52) of PAEESR outperformed two common approaches for processing self-report data with no calibration. Predictive validity was demonstrated by associations with morbidity and mortality, e.g. 14% (95%CI: 11–17%) lower mortality for individuals meeting lower physical activity guidelines. Conclusions: The PAEESR variable has good reliability and validity for ranking individuals, with no mean bias but correlated error at individual-level. PAEESR outperformed uncalibrated estimates and showed stronger inverse associations with disease outcomes. [ABSTRACT FROM AUTHOR]

Background: Inaccurate meniscus allograft size is still an important problem of the currently used sizing methods. The purpose of this study was to evaluate a new three-dimensional (3D) meniscus-sizing method to increase the accuracy of the selected allografts. Methods: 3D triangular surface models were generated from 280 menisci based on 50 bilateral and 40 unilateral knee joint magnetic resonance imaging (MRI) scans. These models served as an imaginary meniscus allograft tissue bank. Meniscus sizing and allograft selection was simulated for all 50 bilateral knee joints by (1) the closest mean surface distance (MeSD) (3D-MRI sizing with contralateral meniscus), (2) the smallest meniscal width/length difference in MRI (2D-MRI sizing with contralateral meniscus), and (3) conventional radiography as proposed by Pollard (2D-radiograph (RX) sizing with ipsilateral tibia plateau). 3D shape and meniscal width, length, and height were compared between the original meniscus and the selected meniscus using the three sizing methods. Results: Allograft selection by MeSD (3D MRI) was superior for all measurement parameters. In particular, the 3D shape was significantly improved (p < 0.001), while the mean differences in meniscal width, length, and height were only slightly better than the allograft selected by the other methods. Outliers were reduced by up to 55% (vs. 2D MRI) and 83% (vs. 2D RX) for the medial meniscus and 39% (vs. 2D MRI) and 56% (vs. 2D RX) for the lateral meniscus. Conclusion: 3D-MRI sizing by MeSD using the contralateral meniscus as a reconstruction template can significantly improve meniscus allograft selection. Sizing using conventional radiography should probably not be recommended. Trial registration: Kantonale Ethikkommission Zürich had given the approval for the study (BASEC-No. 2018-00856). [ABSTRACT FROM AUTHOR]

Background: The use of tissue collected at a forensic post-mortem for forensic genetics research purposes remains of ethical concern as the process involves obtaining informed consent from grieving family members. Two forensic genetics research studies using tissue collected from a forensic post-mortem were recently initiated at our institution and were the first of their kind to be conducted in Cape Town, South Africa.Main Body: This article discusses some of the ethical challenges that were encountered in these research projects. Among these challenges was the adaptation of research workflows to fit in with an exceptionally busy service delivery that is operating with limited resources. Whilst seeking guidance from the literature regarding research on deceased populations, it was noted that next of kin of decedents are not formally recognised as a vulnerable group in the existing ethical and legal frameworks in South Africa. The authors recommend that research in the forensic mortuary setting is approached using guidance for vulnerable groups, and the benefit to risk standard needs to be strongly justified. Lastly, when planning forensic genetics research, consideration must be given to the potential of uncovering incidental findings, funding to validate these findings and the feedback of results to family members; the latter of which is recommended to occur through a genetic counsellor.Conclusion: It is hoped that these experiences will contribute towards a formal framework for conducting forensic genetic research in medico-legal mortuaries in South Africa. [ABSTRACT FROM AUTHOR]

The KHP PCaBB was established in 2013 and recruits donors from the Urology or Oncology Departments at Guy's Hospital in London (UK). Prostate cancer patients may be approached to give their consent for biobanking at any point in their treatment pathway, which allows residual material from their earlier diagnosis to be transferred and used by the Biobank. Currently, patients are specifically asked to donate samples of blood and surplus prostate tissue as well as permitting access to their clinical and pathological data that continues to be added throughout the course of their disease. Between 2013 and 2015, 549 prostate cancer patients gave their consent to the biobank and, the tissue repository collected 489 blood samples, 120 frozen prostate tissue samples and 1064 formalin fixed paraffin embedded diagnostic blocks.Prostate cancer has become a chronic disease in a large proportion of men, with many men receiving multiple subsequent treatments, and their treatment trajectory often spanning over decades. Therefore, this resource aims to provide an ideal research platform to explore potential variations in treatment response as well as disease markers in the different risk categories for prostate cancer.A recent audit of the KHP PCaBB revealed that between 2013 and 2015, 1796 patients were diagnosed with prostate cancer at King's Health Partners (KHP), out of which 549 (30.6%) gave their consent to KHP PCaBB. Comparisons between demographic and clinical characteristics of patients who had consented compared to the total patient population revealed that the KHP PCaBB is demographically representative of the total prostate cancer patient population seen in Guy's and St Thomas' NHS Foundation Trust (GSTT). We observed no differences in distribution of ethnicity (p = 0.507) and socioeconomic status (p = 0.097). Some differences were observed in clinical characteristics, specifically with treatment type - which differed significantly between the patients who had given consent and total patient population.The KHP PCaBB has thereby amassed a rich data and tissue repository that is largely reflective of both the demographic and clinical diversity within the total prostate cancer patient population seen at KHP, making it an ideal platform for prostate cancer research. [ABSTRACT FROM AUTHOR]

Background: In Ethiopia, there is a substantial mismatch between need and supply of corneal transplant. Although corneal transplantation service is affected by various factors, willingness to donate eyes is an essential indicator of its availability, accessibility, and acceptability. Therefore, this study aimed to determine the magnitude of willingness to donate eyes and its associated factors, which help to develop appropriate strategies that can address this undersupply and unmet need.Methods: A community-based cross-sectional survey was conducted on 774 adults who were selected using multistage random sampling in Gondar town, North West, Ethiopia. The data were collected through interviews.Results: In this survey, 774 adults with a median age of 30 ± 14.33 years participated. The proportion of willing to donate eyes was 37.6% [95% CI: 34.3%-41.3%]. It was positively associated with the religious belief of Christianity [AOR = 1.73, 95% CI: 1.08-2.75], having awareness about eye donation [AOR = 1.38, 95% CI: 1.01-1.92], educational level of high school [AOR = 2.90, 95% CI: 1.72-4.90], and College/University [AOR = 2.23, 95% CI: 1.28-3.87].Conclusion: The magnitude of willingness to donate eyes was moderate and positively associated with the higher educational level and awareness. It is, therefore, strategic to plan awareness creation programs to mobilize the community. [ABSTRACT FROM AUTHOR]

Background: Advances in technology and the ability to interrogate disease pathogenesis using systems biology approaches are exploding. As exemplified by the substantial progress in the personalized diagnosis and treatment of cancer, the application of systems biology to enable precision medicine in other disciplines such as Nephrology is well underway. Infrastructure that permits the integration of clinical data, patient biospecimens and advanced technologies is required for institutions to contribute to, and benefit from research in molecular disease classification and to devise specific and patient-oriented treatments.Methods and Results: We describe the establishment of the Biobank for the Molecular Classification of Kidney Disease (BMCKD) at the University of Calgary, Alberta, Canada. The BMCKD consists of a fully equipped wet laboratory, an information technology infrastructure, and a formal operational, ethical and legal framework for banking human biospecimens and storing clinical data. The BMCKD first consolidated a large retrospective cohort of kidney biopsy specimens to create a population-based renal pathology database and tissue inventory of glomerular and other kidney diseases. The BMCKD will continue to prospectively bank all kidney biopsies performed in Southern Alberta. The BMCKD is equipped to perform molecular, clinical and epidemiologic studies in renal pathology. The BMCKD also developed formal biobanking procedures for human specimens such as blood, urine and nucleic acids collected for basic and clinical research studies or for advanced diagnostic technologies in clinical care. The BMCKD is guided by standard operating procedures, an ethics framework and legal agreements with stakeholders that include researchers, data custodians and patients. The design and structure of the BMCKD permits its inclusion in a wide variety of research and clinical activities.Conclusion: The BMCKD is a core multidisciplinary facility that will bridge basic and clinical research and integrate precision medicine into renal pathology and nephrology. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Biobanks and biospecimen collections are becoming a primary means of delivering personalized diagnostics and tailoring individualized therapeutics. This shift towards precision medicine (PM) requires interactions among a variety of stakeholders, including the public, patients, healthcare providers, government, and donors. Very few studies have investigated the role of healthcare students in biobanking and biospecimen donations. The main aims of this study were (1) to evaluate the knowledge of senior healthcare students about biobanks and (2) to assess the students' willingness to donate biospecimens and the factors influencing their attitudes.Methods: A cross-sectional study was conducted among senior healthcare students at King Abdulaziz University (KAU), Saudi Arabia. The data were obtained using a self-administered questionnaire in English. In addition to the respondents' biographical data section, the questionnaire assessed the respondents' general knowledge about biobanking, the factors influencing their willingness to donate biospecimens to biobanks and their general attitudes towards biomedical research.Results: A total of 597 senior healthcare students were included in the study. The general knowledge score was 3.2 (±1.6) out of 7. Only approximately 44% and 27% of students were aware of the terms "Human Genome Project" (HGP) and "biobank," respectively. The majority of the students (89%) were willing to donate biospecimens to biobanks. Multiple factors were significantly associated with their willingness to donate, including their perceived general health (p < 0.001), past experience with both tissue testing (p < 0.04) and tissue donation (p < 0.001), biobanking knowledge score (p < 0.001) and biomedical research attitude score (p < 0.001). The main reasons for students' willingness to donate were advancement of medical research and societal benefits, whereas misuse of biospecimens and confidentiality breaches were the main reasons for a reluctance to donate.Conclusion: Despite their strong willingness to donate biospecimens, students exhibited a notable lack of knowledge about biobanking and the HGP. To expedite the transition towards PM, it is highly recommended to enhance healthcare curricula by including more educational and awareness programmes to familiarize students with OMICs technologies in addition to the scope of research and clinical applications. [ABSTRACT FROM AUTHOR]

Background: Lung cancer aetiology and clinical aspects have been mainly studied in men, although specific risk factors probably exist in women. Here we present the rationale, design and organization of the WELCA study (Women Epidemiology Lung CAncer) that has been launched to investigate lung cancer in women, focusing particularly on hormonal and occupational factors.Methods/design: WELCA is a population based case-control study and planned to recruit 1000 cases and 1000 controls in three years, based on study power calculation. Eligible cases are female patients newly diagnosed with lung cancer, living in Paris and the Ile de France area and aged up to 75 years. Almost all Parisian pneumology and oncology clinical departments are involved. The control group is a random sample of the population living in the same area, frequency-matched on age and additionally stratified on the distribution of socio-professional categories of women residing there. After acquisition of written consent, research nurses administer standardized computer assisted questionnaires to all the subjects in face-to-face interviews and acquire anthropometric measures. Besides usual socio-demographic characteristics, information is gathered about menstrual and reproductive factors, hormonal treatments, lifestyle and leisure characteristics, occupational history, personal and familial medical history. Biological samples are also collected, in order to establish a biobank for molecular epidemiology studies. Molecular characteristics of the tumours will be obtained and patients will be followed up for five years.Discussion: The WELCA study aims to answer key questions in lung cancer aetiology and clinical characteristics specifically in women. The role of hormonal impregnation is investigated, and the interactions with cigarette smoking or body mass index (BMI) will be analyzed in detail. The occupational history of the subjects is carefully reconstructed, focusing in particular on the service sector. The creation of a biobank for collection of serum, plasma, DNA and tumour tissue will allow the genetic and biochemical characterization of both the subjets and the tumours. The follow-up of the patients will help in disentangling the role of hormonal factors and tumour molecular characteristics in survival. [ABSTRACT FROM AUTHOR]

The EU offers a suitable milieu for the comparison and harmonisation of healthcare across different languages, cultures, and jurisdictions (albeit with a supranational legal framework), which could provide improvements in healthcare standards across the bloc. There are specific ethico-legal issues with the use of data in healthcare research that mandate a different approach from other forms of research. The use of healthcare data over a long period of time is similar to the use of tissue in biobanks. There is a low risk to subjects but it is impossible to gain specific informed consent given the future possibilities for research. Large amounts of data on a subject present a finite risk of re-identification. Consequently, there is a balancing act between this risk and retaining sufficient utility of the data. Anonymising methods need to take into account the circumstances of data sharing to enable an appropriate balance in all cases. There are ethical and policy advantages to exceeding the legal requirements and thereby securing the social licence for research. This process would require the examination and comparison of data protection laws across the trading bloc to produce an ethico-legal framework compatible with the requirements of all member states. Seven EU jurisdictions are given consideration in this critique. [ABSTRACT FROM AUTHOR]

Background: Translational researchers need robust IT solutions to access a range of data types, varying from public data sets to pseudonymised patient information with restricted access, provided on a case by case basis. The reason for this complication is that managing access policies to sensitive human data must consider issues of data confidentiality, identifiability, extent of consent, and data usage agreements. All these ethical, social and legal aspects must be incorporated into a differential management of restricted access to sensitive data.Methods: In this paper we present a pilot system that uses several common open source software components in a novel combination to coordinate access to heterogeneous biomedical data repositories containing open data (open access) as well as sensitive data (restricted access) in the domain of biobanking and biosample research. Our approach is based on a digital identity federation and software to manage resource access entitlements.Results: Open source software components were assembled and configured in such a way that they allow for different ways of restricted access according to the protection needs of the data. We have tested the resulting pilot infrastructure and assessed its performance, feasibility and reproducibility.Conclusions: Common open source software components are sufficient to allow for the creation of a secure system for differential access to sensitive data. The implementation of this system is exemplary for researchers facing similar requirements for restricted access data. Here we report experience and lessons learnt of our pilot implementation, which may be useful for similar use cases. Furthermore, we discuss possible extensions for more complex scenarios. [ABSTRACT FROM AUTHOR]

Background: Biomedical research increasingly relies on long-term studies involving use and re-use of biological samples and data stored in large repositories or "biobanks" over lengthy periods, often raising questions about whether and when a re-consenting process should be activated. We sought to investigate the views on re-consent of participants in a longitudinal biobank.Methods: We conducted a qualitative study involving interviews with 24 people who were participating in a longitudinal biobank. Their views were elicited using a semi-structured interview schedule and scenarios based on a hypothetical biobank. Data analysis was based on the constant comparative method.Results: What participants identified as requiring new consent was not a straightforward matter predictable by algorithms about the scope of the consent, but instead was contingent. They assessed whether proposed new research implied a fundamental alteration in the underlying character of the biobank and whether specific projects were within the scope of the original consent. What mattered most to them was that the cooperative bargain into which they had entered was maintained in good faith. They saw re-consent as one important safeguard in this bargain. In determining what required re-consent, they deployed two logics. First, they used a logic of boundaries, where they sought to detect any possible rupture with their existing framework of cooperation. Second, they used a logic of risk, where they assessed proposed research for any potential threats for them personally or the research endeavour. When they judged that a need for re-consent had been activated, participants saw the process as way of re-actualising and renewing the cooperative bargain.Conclusions: Participants' perceptions of research as a process of mutual co-operation between volunteer and researcher were fundamental to their views on consent. Consenting arrangements for biobanks should respect the cooperative values that are important to participants, recognise the two logics used by research volunteers, and avoid rigidity. Agility may be favoured by tiered consent combined with strong oversight mechanisms; this approach requires evaluation. [ABSTRACT FROM AUTHOR]

Background: Family-based designs, from twin studies to isolated populations with their complex genealogical data, are a valuable resource for genetic studies of heritable molecular biomarkers. Existing software for family-based studies have mainly focused on facilitating association between response phenotypes and genetic markers, and no user-friendly tools are at present available to straightforwardly extend association studies in related samples to large datasets of generic quantitative data, as those generated by current-omics technologies. Results: We developed PopPAnTe, a user-friendly Java program, which evaluates the association of quantitative data in related samples. Additionally, PopPAnTe implements data pre and post processing, region based testing, and empirical assessment of associations. Conclusions: PopPAnTe is an integrated and flexible framework for pairwise association testing in related samples with a large number of predictors and response variables. It works either with family data of any size and complexity, or, when the genealogical information is unknown, it uses genetic similarity information between individuals as those inferred from genome-wide genetic data. It can therefore be particularly useful in facilitating usage of biobank data collections from population isolates when extensive genealogical information is missing. [ABSTRACT FROM AUTHOR]

Background: The introduction of genomics and biobanking methodologies to the African research context has also introduced novel ways of doing science, based on values of sharing and reuse of data and samples. This shift raises ethical challenges that need to be considered when research is reviewed by ethics committees, relating for instance to broad consent, the feedback of individual genetic findings, and regulation of secondary sample access and use. Yet existing ethics guidelines and regulations in Africa do not successfully regulate research based on sharing, causing confusion about what is allowed, where and when.Methods: In order to understand better the ethics regulatory landscape around genomic research and biobanking, we conducted a comprehensive analysis of existing ethics guidelines, policies and other similar sources. We sourced 30 ethics regulatory documents from 22 African countries. We used software that assists with qualitative data analysis to conduct a thematic analysis of these documents.Results: Surprisingly considering how contentious broad consent is in Africa, we found that most countries allow the use of this consent model, with its use banned in only three of the countries we investigated. In a likely response to fears about exploitation, the export of samples outside of the continent is strictly regulated, sometimes in conjunction with regulations around international collaboration. We also found that whilst an essential and critical component of ensuring ethical best practice in genomics research relates to the governance framework that accompanies sample and data sharing, this was most sparingly covered in the guidelines.Conclusions: There is a need for ethics guidelines in African countries to be adapted to the changing science policy landscape, which increasingly supports principles of openness, storage, sharing and secondary use. Current guidelines are not pertinent to the ethical challenges that such a new orientation raises, and therefore fail to provide accurate guidance to ethics committees and researchers. [ABSTRACT FROM AUTHOR]

Background: Biobanks are considered to be key infrastructures for research development and have generated a lot of debate about their ethical, legal and social implications (ELSI). While the focus has been on human genomic research, rapid advances in human microbiome research further complicate the debate.Discussion: We draw on two cystic fibrosis biobanks in Toronto, Canada, to illustrate our points. The biobanks have been established to facilitate sample and data sharing for research into the link between disease progression and microbial dynamics in the lungs of pediatric and adult patients. We begin by providing an overview of some of the ELSI associated with human microbiome research, particularly on the implications for the broader society. We then discuss ethical considerations regarding the identifiability of samples biobanked for human microbiome research, and examine the issue of return of results and incidental findings. We argue that, for the purposes of research ethics oversight, human microbiome research samples should be treated with the same privacy considerations as human tissues samples. We also suggest that returning individual microbiome-related findings could provide a powerful clinical tool for care management, but highlight the need for a more grounded understanding of contextual factors that may be unique to human microbiome research.Conclusions: We revisit the ELSI of biobanking and consider the impact that human microbiome research might have. Our discussion focuses on identifiability of human microbiome research samples, and return of research results and incidental findings for clinical management. [ABSTRACT FROM AUTHOR]

Background: Preservation of human skin fibroblasts and keratinocytes is essential for the creation of skin tissue banks. For successful cryopreservation of cells, selection of an appropriate cryoprotectant agent (CPA) is imperative. The aim of this study was to identify CPAs that minimize toxic effects and allow for the preservation of human fibroblasts and keratinocytes in suspension and in monolayers. Results: We cryopreserved human fibroblasts and keratinocytes with different CPAs and compared them to fresh, unfrozen cells. Cells were frozen in the presence and absence of hydroxyethyl starch (HES) or dimethyl sulfoxide (DMSO), the latter of which is a commonly used CPA known to exert toxic effects on cells. Cell numbers were counted immediately post-thaw as well as three days after thawing. Cellular structures were analyzed and counted by labeling nuclei, mitochondria, and actin filaments. We found that successful cryopreservation of suspended or adherent keratinocytes can be accomplished with a 10% HES or a 5% HES, 5% DMSO solution. Cell viability of fibroblasts cryopreserved in suspension was maintained with 10% HES or 5% HES, 5% DMSO solutions. Adherent, cryopreserved fibroblasts were successfully maintained with a 5% HES, 5% DMSO solution. Conclusion: We conclude that skin tissue cells can be effectively cryopreserved by substituting all or a portion of DMSO with HES. Given that DMSO is the most commonly used CPA and is believed to be more toxic than HES, these findings are of clinical significance for tissue-based replacement therapies. Therapies that require the use of keratinocyte and fibroblast cells, such as those aimed at treating skin wounds or skin burns, may be optimized by substituting a portion or all of DMSO with HES during cryopreservation protocols. [ABSTRACT FROM AUTHOR]

Background: Biobanks are precariously situated at the intersection of science, genetics, genomics, society, ethics, the law and politics. This multi-disciplinarity has given rise to a new discourse in health research involving diverse stakeholders. Each stakeholder is embedded in a unique context and articulates his/her biobanking activities differently. To researchers, biobanks carry enormous transformative potential in terms of advancing scientific discovery and knowledge. However, in the context of power asymmetries in Africa and a distrust in science born out of historical exploitation, researchers must balance the scientific imperative of collecting, storing and sharing high quality biological samples with obligations to donors/participants, communities, international collaborators, regulatory and ethics authorities. To date, researcher perspectives on biobanking in South Africa have not been explored and documented. Methods: In-depth qualitative interviews were conducted with a purposive sample of 21 researchers - 8 in the Western Cape, 3 in Gauteng and 10 in Kwa-Zulu Natal. Interviews lasted approximately 40-60 min and were audiotaped with consent. Thematic analysis of the transcribed interviews was conducted by the co-authors. Results: Researchers articulated serious concerns over standardised regulatory approaches that failed to consider the heterogeneity of biobanks. Given that biobanks differ considerably, guidelines and RECs need to stratify risk accordingly and governance processes and structures must be flexible. While RECs were regarded as an important component of the governance structure researchers expressed concern about their expertise in biobanking. Operational management of biobanks was regarded as an ethical imperative and a pre-requisite to building trust during consent processes. While broad general consent was preferred, tiered consent was thought to be more consistent with respect for autonomy and building trust. Material Transfer Agreements (MTAs) were often lacking when biosamples were exported and this was perceived to impact negatively on trust. On the other hand, researchers believed that authentic community engagement would help to build trust. Conclusion: Building trust will best be achieved via a system of governance structures and processes that precede the establishment of a biobank and monitor progress from the point of sample collection through to future use, including export. Such governance structures must be robust and must include comprehensive national legislation, policy and contextualised guidelines. Currently such governance infrastructure appears to be lacking in many African countries including South Africa. Capacity development of all stakeholders including REC members will enhance expeditious and efficient review of biobanking protocols which in turn will reinforce trust in the researcher-donor relationship. Science translation and community engagement in biobanking is integral to the success of biobanking in South Africa. [ABSTRACT FROM AUTHOR]

Biobanks have been heralded as essential tools for translating biomedical research into practice, driving precision medicine to improve pathways for global healthcare treatment and services. Many nations have established specific governance systems to facilitate research and to address the complex ethical, legal and social challenges that they present, but this has not lead to uniformity across the world. Despite significant progress in responding to the ethical, legal and social implications of biobanking, operational, sustainability and funding challenges continue to emerge. No coherent strategy has yet been identified for addressing them. This has brought into question the overall viability and usefulness of biobanks in light of the significant resources required to keep them running. This review sets out the challenges that the biobanking community has had to overcome since their inception in the early 2000s. The first section provides a brief outline of the diversity in biobank and regulatory architecture in seven countries: Australia, Germany, Japan, Singapore, Taiwan, the UK, and the USA. The article then discusses four waves of responses to biobanking challenges. This article had its genesis in a discussion on biobanks during the Centre for Health, Law and Emerging Technologies (HeLEX) conference in Oxford UK, co-sponsored by the Centre for Law and Genetics (University of Tasmania). This article aims to provide a review of the issues associated with biobank practices and governance, with a view to informing the future course of both large-scale and smaller scale biobanks. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stromal cells (MSC) are largely investigated in clinical trials aiming to control inappropriate immune reactions (GVHD, Crohn's disease, solid organ transplantation). As the percentage of MSC precursors in bone marrow is very low, these must be expanded in vitro to obtain therapeutic cell doses. We describe here the constitution of an allogeneic human third-party MSC bank from screened healthy volunteer donors in compliance with quality specifications and ISCT-release criteria and report follow-up of different aspects of this activity since 2007.Methods: 68 clinical-grade large-scale MSC cultures were completed and analyzed. The whole process was described, including volunteer donor screening, bone marrow collection, mononuclear cell isolation and expansion over 4 weeks, harvesting, cryopreservation, release, administration and quality controls of the cells (including microbiology, phenotype, and potency assays).Results: From 59 validated donors, 68 cultures were completed (mean of final yields: 886 × 10(6) cells/culture) and a total of 464 MSC aliquots have been produced and stored in liquid nitrogen (mean of 132.8 × 10(6) cells/bag). Each MSC batch underwent extensive testing to verify its conformity with EBMT and ISCT release criteria and was individually validated. As of June 1 2015, 314 bags have been released and infused to patients included in 6 different clinical protocols. All thawed MSC units satisfied to release criteria and no infusion-related toxicity was reported.Conclusion: In conclusion, despite low passage cultures, we have been able to create an allogeneic "off-the-shelf" MSC bank with a large number of frozen aliquots and report here an efficient clinical-grade MSC banking activity in place for more than 7 years. Our challenge now is to produce MSC in compliance with good manufacturing practices (GMP) as, in the meantime, MSC have become considered as advanced therapy medicinal products (ATMP). Another significant challenge remains the development of relevant potency assay. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is a heterogeneous disease with different molecular characteristics associated with many variables such as the sites from which the tumors originate or the presence or absence of chromosomal instability. Identification of such variables, particularly mutational hotspots, often carries a significant diagnostic and/or prognostic value that could ultimately affect the therapeutic outcome.Methods: High-throughput mutational analysis of 99 CRC formalin-fixed and paraffin-embedded (FFPE) cases was performed using the Cancer Hotspots Panel (CHP) v2 on the Ion Torrent™ platform. Correlation with survival and other Clinicopathological parameters was performed using Fisher's exact test and Kaplan-Meier curve analysis.Results: Targeted sequencing lead to the identification of frequent mutations in TP53 (65 %), APC (36 %), KRAS (35 %), PIK3CA (19 %), PTEN (13 %), EGFR (11 %), SMAD4 (11 %), and FBXW7 (7 %). Other genes harbored mutations at lower frequency. EGFR mutations were relatively frequent and significantly associated with young age of onset (p = 0.028). Additionally, EGFR or PIK3CA mutations were a marker for poor disease-specific survival in our cohort (p = 0.009 and p = 0.032, respectively). Interestingly, KRAS or PIK3CA mutations were significantly associated with poor disease-specific survival in cases with wild-type TP53 (p = 0.001 and p = 0.02, respectively).Conclusions: Frequent EGFR mutations in this cohort as well as the differential prognostic potential of KRAS and PIK3CA in the presence or absence of detectable TP53 mutations may serve as novel prognostic tools for CRC in patients from the Kingdom of Saudi Arabia. Such findings could help in the clinical decision-making regarding therapeutic intervention for individual patients and provide better diagnosis or prognosis in this locality. [ABSTRACT FROM AUTHOR]

Background: Collection and storage of an infant's cord blood at birth is an option available to many new parents. Antenatal health care providers have an important role in providing non-biased and evidence based information to expectant parents about cord blood and tissue banking options. The aim of this paper was to identify and review studies of health care professionals' knowledge, attitudes and practices concerning cord blood banking and the sources by which healthcare professionals obtained their information on this topic.Methods: An integrative review was conducted using several electronic databases to identify papers on health care professionals' knowledge, attitudes and practices pertaining to cord blood banking. The CASP tool was used to determine validity and quality of the studies included in the review.Results: The search of the international literature identified nine papers which met review inclusion criteria. The literature review identified that there was little focus placed on antenatal health care professionals' knowledge of cord blood banking options despite these health care professionals being identified by expectant parents as their preferred, key source of information.Conclusion: Limited high quality studies have investigated what health care professionals know and communicate to expectant parents regarding cord blood banking. Further research should focus on understanding the knowledge, attitudes and practices of healthcare professionals and how they communicate with expectant parents about this issue. In addition, how this knowledge influences professional practice around birth is also important, as this may positively or negatively impact the information that is provided to expectant parents. [ABSTRACT FROM AUTHOR]

Background: Since 2006, the genetic testing company 23andMe has collected biological samples, self-reported information, and consent documents for biobanking and research from more than 1,000,000 individuals (90% participating in research), through a direct-to-consumer (DTC) online genetic-testing service providing a genetic ancestry report and a genetic health report. However, on November 22, 2013, the Food and Drug Administration (FDA) halted the sale of genetic health testing, on the grounds that 23andMe was not acting in accordance with federal law, by selling tests of undemonstrated reliability as predictive tests for medical risk factors. Consumers could still obtain the genetic ancestry report, but they no longer had access to the genetic health report in the United States (US). However, this did not prevent the company from continuing its health research, with previously obtained and future samples, provided that consent had been obtained from the consumers concerned, or with health reports for individuals from other countries. Furthermore, 23andMe was granted FDA authorization on February 19, 2015, first to provide reports about Bloom syndrome carrier status, and, more recently, to provide consumers with "carrier status" information for 35 genes known (with high levels of confidence) to cause disease.Discussion: In this Debate, we highlight the likelihood that the primary objective of the company was probably two-fold: promoting itself within the market for predictive testing for human genetic diseases and ancestry at a low cost to consumers, and establishing a high-value database/biobank for research (one of the largest biobanks of human deoxyribonucleic acid (DNA) and personal information). By dint of this marketing approach, a two-sided market has been established between the consumer and the research laboratories, involving the establishment of a database/DNA biobank for scientific and financial gain. We describe here the profound ethical issues raised by this setup. [ABSTRACT FROM AUTHOR]

Background: The combination of prophylactic pancreatic stent placement (PSP) - a temporary plastic stent placed in the pancreatic duct - and rectal non-steroidal anti-inflammatory drugs (NSAIDs) is recommended for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. Preliminary data, however, suggest that PSP may be unnecessary if rectal NSAIDs are administered. Given the costs and potential risks of PSP, we aim to determine whether rectal indomethacin obviates the need for pancreatic stent placement in patients undergoing high-risk ERCP.Methods/design: The SVI (Stent vs. Indomethacin) trial is a comparative effectiveness, multicenter, randomized, double-blind, non-inferiority study of rectal indomethacin alone versus the combination of rectal indomethacin and PSP for preventing PEP in high-risk cases. One thousand four hundred and thirty subjects undergoing high-risk ERCP, in whom PSP is planned solely for PEP prevention, will be randomized to indomethacin alone or combination therapy. Those who are aware of study group assignment, including the endoscopist, will not be involved in the post-procedure care of the patient for at least 48 hours. Subjects will be assessed for PEP and its severity by a panel of independent and blinded adjudicators. Indomethacin alone will be declared non-inferior to combination therapy if the two-sided 95 % upper confidence bound of the treatment difference is less than 5 % between the two groups. Biological specimens will be obtained from trial participants and centrally banked.Discussion: The SVI trial is designed to determine whether PSP remains necessary in the era of NSAIDs pharmacoprevention. The associated bio-repository will establish the groundwork for important scientific breakthrough.Trial Registration: NCT02476279, registered June 2015. [ABSTRACT FROM AUTHOR]

Background: Balancing the rights and obligations of custodians and applicants in relation to access to biobanks is of utmost importance to guarantee trust and confidence. This study aimed to reveal which issues divide different stakeholders in an attempt to determine the rights and/or obligations held on human biological materials (HBM) and data.Methods: Twenty-eight informants in the Benelux and Scandinavia were interviewed in order to capture the perspectives of experts and stakeholders in relation to the rights and obligations held by custodians and applicants with respect to access to HBM and data.Results: There was no consensus among the informants on whether the custodian of a biobank should decide upon the scientific merits and the utility of an access request. Nearly all informants agreed that a new request or an amendment to the initial request has to be submitted when an applicant wants to use leftover HBM in a new or follow-up project. Several informants felt that it might be justified to charge higher access fees to external or industrial applicants that did not contribute (directly or indirectly) to the collection of HBM and data. Most informants agreed that a custodian of a biobank could request the sharing and return of research results. It was furthermore argued that some of the benefits of research projects should be fed back into biobanks.Conclusions: The interviews revealed a rather complex web of rights and obligations allocated to the custodian and the applicant in relation to access to HBM and data stored in biobanks. Some rights and obligations are negotiated on a case-by-case basis, while others are stipulated in access arrangements. We did find a consensus on the attribution of certain general rights to the custodians and the applicant. [ABSTRACT FROM AUTHOR]

Background: The Lung Cancer Risk Test (LCRT) trial is a prospective cohort study comparing lung cancer incidence among persons with a positive or negative value for the LCRT, a 15 gene test measured in normal bronchial epithelial cells (NBEC). The purpose of this article is to describe the study design, primary endpoint, and safety; baseline characteristics of enrolled individuals; and establishment of a bio-specimen repository.Methods/design: Eligible participants were aged 50-90 years, current or former smokers with 20 pack-years or more cigarette smoking history, free of lung cancer, and willing to undergo bronchoscopic brush biopsy for NBEC sample collection. NBEC, peripheral blood samples, baseline CT, and medical and demographic data were collected from each subject.Discussion: Over a two-year span (2010-2012), 403 subjects were enrolled at 12 sites. At baseline 384 subjects remained in study and mean age and smoking history were 62.9 years and 50.4 pack-years respectively, with 34% current smokers. Obstructive lung disease (FEV1/FVC <0.7) was present in 157 (54%). No severe adverse events were associated with bronchoscopic brushing. An NBEC and matched peripheral blood bio-specimen repository was established. The demographic composition of the enrolled group is representative of the population for which the LCRT is intended. Specifically, based on baseline population characteristics we expect lung cancer incidence in this cohort to be representative of the population eligible for low-dose Computed Tomography (LDCT) lung cancer screening. Collection of NBEC by bronchial brush biopsy/bronchoscopy was safe and well-tolerated in this population. These findings support the feasibility of testing LCRT clinical utility in this prospective study. If validated, the LCRT has the potential to significantly narrow the population of individuals requiring annual low-dose helical CT screening for early detection of lung cancer and delay the onset of screening for individuals with results indicating low lung cancer risk. For these individuals, the small risk incurred by undergoing once in a lifetime bronchoscopic sample collection for LCRT may be offset by a reduction in their CT-related risks. The LCRT biospecimen repository will enable additional studies of genetic basis for COPD and/or lung cancer risk.Trial Registration: The LCRT Study, NCT 01130285, was registered with Clinicaltrials.gov on May 24, 2010. [ABSTRACT FROM AUTHOR]

Background: The Qatar Biobank aims to collect extensive lifestyle, clinical, and biological information from up to 60,000 men and women Qatari nationals and long-term residents (individuals living in the country for ≥15 years) aged ≥18 years (approximately one-fifth of all Qatari citizens), to follow up these same individuals over the long term to record any subsequent disease, and hence to study the causes and progression of disease, and disease burden, in the Qatari population.Methods: Between the 11(th)-December-2012 and 20(th)-February-2014, 1209 participants were recruited into the pilot study of the Qatar Biobank. At recruitment, extensive phenotype information was collected from each participant, including information/measurements of socio-demographic factors, prevalent health conditions, diet, lifestyle, anthropometry, body composition, bone health, cognitive function, grip strength, retinal imaging, total body dual energy X-ray absorptiometry, and measurements of cardiovascular and respiratory function. Blood, urine, and saliva were collected and stored for future research use. A panel of 66 clinical biomarkers was routinely measured on fresh blood samples in all participants. Rates of recruitment are to be progressively increased in the coming period and the recruitment base widened to achieve a cohort of consented individuals broadly representative of the eligible Qatari population. In addition, it is planned to add additional measures in sub-samples of the cohort, including Magnetic Resonance Imaging (MRI) of the brain, heart and abdomen.Results: The mean time for collection of the extensive phenotypic information and biological samples from each participant at the baseline recruitment visit was 179 min. The 1209 pilot study participants (506 men and 703 women) were aged between 28-80 years (median 39 years); 899 (74.4%) were Qatari nationals and 310 (25.6%) were long-term residents. Approximately two-thirds of pilot participants were educated to graduate level or above.Conclusions: The pilot has proven that recruitment of volunteers into the Qatar Biobank project with intensive baseline measurements of behavioural, physical, and clinical characteristics is well accepted and logistically feasible. Qatar Biobank will provide a powerful resource to investigate the major determinants of ill-health and well-being in Qatar, providing valuable insights into the current and future public health burden that faces the country. [ABSTRACT FROM AUTHOR]

Background: This paper discusses the contentious issue of reuse of stored biological samples and data obtained from research participants in past clinical research to answer future ethical and scientifically valid research questions. Many countries have regulations and guidelines that guide the use and exportation of stored biological samples and data. However, there are variations in regulations and guidelines governing the reuse of stored biological samples and data in Sub-Saharan Africa including Malawi.Discussion: The current research ethics regulations and guidelines in Malawi do not allow indefinite storage and reuse of biological samples and data for future unspecified research. This comes even though the country has managed to answer pertinent research questions using stored biological samples and data. We acknowledge the limited technical expertise and equipment unavailable in Malawi that necessitates exportation of biological samples and data and the genuine concern raised by the regulatory authorities about the possible exploitation of biological samples and data by researchers. We also acknowledge that Malawi does not have bio-banks for storing biological samples and data for future research purposes. This creates room for possible exploitation of biological samples and data collected from research participants in primary research projects in Malawi. However, research ethics committees require completion and approval of material transfer agreements and data transfer agreements for biological samples and data collected for research purposes respectively and this requirement may partly address the concern raised by the regulatory authorities. Our concern though is that there is no such requirement for biological samples and data collected from patients for clinical or diagnostic purposes. In conclusion, we propose developing a medical data and material transfer agreement for biological samples and data collected from patients for clinical or diagnostic purposes in both public and private health facilities that may end up in research centers outside Malawi. We also propose revision of the current research ethics regulations and guidelines in Malawi in order to allow secondary use of biological samples and data collected from primary research projects as a way of maximizing the use of collected samples and data. Finally, we call for consultation of all stakeholders within the Malawi research community when regulatory authorities are developing policies that govern research in Malawi. [ABSTRACT FROM AUTHOR]

Background: Tropomyosin-related kinase A (TRKA) is a nerve growth factor (NGF) receptor that belongs to the tyrosine kinase receptor family. It is critical for the correct development of many types of neurons including pain-mediating sensory neurons and also controls proliferation, differentiation and survival of many neuronal and non-neuronal cells. TRKA (also known as NTRK1) gene is a target of alternative splicing which can result in several different protein isoforms. Presently, three human isoforms (TRKAI, TRKAII and TRKAIII) and two rat isoforms (TRKA L0 and TRKA L1) have been described.Results: We show here that human TRKA gene is overlapped by two genes and spans 67 kb--almost three times the size that has been previously described. Numerous transcription initiation sites from eight different 5' exons and a sophisticated splicing pattern among exons encoding the extracellular part of TRKA receptor indicate that there might be a large variety of alternative protein isoforms. TrkA genes in rat and mouse appear to be considerably shorter, are not overlapped by other genes and display more straightforward splicing patterns. We describe the expression profile of alternatively spliced TRKA transcripts in different tissues of human, rat and mouse, as well as analyze putative endogenous TRKA protein isoforms in human SH-SY5Y and rat PC12 cells. We also characterize a selection of novel putative protein isoforms by portraying their phosphorylation, glycosylation and intracellular localization patterns. Our findings show that an isoform comprising mainly of TRKA kinase domain is capable of entering the nucleus.Conclusions: Results obtained in this study refer to the existence of a multitude of TRKA mRNA and protein isoforms, with some putative proteins possessing very distinct properties. [ABSTRACT FROM AUTHOR]

Background: Glomerular diseases are potentially fatal, requiring aggressive interventions and close monitoring. Urine is a readily-accessible body fluid enriched in molecular signatures from the kidney and therefore particularly suited for routine clinical analysis as well as development of non-invasive biomarkers for glomerular diseases.Methods: The Nephrotic Syndrome Study Network (NEPTUNE; ClinicalTrials.gov Identifier NCT01209000) is a North American multicenter collaborative consortium established to develop a translational research infrastructure for nephrotic syndrome. This includes standardized urine collections across all participating centers for the purpose of discovering non-invasive biomarkers for patients with nephrotic syndrome due to minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy. Here we describe the organization and methods of urine procurement and banking procedures in NEPTUNE.Results: We discuss the rationale for urine collection and storage conditions, and demonstrate the performance of three experimental analytes (neutrophil gelatinase-associated lipocalin [NGAL], retinol binding globulin, and alpha-1 microglobulin) under these conditions with and without urine preservatives (thymol, toluene, and boric acid). We also demonstrate the quality of RNA and protein collected from the urine cellular pellet and exosomes.Conclusions: The urine collection protocol in NEPTUNE allows robust detection of a wide range of proteins and RNAs from urine supernatant and pellets collected longitudinally from each patient over 5 years. Combined with the detailed clinical and histopathologic data, this provides a unique resource for exploration and validation of new or accepted markers of glomerular diseases.Trial Registration: ClinicalTrials.gov Identifier NCT01209000. [ABSTRACT FROM AUTHOR]

The Cooperative Health Research In South Tyrol (CHRIS) study is a population-based study with a longitudinal lookout to investigate the genetic and molecular basis of age-related common chronic conditions and their interaction with life style and environment in the general population. All adults of the middle and upper Vinschgau/Val Venosta are invited, while 10,000 participants are anticipated by mid-2017. Family participation is encouraged for complete pedigree reconstruction and disease inheritance mapping. After a pilot study on the compliance with a paperless assessment mode, computer-assisted interviews have been implemented to screen for conditions of the cardiovascular, endocrine, metabolic, genitourinary, nervous, behavioral, and cognitive system. Fat intake, cardiac health, and tremor are assessed instrumentally. Nutrient intake, physical activity, and life-course smoking are measured semi-quantitatively. Participants are phenotyped for 73 blood and urine parameters and 60 aliquots per participant are biobanked (cryo-preserved urine, DNA, and whole and fractionated blood). Through liquid-chromatography mass-spectrometry analysis, metabolite profiling of the mitochondrial function is assessed. Samples are genotyped on 1 million variants with the Illumina HumanOmniExpressExome array and the first data release including 4570 fully phenotyped and genotyped samples is now available for analysis. Participants' follow-up is foreseen 6 years after the first visit. The target population is characterized by long-term social stability and homogeneous environment which should both favor the identification of enriched genetic variants. The CHRIS cohort is a valuable resource to assess the contribution of genomics, metabolomics, and environmental factors to human health and disease. It is awaited that this will result in the identification of novel molecular targets for disease prevention and treatment. [ABSTRACT FROM AUTHOR]