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1. Novel Therapies for Metastatic Non-Small Cell Lung Cancer with MET Exon 14 Alterations: A Spotlight on Capmatinib

Author

Tan AC, Loh TJ, Kwang XL, Tan GS, Lim KH, and Tan DSW

Subjects
capmatinib, met exon 14 skipping, non-small cell lung cancer, targeted therapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Aaron C Tan,1 Tracy J Loh,2 Xue Lin Kwang,1 Gek San Tan,2 Kiat Hon Lim,2 Daniel SW Tan1 1Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 169610, Singapore; 2Department of Pathology, Singapore General Hospital, Singapore, 169608, SingaporeCorrespondence: Daniel SW TanNational Cancer Centre Singapore, 11 Hospital Crescent, Singapore, 169610, SingaporeTel +65 6436 8000Email daniel.tan.s.w@singhealth.com.sgAbstract: MET exon 14 (METex14) alterations are now an established therapeutically tractable target in non-small cell lung cancer (NSCLC). Recently reported trials of several MET tyrosine kinase inhibitors (TKI) in this patient population have demonstrated promising efficacy data in both the treatment naïve and pre-treated settings and have led to regulatory approvals. This review will focus on practical diagnostic considerations for METex14 alterations, the trial evidence for capmatinib in this molecular subset including dosing and toxicity management, and the future therapeutic landscape of METex14 altered NSCLC.Keywords: capmatinib, MET exon 14 skipping, non-small cell lung cancer, targeted therapy

Published
2021

2. Designing Clinical Trials for Combination Immunotherapy: A Framework for Glioblastoma

Author

Singh, K, Batich, KA, Wen, PY, Tan, AC, Bagley, SJ, Lim, M, Platten, M, Colman, H, Ashley, DM, Chang, SM, Rahman, R, Galanis, E, Mansouri, A, Puduvalli, VK, Reardon, DA, Sahebjam, S, Sampson, JH, Simes, J, Berry, DA, Zadeh, G, Cloughesy, TF, Mehta, MP, Piantadosi, S, Weller, M, Heimberger, AB, Khasraw, Mustafa, Singh, K, Batich, KA, Wen, PY, Tan, AC, Bagley, SJ, Lim, M, Platten, M, Colman, H, Ashley, DM, Chang, SM, Rahman, R, Galanis, E, Mansouri, A, Puduvalli, VK, Reardon, DA, Sahebjam, S, Sampson, JH, Simes, J, Berry, DA, Zadeh, G, Cloughesy, TF, Mehta, MP, Piantadosi, S, Weller, M, Heimberger, AB, and Khasraw, Mustafa

Published
2022

3. Clinical Trial Eligibility Criteria and Recently Approved Cancer Therapies for Patients With Brain Metastases

Author

Tan, AC, Boggs, DH, Lee, EQ, Kim, MM, Mehta, MP, Khasraw, Mustafa, Tan, AC, Boggs, DH, Lee, EQ, Kim, MM, Mehta, MP, and Khasraw, Mustafa

Abstract

Brain metastases cause significant morbidity and mortality in patients with advanced cancer. In the era of precision oncology and immunotherapy, there are rapidly evolving systemic treatment options. These novel therapies may have variable intracranial efficacy, and patients with brain metastases remain a population of special interest. Typically, only patients with stable, asymptomatic and/or treated brain metastases are enrolled in clinical trials, or may be excluded altogether, particularly in the setting of leptomeningeal carcinomatosis. Consequently, this leads to significant concerns on the external validity of clinical trial evidence to real-world clinical practice. Here we describe the current trends in cancer clinical trial eligibility for patients with brain metastases in both early and late phase trials, with a focus on targeted and immunotherapies. We evaluate recent newly FDA approved therapies and the clinical trial evidence base leading to approval. This includes analysis of inclusion and exclusion criteria, requirements for baseline screening for brain metastases, surveillance cerebral imaging and incorporation of trial endpoints for patients with brain metastases. Finally, the use of alternative sources of data such as real-world evidence with registries and collaborative studies will be discussed.

Published
2022

5. Health and support service needs of individuals with disability from culturally and linguistically diverse backgrounds: a scoping review protocol.

Author

Pho, JNQ, Tan, AC, Chaudhary, K, Hines, S, Ellison, C, Isaac, V, Lim, D, Pho, JNQ, Tan, AC, Chaudhary, K, Hines, S, Ellison, C, Isaac, V, and Lim, D

Abstract

BACKGROUND: All individuals should have the right to engage meaningfully in occupations that meet their aspirations and life goals as well as promote their health and well-being. For individuals with disability, meaningful engagement in occupations is supported by timely, effective, and adaptive health and support services. However, research has revealed multiple barriers preventing utilization of these services by individuals with disability from culturally and linguistically diverse (CALD) backgrounds. This review aims to identify gaps and solutions in health and support services of individuals with disability from CALD backgrounds to meaningfully engage in occupations. METHODS: A scoping review will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews. A detailed search strategy will be used to search CINAHL, PubMed, Embase, Scopus, PsycInfo, JBI, and Cochrane Library, as well as grey literature in Trove, Mednar, and OpenGrey from January 1974 onwards. Two reviewers will independently screen all citations and full-text articles for eligibility against specific inclusion and exclusion criteria. Potential conflicts will be resolved through discussion. Data will be extracted and presented in a diagrammatic or tabular form accompanied by a narrative summary. DISCUSSION: The scoping review will present the health and support service needs of individuals with disability from CALD backgrounds and will extend the current reviews as it focuses the engagement in meaningful occupation. Findings from this review have the potential to inform local policy discussions and practice-based disability care. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework ( 10.17605/OSF.IO/HW2FB ).

Published
2021

6. International representation of authors, editors and research in neurology journals.

Author

Bojanic, T, Tan, AC, Bojanic, T, and Tan, AC

Abstract

BACKGROUND: Published research informs international healthcare, yet only a few studies have assessed the representation of authors, editors, and research from developing countries in biomedical journals. METHODS: We reviewed all research articles published in five high-ranking peer-reviewed neurology journals (The Lancet Neurology, Acta Neuropathologica, Nature Reviews Neurology, Brain and Annals of Neurology) in 2010 and 2019 to determine the extent of contributions of authors, editors and research from developing countries, and the degree of international research collaboration between developed and developing countries. RESULTS: First authorship was attributed to authors from developing countries in only 2% (11/729) of research articles in 2010 and 3% (19/647) of research articles in 2019. All 144 editorial board members in 2019 were from developed countries. International research collaboration between developing and developed countries accounted for only 4% (30/729) of all research articles in 2010 and 6% (40/647) of all research articles in 2019. CONCLUSIONS: There is urgent need for strategies to support high-quality and contextually appropriate biomedical research in developing countries. Supporting high quality and contextually appropriate biomedical research now is necessary for developing countries to meet the rising healthcare needs of their populations in the future.

Published
2021

7. Systematic review of combinations of targeted or immunotherapy in advanced solid tumors

Author

Tan, AC, Bagley, SJ, Wen, PY, Lim, M, Platten, M, Colman, H, Ashley, DM, Wick, W, Chang, SM, Galanis, E, Mansouri, A, Khagi, S, Mehta, MP, Heimberger, AB, Puduvalli, VK, Reardon, DA, Sahebjam, S, Simes, J, Antonia, SJ, Berry, D, Khasraw, Mustafa, Tan, AC, Bagley, SJ, Wen, PY, Lim, M, Platten, M, Colman, H, Ashley, DM, Wick, W, Chang, SM, Galanis, E, Mansouri, A, Khagi, S, Mehta, MP, Heimberger, AB, Puduvalli, VK, Reardon, DA, Sahebjam, S, Simes, J, Antonia, SJ, Berry, D, and Khasraw, Mustafa

Abstract

With rapid advances in our understanding of cancer, there is an expanding number of potential novel combination therapies, including novel–novel combinations. Identifying which combinations are appropriate and in which subpopulations are among the most difficult questions in medical research. We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic review of trials of novel–novel combination therapies involving immunotherapies or molecular targeted therapies in advanced solid tumors. A MEDLINE search was conducted using a modified Cochrane Highly Sensitive Search Strategy for published clinical trials between July 1, 2017, and June 30, 2020, in the top-ranked medical and oncology journals. Trials were evaluated according to a criterion adapted from previously published Food and Drug Administration guidance and other key considerations in designing trials of combinations. This included the presence of a strong biological rationale, the use of a new established or emerging predictive biomarker prospectively incorporated into the clinical trial design, appropriate comparator arms of monotherapy or supportive external data sources and a primary endpoint demonstrating a clinically meaningful benefit. Of 32 identified trials, there were 11 (34%) trials of the novel–novel combination of anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) therapy, and 10 (31%) trials of anti-PD-1/PD-L1 and anti-vascular endothelial growth factor (VEGF) combination therapy. 20 (62.5%) trials were phase II trials, while 12 (37.5%) were phase III trials. Most (72%) trials lacked significant preclinical evidence supporting the development of the combination in the given indication. A majority of trials (69%) were conducted in biomarker unselected populations or used pre-existing biomarkers within the given indication for patient selection. Most studies (66%) were consid

Published
2021

9. Has the reporting quality of published randomised controlled trial protocols improved since the SPIRIT statement? A methodological study

Author

Tan, ZW, Tan, AC, Li, T, Harris, I, Naylor, JM, Siebelt, M, Van Tiel, J, Pinheiro, M, Harris, L, Chamberlain, K, Adie, S, Tan, ZW, Tan, AC, Li, T, Harris, I, Naylor, JM, Siebelt, M, Van Tiel, J, Pinheiro, M, Harris, L, Chamberlain, K, and Adie, S

Abstract

Objectives To determine the reporting quality of published randomised controlled trial (RCT) protocols before and after the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement (2013), and any association with author, trial or journal factors. Design Methodological study. Data sources MEDLINE, Embase and CENTRAL were electronically searched using optimised search strategies. Eligibility criteria Protocols written for an RCT of living humans, published in full text in a peer-reviewed journal and published in the English language. Main outcome Primary outcome was the overall proportion of checklist items which were adequately reported in RCT protocols published before and after the SPIRIT statement. Results 300 RCT protocols were retrieved; 150 from the period immediately before the SPIRIT statement (9 July 2012 to 28 December 2012) and 150 from a recent period after the SPIRIT statement (25 January 2019 to 20 March 2019). 47.9% (95% CI, 46.5% to 49.3%) of checklist items were adequately reported in RCT protocols before the SPIRIT statement and 56.7% (95% CI, 54.9% to 58.5%) after the SPIRIT statement. This represents an 8.8% (95% CI, 6.6% to 11.1%; p<0.0001) mean improvement in the overall proportion of checklist items adequately reported since the SPIRIT statement. While 40% of individual checklist items had a significant improvement in adequate reporting after the SPIRIT statement, 11.3% had a significant deterioration and there were no RCT protocols in which all individual checklist items were complete. The factors associated with higher reporting quality of RCT protocols in multiple regression analysis were author expertise or experience in epidemiology or statistics, multicentre trials, longer protocol word length and publicly reported journal policy of compliance with the SPIRIT statement. Conclusion The overall reporting quality of RCT protocols has significantly improved since the SPIRIT statement, although a substantial propo

Published
2020

10. Is retrospective assessment of health-related quality of life valid?

Author

Lawson, A, Tan, AC, Naylor, J, Harris, IA, Lawson, A, Tan, AC, Naylor, J, and Harris, IA

Abstract

Background: Health-related quality of life (HRQoL) is a commonly used health outcome. For many acute conditions (e.g. fractures), retrospective measurement of HRQoL is necessary to establish pre-morbid health status. However, the validity of retrospective measurement of HRQoL following an intervening significant health event has not been established. The aim of this study was to test the validity of retrospective measurement (recall) of HRQoL by using a test-retest design to measure reliability and agreement between prospective and retrospective patient-reported HRQoL before and after an intervening health event (elective orthopaedic surgery). Method: Participants were recruited from the pre-admission clinic of a metropolitan hospital. Participants were assessed for their HRQoL using the EQ-5D-5L at two time-points; prospectively at 2 weeks prior to their date of surgery and then retrospectively (recalling their pre-operative health) following elective hip or knee joint replacement surgery. Prospective measurements were compared with retrospective measurements for the five domain scores (nominal data) using intra-class correlation and for the EQ-Index score and EQ-Visual Analogue Scale (VAS) score (continuous data), using Pearson's correlation. Agreement was tested in continuous variables using Lin's coefficient of concordance (pc) and Bland-Altman plots. Results: One hundred seventy-four patients consented to participate. Eighty-eight paired prospective and retrospective scores were collected and there was a median between-test period of 15 days. At a group level, the prospective measurements were similar to the retrospective measurements; the modes and means of the five domain scores were not different and the mean differences (MD) between the scores for EQ-Index (MD = 0.02, on a scale of 0-1) and EQ-VAS (MD = 0.53, on a scale of 1-100) were negligible. However, the correlation of paired scores was varied; the range of domain score correlations was 0.52 to 0.74, t

Published
2020

11. Molecular and clonal evolution in recurrent metastatic gliosarcoma

Author

Anderson, KJ, Tan, AC, Parkinson, J, Back, M, Kastelan, M, Newey, A, Brewer, J, Wheeler, H, Hudson, AL, Amin, SB, Johnson, KC, Barthel, FP, Verhaak, RGW, Khasraw, Mustafa, Anderson, KJ, Tan, AC, Parkinson, J, Back, M, Kastelan, M, Newey, A, Brewer, J, Wheeler, H, Hudson, AL, Amin, SB, Johnson, KC, Barthel, FP, Verhaak, RGW, and Khasraw, Mustafa

Published
2020

14. Prevalence of Chronic Hepatitis B and C in Malaysia- results from a community-based screening campaign

Author

Lim, ZZ, primary, Teo, JS, additional, Tan, AC, additional, Siam, Tan Soek, additional, Mohamed, Rosmawati, additional, Goh, KL, additional, Jaya, Fauziah, additional, Senamjit, K, additional, Aun, Azlida Che’, additional, Said, Rosaida, additional, Lim, EK, additional, Shahar, Hamiza, additional, Muhammad Radzi, AH, additional, Poh, Tee Hoi, additional, Seng, Tan Soon, additional, Menon, Jayaram, additional, Menon, Rena, additional, and Lim, TO, additional

Published
2020
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15. Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Author

Brown, P, Zhou, Y, Tan, AC, El-Esawi, MA, Liehr, T, Blanck, O, Gladue, DP, Almeida, GMF, Cernava, T, Sorzano, CO, Yeung, AWK, Engel, MS, Chandrasekaran, AR, Muth, T, Staege, MS, Daulatabad, SV, Widera, D, Zhang, J, Meule, A, Honjo, K, Pourret, O, Yin, CC, Zhang, Z, Cascella, M, Flegel, WA, Goodyear, CS, van Raaij, MJ, Bukowy-Bieryllo, Z, Campana, LG, Kurniawan, NA, Lalaouna, D, Hüttner, FJ, Ammerman, BA, Ehret, F, Cobine, PA, Tan, EC, Han, H, Xia, W, McCrum, C, Dings, RPM, Marinello, F, Nilsson, H, Nixon, B, Voskarides, K, Yang, L, Costa, VD, Bengtsson-Palme, J, Bradshaw, W, Grimm, DG, Kumar, N, Martis, E, Prieto, D, Sabnis, SC, Amer, SEDR, Liew, AWC, Perco, P, Rahimi, F, Riva, G, Zhang, C, Devkota, HP, Ogami, K, Basharat, Z, Fierz, W, Siebers, R, Tan, KH, Boehme, KA, Brenneisen, P, Brown, JAL, Dalrymple, BP, Harvey, DJ, Ng, G, Werten, S, Bleackley, M, Dai, Z, Dhariwal, R, Gelfer, Y, Hartmann, MD, Miotla, P, Tamaian, R, Govender, P, Gurney-Champion, OJ, Kauppila, JH, Zhang, X, Echeverría, N, Subhash, S, Sallmon, H, Tofani, M, Bae, T, Bosch, O, Cuív, PO, Danchin, A, Diouf, B, Eerola, T, Evangelou, E, Filipp, F, Klump, H, Kurgan, L, Smith, SS, Terrier, O, Tuttle, N, Brown, P, Zhou, Y, Tan, AC, El-Esawi, MA, Liehr, T, Blanck, O, Gladue, DP, Almeida, GMF, Cernava, T, Sorzano, CO, Yeung, AWK, Engel, MS, Chandrasekaran, AR, Muth, T, Staege, MS, Daulatabad, SV, Widera, D, Zhang, J, Meule, A, Honjo, K, Pourret, O, Yin, CC, Zhang, Z, Cascella, M, Flegel, WA, Goodyear, CS, van Raaij, MJ, Bukowy-Bieryllo, Z, Campana, LG, Kurniawan, NA, Lalaouna, D, Hüttner, FJ, Ammerman, BA, Ehret, F, Cobine, PA, Tan, EC, Han, H, Xia, W, McCrum, C, Dings, RPM, Marinello, F, Nilsson, H, Nixon, B, Voskarides, K, Yang, L, Costa, VD, Bengtsson-Palme, J, Bradshaw, W, Grimm, DG, Kumar, N, Martis, E, Prieto, D, Sabnis, SC, Amer, SEDR, Liew, AWC, Perco, P, Rahimi, F, Riva, G, Zhang, C, Devkota, HP, Ogami, K, Basharat, Z, Fierz, W, Siebers, R, Tan, KH, Boehme, KA, Brenneisen, P, Brown, JAL, Dalrymple, BP, Harvey, DJ, Ng, G, Werten, S, Bleackley, M, Dai, Z, Dhariwal, R, Gelfer, Y, Hartmann, MD, Miotla, P, Tamaian, R, Govender, P, Gurney-Champion, OJ, Kauppila, JH, Zhang, X, Echeverría, N, Subhash, S, Sallmon, H, Tofani, M, Bae, T, Bosch, O, Cuív, PO, Danchin, A, Diouf, B, Eerola, T, Evangelou, E, Filipp, F, Klump, H, Kurgan, L, Smith, SS, Terrier, O, and Tuttle, N

Abstract

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science.

Published
2019

16. Why unidimensional pain measurement prevails in the pediatric acute pain context and what multidimensional self-report methods can offer

Author

Jaaniste, T, Noel, M, Yee, RD, Bang, J, Tan, AC, Champion, GD, Jaaniste, T, Noel, M, Yee, RD, Bang, J, Tan, AC, and Champion, GD

Abstract

Although pain is widely recognized to be a multidimensional experience and defined as such, unidimensional pain measurement focusing on pain intensity prevails in the pediatric acute pain context. Unidimensional assessments fail to provide a comprehensive picture of a child’s pain experience and commonly do little to shape clinical interventions. The current review paper overviews the theoretical and empirical literature supporting the multidimensional nature of pediatric acute pain. Literature reporting concordance data for children’s self-reported sensory, affective and evaluative pain scores in the acute pain context has been reviewed and supports the distinct nature of these dimensions. Multidimensional acute pain measurement holds particular promise for identifying predictive markers of chronicity and may provide the basis for tailoring clinical management. The current paper has described key reasons contributing to the widespread use of unidimensional, rather than multidimensional, acute pediatric pain assessment protocols. Implications for clinical practice, education and future research are considered.

Published
2019

17. Chronic Widespread Pain and Fibromyalgia Syndrome: Life-Course Risk Markers in Young People

Author

Tan, AC, Jaaniste, T, Champion, D, Tan, AC, Jaaniste, T, and Champion, D

Abstract

Although the life-course concept of risk markers as potential etiological influences is well established in epidemiology, it has not featured in academic publications or clinical practice in the context of chronic widespread pain (CWP) and fibromyalgia syndrome (FMS). Studies of risk markers are required considerations for evaluation of patients and for research because there is no single cause, pathological feature, laboratory finding, or biomarker for CWP or FMS. The early-life risk markers identified by extensive literature review with best evidence for potential causal influence on the development and progression of CWP and FMS include genetic factors, premature birth, female sex, early childhood adversity, cognitive and psychosocial influences, impaired sleep, primary pain disorders, multiregional pain, physical trauma, infectious illness, obesity and inactivity, hypermobility of joints, iron deficiency, and small-fiber polyneuropathy. The case history illustrates the potential etiological influence of multiple risk markers offset by personal resilience.

Published
2019

18. Data quality audit of a clinical quality registry: A generic framework and case study of the Australian and New Zealand Hip Fracture Registry

Author

Tan, AC, Armstrong, E, Close, J, Harris, IA, Tan, AC, Armstrong, E, Close, J, and Harris, IA

Abstract

The value of a clinical quality registry is contingent on the quality of its data. This study aims to pilot methodology for data quality audits of the Australian and New Zealand Hip Fracture Registry, a clinical quality registry of hip fracture clinical care and secondary fracture prevention. Methods A data quality audit was performed by independently replicating the data collection and entry process for 163 randomly selected patient records from three contributing hospitals, and then comparing the replicated data set to the registry data set. Data agreement, as a proxy indicator of data accuracy, and data completeness were assessed. Results An overall data agreement of 82.3% and overall data completeness of 95.6% were found, reflecting a moderate level of data accuracy and a very high level of data completeness. Half of all data disagreements were caused by information discrepancies, a quarter by missing discrepancies and a quarter by time, date and number discrepancies. Transcription discrepancies only accounted for 1 in every 50 data disagreements. The sources of inaccurate and incomplete data have been identified with the intention of implementing data quality improvement. Conclusions Regular audits of data abstraction are necessary to improve data quality, assure data validity and reliability and guarantee the integrity and credibility of registry outputs. A generic framework and model for data quality audits of clinical quality registries is proposed, consisting of a three-step data abstraction audit, registry coverage audit and four-step data quality improvement process. Factors to consider for data abstraction audits include: central, remote or local implementation; single-stage or multistage random sampling; absolute, proportional, combination or alternative sample size calculation; data quality indicators; regular or ad hoc frequency; and qualitative assessment.

Published
2019

21. The Transient Collaborative Network Approach: Theoretical and Practical Considerations

Author

Noori H and Tan Ac

Subjects
Supply chain management, Knowledge management, Computer science, business.industry, Supply chain, Collaborative network, 05 social sciences, Competitive advantage, Field (computer science), Through-the-lens metering, Contingency theory, 0502 economics and business, Supply network, 050211 marketing, business, 050203 business & management
Abstract

This conceptual article analyzes and connects theory to the practice of a novel inter-organizational form we call the transient collaboration network or TCN approach. Field observations in China suggest that emerging entrepreneurs enter into collaborations with supply chain partners under very different mindsets regarding interorganizational relationships, trust, collaboration and long-term expectations from traditional supply network practices. Briefly, these organizations cannot themselves build all resources needed for competitive advantages in volatile business environments. These entrepreneurs develop the TCN approach to allow their organizations to achieve full potential to locate and access the right resources at the right time through trusted collaborations in these dynamic or turbulent business environments. This paper analyzes principles that govern TCN interactions through the lens of Structural Contingency Theory, as extended to the inter-organizational level. Propositions explain how relations between structures and contingencies affect inter-organizational collaborative performances, and suggest how the TCN approach may be applicable to supply chain networks in general.

Published
2016

22. Preclinical Activity of the Rational Combination of Selumetinib (AZD6244) in Combination with Vorinostat in KRAS-Mutant Colorectal Cancer Models

Author

Morelli MP, Tentler JJ, Kulikowski GN, Tan AC, Bradshaw Pierce EL, Pitts TM, Brown AM, Nallapareddy S, Arcaroli JJ, Serkova NJ, Hidalgo M, Eckhardt S.G., CIARDIELLO, Fortunato, Morelli, Mp, Tentler, Jj, Kulikowski, Gn, Tan, Ac, Bradshaw Pierce, El, Pitts, Tm, Brown, Am, Nallapareddy, S, Arcaroli, Jj, Serkova, Nj, Hidalgo, M, Ciardiello, Fortunato, and Eckhardt, S. G.

Published
2012

24. Intestinal barrier dysfunction in a randomised placebo-controlled trial of probiotic prophylaxis in acute pancreatitis

Author

Besselink, MG, van Santvoort, HC, Boermeester, MA, Fischer, K, Renooij, W, de Smet, MB, Ali, UA, Cirkel, GA, Bollen, TL, van Ramshorst, B, Weusten, BL, Schaapherder, AF, Witteman, BJ, Ploeg, RJ, van Goor, H, van Laarhoven, CJ, Tan, AC, Brink, MA, Van der Harst, E, Wahab, PJ, van Eijck, CH, Dejong, CH, van Erpecum, KJ, Akkermans, LM, Gooszen, HG, and Grp, DAPS

Published
2009

29. Novel agents in the treatment of metastatic colorectal cancer.

Author

Leong S, Messersmith WA, Tan AC, and Eckhardt SG

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer death in the United States. Research has led to an explosion of knowledge into the molecular basis of CRC in the past decades. Numerous receptors and intracellular proteins have been identified and implicated in the growth and progression of metastatic CRC, thus creating novel targets for drug development. Many agents are under development and have begun to enter early and even later-stage clinical trials. Results of these agents have demonstrated some encouraging activity but in a small number of patients. Research into predictive biomarkers aims to select the patients who may benefit from these novel agents. This review will address several of these promising new agents, their potential relevance to CRC, results from early clinical studies, and their incorporation into future and ongoing CRC clinical trials. Clearly, there is an urgent need for new agents in this disease, but as we learned from the experience with epidermal growth factor receptor-targeted antibodies, patient selection will be increasingly be required for individualized therapy to become a reality in CRC. [ABSTRACT FROM AUTHOR]

Published
2010
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30. Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Author

Zeineb, Zian, Brown, Peter, Tan, Aik-Choon, El-Esawi, Mohamed A., Liehr, Thomas, Blanck, Oliver, Gladue, Douglas P., Almeida, Gabriel M. F., Cernava, Tomislav, Sorzano, Carlos O., Yeung, Andy W. K., Engel, Michael S., Chandrasekaran, Arun Richard, Muth, Thilo, Staege, Martin S., Daulatabad, Swapna V., Widera, Darius, Zhang, Junpeng, Meule, Adrian, Honjo, Ken, Pourret, Olivier, Yin, Cong-Cong, Zhang, Zhongheng, Cascella, Marco, Flegel, Willy A., Goodyear, Carl S., Raaij, Mark J. van, Bukowy-Bieryllo, Zuzanna, Campana, Luca G., Kurniawan, Nicholas A., Lalaouna, David, Hüttner, Felix J., Ammerman, Brooke A., Ehret, Felix, Cobine, Paul A., Tan, Ene-Choo, Han, Hyemin, Xia, Wenfeng, McCrum, Christopher, Dings, Ruud P. M., Marinello, Francesco, Nilsson, Henrik, Nixon, Brett, Voskarides, Konstantinos, Yang, Long, Costa, Vincent D., Bengtsson-Palme, Johan, Bradshaw, William, Grimm, Dominik G., Kumar, Nitin, Martis, Elvis, Prieto, Daniel, Sabnis, Sandeep C., Amer, Said E. D. R., Liew, Alan W. C., Perco, Paul, Rahimi, Farid, Riva, Giuseppe, Zhang, Chongxing, Devkota, Hari P., Ogami, Koichi, Basharat, Zarrin, Fierz, Walter, Siebers, Robert, Tan, Kok-Hian, Boehme, Karen A., Brenneisen, Peter, Brown, James A. L., Dalrymple, Brian P., Harvey, David J., Ng, Grace, Werten, Sebastiaan, Bleackley, Mark, Dai, Zhanwu, Dhariwal, Raman, Gelfer, Yael, Hartmann, Marcus D., Miotla, Pawel, Tamaian, Radu, Govender, Pragashnie, Gurney-Champion, Oliver J., Kauppila, Joonas H., Zhang, Xiaolei, Echeverría, Natalia, Subhash, Santhilal, Sallmon, Hannes, Tofani, Marco, Bae, Taeok, Bosch, Oliver, Cuív, Páraic O., Danchin, Antoine, Diouf, Barthelemy, Eerola, Tuomas, Evangelou, Evangelos, Filipp, Fabian V., Klump, Hannes, Kurgan, Lukasz, Smith, Simon S., Terrier, Olivier, Tuttle, Neil, Ascher, David B., Janga, Sarath C., Schulte, Leon N., Becker, Daniel, Browngardt, Christopher, Bush, Stephen J., Gaullier, Guillaume, Ide, Kazuki, Meseko, Clement, Werner, Gijsbert D. 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H., Schwotzer, Daniela, Sebastian, Agata, Selinski, Jennifer, Seltmann, Stefanie, Sha, Feng, Shalev, Nir, Shang, Jin-Long, Singer, Josef, Singh, Mandeep, Smith, Taylor, Solomon-Moore, Emma, Song, Lijuan, Soraggi, Samuele, Stanley, Ryan, Steckhan, Nico, Strobl, Frederic, Subissi, Lorenzo, Supriyanto, Irwan, Surve, Chinmay R., Suzuki, Tomo, Syme, Caitlin, Sörelius, Karl, Tang, Young, Tantawy, Marwa, Tennakoon, Sumudu, Teseo, Serafino, Toelzer, Christine, Tomov, Nikola, Tovar, Miguel, Tran, Linh, Tripathi, Sushil, Tuladhar, Anil M., Ukubuiwe, Azubuike C., Ung, Carolina O. L., Valgepea, Kaspar, Vatanparast, Hamid, Vidal, Arnau, Wang, Fang, Wang, Qing, Watari, Ricky, Webster, Rebecca, Webster, Ruth, Wei, Junnian, Wibowo, David, Wingenbach, Tanja S. H., Xavier, Rose M., Xiao, Shumin, Xiong, Peng, Xu, Shicai, Xu, Shilin, Yao, Ruifeng, Yao, Wen, Yin, Qinan, Yu, Yongbo, Zaitsu, Masayoshi, Zhan, Xiao-Yong, Zhang, Jilei, Zhang, Rongqiang, Zhang, Wei, Zhang, Xianglilan, Zheng, Shan, Zhou, Bailing, Zhou, Xiaoyan, Ahmad, Haroon, Akinwumi, Sayo A., Albery, Gregory F., Alhowimel, Ahmed, Ali, Junaid, Alshehri, Mansour, Alsuhaibani, Mohammed, Anikin, Andrey, Azubuike, Samuel O., Bach-Mortensen, Anders, Baltiansky, Lior, Bartas, Martin, Belachew, Kiflemariam Y., Bhardwaj, Vivek, Binder, Karin, Bland, Nicholas S., Boah, Michael, Bullen, Benjamin, Calabrò, Giovanna E., Callahan, Tiffany J., Cao, Bing, Chalmers, Kelsey, Chang, Wei, Che, Zhengping, Chen, Andrew T. Y., Chen, Haimin, Chen, Huaming, Chen, Youning, Chen, Zhao, Choi, YoungRok, Chowdhury, Mohiuddin A. K., Christensen, Martin R., Cooke, Robert S. C., Cottini, Marzia, Covington, Natalie V., Cunningham, Catriona, Delarocque, Julien, Devos, Lucie, Dhar, Aurup R., Ding, Ke-Feng, Dong, Kexian, Dong, Zheng, Dreyer, Niklas, Ekstrand, Chelsea, Fardet, Tanguy, Feleke, Berhanu E., Feurer, Thomas, Freitas, Angela, Gao, Tian, Asefa, N. G., Giganti, Francesco, Grabowski, Piotr, Guerra-Mora, José R., Guo, Chengying, Guo, Xinyi, Gupta, Himanshu, He, Shuonan, Heijne, Marloes, Heinemann, Stephanie, Hogrebe, Alexander, Huang, Zhengping, Iskander-Rizk, Sophinese, Iyer, Lavanya M., Jahan, Yasmin, James, Ameh S., Joel, Emmanuel, Joffroy, Bastian, Jégousse, Clara, Kambondo, George, Karnati, Priyanka, Kaya, Cihan, Ke, An, Kelly, Daniel, Kickert, Rob, Kidibule, Peter E., Kieselmann, Jennifer P., Kim, Hyeon J., Kitazawa, Takeshi, Lamberts, Aniek, Li, You, Liang, Huakang, Linn, Sabrina N., Litfin, Thomas, Liusuo, Wang, Lygirou, Vasiliki, Mahato, Ajay K., Mai, Zhi-Ming, Major, Rupert W., Mali, Samira, Mallis, Panagiotis, Mao, Wenzhi, Marvin-Dowle, Katie, Mason, Leanda D., Merideth, Ben, Merino-Plaza, Maria J., Merlaen, Britt, Messina, Rossella, Mishra, Anand K., Muhammad, Junaid, Musinguzi, Conrad, Nanou, Afroditi, Naqash, Amreen, Nguyen, Joe T., Nguyen, Thi T. H., Ni, Duan, Nida, Notcovich, Shirli, Ohst, Barnabas, Ollivier, Quinn R., Osses, Daniël F., Peng, Xiangda, Plantinga, Arnoud, Pulia, Michael, Rafiq, Muhammad, Raman, Ayush, Raucher-Chéné, Delphine, Rawski, Rafał, Ray, Asit, Razak, Lubna A., Rudolf, Kevin, Rusch, Peter, Schmidt, Axel, Schurr, Roey, Searles, Stephen, Sharma, Saurab, Sheehan, Barry, Shi, Chunhu, Shohayeb, Belal, Sommerlad, Andrew, Strehlow, Jan, Sun, Xianbao, Sundar, Raghav, Taherzadeh, Ghazaleh, Tahir, Nur D. M., Tang, Jun, Testa, Jean, Tian, Zhiqi, Tingting, Qian, Verheijen, Geert P., Vickstrom, Casey, Wang, Teng, Wang, Xiaomin, Wang, Zhenxing, Wei, Pan, Wilson, Alex, Wyart, Yassine, Abdul-Amir, Yousefzadeh, Abbas, Zare, Asma, Zeng, Zhen, Zhang, Chengrong, Zhang, Haowen, Zhang, Linxing, Zhang, Tongchuan, Zhang, Weijia, Zhang, Zhe, Zhou, Jianyu, Zhu, Dongjie, Adamo, Vincenzo, Adeyemo, Adebolajo A., Aggelidou, Maria, Al-Owaifeer, Adi M., Al-Riyami, Arwa Z., Alzghari, Saeed K., Andersen, Vibeke, Angus, Kathryn, Asaduzzaman, Muhammad, Asady, Hadi, Ato, Dai, Bai, Xiaoyong, Baines, Rebecca L., Ballantyne, Maghan, Ban, Bo, Beck, Jill, Ben-Nafa, Walid, Black, Emma, Blancher, Antoine, Blankstein, Ron, Bodagh, Neil, Borges, Paulo A. V., Brooks, Anastasia, Brox-Ponce, Josue, Brunetti, Arturo, Canham, Colin D., Carninci, Piero, Carvajal, Richard, Chang, Shun C., Chao, Jie, Chatterjee, Pranab, Chen, He, Chen, Yi-Chun, Chhatriwalla, Adnan K., Chikowe, Ibrahim, Chuang, Trees-Juen, Collevatti, Rosane G., Valera-Cornejo, Diego A., Cuenda, Ana, Dao, Myriam, Dauga, Delphine, Deng, Zaian, Devkota, Kiran, Doan, Lisa V., Elewa, Yaser H. A., Fan, Dongsheng, Faruk, Mohammed, Feifei, Shi, Ferguson, Trevor S., Fleres, Francesco, Foster, Emma J., Foster, C. Stephen, Furer, Tzvi, Gao, Yibo, Garcia-Rivera, Enid J., Gazdar, Adi, George, Ronald B., Ghosh, Sayantan, Gianchecchi, Elena, Gleason, Joshua M., Hackshaw, Allan, Hall, Adam, Hall, Richard, Harper, Paul, Hogg, William E., Huang, Guangqun, Hunter, Kylie E., IJzerman, Adriaan P., Jesus, Carlos, Jian, Gao, Jr, James S. Lewis, Kanj, Souha S., Kaur, Harsheen, Kelly, Shona, Kheir, Fayez, Kichatova, V. S., Kiyani, Musa, Klein, Reinhild, Kovesi, Tom, Kraschnewski, Jennifer L., Kumar, Addanki P., Labutin, Dmitry, Lazo-Langner, Alejandro, Leclercq, Guy, Li, Maoteng, Li, Qingchun, Li, Tangliang, Li, Yongzhe, Liao, Wei-Ting, Liao, Zheng-yin, Lin, Jessica, Lizer, J., Lobreglio, Giambattista, Lowies, Cher, Lu, Cheng, Majeed, Haroon, Martin, Adam, Martinez-Sobrido, Luis, Meresh, Edwin, Middelveen, Marianne, Mohebbi, Alireza, Mota, Jorge, Mozaheb, Zahra, Muyaya, Ley, Nandhakumar, Amar, Ng, Sheryl H. X., Obeidat, Monther, Oh, Deog-Hwan, Owais, Mohammed, Pace-Asciak, Pia, Panwar, Ajay, Park, Caroline, Patterson, Chris, Penagos-Tabaree, Felipe, Pianosi, Paolo T., Pinzi, Valentina, Pridans, Clare, Psaroulaki, Anna, Pujala, Ravi Kumar, Pulido-Arjona, Leonardo, Qi, Peng-Fei, Rahman, Proton, Rai, Nayanjot K., Rassaf, Tienush, Refardt, Julie, Ricciardi, Walter, Riess, Olaf, Rovas, Alexandros, Sacks, Frank M., Saleh, Sherif, Sampson, Christopher, Schmutz, Axel, Sepanski, Robert, Sharma, Neeraj, Singh, Manisha, Spearman, Paul, Subramaniapillai, Mehala, Swali, Ritu, Tan, Cher M., Tellechea, Juan I., Thomas, Lisa-Marie, Tong, Xin, Vavvas, Demetrios G., Veys, Ralf, Vitriol, Veronica, Wang, Horng-Dar, Wang, Jinhui, Wang, Jiucun, Waugh, Jason, Webb, S. A., Williams, Brendan A., Workman, Alan D., Xiang, Tingxiu, Xie, Li-Xin, Xu, Jun, Xu, Taosheng, Yang, Chongjun, Yoon, Jihoon G., Yuan, Christina M., Zaritsky, Arno, Zhang, Yao, Zhao, Haochen, Zuckerman, Hannah, Lyu, Ran, Pullan, Wayne, Zhou, Yaoqi, Gobet, Angélique, Sadoine, Margaux L., Ontwikkelingspsychologie (Psychologie, FMG), British Lung Foundation, Brown, P, Zhou, Y, Tan, A, El-Esawi, M, Liehr, T, Blanck, O, Gladue, D, Almeida, G, Cernava, T, Sorzano, C, Yeung, A, Engel, M, Chandrasekaran, A, Muth, T, Staege, M, Daulatabad, S, Widera, D, Zhang, J, Meule, A, Honjo, K, Pourret, O, Yin, C, Zhang, Z, Cascella, M, Flegel, W, Goodyear, C, van Raaij, M, Bukowy-Bieryllo, Z, Campana, L, Kurniawan, N, Lalaouna, D, Huttner, F, Ammerman, B, Ehret, F, Cobine, P, Tan, E, Han, H, Xia, W, Mccrum, C, Dings, R, Marinello, F, Nilsson, H, Nixon, B, Voskarides, K, Yang, L, Costa, V, Bengtsson-Palme, J, Bradshaw, W, Grimm, D, Kumar, N, Martis, E, Prieto, D, Sabnis, S, Amer, S, Liew, A, Perco, P, Rahimi, F, Riva, G, Zhang, C, Devkota, H, Ogami, K, Basharat, Z, Fierz, W, Siebers, R, Tan, K, Boehme, K, Brenneisen, P, Brown, J, Dalrymple, B, Harvey, D, Ng, G, Werten, S, Bleackley, M, Dai, Z, Dhariwal, R, Gelfer, Y, Hartmann, M, Miotla, P, Tamaian, R, Govender, P, Gurney-Champion, O, Kauppila, J, Zhang, X, Echeverria, N, Subhash, S, Sallmon, H, Tofani, M, Bae, T, Bosch, O, Cuiv, P, Danchin, A, Diouf, B, Eerola, T, Evangelou, E, Filipp, F, Klump, H, Kurgan, L, Smith, S, Terrier, O, Tuttle, N, Ascher, D, Janga, S, Schulte, L, Becker, D, Browngardt, C, Bush, S, Gaullier, G, Ide, K, Meseko, C, Werner, G, Zaucha, J, Al-Farha, A, Greenwald, N, Popoola, S, Rahman, S, Xu, J, Yang, S, Hiroi, N, Alper, O, Baker, C, Bitzer, M, Chacko, G, Debrabant, B, Dixon, R, Forano, E, Gilliham, M, Kelly, S, Klempnauer, K, Lidbury, B, Lin, M, Lynch, I, Ma, W, Maibach, E, Mather, D, Nandakumar, K, Ohgami, R, Parchi, P, Tressoldi, P, Xue, Y, Armitage, C, Barraud, P, Chatzitheochari, S, Coelho, L, Diao, J, 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Liegbig Univ, EBI, Max Planck Inst Marine Microbiol, Max Planck Inst Human Dev, King Faisal Univ, Iowa State Univ, Delft Univ Technol, Shinko Mem Hosp, James Madison Univ, Univ Hosp Ulm, Univ Essex, Alpha Altis, Fed Univ Oye, Helsinki Univ Hosp, Univ Aveiro, Univ Botswana, Universidade Federal da Bahia (UFBA), Queen Mary Univ London, Natl Univ Pharm, Univ Bolton, Gen Hosp Northern Theater Command, Doctors Hosp, Hannover Med Sch, Iran Univ Sci & Technol, Khalifa Univ Sci & Technol, Shaoxing Peoples Hosp, AIIMS, Tokyo Med Univ, Univ Hosp Zurich, Univ Maryland, Stellenbosch Univ, China Agr Univ, Osaka Univ, Univ Washington, Natl Res Council Italy, Charles Sturt Univ, Shantou Univ, Shanxi Univ, Georgia Inst Technol, XtalPi Inc, Consejo Nacl Invest Cient & Tecn, Jinan Univ, Univ Texas Hlth Sci Ctr Houston, Weill Cornell Med, Guangdong Inst Appl Biol Resources, Shandong Normal Univ, South China Agr Univ, Liaoning Acad Agr Sci, Lawson Hlth Res Inst, Univ Canberra, Emory Univ, Nottingham Trent Univ, Univ Exeter, Hillingdon Hosp NHS Fdn Trust, Natl & Kapodistrian Univ Athens, Lausanne Univ Hosp, Queens Univ Belfast, Cold Spring Harbor Lab, Hosp Clin Porto Alegre, Univ Paris 05, Indian Inst Adv Res, Bambino Ges Childrens Res Hosp, Univ Cadiz, Mansoura Univ Hosp, Ctr Expertise & Biol Diagnost Cameroon, Swiss Fed Labs Mat Sci & Technol, Assiut Univ, Univ Derby, SUNY Stony Brook, Walter & Eliza Hall Inst Med Res, Janelia Res Campus, USDA ARS, Med Univ Graz, Ajou Univ, Univ Dundee, Tech Univ Dresden, Natl Univ Hlth Syst, Univ Canterbury, Univ Hosp Southern Denmark, Baylor Coll Med, Adnan Menderes Univ Aydin, Oasi Res Inst IRCCS, LSHTM, Leibniz Univ Hannover, Xi An Jiao Tong Univ, Shenzhen Univ, Cent South Univ, Univ Bridgeport, Texas Tech Univ, Univ Montana, NHLBI, Cleveland Clin, NARO, Eduardo Mondlane Univ, RAS, Beijing Inst Technol, Univ Hlth Network, Univ Bath, Fisheries & Oceans Canada, Queensland Govt, Uppsala Univ, Childrens Canc Hosp, Leibniz Inst Nat Prod Res & Infect Biol, Duy Tan Univ, Henan Agr Univ, Beijing Inst Microbiol & Epidemiol, Minist Hlth, Prince Sattam Bin Abdulaziz Univ, Univ Auckland, Osped Niguarda Ca Granda, Univ Vet Med, Univ Saskatchewan, Univ Coimbra, South Cent High Specialty Hosp, Wageningen Bioveterinary Res, Guangdong Second Prov Gen Hosp, Hiroshima Univ, Univ Iceland, Kathmandu Univ, Fraunhofer MEVIS, Univ Tehran Med Sci, Univ Messina, AO Papardo Hosp Messina, Univ Stirling, Saveh Univ Med Sci, Gakujutsu Shien Co Ltd, Univ Plymouth, CHU Toulouse, Azorean Biodivers Grp, Univ Acores, Univ Malawi, Bioself Commun, Ahmadu Bello Univ, Dalhousie Univ, VisMederi Srl, Amer Univ Beirut, Mechnikov Res Inst Vaccines & Sera, Vreden Russian Res Inst Traumatol & Orthopaed, Hangzhou Ctr Dis Control & Prevent, Kaohsiung Med Univ, Zoetis, Aintree Univ Hosp NHS Fdn Trust, Wrightington Hosp, Loyola Univ, Atkins Vet Serv, Kangwon Natl Univ, Kakatiya Med Coll, Univ Antioquia, IISER, Univ Rosario, Univ Hosp Basel, Univ Hosp Munster, Univ Kentucky, Univ Calif Irvine, Univ Hosp Leuven, Chongqing Med Univ, Childrens Hosp Kings Daughters, China Three Gorges Univ, and Xiangtan Univ

Subjects
Technology and Engineering, SCIENTIFIC SEARCH, Expert-curated database, Biokemia, solu- ja molekyylibiologia - Biochemistry, cell and molecular biology, Databases, RElevant LIterature SearcH consortium, Medicine and Health Sciences, Biomedical research, benchmarking, Biology, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Settore MED/42 - IGIENE GENERALE E APPLICATA, database, Computer. Automation, Science & Technology, 0804 Data Format, relisch, Scientific research in health sciences, Mathematics and Statistics, litearture search, relisch , database, biomedical research, Biomedical literature, Original Article, RELISH, Mathematical & Computational Biology, RECOMMENDER-SYSTEMS, Life Sciences & Biomedicine, Mathematics, 0807 Library and Information Studies
Abstract

Made available in DSpace on 2020-12-11T01:57:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-10-29 Griffith University Gowonda HPC Cluster Queensland Cyber Infrastructure Foundation Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research. Griffith Univ, Sch Informat & Commun Technol, Gold Coast, Qld 4222, Australia Griffith Univ, Inst Glyc, Gold Coast, Qld 4222, Australia Univ Colorado, Dept Med Med Oncol, Anschutz Med Campus, Denver, CO USA Tanta Univ, Fac Sci, Bot Dept, Tanta, Egypt Friedrich Schiller Univ, Jena Univ Hosp, Inst Human Genet, Jena, Germany Univ Med Ctr Schleswig Holstein, Dept Radiat Oncol, Campus Kiel, Kiel, Germany ARS, USDA, Plum Isl Anim Dis Ctr, Greenport, NY 11944 USA Univ Jyvaskyla, Dept Biol & Environm Sci, Jyvaskyla, Finland Graz Univ Technol, Inst Environm Biotechnol, Graz, Austria CSIC, CNB, Natl Biotechnol Ctr, Dept Macromol Struct, Madrid, Spain Univ Hong Kong, Fac Dent, Oral & Maxillofacial Radiol Appl Oral Sci & Commu, Hong Kong, Peoples R China Univ Kansas, Div Entomol, Biodivers Inst, Lawrence, KS 66045 USA SUNY Albany, RNA Inst, Albany, NY 12222 USA Robert Koch Inst, Dept Methods Dev & Res Infrastruct, Berlin, Germany Martin Luther Univ Halle Wittenberg, Dept Surg & Conservat Pediat & Adolescent Med, Halle, Germany Indiana Univ Purdue Univ, IU Sch Informat & Comp, Dept BioHlth Informat, Indianapolis, IN 46202 USA Univ Reading, Sch Pharm Stem Cell Biol & Regenerat Med, Reading, Berks, England Dali Univ, Sch Engn, Dali City, Yunnan, Peoples R China Univ Hosp Munich LMU, Dept Psychiat & Psychotherapy, Munich, Germany Univ Tsukuba, Fac Life & Environm Sci, Ibaraki, Japan UniLaSalle, Aghyle, Beauvais, France Henry Ford Hlth Syst, Dept Immunol, Detroit, MI USA Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Emergency, Hangzhou 310016, Zhejiang, Peoples R China Ist Nazl Tumori Fdn Pascale IRCCS, Anesthesia & Pain Med, Naples, Italy NIH, Dept Transfus Med, Bethesda, MD USA Univ Glasgow, Inst Infect Immun & Inflammat, Glasgow, Lanark, Scotland Polish Acad Sci, Inst Human Genet, Poznan, Poland Univ Padua, Dept Surg Oncol & Gastroenterol DISCOG, Padua, Italy Eindhoven Univ Technol, Biomed Engn, Eindhoven, Netherlands Univ Strasbourg, IBMC, Strasbourg, France Heidelberg Univ, Dept Gen Visceral & Transplantat Surg, Heidelberg, Germany Univ Notre Dame, Psychol, Notre Dame, IN 46556 USA Harvard Med Sch, Massachusetts Gen Hosp, Radiol & Pathol, Boston, MA 02115 USA Auburn Univ, Dept Biol Sci, Auburn, AL 36849 USA KK Womens & Childrens Hosp, KK Res Ctr, Singapore, Singapore Univ Alabama, Educ Psychol, Tuscaloosa, AL USA UCL, Wellcome EPSRC Ctr Intervent & Surg Sci, London, England Maastricht Univ, Dept Nutr & Movement Sci, Maastricht, Netherlands Univ Arkansas Med Sci, Dept Radiat Oncol, Little Rock, AR 72205 USA Univ Padua, Dept Land Environm Agr & Forestry, Padua, Italy Univ Gothenburg, Dept Biol & Environm Sci, Gothenburg, Sweden Univ Newcastle, Prior Res Ctr Reprod Sci, Callaghan, NSW, Australia Univ Cyprus, Med Sch, Nicosia, Cyprus Shandong Agr Univ, Coll Plant Protect, Agr Big Data Res Ctr, Tai An, Shandong, Peoples R China NIMH, Neuropsychol Lab, Bldg 9, Bethesda, MD 20892 USA Univ Wisconsin, Wisconsin Inst Discovery, Madison, WI USA Univ Oxford, 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Ramnicu Valcea, VL, Romania Univ KwaZulu Natal, Occupat Therapy, Westville Campus, Durban, South Africa Inst Canc Res, Joint Dept Phys, London, England Karolinska Inst, Dept Mol Med & Surg, Solna, Sweden Wenzhou Med Univ, Affiliated Hosp 2, Orthopaed, Wenzhou, Zhejiang, Peoples R China Univ Republica, Fac Ciencias, Ctr Invest Nucl, Lab Virol Mol, Montevideo, Uruguay Univ Gothenburg, Dept Med Biochem & Cell Biol, Gothenburg, Sweden Charite Med Univ Berlin, Pediat Cardiol, Berlin, Germany Bambino Gesu Pediat Hosp, Dept Neurosci & Neurorehabil, Neurorehabil Unit, Rome, Italy Indiana Univ Sch Med Northwest, Microbiol & Immunol, Gary, IN USA Univ Regensburg, Dept Behav & Mol Neurobiol, Regensburg, Germany Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia Translat Res Inst, Brisbane, Qld, Australia Univ Hong Kong, Sch Biomed Sci, Hong Kong, Peoples R China St Jude Childrens Res Hosp, Pharmaceut Sci Dept, 332 N Lauderdale St, Memphis, TN 38105 USA Univ Durham, Mus, Durham, England Univ Ioannina, Med Sch, Dept Hyg & Epidemiol, Ioannina, Greece Tech Univ Munich, Sch Life Sci Weihenstephan, Maximus von Imhof Forum 3, D-85354 Freising Weihenstephan, Germany Univ Hosp Essen, Inst Transfus Med, Essen, Germany Virginia Commonwealth Univ, Comp Sci, Richmond, VA USA Univ Queensland, Inst Social Sci Res, Brisbane, Qld, Australia Univ Lyon, Ctr Int Rech Infectiol, Lyon, France Griffith Univ, Sch Allied Hlth Sci, Gold Coast, Qld, Australia Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic, Australia Indiana Univ Purdue Univ, Dept Biohlth Informat, Sch Informat & Comp, Indianapolis, IN 46202 USA Philipps Univ Marburg, Inst Lung Res, Marburg, Germany Indiana Univ, Dept Biol, Bloomington, IN USA Univ Florida, Oral Biol, Gainesville, FL USA Univ Colorado, Dept Biochem, Boulder, CO 80309 USA Kyoto Univ, Ctr Promot Interdisciplinary Educ & Res, Kyoto, Japan Friedrich Loeffler Inst, Inst Virus Diagnost, Greifswald, Germany Univ Oxford, Dept Zool, Oxford, England Tech Univ Munich, Dept Bioinformat, Munich, Germany Univ Adelaide, Sch Anim & Vet Sci, Adelaide, SA, Australia Stanford Univ, Canc Biol, Palo Alto, CA 94304 USA Covenant Univ, Dept Elect & Informat Engn, Ota, Nigeria Heinrich Heine Univ, Inst Stem Cell Res & Regenerat Med, Dusseldorf, Germany Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC, Canada Albert Einstein Coll Med, Psychiat, New York, NY USA Akdeniz Univ, Med Biol & Genet, Antalya, Turkey NIMH, NIH, Bethesda, MD 20892 USA Med Univ Hosp, Internal Med 1, Tubingen, Germany NET ESolut, Netelabs, Mclean, VA USA Univ Southern Denmark, Inst Publ Hlth, Odense, Denmark John Innes Ctr, Mol Microbiol, Norwich, Norfolk, England Univ Adelaide, Waite Res Precinct, Australian Res Council, Ctr Excellence Plant Energy Biol, Adelaide, SA, Australia Univ Cambridge, Cambridge Inst Publ Hlth, Cambridge, England Univ Munster, Inst Biochem, Munster, Germany Australian Natl Univ, Natl Ctr Epidemiol & Populat Hlth RSPH, Canberra, ACT, Australia Stanford Univ, Neurobiol & Bioengn, Palo Alto, CA 94304 USA Univ Birmingham, Geog Earth & Environm Sci, Birmingham, W Midlands, England Murdoch Univ, Sch Vet & Life Sci, Perth, WA, Australia George Mason Univ, Ctr Climate Change Commun, Fairfax, VA 22030 USA Univ Adelaide, Sch Agr Food & Wine, Adelaide, SA, Australia Southern Med Univ, Sch Pharmaceut Sci, Guangzhou, Guangdong, Peoples R China Stanford Univ, Pathol, Palo Alto, CA 94304 USA Univ Bologna, Dept Expt Diagnost & Specialty Med, Bologna, Italy Univ Padua, Dept Gen Psychol, Padua, Italy Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Dept Bioinformat & Syst Biol, Key Lab Mol Biophys,Minist Educ, Wuhan, Hubei, Peoples R China Huazhong Univ Sci & Technol, Collaborat Innovat Ctr Biomed Engn, Wuhan, Hubei, Peoples R China Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld, Australia French Natl Ctr Sci Res, CNRS, Inst Biol Physicochim, Paris, France Univ Warwick, Dept Sociol, Coventry, W Midlands, England European Mol Biol Lab, Struct & Computat Biol, Heidelberg, Germany Univ Cincinnati, Coll Med, Canc Biol, Cincinnati, OH USA Univ Waterloo, Biol, Waterloo, ON, Canada Sorbonne Univ, CNRS, Integrat Biol Marine Models LBI2M, SBR, Roscoff, France Univ Manitoba, Biochem & Med Genet, Winnipeg, MB, Canada Max Planck Inst Solid State Res, Ultrafast Solid State Spect, Stuttgart, Germany Imperial Coll London, Sch Publ Hlth, Dept Infect Dis Epidemiol, London, England Mansoura Univ, Fac Vet Med, Biochem, Mansoura, Egypt Univ Virginia, Mol Physiol & Biol Phys, Charlottesville, VA USA China Univ Geosci, State Key Lab Biogeol & Environm Geol, Wuhan, Hubei, Peoples R China Clin Neurol & Psychiat Children & Youth, Child Psychiat, Belgrade, Serbia Ahvaz Jundishapur Univ Med Sci, Med Phys, Ahwaz, Iran Univ Iowa City, Coll Dent, Div Biostat & Computat Biol, Dept Prevent & Community Dent, Iowa City, IA USA Univ Iowa City, Coll Dent, Div Biostat & Computat Biol, Dept Biomed Engn, Iowa City, IA USA Univ Iowa City, Coll Dent, Div Biostat & Computat Biol, Dept Biostat, Iowa City, IA USA Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany Univ Ibadan, Dept Zool, Ibadan, Nigeria Kansas State Univ, Coll Vet Med, Manhattan, KS 66506 USA Univ Tasmania, Sch Technol Environm & Design, Discipline ICT, Hobart, Tas, Australia Childrens Mercy Hosp, Radiol, Kansas City, MO 64108 USA Stockholm Univ, Dept Phys, Stockholm, Sweden Oslo Univ Hosp, Inst Canc Genet & Informat, Oslo, Norway CSIRO, CSIRO Mfg, Pullenvale, Qld, Australia Johns Hopkins Sch Med, Urol, Baltimore, MD USA Univ South Africa, Life & Consumer Sci, Johannesburg, South Africa German Ctr Neurodegenerat Dis, Mech Induced Plast Brain, Bonn, Germany UCL, Inst Child Hlth, Dev Biol & Canc, London, England Simon Fraser Univ, Biomed Physiol & Kinesiol, Burnaby, BC, Canada Univ Manchester, Ctr Hlth Informat, Manchester, Lancs, England Univ Queensland, Sch Human Movement & Nutr Sci, Brisbane, Qld, Australia Albert Einstein Coll Med, Dept Med, New York, NY USA Georgetown Univ, Kennedy Inst Eth, Washington, DC 20057 USA Dermatol Skin & Canc Fdn, Carlton, Vic, Australia Med Coll Wisconsin, Div Hematol, Milwaukee, WI 53226 USA Med Coll Wisconsin, Div Oncol, Milwaukee, WI 53226 USA Med Coll Wisconsin, Div Infect Dis, Milwaukee, WI 53226 USA US FDA, Off Biotechnol Prod, Washington, DC 20204 USA Worcester Polytech Inst, Biomed Engn, Worcester, MA 01609 USA Univ Adelaide, Ctr Orthopaed & Trauma Res, Adelaide, SA, Australia Publ Hlth England, Natl Infect Serv, Bristol, Avon, England Univ Utrecht, Fac Sci Chem, Utrecht, Netherlands Natl Univ Ireland Galway, Pathol, Galway, Ireland Imperial Coll London, NHLI, London, England Danube Private Univ, Neurodegenerat, Krems Donau, Austria Imperial Coll London, Dept Chem, London, England Univ Helsinki, Finnish Museum Nat Hist, Helsinki, Finland Univ Sydney, Sch Life & Environm Sci, Sydney, NSW, Australia Univ Nottingham, Nottingham Digest Dis Ctr, Nottingham, England Univ Toulouse, CNRS, ITAV, USR3505, Toulouse, France ASCR, Inst Mol Genet, CZ Openscreen, Prague, Czech Republic Univ Turku, Inst Biomed, Turku, Finland York Univ, Sch Kinesiol & Hlth Sci, Toronto, ON, Canada Univ Calif Los Angeles, Stein Eye Inst, Ophthalmol, Los Angeles, CA USA Agr & Agri Food Canada, Ottawa Res & Dev Ctr, Ottawa, ON, Canada Helmholtz Zentrum Geesthacht, Mat Design & Characterizat, Geesthacht, Germany Unvers Genova, Internal Med, Genoa, Italy Otto von Guericke Univ, Intelligent Catheter INKS, Magdeburg, Germany Univ Toledo, Canc Biol, 2801 W Bancroft St,Hlth Sci Campus, Toledo, OH 43606 USA CRUK Beatson Inst, Struct Biol, Glasgow, Lanark, Scotland Leibniz Inst Primate Res, Med RNA Biol, Gottingen, Germany Univ Limoges, PEIRENE, EA 7500, Limoges, France Hainan Univ, Vet Med, Haikou, Hainan, Peoples R China UCL, Sch Pharam, Pharmacognosy & Phytotherapy, London, England Univ Oulu, Ecol & Genet Res Unit, Oulu, Finland Rhein Westfal TH Aachen, Inst Biochem & Mol Immunol, Aachen, Germany Univ Stuttgart, Inst Biochem & Tech Biochem, Stuttgart, Germany Peking Univ, Shenzhen Grad Sch, Sch Chem Biol & Biotechnol, Shenzhen, Peoples R China GIGA Res Inst, Med Oncol, Liege, Belgium CHULiege, Liege, Belgium Fdn Bruno Kessler, MPBA, Trento, Italy Hokkaido Univ, Grad Sch Med, Dept Neurobiol, Sapporo, Hokkaido, Japan Univ Leuven, Oncol, Leuven, Belgium Chalmers Univ Technol, Dept Math Sci, Gothenburg, Sweden Radboud Univ Nijmegen, Med Ctr, Dept Neurol, Nijmegen, Netherlands Univ South Australia, Sch Informat Technol & Math Sci, Adelaide, SA, Australia Bio Thera Solut Ltd, Dept Computat Biol, Guangzhou, Guangdong, Peoples R China Inst Invest Biosanitario Granada IBS, Otolaryngol, Granada, Spain Curtin Univ, Sch Mol & Life Sci, Perth, WA, Australia Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England Goethe Univ, Biol DCAL, Inst Pharm, Frankfurt, Germany Univ Lyon, ICBMS, UMR 5246, Lyon, France Inst Pasteur, Dept Genomes & Genet, Paris, France Univ Valencia, Pharmacol, Valencia, Spain Council Agr Res & Econ, Res Ctr Olive Citrus & Tree Fruit, Caserta, Italy Fraunhofer Inst Toxicol & Expt Med ITEM, Preclin Pharmacol & Vitro Toxicol, Hannover, Germany Univ Tasmania, Sch Med, Hobart, Tas, Australia Chugai Pharmaceut Co Ltd, Oncol Lifecycle Management Dept, Tokyo, Japan Univ Lubeck, Inst Neurobiol, Lubeck, Germany NYU, Sch Med, Neurol, New York, NY USA Univ Putra Malaysia, Dept Plant Pathol, Seri Kembangan, Malaysia Univ N Carolina, Biol, Chapel Hill, NC 27515 USA Univ Southampton, Fac Hlth Sci, Southampton, Hants, England Univ Highlands & Islands, Genet & Immunol Res Grp, Inverness, Scotland Heidelberg Univ, Inst Pathol, Heidelberg, Germany Indraprastha Inst Informat Technol, Dept Computat Biol, New Delhi, India Glasgow Caledonian Univ, Sch Hlth & Life Sci, Glasgow, Lanark, Scotland Liverpool John Moores Univ, Pharm & Biomol Sci, Liverpool, Merseyside, England Parkinsons Inst & Clin Ctr, Basic Res, Sunnyvale, CA USA Luxembourg Inst Sci & Technol, Environm Res & 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Kansas, Med Ctr, Family Med Res Div, Kansas City, KS 66103 USA ASTAR, Inst Mol & Cell Biol, Multimodal Mol Biol, Singapore, Singapore Univ Leuven, Dept Chron Dis Metab & Ageing, Leuven, Belgium Int Iberian Nanotechnol Lab INL, Braga, Portugal Anglia Ruskin, Comp & Technol, Cambridge, England Max Planck Inst Biochem, Struct Cell Biol, Planegg, Germany Univ Seville, Dept Comp Architecture & Technol, Seville, Spain Univ Colorado, EBIO, Boulder, CO 80309 USA Univ Manchester, Canc Sci, Manchester, Lancs, England Australian Natl Univ, Res Sch Populat Hlth, Canberra, ACT, Australia Singapore MIT Alliance Res & Technol, Biosyst, Singapore, Singapore Australian Catholic Univ, Mary MacKillop Inst Hlth Res, Musculoskeletal Hlth & Ageing Res Program, Melbourne, Vic, Australia Ruhr Univ Bochum, Gen Surg, St Josef Hosp, Bochum, Germany Northwest A&F Univ, Coll Life Sci, Xianyang, Shaanxi, Peoples R China Australian Natl Univ, Res Sch Biol, Div Plant Sci, Canberra, ACT, Australia Battelle Mem Inst, Clin & Nonclin Res, Columbus, OH USA Southern Methodist Univ, Biol Sci, Dallas, TX 75275 USA Teikyo Univ, Inst Med Mycol, Tokyo, Japan Tempus Labs, Bioinformat, Chicago, IL USA Hunan Univ, Coll Biol, Changsha, Hunan, Peoples R China Inst Cochin, Dept Infect Immun & Inflammat, Paris, France Royal Coll Surgeons Ireland, FutureNeuro Res Ctr Physiol & Med Phys, Dublin, Ireland Univ Jyvaskyla, Gerontol Res Ctr, Jyvaskyla, Finland Heidelberg Univ, Dept Anesthesiol, Heidelberg, Germany Penn State Univ, Biol, University Pk, PA 16802 USA Chinese Acad Sci, Inst Microbiol, State Key Lab Microbial Resources, Beijing, Peoples R China Univ Sci & Technol China, Sch Life Sci, Hefei, Anhui, Peoples R China Michigan State Univ, Anim Sci, E Lansing, MI 48824 USA SUNY Buffalo, Jacobs Sch Med & Biomed Sci, Dept Neurol, Buffalo Neuroimaging Anal Ctr, New York, NY USA Univ Rostock, Inst Biol Sci, Rostock, Germany South China Normal Univ, Sch Environm, Environm Res Inst, Guangzhou, Guangdong, Peoples R China Univ Bari, Dept Vet Med, Bari, Italy Radboud Univ Nijmegen, Med Ctr, Primary & Community Care, Nijmegen, Netherlands EcoHlth Alliance, New York, NY USA Mayo Clin, Cardiovasc Dept, Rochester, MN USA Med Univ Silesia, Sch Med Katowice, Dept Epidemiol, Katowice, Poland Univ Lleida, Anim Sci, Lleida, Spain Univ Florida, Coll Pharm, Pharmaceut Outcomes & Policy, Gainesville, FL USA Pacific Northwest Natl Lab, Earth & Biol Sci Directorate, Richland, WA 99352 USA Univ Edinburgh, Ctr Discovery Brain Sci, Edinburgh, Midlothian, Scotland Harvard Med Sch, Dept Biomed Informat, Boston, MA 02115 USA Univ Penn, Radiol, Philadelphia, PA 19104 USA Humanitas Univ & Res Hosp, Asthma & Allergy Unit, Biomed Sci Personalized Med, Rozzano, Italy Australian Natl Univ, Dept Quantum Sci, Canberra, ACT, Australia Carl von Ossietzky Univ Oldenburg, Ecol Genom, Oldenburg, Germany Int Med Univ, Paediat Dent & Orthodont, Kuala Lumpur, Malaysia Univ Ottawa, Sch Nursing, Ottawa, ON, Canada Maastricht Univ, Dept Educ Support, Maastricht, Netherlands Univ Manchester, Math, Manchester, Lancs, England Kings Coll London, Fac Life Sci & Med, Sch Populat Hlth Sci, London, England Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia Harbin Med Univ, Publ Hlth Sch, Epidemiol, Harbin, Heilongjiang, Peoples R China UiT Arctic Univ Norway, Dept Chem, Tromso, Norway Cornell Univ, Biol Stat & Computat Biol, Ithaca, NY USA East China Normal Univ, Sch Ecol & Environm Sci, Shanghai Key Lab Urban Ecol Proc & Ecorestorat, Shanghai, Peoples R China Johannes Gutenberg Univ Mainz, Fac Biol, Mainz, Germany Univ Massachusetts, Food Sci, Amherst, MA 01003 USA Max Planck Inst Terr Microbiol, Complex Adapt Traits Res Grp, Marburg, Germany NIHR Biomed Res Ctr Resp, Ctr Exercise & Rehabil Sci, Leicester, Leics, England Yale Univ, Dept Internal Med, Sect Endocrinol, New Haven, CT USA Sardar Patel Univ, Dept Biosci, Anand, Gujarat, India Univ Tokyo, Dept Appl Phys, Tokyo, Japan Univ Cologne, Vivo Res Facil ivRF, Cologne Excellence Cluster Cellular Stress Respon, Cologne, Germany Natl Open Univ Nigeria, Dept Publ Hlth Sci, Lagos, Nigeria Univ Hosp Regensburg, Dept Radiol, Regensburg, Germany Natl Univ Singapore, Geog, Singapore, Singapore Alfaisal Univ, Coll Med, Riyadh, Saudi Arabia Abdelmalek Essaadi Univ, Fac Sci & Techn Tangier, Biomed Genom & Oncogenet Res Lab, Tetouan, Morocco Tech Univ Munich, Fac Sport & Hlth Sci, Exercise Biol Grp, Munich, Germany Univ Santiago de Compostela, Dept Psicoloxia Social Basica & Metodoloxia, Galiza, Spain Griffith Univ, Signal Proc Lab, Brisbane, Qld, Australia Univ Ghent, Dept Neurol, Ghent, Belgium Ghent Univ Hosp, Ghent, Belgium Univ Ghent, Fac Vet Med, Merelbeke, Belgium Albert Einstein Coll Med, Inst Clin & Translat Res, New York, NY USA Anglia Ruskin Univ, Fac Med Sci, Cambridge, England Peking Univ, Coll Chem & Mol Engn, Beijing, Peoples R China Herlev & Gentofte Hosp, Dept Dermatol & Allergy, Hellerup, Denmark Lady Cilento Childrens Hosp, Med Imaging & Nucl Med, Brisbane, Qld, Australia Univ Gambia, Sch Med & Allied Hlth Sci, Nursing & Reprod Hlth, Brikama, Gambia Univ Sydney, Woolcock Inst Med Res, Sydney, NSW, Australia Wayne State Univ, Comp Sci, Detroit, MI USA Aberdeen Royal Infirm, Otolaryngol, Aberdeen, Scotland Univ Toronto, Lab Med & Pathobiol, Toronto, ON, Canada Chinese Univ Hong Kong, Inst Ageing, Hong Kong, Peoples R China Univ Nebraska Med Ctr, Emergency Med, Omaha, NE USA Univ Florida, Coll Med, Pathol, Gainesville, FL USA Univ Texas MD Anderson Canc Ctr, Radiat Oncol, Houston, TX 77030 USA Univ Pisa, Translat Res NTMS, Pisa, Italy Magna Grecia Univ, Clin & Expt Med, Catanzaro, Italy Univ Vermont, Larner Coll Med, Pediat, Burlington, VT USA Sun Yat Sen Univ, Canc Ctr, Diagnost & Intervent Ultrasound, Guangzhou, Guangdong, Peoples R China Fudan Univ, Inst Brain Sci, Shanghai, Peoples R China Shanxi Agr Univ, Coll Agron, Jinzhong, Shanxi, Peoples R China Univ Toronto, Inst Med Sci, Toronto, ON, Canada Univ Adelaide, ARCPOH, Adelaide, SA, Australia Pelita Harapan Univ, Fac Med, Cardiol & Vasc Med, Tangerang, Indonesia Inst Mental Hlth, Res Div, Singapore, Singapore UCL, MRC Clin Trials Unit, London, England Univ Padua, Dept Philosophy Sociol Educ & Appl Psychol FISPPA, Padua, Italy Univ Lubeck, Dept Psychiat & Psychotherapy, Lubeck, Germany Dalian Univ Technol, Ctr Mol Med, Dalian, Liaoning, Peoples R China Tianjin United Family Healthcare, Reprod Med, Tianjin, Peoples R China Univ Autonoma Barcelona, Dept Engn Quim Biol & Ambiental, Barcelona, Spain Sao Paulo State Univ UNESP, Dept Anim Sci, Sao Paulo, Brazil Helmholtz Zentrum Munchen, Inst Computat Biol, Canc Syst Biol, Ingolstadter Land Str 1, D-85764 Munich, Germany Univ Tokyo, Dept Cardiovasc Med, Tokyo, Japan Sao Paulo State Univ, Vet Clin, Sao Paulo, Brazil Zhejiang Univ, Inst Biotechnol, Hangzhou, Zhejiang, Peoples R China Aarhus Univ, Dept Mol Biol & Genet, Aarhus, Denmark Univ Manchester, St Marys Hosp, Maternal & Fetal Hlth, Manchester, Lancs, England Univ New Mexico, Internal Med, Albuquerque, NM 87131 USA Mayo Clin, Div Biomed Stat & Informat, Jacksonville, FL 32224 USA King Saud Univ, Plant Prod, Riyadh, Saudi Arabia Polish Acad Sci, Inst Genet & Anim Breeding, Dept Mol Biol, Warsaw, Poland Queensland Univ Technol, Optometry & Vis Sci, Brisbane, Qld, Australia Univ Nottingham, Sch Life Sci, Nottingham, England Canc Council Queensland, Canc Res Ctr, Brisbane, Qld, Australia Umea Univ, Dept Chem, Umea, Sweden Publ Hlth England, Ctr Radiat Chem & Environm Hazards, Bristol, Avon, England Univ Campania L Vanvitelli, DISTABIF, Caserta, Italy Bartshealth, Obstet & Gyanecol, London, England Univ Clermont Auvergne, GReD Lab, Clermont Ferrand, France INRA Abeilles & Environm, Avignon, France Queensland Univ Technol, Sch Publ Hlth & Social Work, Brisbane, Qld, Australia Univ Penn, Psychiat, Philadelphia, PA 19104 USA Novosibirsk State Univ, Res Inst Physiol & Basic Med, Novosibirsk, Russia UCL, Dept Chem, London, England La Trobe Univ, Anim Plant & Soil Sci, Melbourne, Vic, Australia Univ Arizona, Epidemiol & Biostat, Tucson, AZ USA Univ Groningen, Univ Med Ctr Groningen, ERIBA, Groningen, Netherlands Univ Gothenburg, Inst Clin Sci, Dept Radiat Phys, Gothenburg, Sweden SUNY Upstate Med Univ, Biochem & Mol Biol, Syracuse, NY 13210 USA Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, Salvador, Bahia, Brazil Inst Environm Sci & Res ESR, Food Water & Environm Microbiol, Christchurch, New Zealand Univ Otago, Food Sci, Dunedin, New Zealand Florida Atlantic Univ, Biomed Sci, Boca Raton, FL 33431 USA Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia Univ Hosp Wurzburg, Inst Clin Neurobiol, Wurzburg, Germany Inst Trop Med, Publ Hlth, Antwerp, Belgium Univ Thessaly, Sch Hlth Sci, Fac Med, Dept Rheumatol & Clin Immunol, Larisa, Greece Univ Basel, UZB Univ Ctr Dent Med, Dept Orthodont & Pediat Dent, Basel, Switzerland Sorbonne Univ, Museum Natl Hist Nat, Inst Systemat Evolut Biodiversite ISYEB, MNHN,CNRS,UMR 7205,EPHE, Paris, France CNRS, Inst Adv Biosci, Paris, France Univ Western Australia, Sch Mol Sci, Perth, WA, Australia Univ Ft Hare, Biochem & Microbiol, Alice, South Africa Univ Tubingen, Phys, Tubingen, Germany Griffith Univ, Sch Environm & Sci, Brisbane, Qld, Australia Philosoph Theol Hsch Vallendar, Stat & Standardised Methods, Vallendar, Germany Imperial Coll London, Life Sci, London, England Univ Adelaide, Adelaide Med Sch, Adelaide, SA, Australia Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE USA Technol Univ Dublin, FOCAS Res Inst, Dublin, Ireland INSERM, Natl Inst Hlth & Med Res, Canc Res Ctr Toulouse, Paris, France Univ Santiago de Compostela, Dept Bioloxia Func, Grp BRAINSHARK, Galiza, Spain Univ Nebraska, Biol, Kearney, NE USA Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona, Spain Univ Pisa, Chem & Ind Chem, Pisa, Italy Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Manchester, Lancs, England Univ Montpellier, CNRS, Inst Human Genet, Montpellier, France Czech Acad Sci, Inst Organ Chem & Biochem, Prague, Czech Republic CSIC, Natl Ctr Biotechnol CNB, Computat Syst Biol Grp, Madrid, Spain Natl Cheng Kung Univ, Dept Biochem & Mol Biol, Tainan, Taiwan Harvard Med Sch, Schepens Eye Res Inst, Ophthalmol, Boston, MA 02115 USA Lanzhou Univ, Hosp 2, Dept Gen Surg, Lanzhou, Gansu, Peoples R China Univ Technol Sydney, Sch Life Sci, Sydney, NSW, Australia JT Chen Clin, Gynecol, Tokyo, Japan Univ Western Australia, Sch Agr & Environm, Perth, WA, Australia Beijing Normal Univ, Fac Geog Sci, Beijing, Peoples R China Univ Missouri, Elect Engn & Comp Sci, Columbia, MO USA Vrije Univ Amsterdam Med Ctr, Amsterdam Publ Hlth Res Inst, Dept Publ & Occupat Hlth, Amsterdam, Netherlands Semmelweis Univ, Med Biochem, Budapest, Hungary Queen Elizabeth Hosp, Dept Clin Oncol, Hong Kong, Peoples R China Univ Pittsburgh, Chem, Pittsburgh, PA USA GB Pant Inst Post Grad Med Educ & Res, Neurol, New Delhi, India Univ Copenhagen, Vet & Anim Sci, Copenhagen, Denmark Univ Palermo, Biomed Dept Internal & Specialist Med DIBIMIS, Sect Endocrinol, Palermo, Italy UCL, NPP, London, England Univ Florida, Microbiol & Cell Sci, Gainesville, FL USA Univ Salford, Sch Hlth Sci, Manchester, Lancs, England Cardiff Univ, Inst Med Genet, Cardiff, S Glam, Wales INSERM, ICO Canc Ctr, Angers, France Univ Colombo, Fac Med, Microbiol, Colombo, Sri Lanka Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing, Peoples R China Univ Porto, Fac Pharm, Porto, Portugal Univ Nottingham, Div Primary Care, Nottingham, England Univ Illinois, Pharm Syst Outcomes & Policy, Chicago, IL USA Pontificia Univ Catolica Goias, Escola Ciencias Agr & Biol, Goiania, Go, Brazil China Japan Friendship Hosp, Dept Oncol, Beijing, Peoples R China Boston Univ, Chem, Boston, MA 02215 USA Amer Univ, Environm Sci, Washington, DC 20016 USA Carleton Univ, Neurosci, Ottawa, ON, Canada Univ Regina, Chem & Biochem, Regina, SK, Canada Univ Montreal, Microbiolgy, Montreal, PQ, Canada Univ Leicester, Dept Genet & Genome Biol, Leicester, Leics, England Univ Queensland, Sch Agr & Food Sci, Gatton, Qld, Australia CNRS, BIOM, Paris, France UCL, Hatter Cardiovasc Inst, London, England Flinders Univ S Australia, Sci & Engn, Adelaide, SA, Australia Univ Warwick, Engn, Coventry, W Midlands, England Katholieke Univ Leuven, Ctr Human Genet, Leuven, Belgium Fudan Univ, Dept Macromol Sci, Shanghai, Peoples R China Dokuz Eylul Univ, Biol Educ, Izmir, Turkey Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA Mondo Med, Pulm Dis, Borgomanero, Italy US Naval, Res Lab, Ctr Bio Mol Sci & Engn, Washington, DC USA Univ Oslo, Inst Basic Med Sci, Dept Nutr, Oslo, Norway Peking Univ, Dept Mech & Engn Sci, Beijing, Peoples R China Saarland Univ, Dept Pharm Pharmaceut & Med Chem, Saarbrucken, Germany INSERM, Natl Inst Hlth & Med Res, Skin Res Inst, Paris, France Shanghai Proton & Heavy Ion Ctr, Res & Dev, Shanghai, Peoples R China Univ Georgia, Epidemiol, Athens, GA 30602 USA Univ Freiburg, Med Ctr, Dept Plast & Hand Surg, Freiburg, Germany Sidra Med, Res, Doha, Qatar Rostock Univ, Med Ctr, Dept Oral Maxillofacial & Plast Surg, Rostock, Germany Harvard Med Sch, Brigham & Womens Hosp, Emergency Med, Boston, MA 02115 USA AgResearch, Forage Sci, Palmerston North, New Zealand Univ Calif Los Angeles, Med, Los Angeles, CA USA Arizona State Univ, Biodesign Inst, Virginia G Piper Ctr Personalized Diagnost, Tempe, AZ USA Sheffield Hallam Univ, Res Inst, Mat & Engn, Sheffield, S Yorkshire, England Aneurin Bevan Univ Healthboard, Resp Med, Newport, Shrops, England Univ Calif San Francisco, Neurol Surg, San Francisco, CA 94143 USA Univ Western Australia, UWA Dent Sch, Perth, WA, Australia Fordham Univ, Biol Sci, Bronx, NY 10458 USA Univ Helsinki, Inst Biotechnol, Helsinki, Finland Fujian Normal Univ, Coll Life Sci, Fuzhou, Fujian, Peoples R China Univ Fukui, Dept Frontier Fiber Technol & Sci, Fukui, Japan Univ Southampton, Fac Med, Clin & Expt Sci, Southampton, Hants, England Univ Urbino, Dept Biomol Sci, Urbino, Italy Osped San Luigi, Allergol Unit, Turin, Italy Muljibhai Patel Urol Hosp, Dept Urol, Nadiad, Gujarat, India Univ Granada, Stratig & Paleontol, Granada, Spain Massey Univ, Sch Vet Sci, Auckland, New Zealand CNR, High Performance Comp & Networking Inst, Naples, Italy Univ Childrens Hosp Zurich, Div Metab, Zurich, Switzerland Univ Childrens Hosp Zurich, Childrens Res Ctr, Zurich, Switzerland Univ Melbourne, Biochem & Mol Biol, Parkville, Vic, Australia Inst Pasteur, Leptospirosis Res & Expertise Unit, Noumea, New Caledonia Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China Cheikh Anta Diop Univ UCAD, Sci Fac, Biol Anim Dept, Dakar, Senegal Providence Portland Med Ctr, Earle A Chiles Res Inst, Portland, OR USA Agr & Agri Food Canada, Lacombe Res & Dev Ctr, Lacombe, AB, Canada Alberta Innovates, Performance Management & Evaluat, Edmonton, AB, Canada Univ Malaga, CSIC, Inst Hortofruticultura Subtrop Mediterranea La Ma, IHSM,UMA, Malaga, Spain James Cook Univ, Coll Publ Hlth Med & Vet Sci, Cairns, Qld, Australia European Commiss, Joint Res Ctr, Ispra, Italy Univ Montpellier, Montpellier, France CSIRO, Floreat, WA, Australia Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangzhou, Guangdong, Peoples R China Vanderbilt Univ, Pharmacol, 221 Kirkland Hall, Nashville, TN 37235 USA RIKEN, KFU RIKEN Translat Genom Unit, Yokohama, Kanagawa, Japan Univ Tubingen, Neurobiol Vocal Commun, Tubingen, Germany Univ Colorado, UCCS Ctr Biofrontiers Inst, Colorado Springs, CO 80907 USA Fred Hutchinson Canc Ctr, Div Basic Sci, Seattle, WA USA Univ Geneva, Fac Med, Primary Care Unit, Geneva, Switzerland Ernst Moritz Arndt Univ Greifswald, Dept Mol Genet & Infect Biol, Greifswald, Germany East China Univ Sci & Technol, Dept Fine Chem, Shanghai, Peoples R China Ohio State Univ, Surg, Columbus, OH 43210 USA Oragenics, R&D, Tampa, FL USA Natl Environm Agcy, Environm Hlth Inst, Singapore, Singapore Friedrich Loeffler Inst, Inst Diagnost Virol, Greifswald, Germany Queen Elizabeth Hosp, Oncol, Woodville, SA, Australia USDA, Emerging Pests & Pathogens Res Unit, Ithaca, NY USA Univ Freiburg, Med Ctr, Dept Neurosurg, Epilepsy Ctr, Freiburg, Germany Univ Hong Kong, Fac Educ, Informat & Technol Studies, Hong Kong, Peoples R China Univ Tokyo, Grad Sch Agr & life Sci, Agr & Environm Biol, Tokyo, Japan Univ Pittsburgh, Dept Med, Pittsburgh Heart Lung & Blood Vasc Med Inst, Pittsburgh, PA USA Guys & St Thomas NHS Fdn Trust, Directorate Transplant Renal & Urol, London, England Univ Sarajevo, Clin Ctr, Clin Heart Blood Vessel & Rheumat Dis, Sarajevo, Bosnia & Herceg Univ Kent, Sch Math Stat & Actuarial Sci, Canterbury, Kent, England Tokyo Inst Technol, Dept Life Sci & Technol, Tokyo, Japan Univ Appl Sci Munich, Laser Ctr Dept Appl Sci & Mechatron, Munich, Germany CIC NanoGUNE, Nanodevices, San Sebastian, Spain Vrije Univ Amsterdam Med Ctr, Gynaecol, Amsterdam, Netherlands Cardiff Univ, Med Sch, Div Populat Med, Cardiff, S Glam, Wales Karolinska Inst, Dept Med, Solna, Sweden Natl Inst Genet, Ctr Informat Biol, Mishima, Shizuoka, Japan Murdoch Univ, Harry Perkins Inst Med Res, Perth, WA, Australia Univ Limerick, Phys Educ & Sport Sci, Limerick, Ireland Ruhr Univ Bochum, Campus Clin Gynecol, Univ Str, Bochum, Germany Southwest Med Univ, Sch Publ Hlth, Epidemiol & Biostat, Luzhou, Sichuan, Peoples R China Beijing Canc Hosp, Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Ctr Mol Diagnost, Beijing, Peoples R China Chinese Acad Sci, Chengdu Inst Biol, Herpetol Dept, Chengdu, Sichuan, Peoples R China Key Lab Nano Biol Effects & Safety, Beijing, Peoples R China NIBR, PK Sci, Basel, Switzerland Daejeon St Marys Hosp, Pain Ctr, Daejeon, South Korea Univ Western Ontario, Sch Hlth Studies, London, ON, Canada Univ Aberdeen, Hlth Psychol Grp, Aberdeen, Scotland Univ Colorado, Anesthesiol, Anschutz Med Campus, Boulder, CO 80309 USA Univ Antwerp, UZA Antwerp Univ Hosp, Crit Care Med, Edegem, Belgium Aarhus Univ Hosp, Endocrinol, Aarhus, Denmark Univ Pretoria, Ctr Transport Dev, Ind & Syst Engn, Pretoria, South Africa Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA Pontificia Univ Catolica Goias, Med Pharmaceut & Biomed Sci Sch, Goiania, Go, Brazil Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Div Cardiovasc Med, Stockholm, Sweden UCL, Clin Educ & Hlth Psychol, London, England KRIBB, Dev & Differentiat Res Ctr, Daejeon, South Korea Univ dArtois, Lab Barriere Hematoencephal, Arras, France AstraZeneca, IMED Biotech Unit, Discovery Sci, Quantitat Biol, Cambridge, England Pacific Northwest Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA Coventry Univ, Appl Maths Res Ctr, Stat Phys Grp, Coventry, W Midlands, England Wilton Ctr, Invista Performance Technol, Cleveland, England Thunen Inst Forest Genet, Genome Res, Grosshansdorf, Germany Lebanese Amer Univ, Nat Sci, Byblos, Lebanon Takeda, Evidence & Value Generat, Osaka, Japan King Abdullah Int Med Res Ctr, Stem Cell & Regenerat Med, Riyadh, Saudi Arabia Univ Bahri, Ind Pulp & Paper, Khartoum, Sudan Univ Queensland, Mater Med Res Inst, Mater Res Inst, Brisbane, Qld, Australia Colorado State Univ, NREL, Ft Collins, CO 80523 USA Rzeszow Univ Hosp, Ob Gyn Dept, Rzeszow, Poland Univ Leeds, Fac Biol Sci, Leeds, W Yorkshire, England Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA Carl von Ossietzky Univ Oldenburg, Neurosci, Oldenburg, Germany UNSW, St George & Sutherland Clin Sch, Microbiome Res Ctr, Sydney, NSW, Australia NYU, Sch Med, Dept Biochem, New York, NY 10016 USA NYU, Sch Med, Dept Mol Pharmacol, New York, NY USA Univ Mississippi, Med Ctr, Med Infect Dis, Jackson, MS 39216 USA Tampere Univ, Fac Social Sci Psychol, Tampere, Finland Univ Cyprus, Dept Biol Sci, Nicosia, Cyprus Goethe Univ, Inst Med Microbiol & Infect Control, Frankfurt, Germany Charite Med Univ Berlin, Inst Radiol, Berlin, Germany Univ Cologne, Univ Hosp Cologne, Internal Med 1, Cologne, Germany Univ Calif Los Angeles, Sch Dent, Sect Periodont, Los Angeles, CA 90024 USA Aalborg Univ Hosp, Dept Clin Biochem, Aalborg, Denmark Manipal Acad Higher Educ, Pharm Practice, Manipal, Karnataka, India Univ Tokyo, Inst Med Sci, Dept Radiol, Tokyo, Japan Cukurova Univ, Family Med, Fac Med, Adana, Turkey Catholic Univ Korea, Coll Med, Dept Humanities & Social Med, Seoul, South Korea Univ Ghent, Food Technol Safety & Hlth, Ghent, Belgium UNSW Sydney, Sch Biol Earth & Environm Sci BEES, Sydney, NSW, Australia St Vincent Shoulder & Sports Clin, Res Unit, Vienna, Austria Cornell Univ, Biomed Engn, Ithaca, NY USA Leibniz Inst Plant Genet & Crop Plant Res IPK, Res Grp Bioinformat & Informat Technol, Gatersleben, Germany Univ Europea Madrid, Sch Doctoral Studies, Madrid, Spain CSIRO Mfg, Biomed Mfg, Melbourne, Vic, Australia Depaul Univ, Biol Sci, Chicago, IL 60604 USA Konkuk Univ, Dept Anim Sci & Technol, Seoul, South Korea Chang Gung Univ, Grad Inst Med Mechatron, Taoyuan, Taiwan Korea Univ, Coll Med, Psychiat, Seoul, South Korea Princeton Univ, Chem, Princeton, NJ 08544 USA Henan Univ Chinese Med, Henan Key Lab Chinese Med Resp Dis, Zhengzhou, Henan, Peoples R China Univ Med Ctr Mainz, Dept Psychiat & Psychotherapy, Mainz, Germany Monash Univ Malaysia, Sch Sci, Selangor, Malaysia Univ Mississippi, Med Ctr, Physiol & Biophys, Jackson, MS 39216 USA Univ Oslo, Dept Transplantat Med, Oslo, Norway Sichuan Agr Univ, Triticeae Res Inst, Yaan, Sichuan, Peoples R China Guangzhou Univ Chinese Med, Gastroenterol, Guangzhou, Guangdong, Peoples R China Southeast Univ, Sch Biol Sci & Med Engn, Suzhou, Jiangsu, Peoples R China Mt Allison Univ, Biol, Sackville, NB, Canada Ithaca Coll, Biol, Ithaca, NY 14850 USA Univ Cagliari, Dept Med Sci & Publ Hlth, Monserrato, Italy Univ Vienna, Chromosome Biol, Vienna, Austria Univ Zurich, Nephrol, Zurich, Switzerland Friedrich Schiller Univ, Inst Nutr Sci, Jena, Germany UNSW Sydney, Grad Sch Biomed Engn, Sydney, NSW, Australia Tulane Univ, Sch Med, Biochem & Mol Biol, 1430 Tulane Ave, New Orleans, LA 70112 USA NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA NIH, NCBI, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA LOreal Res & Innovat, Aulnay Sous Bois, France Lund Univ, Dept Psychol, Malmo, Sweden Catholic Univ Louvain, Inst Rech Expt & Clin, Brussels, Belgium Georgia State Univ, Neurosci Inst, Atlanta, GA 30303 USA Univ Melbourne, Ophthalmol, Surg, Parkville, Vic, Australia Univ Western Australia, Ctr Ophthalmol & Visual Sci, Perth, WA, Australia Iran Univ Med Sci, Med Phys, Fac Med, Tehran, Iran Salk Inst Biol Studies, Cellular Neurobiol, La Jolla, CA USA Imperial Coll London, Fibrosis Res Grp, London, England Univ Texas MD Anderson Canc Ctr, Genitourinary Med Oncol, Houston, TX 77030 USA Univ Liege, GIGA Neurosci, Liege, Belgium Univ Crete, Sch Med, Urol, Iraklion, Greece Flinders Univ S Australia, Flinders Med Ctr, Dept Clin Pharmacol, Adelaide, SA, Australia Max Planck Inst Immunobiol & Epigenet, Bioinformat, Breisgau, Germany Cardiff Univ, Sch Psychol, Cardiff, S Glam, Wales Imperial Coll London, Chem Engn, London, England Lund Univ, Skane Univ Hosp, Clin Sci, Malmo, Sweden Sahlgrens Acad, Inst Clin Sci, Dept Mol & Clin Med, Gothenburg, Sweden Univ Cent Lancashire, Sch Pharm & Biomed Sci, Preston, Lancs, England Hosp Univ Doctor Peset, Psychiat & Clin Psychol, Valencia, Spain Ctr Biol Mol Severo Ochoa, Genome Dynam & Funct, Madrid, Spain Unvivers Hosp Lille, Dept Intens Care, Lille, France Kansai Med Univ, Surg, Osaka, Japan Univ Toulouse, Inst Natl Polytech Toulouse, Ecole Natl Super Agron Toulouse, Lab Genom & Biotechnol Fruit, Toulouse, France UiT Arctic Univ Norway, Inst Psychol, Tromsto, Norway Queens Univ, Ctr Publ Hlth, Belfast, Antrim, North Ireland Univ Manchester, Ctr Primary Care & Hlth Serv Res, Manchester, Lancs, England Griffith Univ, Menzies Hlth Inst, Gold Coast, Qld, Australia Anglia Ruskin Univ, FHSCE, Cambridge, England Univ Lleida, Dept Expt Med, Lleida, Spain NIEHS, Biomol Screening Branch, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA Albany Med Coll, Immunol & Microbial Dis, Albany, NY 12208 USA Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia Univ Kent, Sch Biosci, Canterbury, Kent, England Univ Bourgogne Franche Comte, INSERM, LNC, UMR 1231, Besancon, France Ritsumeikan Univ, Coll Life Sci, Dept Biotechnol, Shiga, Japan Kent State Univ, Biol Sci, Kent, OH 44242 USA Natl Inst Infect Dis, Dept Safety Res Blood & Biol Prod, Tokyo, Japan European Inst Marine Studies, Lab Microbiol Extreme Environm, Plouzane, France Univ Iowa, Dept Pharmacol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA Natl Univ Singapore, Biol Sci, Singapore, Singapore Conservatoire Natl Arts & Metiers, Lab GBA, EA4627, Paris, France Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA Lomonosov Moscow State Univ, Belozersky Inst Physicochem Biol, Moscow, Russia Jikei Univ, Sch Med, Dept Mol Biol, Tokyo, Japan Univ South Wales, 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Phys & Mech Engn, Brisbane, Qld, Australia Otto von Guericke Univ, Psychol, Magdeburg, Germany Univ Med Ctr Gottingen, Dept Expt Neurodegenerat, Gottingen, Germany Harvard Med Sch, Spaulding Rehabil Hosp, Phys Med & Rehabil, Boston, MA 02115 USA Quadram Inst Biosci, Sci Operat, Norwich, Norfolk, England Ostbayer Tech Hsch Regensburg OTH Regensburg, Regensburg Med Image Comp ReMIC, Regensburg, Germany Deakin Univ, Fac Arts & Educ, Melbourne, Vic, Australia Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England INSERM, Natl Inst Hlth & Med Res, Biochem & Mol Biol, Paris, France Univ Liege, Tax Inst, Liege, Belgium Univ Leeds, Sch Mol & Cellular Biol, Leeds, W Yorkshire, England IRCCS Ist Giannina Gaslini, UOC Genet Med, Genoa, Italy Res Diets Inc, Sci, New Brunswick, NJ USA Univ Perugia, Dept Phys & Geol, Perugia, Italy Walter Reed Natl Mil Med Ctr, Cellular Immunol, Bethesda, MD USA Univ Fed Santa Catarina, Biol Sci Ctr, Microbiol Immunol & Parasitol Dept, Florianopolis, SC, Brazil Univ Edinburgh, Royal Infirm, Ctr Liver & Digest Disorders, Edinburgh, Midlothian, Scotland Orion Pharma, Crit Care Proprietary Prod Div, Espoo, Finland MIT, Dept Civil & Environm Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA Univ Turin, Dept Vet Sci, Turin, Italy Univ G dAnnunzio, Dept Psychol Hlth & Territorial Sci, Chieti, Italy NYU, Sch Med, OB GYN, New York, NY USA Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland Univ Turku, Dept Biol, Turku, Finland Tech Univ Berlin, Bioanalyt, Berlin, Germany Univ Goettingen, Inst Phys Biophys 3, Gottingen, Germany Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Translat Res Adv Therapeut & Innovat Oncol TRACTI, Houston, TX 77030 USA Univ Liege, Life Sci, Liege, Belgium Tarbiat Modares Univ, Fac Med Sci, Dept Toxicol, Tehran, Iran ARS, USDA, Stoneville, MS USA Univ Regensburg, RCI Regensburg Ctr Intervent Immunol, Regensburg, Germany Univ Nottingham, Sch Psychol, Nottingham, England NIH, Pathol Lab, Bethesda, MD 20892 USA Univ Carlos III Madrid, Elect Engn, Madrid, Spain Inst Med Mol, Chem Biol, Lisbon, Portugal Univ Costa Rica, CIET, San Jose, Costa Rica Univ Stavanger, Fac Hlth Sci, Stavanger, Norway Erasmus MC, Urol, Rotterdam, Netherlands Univ Edinburgh, Sch Biol Sci, Edinburgh, Midlothian, Scotland German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol IBIS, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany Leiden Univ, Huygens Kamerlingh Onnes Lab, Leiden, Netherlands Univ Vienna, Nutr Sci, Vienna, Austria Kolling Inst Med Res, Med, St Leonards, NSW, Australia Johns Hopkins Sch Med, Biol Chem, Baltimore, MD USA Univ Montreal, Med Nutr & Microbiome Lab, Montreal, PQ, Canada GlaxoSmithKline, Cell & Gene Therapy, Stevenage, Herts, England Univ Trieste, Life Sci, Trieste, Italy Rhein Westfal TH Aachen, Dept Radiol, Aachen, Germany Univ Duisburg Essen, Univ Hosp Essen, West German Canc Ctr, Dept Med Oncol, Essen, Germany Med Univ Vienna, Obstet & Gynecol, Vienna, Austria FHI 360, Social & Behav Hlth Sci Div, Washington, DC USA KU Leuven VIB, Switch Lab, Leuven, Belgium Bielefeld Univ, Fac Technol, Bielefeld, Germany Capital Med Univ, Beijing Shijitan Hosp, Dept Clin Nutr, Dept Gastrointestinal Surg, Beijing, Peoples R China Meiji Univ, Dept Agr Chem, Kawasaki, Japan Yonsei Univ, Coll Med, Microbiol, Seoul, South Korea Johnson & Johnson EAME, Maidenhead, Berks, England Penn State Coll Med, Pediat, Hershey, PA USA Univ N Carolina, Dept Social Med, Chapel Hill, NC 27515 USA Univ Western Australia, ARC CoE Plant Energy Biol, Perth, WA, Australia Wageningen Univ, Div Human Nutr & Hlth, Wageningen, Netherlands Kings Coll London, Dept Neuroimaging, London, England Univ Murcia, Biochem & Mol Biol, Murcia, Spain Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA Monash Univ, Biochem & Mol Biol, Melbourne, Vic, Australia Chinese Acad Sci, Inst Genet & Dev Biol, Beijing, Peoples R China Univ Pittsburgh, Pharmacol & Chem Biol, Pittsburgh, PA USA Univ Lausanne, Ctr Integrat Genom, Lausanne, Switzerland Univ Queensland, Sch Pharm, Brisbane, Qld, Australia Leibniz Inst Plant Genet & Crop Plant Res IPK Gat, Genebank, Gatersleben, Germany Piramal Imaging, Res & Dev, Berlin, Germany Univ Leeds, Civil Engn, Leeds, W Yorkshire, England Univ Missouri, Chem & Biochem, St Louis, MO 63121 USA US Geol Survey, Coastal & Marine Geol Program, Pacific Coastal & Marine Sci Ctr, Santa Cruz, CA USA Ajinomoto Genet Res Inst, Moscow, Russia Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, Dept Plant Biotechnol, Krakow, Poland Univ Puerto Rico, Engn Sci & Mat, Mayaguez, PR USA Univ Regina, Dept Chem & Biochem, Regina, SK, Canada Argonne Natl Lab, Ctr Nanoscale Mat, 9700 S Cass Ave, Argonne, IL 60439 USA Univ Sunshine Coast, Sunshine Coast Mind & Neurosci Thompson Inst, Sippy Downs, Qld, Australia Chinese Peoples Liberat Army Gen Hosp, Dept Gastroenterol & Hepatol, Beijing, Peoples R China Griffith Univ, Griffith Ctr Social & 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Maximilians Univ Munchen, Phys Chem, NanoBioSci, Munich, Germany Bandung Inst Technol, Sch Pharm, Med Chem, Bandung, Indonesia Univ Luxembourg, Life Sci Res Unit, Luxembourg, Luxembourg Lund Univ, Skane Univ Hosp, Dept Gastroenterol, Malmo, Sweden Millennium Hlth, Translat Genet, San Diego, CA USA Aristotle Univ Thessaloniki, Med Dept 2, Clin Res & Evidence Based Med Unit, Thessaloniki, Greece Jan Kochanowski Univ Humanities & Sci, Piotrkow Trybunalski Branch, Dept Psychol, Kielce, Poland McMaster Univ, Engn Phys, Hamilton, ON, Canada Marche Polytech Univ, Dept Agr Food & Environm Sci, Ancona, Italy Kuwait Univ, Fac Med, Microbiol, Kuwait, Kuwait Fujita Hlth Univ, Dept Breast Surg, Toyoake, Aich, Japan North West Reg Spinal Injuries Ctr, Spinal Injuries Ctr, Southport, Merseyside, England Luxembourg Inst Hlth, Competence Ctr Methodol & Stat, Luxembourg, Luxembourg Nestle Inst Hlth Sci SA, Metab Hlth, Ecublens, Vaud, Switzerland Ctr Inflammat Res VIB, Ghent, Belgium Univ Ghent, Dept Biomed Mol Biol, Ghent, Belgium Univ Lisbon, Inst Educ, Curriculo Formacao Prof & Tecnol, Lisbon, Portugal Univ Edinburgh, Ctr Inflammat Res, Edinburgh, Midlothian, Scotland Univ Melbourne, Sch BioSci, Parkville, Vic, Australia Northumbria Univ, Comp & Informat Sci, Newcastle Upon Tyne, Tyne & Wear, England Univ Valencia, Endocrinol, Valencia, Spain INRS, Inst Armand Frappier, Laval, PQ, Canada Univ Laval, INAF, Sch Nutr, Quebec City, PQ, Canada Univ Konstanz, Dept Biol, Constance, Germany Univ Cote dAzur, LAMHESS, Nice, France Scion, Syst Ecol, Christchurch, New Zealand CUNY, Grad Sch Publ Hlth & Hlth Policy, Epidemiol & Biostat, New York, NY 10021 USA Univ Queensland, Sch Dent, Brisbane, Qld, Australia George Inst Global Hlth, Renal & Metab Div, Sydney, NSW, Australia Wuhan Univ, Coll Chem & Mol Sci, Wuhan, Hubei, Peoples R China Griffith Univ, Sch Environm & Sci, Gold Coast, Qld, Australia Univ Minnesota, Radiat Oncol, Minneapolis, MN USA Goethe Univ, Fac Med, Frankfurt, Germany 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Tradit Chinese Med, Inst Interdisciplinary Med Sci, Shanghai, Peoples R China McMaster Univ, Biol, Hamilton, ON, Canada Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL USA Hacettepe Univ, Inst Canc, Med Oncol, Ankara, Turkey City Univ Hong Kong, Dept Elect Engn, Hong Kong, Peoples R China Natl Taiwan Univ, Dept Entomol, Taipei, Taiwan Chinese Acad Agr Sci, Inst Environm & Sustainable Dev Agr, Ecol Secur, Beijing, Peoples R China Florida State Univ, Inst Mol Biophys, Chem & Biochem, Tallahassee, FL USA Peking Univ, Shenzhen Grad Sch, State Key Lab Chem Oncogen, Lab Computat Chem & Drug Design, Shenzhen, Peoples R China Univ Helsinki, Fac Pharm, Div Pharmaceut Chem & Technol, Drug Res Program, Helsinki, Finland Tohoku Univ, Microbial Biotechnol, Sendai, Miyagi, Japan Tianjin Med Univ, Sch Basical Med Sci, Dept Pharmacol, Tianjin, Peoples R China Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA Natl Hlth Res Inst, Inst Mol & Genom Med, Zhunan, Taiwan Univ Oxford, Physiol Anat & Genet, Oxford, England George Washington Univ, Phys, Washington, DC USA Univ Nebraska, Sch Biol Sci, Lincoln, NE USA Toronto Gen Hosp, Res Inst, Dept Lab Med & Pathobiol, Toronto, ON, Canada Univ Texas Dallas, Biol Sci, Richardson, TX 75083 USA NYU, Dept Chem, New York, NY USA Shandong Univ, Sch Math & Stat, Jinan, Shandong, Peoples R China Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei, Anhui, Peoples R China Purdue Univ, Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA NIBSC, Adv Therapies, Ridge, Herts, England Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Pulm & Crit Care Med, Shanghai, Peoples R China Charite Med Univ Berlin, Dermatol & Allergy, Berlin, Germany Univ Hosp St Etienne, Hematol, St Etienne, France Inland Norway Univ Appl Sci, Inst Biotechnol, Elverum, Norway Univ Jordan, Pediat, Amman, Jordan Inst Pasteur, Mol Mycol Unit, Paris, France Cardiff Univ, Sch Med, Inst Psychol Med & Clin Neurosci, Med Res Council Ctr Neuropsychiat Genet & Genom, Cardiff, S Glam, Wales Zurich Univ Appl Sci, Social Work, Zurich, Switzerland Jawaharlal Nehru Univ, Sch Life Sci, New Delhi, India Univ Burgundy Franche Comte, LE2I, Dijon, France Univ Roehampton, Life Sci, London, England Ghent Univ Hosp, Gen & HPB Surg, Ghent, Belgium Univ Wurzburg, Insect Fungus Symbiosis Lab, Wurzburg, Germany Radboud Univ Nijmegen, Behav Sci Inst, Nijmegen, Netherlands Fraunhofer WKI, Applicat Ctr HOFZET, Hannover, Germany UCL, Struct & Mol Biol, London, England Univ Amsterdam, Dev Psychol, Amsterdam, Netherlands Aalborg Univ, Hlth Sci & Technol, CNAP, SMI, Aalborg, Denmark VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA Cedars Sinai Med Ctr, Neurosurg, Los Angeles, CA 90048 USA Sun Yat Sen Univ, Sch Data & Comp Sci, Guangzhou, Guangdong, Peoples R China Dezhou Univ, Shandong Prov Key Lab Biophys, Guangzhou, Guangdong, Peoples R China Maison Teledetection, Inst Rech Dev, UMR Espace DEv, Montpellier, France Xiamen Univ, Sch Life Sci, Xiamen, Fujian, Peoples R China Nanjing Univ, Sch Med, Jinling Hosp, Natl Clin Res Ctr Kidney Dis,Dept Med Imaging, Nanjing, Jiangsu, Peoples R China Univ Kent, Sch Social Policy Sociol & Social Res, Canterbury, Kent, England Univ Fed Minas Gerais, Infect Dis & Trop Med, Belo Horizonte, MG, Brazil Univ Minho, Sch Med, Life & Hlth Sci Res Inst ICVS, Braga, Portugal Univ Montreal, Biochim & Med Mol, Montreal, PQ, Canada Johns Hopkins Bloomberg Sch Publ Hlth, Epidemiol, Baltimore, MD USA Max Planck Inst Biol Ageing, Metab & Genet Regulat Ageing, Cologne, Germany Univ Swaziland, Hlth Sci, Kwaluseni, Eswatini Queensland Univ Technol, Inst Future Environm, Brisbane, Qld, Australia Ctr Sci Monaco, Dept Biol Med, Monaco, Monaco HELIOS Hosp, Urol, Bad Saarow Pieskow, Germany Tech Univ Carolo Wilhelmina Braunschweig, Inst Microbiol, Braunschweig, Germany Univ Barcelona, Barcelona Ctr Maternal Fetal & Neonatal Med, Fetal i D Fetal Med Res Ctr, IDIBAPS BCNatal,Hosp Clin, Barcelona, Spain Univ Barcelona, Hosp St Joan de Deu, Barcelona, Spain Friedrich Loeffler Inst, Inst Bacterial Infect & Zoonoses, Jena, Germany Charite Med Univ Berlin, Neurol, Berlin, Germany Dublin City Univ, Natl Inst Cellular Biotechnol, Mol Therapeut Canc Ireland, Dublin, Ireland Schoen Clin Roseneck, Prien Am Chiemsee, Germany Univ Med Ctr Hamburg Eppendorf, Inst Sex Res & Forens Psychiat, Hamburg, Germany Nankai Univ, Sch Math Sci, Tianjin, Peoples R China Nankai Univ, LPMC, Tianjin, Peoples R China Univ Oxford, Oncol, Oxford, England Royal Holloway Univ London, Class, Egham, Surrey, England Cornell Univ, Clin Sci, Ithaca, NY USA Univ KwaZulu Natal, Pharmaceut Chem, Westville Campus, Durban, South Africa Royal Coll Surgeons Ireland, Med, Dublin, Ireland Univ Oslo, Dept Immunol, Oslo, Norway Bermuda Inst Ocean Sci, Marine Nitrogen Cycling Lab, St Georges, Bermuda Kanazawa Univ, Inst Liberal Arts & Sci, Kanazawa, Ishikawa, Japan World Hlth Org Reg Off Africa, Brazzaville, Rep Congo Univ Hosp BesanCon, Infect Control Dept, Besancon, France Galapagos NV, Clin Dev, Mechelen, Belgium Univ Tasmania, Integrated Marine Observing Syst, Hobart, Tas, Australia Georg August Univ Gottingen, Albrecht von Haller Inst Plant Sci, Dept Systemat Biodivers & Evolut Plants, Gottingen, Germany Univ Occupat & Environm Hlth, Dept Psychiat, Fukuoka, Fukuoka, Japan IMDEA Food, Program Precis Nutr & Aging, Madrid, Spain Radboud Univ Nijmegen, Med Sch, IQHealthcare, Nijmegen, Netherlands Maastricht Univ, Dept Cardiovasc Surg, Maastricht, Netherlands German Diabet Ctr, Inst Clin Biochem & Pathobiochem, Dusseldorf, Germany Juntendo Univ, Grad Sch Med, Dept Radiol, Tokyo, Japan Deakin Univ, Sch Informat Technol, Melbourne, Vic, Australia Max Planck Inst Eusenforschung, Dept Interface Chem & Surface Sci, Dusseldorf, Germany Edge Hill Univ, Dept Psychol, Ormskirk, England Aga Khan Univ, Psychiat, Karachi, Pakistan KRIBB, Korean Bioinformat Ctr, Seoul, South Korea Cardinal Hlth Specialty Solut, Hlth Econ & Outcomes Res, Dallas, TX USA Klinikum Univ Munchen, Div Clin Pharmacol, Munich, Germany Univ Pittsburgh, Neurol Surg, Pittsburgh, PA USA Rhein Westfal TH Aachen, Dept Child & Adolescent Psychiat Psychosomat & Ps, Aachen, Germany Univ Copenhagen, Inst Mol & Cellular Biol, Copenhagen, Denmark St Jude Childrens Res Hosp, Struct Biol, 332 N Lauderdale St, Memphis, TN 38105 USA Royal Shrewsbury Hosp, Colorectal Surg, Shrewsbury, Salop, England Univ Nottingham, Fac Med & Hlth Sci, Nottingham, England Karolinska Inst, Dept Physiol & Pharmacol, Solna, Sweden Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Electroanalyt Chem, Jilin, Jilin, Peoples R China Univ British Columbia, Pediat, Vancouver, BC, Canada Chinese Acad Agr Sci, State Key Lab Cotton Biol, Res Base Anyang Inst Technol, Cotton Germplasm Resources,Inst Cotton Res, Beijing, Peoples R China Chinese Univ Hong Kong, Anaesthesia & Intens Care, Hong Kong, Peoples R China Univ Macau, ICMS, Zhuhai, Guangdong, Peoples R China North China Elect Power Univ, Sch Renewable Energy, Beijing, Peoples R China Justus Liegbig Univ, Dept Internal Med, Giessen, Germany Aarhus Univ, Biosci, Aarhus, Denmark Univ Dublin, Trinity Coll Dublin, Irish Longitudinal Study Ageing TILDA, Dublin, Ireland Univ Groningen, Univ Med Ctr Groningen, Hematol, Groningen, Netherlands Vrije Univ Amsterdam Med Ctr, Child Neurol, Amsterdam, Netherlands EBI, EMBL, Cambridge, England Max Planck Inst Marine Microbiol, HGF MPG Joint Res Grp Deep Sea Ecol & Technol, Bremen, Germany Max Planck Inst Human Dev, Ctr Adapt Rat, Berlin, Germany King Faisal Univ, Math, Al Hufuf, Saudi Arabia Griffith Univ, Sch Nursing & Midwifery, Gold Coast, Qld, Australia Iowa State Univ, Roy J Carver Dept Biochemsitry Biophys & Mol Biol, Ames, IA USA Delft Univ Technol, Fac Mech Maritime & Mat Engn, Engn Thermodynam Proc & Energy Dept, Leeghwaterstr 39, NL-2628 CB Delft, Netherlands Univ Nebraska Med Ctr, Coll Allied Hlth Profess, Cytotechnol Educ, Omaha, NE USA Shinko Mem Hosp, Dept Cardiovasc Med, Kobe, Hyogo, Japan Imperial Coll London, Mat, London, England Tech Univ Munich, Dept Surg, Munich, Germany Chinese Acad Agr Sci, Res Inst Pomol, Minist Agr, Lab Qual & Safety Risk Assessment Fruit Xingcheng, Shenyang, Liaoning, Peoples R China James Madison Univ, Commun Sci & Disorders, Harrisonburg, VA 22807 USA Univ Hosp Ulm, Inst Orthopaed Res & Biomech, Ulm, Germany Univ Essex, Sch Hlth & Social Care, Colchester, Essex, England Alpha Altis, Res Serv, Nottingham, England Erasmus MC, Med Oncol, Rotterdam, Netherlands Fed Univ Oye, Dept Ind Chem, Ekiti, Nigeria Duke Univ, Med Ctr, Cell Biol, Durham, NC USA Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England Univ Manchester, Canc Res UK Manchester Inst, Manchester, Lancs, England Helsinki Univ Hosp, Childrens Hosp, Helsinki, Finland Univ Aveiro, CESAM Ctr Environm & Marine Studies, Dept Biol, Aveiro, Portugal Univ Botswana, Psychol, Gaborone, Botswana Univ Fed Bahia, Nursing Sch, Salvador, BA, Brazil Queen Mary Univ London, Biol & Expt Psychol, London, England Natl Univ Pharm, Med Chem Dept, Kharkov, Ukraine Univ Bolton, Dept Educ & Psychol, Bolton, England La Trobe Univ, Dept Chem & Phys, Melbourne, Vic, Australia Gen Hosp Northern Theater Command, Dept Gastroenterol, Shenyang, Liaoning, Peoples R China Doctors Hosp, Dept Nephrol, Athens, Greece Univ Hosp Essen, Pediat 3, Essen, Germany Imperial Coll London, Infect Dis Epidemiol, London, England Sorbonne Univ, Dept Psychiat, Paris, France UNSW Sydney, Educ, Sydney, NSW, Australia Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA Hannover Med Sch, Clin Laryngol Rhinol & Otol, Hannover, Germany Curtin Univ, Ctr Aboriginal Studies, Perth, WA, Australia Iran Univ Sci & Technol, Biomed Engn Dept, Tehran, Iran Univ Calif San Francisco, Anesthesiol, San Francisco, CA 94143 USA Khalifa Univ Sci & Technol, Mech Engn, Abu Dhabi, U Arab Emirates Univ Florida, Hort Sci, Gainesville, FL USA James Cook Univ, Australian Inst Trop Hlth & Med, Ctr Biodiscovery & Mol Dev Therapeut, Cairns, Qld, Australia Univ Porto, Fac Med, CINTESIS, Porto, Portugal Shaoxing Peoples Hosp, Med Res Ctr, Shaoxing, Zhejiang, Peoples R China NIH, Dept Transfus Med, Bethesda, MD 20892 USA AIIMS, Dept Biotechnol, New Delhi, India Univ Ottawa, Biochem Microbiol & Immunol, Ottawa, ON, Canada Univ Oslo, Inst Clin Med, Div Mental Hlth & Addict, Oslo, Norway Univ Groningen, Univ Med Ctr Groningen, Dept Radiol, Groningen, Netherlands Univ Hong Kong, Sch Nursing, Hong Kong, Peoples R China Tokyo Med Univ, Ibaraki Med Ctr, Urol, Tokyo, Japan Univ Hosp Zurich, Dept Radiat Oncol, Zurich, Switzerland Univ Maryland, Inst Human Virol, Div Immunotherapy, Baltimore, MD 21201 USA Univ Maryland, Dept Surg, Baltimore, MD 21201 USA Stellenbosch Univ, Fac Med & Hlth Sci, Div Mol Biol & Human Genet, Stellenbosch, South Africa China Agr Univ, Coll Biol Sci, Beijing, Peoples R China Osaka Univ, Grad Sch Pharmaceut Sci, Suita, Osaka, Japan Univ Washington, Biochem, Seattle, WA 98195 USA Natl Res Council Italy, Inst Biosci & BioResources, Naples, Italy Univ Lyon, Phys, Lyon, France Univ Basel, Fac Psychol, Ctr Social Psychol, Basel, Switzerland Queen Mary Univ London, Barts Canc Inst, Ctr Mol Oncol, London, England EBI, EMBL, Samples Phenotypes & Ontol Team, Cambridge, England Charles Sturt Univ, Fac Arts & Educ, Bathurst, NSW, Australia Shandong Univ, Helmholtz Inst Biotechnol, Sch Life Sci, State Key Lab Microbial Technol, Jinan, Shandong, Peoples R China Shantou Univ, Dept Biol, Shantou, Guangdong, Peoples R China Shanxi Univ, Inst Biomed Sci, Taiyuan, Shanxi, Peoples R China St Jude Childrens Res Hosp, Computat Biol, 332 N Lauderdale St, Memphis, TN 38105 USA Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin, Heilongjiang, Peoples R China NIH, Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA Georgia Inst Technol, Dept Biol Sci, Atlanta, GA 30332 USA XtalPi Inc, Cambridge, MA USA Consejo Nacl Invest Cient & Tecn, Partner Inst Max Planck Soc, Inst Invest Biomed Buenos Aires IBioBA, Bioinformat, Buenos Aires, DF, Argentina Univ Sydney, Save Sight Inst, Sydney, NSW, Australia Univ South Australia, Canc Res Inst, Australian Ctr Precis Hlth, Adelaide, SA, Australia Jinan Univ, Inst Life & Hlth Engn, Guangdong Higher Educ Inst, Key Lab Funct Prot Res, Guangzhou, Guangdong, Peoples R China Univ Texas Hlth Sci Ctr Houston, Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA Weill Cornell Med, Dept Microbiol & Immunol, New York, NY USA Guangdong Inst Appl Biol Resources, Biotechnol Lab, Guangzhou, Guangdong, Peoples R China Shandong Normal Univ, Coll Life Sci, Jinan, Shandong, Peoples R China Shandong Univ, Life Sci Dept, Jinan, Shandong, Peoples R China South China Agr Univ, Integrat Microbiol Res Ctr, Guangzhou, Guangdong, Peoples R China Liaoning Acad Agr Sci, Crop Mol Improving Lab, Shenyang, Liaoning, Peoples R China Lawson Hlth Res Inst, Med Biophys, London, ON, Canada Univ Melbourne, Infrastruct Engn, Parkville, Vic, Australia Univ Canberra, Fac Hlth, Canberra, ACT, Australia Univ Cambridge, MRC Cognit & Brain Sci Unit, Cambridge, England Emory Univ, Biostat & Bioinformat, Atlanta, GA 30322 USA Johns Hopkins Sch Med, Anesthesiol & Crit Care Med, Baltimore, MD USA Nottingham Trent Univ, Sch Anim Rural & Environm Sci, Nottingham, England Univ Exeter, Biosci, Exeter, Devon, England Hillingdon Hosp NHS Fdn Trust, London, England Univ Glasgow, MRC CSO Social & Publ Hlth Sci Unit, Glasgow, Lanark, Scotland Natl & Kapodistrian Univ Athens, Evaggelismos Athens Hosp, ICU, Athens, Greece Univ Newcastle, Biol Sci, Callaghan, NSW, Australia Coventry Univ, Fac Hlth & Life Sci, Ctr Innovat Res Life Course, Coventry, W Midlands, England Lausanne Univ Hosp, Serv Endocrinol Diabet & Metab, Lausanne, Switzerland Charles Sturt Univ, Sch Community Hlth, Bathurst, NSW, Australia Queens Univ Belfast, Inst Global Food Secur, Belfast, Antrim, North Ireland Natl Univ Singapore, Inst Policy Studies, Singapore, Singapore Univ Penn, Intitute Med & Engn, Philadelphia, PA 19104 USA Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA Univ Michigan, EECS, Ann Arbor, MI 48109 USA Univ British Columbia, Ctr Blood Res, Vancouver, BC, Canada UiT Arctic Univ Norway, Dept Hlth & Care Sci, Fac Hlth Sci, Tromso, Norway Hosp Clin Porto Alegre, Physiotherapy, Porto Alegre, RS, Brazil Univ Paris 05, Med Sch, Paris, France Chinese Acad Agr Sci, Inst Crop Sci, Natl Key Facil Crop Gene Resources & Genet Improv, Beijing, Peoples R China Univ Ghent, Expt Clin & Hlth Psychol, Ghent, Belgium Indian Inst Adv Res, Bioinformat & Struct Biol, Gandhinagar, Gujart, India Bambino Ges Childrens Res Hosp, Lab Mol Med, Rome, Italy Heidelberg Univ, Ctr Infect Dis Parasitol, Heidelberg, Germany Stanford Univ, Elect Engn, Palo Alto, CA 94304 USA Univ Cadiz, Biol, Andalucia, Spain Mansoura Univ Hosp, Gen Surg, Mansoura, Egypt Inst Pasteur, Virol Pole, Dakar, Senegal Cardiff Univ, Div Canc & Genet, Cardiff, S Glam, Wales Ctr Expertise & Biol Diagnost Cameroon, Food Safety & Environm Microbiol, Yaounde, Cameroon Swiss Fed Labs Mat Sci & Technol, Lab Thin Films & Photovolta, Dubendorf, Switzerland Assiut Univ, Assiut Urol & Nephrol Hosp, Fac Med, Assiut, Egypt UCL, GEE, London, England UCL, IHA, London, England Univ Derby, Univ Derby Online Learning, Derby, England SUNY Stony Brook, Family Populat & Prevent Med, Stony Brook, NY 11794 USA Walter & Eliza Hall Inst Med Res, Mol Med Div, Melbourne, Vic, Australia Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England German Ctr Neurodegenerat Dis, Clin Dementia Res, Bonn, Germany Sorbonne Univ, CNRS, UMR 7144, Stn Biol, Paris, France Univ Barcelona, Odontoestomatol, Barcelona, Spain Janelia Res Campus, Comp Sci, Ashburn, VA USA Univ Oxford, Ctr Trop Med & Global Hlth, Oxford, England Univ Bern, ARTORG Ctr Biomed Engn Res, Bern, Switzerland Australian Natl Univ, Eccles Inst Neurosci, John Curtain Sch Med Res, Canberra, ACT, Australia John Innes Ctr, Metab Biol, Norwich, Norfolk, England USDA ARS, Genom & Bioinformat Res Unit, Raleigh, NC 27695 USA Med Univ Graz, Inst Med Informat Stat & Documentat, Holzinger Grp, Graz, Austria Ajou Univ, Pharm, Suwon, South Korea City Univ Hong Kong, Sch Energy & Environm, Hong Kong, Peoples R China Univ British Columbia, Sch Kinseiol, Vancouver, BC, Canada Univ Copenhagen, Marine Biol Sect, Dept Biol, Copenhagen, Denmark Univ Vienna, Dept Commun, Vienna, Austria Univ Dundee, Sch Social Sci, Dundee, Scotland Tech Univ Dresden, Inst Bot, Dresden, Germany Univ Oxford, Div Struct Biol, Oxford, England Natl Univ Hlth Syst, Med, Singapore, Singapore Univ Canterbury, Sch Biol Sci, Christchurch, New Zealand Univ Hosp Southern Denmark, Focused Res Unit Mol Diagnost & Clin Res, Odense, Denmark Univ Oxford, Primary Care Hlth Sci, Oxford, England Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA Adnan Menderes Univ Aydin, Fac Nursing, Dept Publ Hlth Nursing, Aydin, Turkey Oasi Res Inst IRCCS, Dept Neurol IC, Troina, Italy Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA Kings Coll London, Kings Ctr Mil Hlth Res, London, England LSHTM, Dept Infect Dis Epidemiol, London, England Leibniz Univ Hannover, BMWZ Organ Chem, Hannover, Germany Xi An Jiao Tong Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Xian, Shaanxi, Peoples R China Univ South Australia, Sch Pharm & Med Sci, Adelaide, SA, Australia Univ Fed Santa Catarina, Dept Phys Educ, Florianopolis, SC, Brazil Southern Med Univ, Nanfang Hosp, Dept Oncol, Guangzhou, Guangdong, Peoples R China Stanford Univ, Hansen Expt Phys Lab, Palo Alto, CA 94304 USA Shenzhen Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp 2, Inst Translat Med, Shenzhen, Guangdong, Peoples R China Univ Hong Kong, Dept Stat & Actuarial Sci, Hong Kong, Peoples R China UCL, Dept Mech Engn, London, England ASTAR, Singapore Immunol Network, Lab Microbial Immun, Singapore, Singapore Cent South Univ, State Key Lab Powder Met, Changsha, Hunan, Peoples R China Univ Aberdeen, Inst Appl Hlth Sci, Aberdeen, Scotland Univ Bridgeport, Biomed Engn, Bridgeport, CT 06601 USA Texas Tech Univ, Hlth Sci Ctr, Pharmaceut Sci, Lubbock, TX 79430 USA Univ Montana, Ecosyst & Conservat Sci, Missoula, MT 59812 USA Univ Goettingen, Dept Syst Neurosci, Gottingen, Germany NHLBI, Lab Syst Genet, Bldg 10, Bethesda, MD 20892 USA Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Imaging, Las Vegas, NV USA Flinders Univ S Australia, Coll Nursing & Hlth Sci, Nutr & Dietet, Adelaide, SA, Australia Univ Padua, Dept Math, Padua, Italy Lund Univ, Fac Law, Lund, Sweden Univ Gothenburg, Dept Microbiol & Immunol, Gothenburg, Sweden NARO, Kachwekano Zardi, Entebbe, Uganda Natl Yunlin Univ Sci & Technol, Bachelor Program Interdisciplinary Studies, Touliu, Yunlin, Taiwan Aarhus Univ, Dept Biomed, Danish Res Inst Translat Neurosci DANDRITE, Aarhus, Denmark Eduardo Mondlane Univ, Math & Comp Sci, Maputo, Mozambique Univ Bern, Dept Old Age Psychiat & Psychotherapy, Bern, Switzerland RAS, Inst Cytol, Lab Cytol Unicellular Organisms, St Petersburg, Russia Beijing Inst Technol, Sch Chem & Chem Engn, Beijing, Peoples R China Univ Queensland, Queensland Alliance Agr & Food Innovat, Brisbane, Qld, Australia Fraunhofer Inst Toxicol & Expt Med ITEM, Inhalat Toxicol, Hannover, Germany Univ Hong Kong, Publ Hlth, Hong Kong, Peoples R China Univ Hlth Network, Anesthesia & Pain Med, Toronto, ON, Canada Univ Toronto, Toronto, ON, Canada Univ Bath, Dept Hlth, Bath, Avon, England Univ Copenhagen, Computat & RNA Biol, Copenhagen, Denmark Fisheries & Oceans Canada, Bedford Inst Oceanog, Dartmouth, NS, Canada Goethe Univ, CEF MC, BMLS, Phys Biol, Frankfurt, Germany Albert Einstein Coll Med, Anat & Struct Biol, New York, NY USA Queensland Govt, Dept Environm & Sci, Brisbane, Qld, Australia Uppsala Univ, Vasc Surg Sect, Dept Surg Sci, Uppsala, Sweden Childrens Canc Hosp, Res, Cairo, Egypt Leibniz Inst Nat Prod Res & Infect Biol, Bio Pilot Plant, Jena, Germany Duy Tan Univ, Inst Res & Dev, Da Nang, Vietnam Univ Helsinki, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland Univ Queensland, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld, Australia George Inst Global Hlth, Sydney, NSW, Australia Griffith Univ, Griffith Inst Drug Discovery, Brisbane, Qld, Australia Dezhou Univ, Coll Phys & Elect Informat, Shandong Prov Key Lab Biophys, Dezhou, Peoples R China Henan Agr Univ, Coll Life Sci, Zhengzhou, Henan, Peoples R China Univ Tokyo, Publ Hlth, Tokyo, Japan Sun Yat Sen Univ, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China Univ Illinois, Dept Med, Chicago, IL USA Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing, Peoples R China Minist Hlth, Key Lab Neonatal Dis, Shanghai, Peoples R China Covenant Univ, Dept Phys, Ota, Nigeria Prince Sattam Bin Abdulaziz Univ, Dept Phys Therapy & Hlth Rehabil, Al Kharj, Saudi Arabia Lund Univ, Cognit Sci, Malmo, Sweden Natl Open Univ Nigeria, Dept Publ & Environm Hlth, Abuja, Nigeria Peking Univ, Sch Publ Hlth, Dept Lab Sci & Technol, Beijing, Peoples R China Univ Sydney, Sch Publ Hlth, Menzies Ctr Hlth Policy, Sydney, NSW, Australia Univ Auckland, Dept Elect & Comp Engn, Auckland, New Zealand Beijing Univ Chinese Med, Res Ctr TCM Informat Engn, Beijing, Peoples R China Osped Niguarda Ca Granda, Cardiac Surg, Milan, Italy Univ Vet Med, Clin Horses, Hannover, Germany Harbin Med Univ, Lab Med Genet, Harbin, Heilongjiang, Peoples R China Univ Saskatchewan, Dept Psychol, Saskatoon, SK, Canada Univ Coimbra, Ctr Studies Geog & Spatial Planning CEGOT, Coimbra, Portugal Univ Groningen, Univ Med Ctr Groningen, Epidemiol, Groningen, Netherlands South Cent High Specialty Hosp, Dept Neurol & Neurosurg, Pemex, Mexico Shandong Agr Univ, Coll Informat Sci & Engn, Tai An, Shandong, Peoples R China Curtin Univ, Natl Drug Res Inst, Perth, WA, Australia Wageningen Bioveterinary Res, Bacteriol & Epidemiol, Lelystad, Netherlands Guangdong Second Prov Gen Hosp, Dept Rheumatol & Immunol, Guangzhou, Guangdong, Peoples R China Erasmus MC, Biomed Rngineering, Rotterdam, Netherlands Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Hiroshima, Japan Univ Iceland, Sch Hlth Sci, Reykjavik, Iceland Ohio State Univ, Mat Sci & Engn, Columbus, OH 43210 USA Kathmandu Univ, Sch Med Sci, Dept Physiotherapy, Dhulikhel, Nepal Univ Queensland, Sch Biomed Sci, Brisbane, Qld, Australia Fraunhofer MEVIS, Image Guided Therapies, Bremen, Germany Natl Univ Hlth Syst, Haematol Oncol, Singapore, Singapore Sun Yat Sen Univ, Canc Ctr, Breast Oncol, Guangzhou, Guangdong, Peoples R China Med Coll Wisconsin, Pharmacol & Toxicol, Wauwatosa, WI USA Queensland Univ Technol, Sci & Engn Fac, Sch Chem Phys & Mech Engn, Brisbane, Qld, Australia Univ Turin, Dept Mol Biotechnol & Hlth Sci, Turin, Italy Univ Tehran Med Sci, Sch Rehabil, Physiotherapy Dept, Tehran, Iran Univ Helsinki, Dept Forest Sci, Helsinki, Finland Univ Messina, Human Pathol, Messina, Italy AO Papardo Hosp Messina, Messina, Italy Univ Ibadan, Coll Med, Inst Child Hlth, Ibadan, Nigeria King Faisal Univ, Coll Med, Fac Ophthalmol, Al Hasa, Saudi Arabia Univ Stirling, Inst Social Mkt, Stirling, Scotland Saveh Univ Med Sci, Social Determinants Hlth Res Ctr, Saveh, Iran Gakujutsu Shien Co Ltd, Tokyo, Japan Chinese Acad Sci, Inst Geochem, Guiyang, Guizhou, Peoples R China Univ Plymouth, Med Sch, Plymouth, Devon, England CHU Toulouse, Immunol, Toulouse, France Azorean Biodivers Grp, Ctr Ecol Evolut & Environm Changes, Azores, Portugal Univ Acores, Azores, Portugal RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan Peking Univ, Sch Publ Hlth, Dept Global Hlth, Beijing, Peoples R China Chang Gung Univ, Chang Gung Mem Hosp, Dept Neurol, Linkou Med Ctr, Taoyuan, Taiwan Chang Gung Univ, Coll Med, Taoyuan, Taiwan Univ Malawi, Coll Med, Biomed Sci Dept, Blantyre, Malawi Univ Malawi, Coll Med, Pharm Dept, Blantyre, Malawi Bioself Commun, Biocurat, Marseille, France Peking Univ, Hosp 3, Dept Neurol, Beijing, Peoples R China Ahmadu Bello Univ, Fac Basic Clin Sci, Coll Hlth Sci, Dept Pathol, Zaria, Nigeria Dalhousie Univ, Dept Anesthesia Pain Management & Perioperat Med, Halifax, NS, Canada VisMederi Srl, Siena, Italy UCL, Canc Res UK, London, England UCL, UCL Canc Trials Ctr, London, England Univ Ottawa, Family Med, Ottawa, ON, Canada China Agr Univ, Coll Engn, Beijing, Peoples R China Leiden Univ, Leiden Acad Ctr Drug Res, Div Drug Discovery & Safety, Leiden, Netherlands Sun Yat Sen Univ, Affiliated Hosp 1, Dept Intervent Radiol, Guangzhou, Guangdong, Peoples R China Amer Univ Beirut, Med Ctr, Infect Dis, Beirut, Lebanon Sheffield Hallam Univ, Dept Social Work Social Care & Community Studies, Sheffield, S Yorkshire, England Mechnikov Res Inst Vaccines & Sera, Viral Hepatitis, Moscow, Russia Univ Ottawa, Pediat, Ottawa, ON, Canada Vreden Russian Res Inst Traumatol & Orthopaed, Dept Wound Infect Treatment & Prevent, St Petersburg, Russia Hangzhou Ctr Dis Control & Prevent, Dept TB Control & Prevent, Hangzhou, Zhejiang, Peoples R China Kaohsiung Med Univ, Dept Biotechnol, Kaohsiung, Taiwan Zoetis, Diagnost, Kalamazoo, MI USA Aintree Univ Hosp NHS Fdn Trust, Head & Neck Oncol Res, Liverpool, Merseyside, England Wrightington Hosp, Trauma & Orthopaed, Manchester, Lancs, England Loyola Univ, Med Ctr, Dept Psychiat, 2160 S 1st Ave, Maywood, IL 60153 USA Atkins Vet Serv, Microbiol, Calgary, AB, Canada Univ Porto, FADEUP, CIAFEL, Porto, Portugal Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore Kangwon Natl Univ, Coll Biotechnol & Biosci, Dept Food Sci & Biotechnol, Chunchon, South Korea Kakatiya Med Coll, Internal Med, Warangal, Telangana, India Univ Antioquia, Vet Med Sch, CIBAV Res Grp, Medellin, Colombia IISER, Dept Phys, Soft & Act Matter Grp, Tirupati 517507, Andhra Pradesh, India Univ Rosario, Sch Med & Hlth, Ctr Studies Phys Activ Measurements, Bogota, Colombia Univ Hosp Essen, Cardiol & Vasc Med, Essen, Germany Univ Hosp Basel, Endocrinol, Basel, Switzerland Univ Tubingen, Inst Med Genet & Appl Genom, Tubingen, Germany Univ Hosp Munster, Div Gen Internal Med Nephrol & Rheumatolog, Dept Med D, Munster, Germany Univ Kentucky, Dept Nephrol, Lexington, KY USA Univ Freiburg, Dept Anaesthesiol & Crit Care, Med Ctr, Freiburg, Germany Univ Calif Irvine, Dept Med, Orange, CA 92668 USA Univ Hosp Leuven, Dept Urol, Leuven, Belgium Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China Univ Florida, Orthopaed & Rehabil, Gainesville, FL USA Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Mol Oncol & Epigenet, Chongqing, Peoples R China Tsinghua Univ, Dept Chem Engn, Beijing, Peoples R China Yonsei Univ, Coll Med, Dept Pharmacol, Seoul, South Korea Childrens Hosp Kings Daughters, Eastern Virginia Med Sch, Dept Pediat, Norfolk, VA USA China Three Gorges Univ, Coll Sci, Dept Math, Yichang, Peoples R China Xiangtan Univ, Coll Informat Engn, Xiangtan, Hunan, Peoples R China Univ Hlth Network, Mood Disorders & Psychopharmacol, Toronto, ON, Canada Sao Paulo State Univ UNESP, Dept Anim Sci, Sao Paulo, Brazil Sao Paulo State Univ, Vet Clin, Sao Paulo, Brazil

Published
2019

31. Data sharing policies across health research globally: Cross-sectional meta-research study.

Author

Tan AC, Webster AC, Libesman S, Yang Z, Chand RR, Liu W, Palacios T, Hunter KE, and Seidler AL

Subjects
Cross-Sectional Studies, Humans, Registries, COVID-19, Clinical Trials as Topic, Periodicals as Topic, Information Dissemination, Biomedical Research
Abstract

Background: Data sharing improves the value, synthesis, and integrity of research, but rates are low. Data sharing might be improved if data sharing policies were prominent and actionable at every stage of research. We aimed to systematically describe the epidemiology of data sharing policies across the health research lifecycle., Methods: This was a cross-sectional analysis of the data sharing policies of the largest health research funders, all national ethics committees, all clinical trial registries, the highest-impact medical journals, and all medical research data repositories. Stakeholders' official websites, online reports, and other records were reviewed up to May 2022. The strength and characteristics of their data sharing policies were assessed, including their policies on data sharing intention statements (a.k.a. data accessibility statements) and on data sharing specifically for coronavirus disease studies. Data were manually extracted in duplicate, and policies were descriptively analysed by their stakeholder and characteristics., Results: Nine hundred and thirty-five eligible stakeholders were identified: 110 funders, 124 ethics committees, 18 trial registries, 273 journals, and 410 data repositories. Data sharing was required by 41% (45/110) of funders, no ethics committees or trial registries, 19% (52/273) of journals and 6% (24/410) of data repositories. Among funder types, a higher proportion of private (63%, 35/55) and philanthropic (67%, 4/6) funders required data sharing than public funders (12%, 6/49)., Conclusion: Data sharing requirements, and even recommendations, were insufficient across health research. Where data sharing was required or recommended, there was limited guidance on implementation. We describe multiple pathways to improve the implementation of data sharing. Public funders and ethics committees are two stakeholders with particularly important untapped opportunities., (© 2024 The Author(s). Research Synthesis Methods published by John Wiley & Sons Ltd.)

Published
2024
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32. The classification of melanocytic gene signatures.

Author

Hu M, Coleman S, Judson-Torres RL, and Tan AC

Subjects
Humans, Skin Neoplasms genetics, Skin Neoplasms classification, Skin Neoplasms pathology, Phenotype, Melanoma genetics, Melanoma classification, Melanoma pathology, Melanocytes metabolism, Melanocytes pathology, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Transcriptome
Abstract

Gene expression profiling technologies have revolutionized cell biology, enabling researchers to identify gene signatures linked to various biological attributes of melanomas, such as pigmentation status, differentiation state, proliferative versus invasive capacity, and disease progression. Although the discovery of gene signatures has significantly enhanced our understanding of melanocytic phenotypes, reconciling the numerous signatures reported across independent studies and different profiling platforms remains a challenge. Current methods for classifying melanocytic gene signatures depend on exact gene overlap and comparison with unstandardized baseline transcriptomes. In this study, we aimed to categorize published gene signatures into clusters based on their similar patterns of expression across clinical cutaneous melanoma specimens. We analyzed nearly 800 melanoma samples from six gene expression repositories and developed a classification framework for gene signatures that is resilient against biases in gene identification across profiling platforms and inconsistencies in baseline standards. Using 39 frequently cited published gene signatures, our analysis revealed seven principal classes of gene signatures that correlate with previously identified phenotypes: Differentiated, Mitotic/MYC, AXL, Amelanotic, Neuro, Hypometabolic, and Invasive. Each class is consistent with the phenotypes that the constituent gene signatures represent, and our classification method does not rely on overlapping genes between signatures. To facilitate broader application, we created WIMMS (what is my melanocytic signature, available at https://wimms.tanlab.org/), a user-friendly web application. WIMMS allows users to categorize any gene signature, determining its relationship to predominantly cited signatures and its representation within the seven principal classes., (© 2024 The Author(s). Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)

Published
2024
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33. Fingerprinting Tertiary Structure in Complex RNAs Using Single-Molecule Correlated Chemical Probing.

Author

Tan AC, Irving PS, Koehn JT, Jin S, Qiu DY, and Weeks KM

Subjects
RNA chemistry, Base Pairing, Models, Molecular, Single Molecule Imaging methods, Nucleic Acid Conformation, Riboswitch
Abstract

Single-molecule correlated chemical probing (smCCP) is an experimentally concise strategy for characterizing higher-order structural interactions in RNA. smCCP data yield rich, but complex, information about base pairing, conformational ensembles, and tertiary interactions. To date, through-space communication specifically measuring RNA tertiary structure has been difficult to isolate from structural communication reflective of other interactions. Here, we introduce mutual information as a filtering metric to isolate tertiary structure communication contained within smCCP data and use this strategy to characterize the structural ensemble of the SAM-III riboswitch. We identified an smCCP fingerprint that is selective for states containing a tertiary structure that forms concurrently with cognate ligand binding. We then successfully applied mutual information filters to independent RNAs and isolated through-space tertiary interactions in riboswitches and large RNAs with complex structures. smCCP, coupled with mutual information criteria, can now be used as a tertiary structure discovery tool, including to identify specific states in an ensemble that have a higher-order structure. These studies pave the way for the use of the straightforward smCCP experiment for discovery and characterization of tertiary structure motifs in complex RNAs.

Published
2024
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34. The impact of the COVID-19 pandemic on dyslipidemia in peritoneal dialysis patients.

Author

Chen FY, Li SE, Tsai JE, Lu PY, Li YH, Tan AC, Li SY, Chuang YF, Chen CM, and Lin CC

Abstract

Background: The COVID-19 pandemic has had a profound impacted on various aspects of society, including the healthcare system and patient care. In this context, this study aims to evaluate the impact of COVID-19 control strategies on the lipid profile and blood sugar levels of peritoneal dialysis (PD) patients in Taiwan, a crucial focus for understanding the pandemic's influence on individuals with chronic kidney disease (CKD)., Methods: A retrospective cohort study was conducted, analyzing data from the medical records of 170 PD patients who visited the nephrology division of Taipei Veterans General Hospital in 2021. The generalized estimating equations method was used to analyze the longitudinal data and assess the changes in biomarker levels over different periods. Covariates were taken into consideration in the statistical models. The data were analyzed using R 4.3.0., Results: The study enrolled 70 males (41%) and 100 females (59%), with an average age of 56 years old. Over 12 months in 2021, from the first period (January-April: pre-COVID-19) to the second period (May-August: COVID-19 surge), there was a notable decline in both high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels, and a significant surge in triglyceride (TG) levels. However, total cholesterol (TC) and hemoglobin (HbA1c) levels remained stable. Furthermore, the TG to HDL, TG to LDL, TC to HDL, and TC to LDL ratios were analyzed, revealing a pronounced increase during the second period., Conclusion: Our findings underscore the significant impact of COVID-19 pandemic-related disruptions in the healthcare system and the subsequent management strategies on dyslipidemia in PD patients while not affecting dysglycemia. These results provide valuable insights for healthcare professionals to enhance their strategies and interventions for CKD patients undergoing PD during a pandemic., Competing Interests: Conflicts of Interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Published
2024
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35. The Tumor Microbiome as a Predictor of Outcomes in Patients with Metastatic Melanoma Treated with Immune Checkpoint Inhibitors.

Author

Dravillas CE, Coleman SS 4th, Hoyd R, Caryotakis G, Denko L, Chan CHF, Churchman ML, Denko N, Dodd RD, Eljilany I, Hardikar S, Husain M, Ikeguchi AP, Jin N, Ma Q, McCarter MD, Osman AEG, Robinson LA, Singer EA, Tinoco G, Ulrich CM, Zakharia Y, Spakowicz D, Tarhini AA, and Tan AC

Subjects
Humans, Male, Female, Middle Aged, Aged, Adult, Aged, 80 and over, Young Adult, Treatment Outcome, Skin Neoplasms drug therapy, Skin Neoplasms microbiology, Skin Neoplasms immunology, Skin Neoplasms pathology, Neoplasm Metastasis, Prognosis, Melanoma drug therapy, Melanoma microbiology, Melanoma immunology, Melanoma secondary, Immune Checkpoint Inhibitors therapeutic use, Immune Checkpoint Inhibitors pharmacology, Microbiota drug effects
Abstract

Emerging evidence supports the important role of the tumor microbiome in oncogenesis, cancer immune phenotype, cancer progression, and treatment outcomes in many malignancies. In this study, we investigated the metastatic melanoma tumor microbiome and its potential roles in association with clinical outcomes, such as survival, in patients with metastatic disease treated with immune checkpoint inhibitors (ICI). Baseline tumor samples were collected from 71 patients with metastatic melanoma before treatment with ICIs. Bulk RNA sequencing (RNA-seq) was conducted on the formalin-fixed, paraffin-embedded and fresh frozen tumor samples. Durable clinical benefit (primary clinical endpoint) following ICIs was defined as overall survival >24 months and no change to the primary drug regimen (responders). We processed RNA-seq reads to carefully identify exogenous sequences using the {exotic} tool. The age of the 71 patients with metastatic melanoma ranged from 24 to 83 years, 59% were male, and 55% survived >24 months following the initiation of ICI treatment. Exogenous taxa were identified in the tumor RNA-seq, including bacteria, fungi, and viruses. We found differences in gene expression and microbe abundances in immunotherapy-responsive versus nonresponsive tumors. Responders showed significant enrichment of bacteriophages in the phylum Uroviricota, and nonresponders showed enrichment of several bacteria, including Campylobacter jejuni. These microbes correlated with immune-related gene expression signatures. Finally, we found that models for predicting prolonged survival with immunotherapy using both microbe abundances and gene expression outperformed models using either dataset alone. Our findings warrant further investigation and potentially support therapeutic strategies to modify the tumor microbiome in order to improve treatment outcomes with ICIs., Significance: We analyzed the tumor microbiome and interactions with genes and pathways in metastatic melanoma treated with immunotherapy and identified several microbes associated with immunotherapy response and immune-related gene expression signatures. Machine learning models that combined microbe abundances and gene expression outperformed models using either dataset alone in predicting immunotherapy responses., (©2024 The Authors; Published by the American Association for Cancer Research.)

Published
2024
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37. The Tumor Microbiome Reacts to Hypoxia and Can Influence Response to Radiation Treatment in Colorectal Cancer.

Author

Benej M, Hoyd R, Kreamer M, Wheeler CE, Grencewicz DJ, Choueiry F, Chan CHF, Zakharia Y, Ma Q, Dodd RD, Ulrich CM, Hardikar S, Churchman ML, Tarhini AA, Robinson LA, Singer EA, Ikeguchi AP, McCarter MD, Tinoco G, Husain M, Jin N, Tan AC, Osman AEG, Eljilany I, Riedlinger G, Schneider BP, Benejova K, Kery M, Papandreou I, Zhu J, Denko N, and Spakowicz D

Subjects
Animals, Mice, Humans, Microbiota radiation effects, Cell Line, Tumor, Female, Colorectal Neoplasms radiotherapy, Colorectal Neoplasms microbiology, Tumor Hypoxia radiation effects, Mice, Inbred BALB C, Mice, Nude
Abstract

Tumor hypoxia has been shown to predict poor patient outcomes in several cancer types, partially because it reduces radiation's ability to kill cells. We hypothesized that some of the clinical effects of hypoxia could also be due to its impact on the tumor microbiome. Therefore, we examined the RNA sequencing data from the Oncology Research Information Exchange Network database of patients with colorectal cancer treated with radiotherapy. We identified microbial RNAs for each tumor and related them to the hypoxic gene expression scores calculated from host mRNA. Our analysis showed that the hypoxia expression score predicted poor patient outcomes and identified tumors enriched with certain microbes such as Fusobacterium nucleatum. The presence of other microbes, such as Fusobacterium canifelinum, predicted poor patient outcomes, suggesting a potential interaction between hypoxia, the microbiome, and radiation response. To experimentally investigate this concept, we implanted CT26 colorectal cancer cells into immune-competent BALB/c and immune-deficient athymic nude mice. After growth, in which tumors passively acquired microbes from the gastrointestinal tract, we harvested tumors, extracted nucleic acids, and sequenced host and microbial RNAs. We stratified tumors based on their hypoxia score and performed a metatranscriptomic analysis of microbial gene expression. In addition to hypoxia-tropic and -phobic microbial populations, analysis of microbial gene expression at the strain level showed expression differences based on the hypoxia score. Thus, hypoxia gene expression scores seem to associate with different microbial populations and elicit an adaptive transcriptional response in intratumoral microbes, potentially influencing clinical outcomes., Significance: Tumor hypoxia reduces radiotherapy efficacy. In this study, we explored whether some of the clinical effects of hypoxia could be due to interaction with the tumor microbiome. Hypoxic gene expression scores associated with certain microbes and elicited an adaptive transcriptional response in others that could contribute to poor clinical outcomes., (©2024 The Authors; Published by the American Association for Cancer Research.)

Published
2024
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38. Real-world outcomes of pemetrexed-platinum chemotherapy plus osimertinib after progression on first-line osimertinib in advanced EGFR-mutated NSCLC.

Author

Saw SPL, Low YF, Lai GGY, Chan LL, Wong WKY, Tsui G, Chen OH, Seet AOL, Tan WC, Tan AC, Chan JWK, Teh YL, Tan WL, Ng QS, Ang MK, Kanesvaran R, Lim DWT, Tan DSW, Mok TSK, and Li MSC

Subjects
Female, Humans, Male, Middle Aged, Disease Progression, Indoles, Platinum therapeutic use, Platinum administration & dosage, Pyrimidines, Retrospective Studies, Treatment Outcome, Acrylamides therapeutic use, Aniline Compounds therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung pathology, ErbB Receptors genetics, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms mortality, Lung Neoplasms pathology, Mutation, Pemetrexed therapeutic use, Pemetrexed administration & dosage
Abstract

Objectives: First-line pemetrexed-platinum chemotherapy + osimertinib(Pem-Plat-Osi) improves progression-free survival as compared to osimertinib alone in advanced epidermal growth factor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, many patients are hesitant to commence chemotherapy upfront. We describe outcomes to Pem-Plat-Osi after first-line osimertinib failure., Materials and Methods: Patients with advanced EGFR-mutated (ex19del/L858R) NSCLC who had Pem-Plat-Osi between 1/7/2018-30/9/2023 after progression on first-line osimertinib at National Cancer Centre Singapore, Prince of Wales Hospital and Chinese University of Hong Kong were identified. Key endpoints were time to treatment failure (TTF) and overall survival (OS)., Results: A total of 60 patients were included. Median age at diagnosis was 62, 53.3 % (32/60) were male and 76.7 % (46/60) were never smokers. Ex19del comprised 56.7 % (34/60) and L858R 43.3 % (26/60). Baseline central nervous system (CNS) metastases were present in 66.7 % (40/60). Median TTF on osimertinib (TTF1) was 14.4 months(m) and median time to initiation of Pem-Plat-Osi was 41 days(d) (range 0-652) after progression on osimertinib. Partial response (PR) or stable disease to Pem-Plat-Osi was achieved in 81.7 %(49/60). Intracranial disease control was achieved in 90.6 % (29/32) of patients with measurable CNS metastases, including those who did not undergo brain radiotherapy. At median follow up of 31.2 m, median TTF on Pem-Plat-Osi (TTF2) was 6.6 m. Median TTF1 + TTF2 was 23.4 m and median OS was 34.2 m. Survival outcomes were similar comparing ex19del and L858R (median TTF1 + TTF2 21.8 m vs 23.5 m, p = 0.90; median OS 34.2 m vs 36.8 m, p = 0.37) and in patients without/with baseline CNS metastases (median TTF1 + TTF2 21.8 m vs 23.4 m, p = 0.44; median OS 36.2 m vs 31.9 m, p = 0.65). TTF1 duration was not significantly associated with TTF2 (p = 0.76). Patients who started Pem-Plat-Osi within 20d of progression on osimertinib had significantly longer TTF2 as compared to patients who started after 20d (median 8.4 m versus 6.0 months, p = 0.03), which remained statistically significant on multivariable analysis., Conclusions: Our real-world data supports the efficacy of Pem-Plat-Osi after progression on first-line osimertinib, including L858R and baseline CNS metastases. Chemotherapy initiation within 20d of Osi progression was predictive of superior TTF2., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr Saw reports grants from Astra Zeneca, consulting fees from Pfizer, Bayer, Astra Zeneca and Daiichi Sankyo, honoraria from Astra Zeneca, MSD, Bristol-Myers Squibb, Daiichi Sankyo, Roche and Takeda, meeting support from MSD and Astra Zeneca from Pfizer, advisory board participation from Astra Zeneca, Daiichi Sankyo and Pfizer, outside the submitted work. Dr Lai reports grants from Astra Zeneca, Roche and Amgen and meeting support from Astra Zeneca, outside the submitted work. Dr Chan reports meeting support from Roche, Astra Zeneca and Ipsen, outside the submitted work. Dr W.C. Tan reports grants from Singhealth, honoraria from Merck & Co, MSD and Astra Zeneca, meeting support from Ipsen Pharmaceuticals and Merck & Co, outside the submitted work. Dr A. Tan reports consulting fees from Amgen, Bayer and Pfizer, honoraria from Amgen, Guardant Health, Takeda, Juniper Biologics and Astra Zeneca, outside the submitted work. Dr W.L. Tan reports grants from Astra Zeneca, honoraria from Novartis and Merck, meeting support from Astra Zeneca, MSD, Boehringer Ingelheim and Ipsen, outside the submitted work. Dr Kanesvaran reports honoraria from Astellas, MSD and Ipsen, leadership roles in ESMO and SIOG, outside the submitted work. Dr Lim reports grants from Taiho Pharmaceuticals, consulting fees from Daiichi Sankyo, Amgen, Janssen and Alentis Therapeutics, honoraria from MSD and Takeda, meeting support from Astra Zeneca and Alentis Therapeutics, outside the submitted work. Dr. Tan reports grants from ACM Biolabs, Amgen, Astra Zeneca, Bayer and Pfizer, consulting fees from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, DKSH, GlaxoSmithKline, Merck, Novartis, Pfizer, Roche and Takeda, honoraria from Amgen, Bayer, Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, Takeda, Beigene, Regeneron, Zymeworks, meeting support from Bayer, Merck, Pfizer, Regeneron and Zymeworks, outside the submitted work. Dr Mok reportsgrantsfrom AstraZeneca, Bristol Myers Squibb, G1 Therapeutics, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Roche, SFJ, Takeda, XCovery, consulting fees from Abbvie Inc, ACEA Pharma, Adagene, Alentis Therapeutics AG, Alpha Biopharma Co., Ltd, Amgen, Amoy Diagnostics Co,AnHeart Therapeutics Inc,AVEO Pharmaceuticals, Inc,Bayer Healthcare Pharmaceuticals Ltd,BeiGene,BerGenBio ASA,Berry Oncology,Boehringer Ingelheim,Blueprint Medicines Corporation,Bristol Myers Squibb,Bowtie Life Insurance Company Limited,Bridge Biotherapeutics Inc,Covidien LP,C4 Therapeutics Inc,Cirina Ltd,CStone Pharmaceuticals,Curio Science,D3 Bio Ltd,Da Volterra,Daiichi Sankyo,Eisai,Elevation Oncology,F. Hoffmann-La Roche Ltd./ Genentech,Fishawack Facilitate Ltd,G1 Therapeutics Inc,geneDecode Co., Ltd,Gilead Sciences, Inc,GLG’s Healthcare,Gritstone Oncology, Inc,Guardant Health,Hengrui Therapeutics Inc,HiberCell, Inc.,HutchMed,Ignyta Inc.,Illumina Inc.,IncyteCorporation,Inivata,IQVIA,Janssen,Lakeshore Biotech Ltd,Lilly,Lunit USA, Inc,Loxo-Oncology,Lucence Health Inc,Medscape LLC/ WebMD,Medtronic,Merck Serono,MSD,Mirati Therapeutics Inc,MiRXES,MoreHealth,Novartis,Novocure GmbH,Omega Therapeutics Inc,OrigiMed,OSE Immunotherapeutics,PeerVoice,Pfizer,PrIME Oncology,Prenetics Global Limited,Puma Biotechnology Inc,Qiming Development (HK) Ltd,Regen Medtech Holdings Limited,Regeneron Pharmaceuticals Inc.,Roche Pharmaceuticals/ Diagnostics/ Foundation One,Sanofi-Aventis,SFJ Pharmaceutical Ltd,Simcere of America Inc,Synergy Research,Summit Therapeutics Sub, Inc,Takeda Pharmaceuticals HK Ltd,Tigermed,Vertex Pharmaceuticals,Virtus Medical Group,XENCOR, Inc,Yuhan Corporation,honorariafromACEA Pharma,Alpha Biopharma Co.Ltd,Amgen,Amoy Diagnostics Co. Ltd,AstraZeneca (before 1/1/19),BeiGene,BI,BMS,Daiichi Sankyo,Daz Group,Fishawack Facilitate Ltd.,InMed Medical Communication,Janssen Pharmaceutica NV,Jiahui Holdings Co. Limited,LiangYiHui Healthcare,Lilly,Lucence Health Inc.,MD Health Brazil,Medscape LLC,Merck Pharmaceuticals HK Ltd.,Merck Sharp & Dohme,MiRXES,Novartis,OrigiMed Co. Ltd.,P. Permanyer SL,PeerVoice, Physicians’ Education Resource,Pfizer,PrIME Oncology,Research to Practice,Roche Pharmaceuticals/ Diagnostics/ Foundation One,Sanofi-Aventis,Shanghai BeBirds Translation & Consulting Co. Ltd,Taiho Pharmaceutical Co. Ltd,Takeda Oncology,Touch Independent Medical Education Ltd,meeting support fromNovartis,Roche,Pfizer, AstraZeneca,Daiichi Sankyo,BI,MiRXES,BMS,MSD,Abbvie,Zai Lab,Liangyihui,advisory boardforAbbVie Inc.,ACEA Pharma,Amgen,AstraZeneca,Alentis Therapeutics AG,BerGenBio ASA,Berry Oncology,Blueprint Medicines Corporation,Boehringer Ingelheim,Bowtie Life Insurance Co Ltd,Bristol Myers Squibb,C4 Therapeutics Inc,Covidien LP,CStone Pharmaceuticals,Curio Science,D3 Bio Ltd.,Daiichi Sankyo Inc.,Eisai,Fishawack Facilitate Ltd.,G1 Therapeutics Inc.,Gilead Sciences Inc.,Gritstone Oncology Inc,Guardant Health,geneDecode Co. Ltd. (uncompensated),Hengrui Therapeutics Inc.,HutchMed,Ignyta Inc.,Incyte Corporation,Imagene AI Ltd.,Inivata,IQVIA,Janssen,Lakeshore Biotech,Lily,Loxo-Oncology Inc.,Lunit Inc,Merck Serono,Merck Sharp & Dohme,Mirati Therapeutics Inc.,MiRXES Group,Novartis,OrigiMed,Pfizer,Prenetics Global Limited,Puma Biotechnology Inc.,Roche/Genentech,Regeneron Pharmaceuticals Inc,Sanofi-Aventis R&D,SFJ Pharmaceutical,Simcere of America Inc.,Simcere Zaiming, Inc.,Takeda,Vertex Pharmaceuticals,Virtus Medical Group,XENCOR, Inc,Yuhan Corporation,being member in the Board of DirectorsforAstraZeneca PLC,HutchMed,Aurora,Insighta,holding stock / stock optionofAstraZeneca,Aurora Tele-Oncology Ltd.,Biolidics Ltd.,HutchMed,Prenetics Global Limited,D3 Bio,Lunit,Bowtie Life Insurance, Lakeshore Biotech Ltd,Loxo-oncology,Virtus Medical Group,Yinson Capital Pte. Ltd.,Phanes Therapeutics, Inc.,Insighta,Alentis Therapeutics AG, outside the submitted work. Dr Li reports grants from Gilead, MSD and Astra Zeneca, honoraria from Astra Zeneca, Novartis, Amgen, Pfizer. Takeda, ACE Oncology, Merck, Guardant Health, Gilead, Janssen and MSD, meeting support from Astra Zeneca, Pfizer, Daiichi Sankyo, MSD, Amgen, advisory board for Astra Zeneca, Pfizer, AnHeart Therapeutics, Amgen, Takeda, Yuhan and Blossomhill therapeutics, outside the submitted work. No other conflicts of interest were declared.]., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2024
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39. Transcriptome Deconvolution Reveals Absence of Cancer Cell Expression Signature in Immune Checkpoint Blockade Response.

Author

Guo YA, Kulshrestha T, Chang MM, Kassam I, Revkov E, Rizzetto S, Tan AC, Tan DSW, Tan IB, and Skanderup AJ

Subjects
Humans, Gene Expression Profiling, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Gene Expression Regulation, Neoplastic, Tumor Microenvironment immunology, Tumor Microenvironment genetics, B7-H1 Antigen genetics, B7-H1 Antigen metabolism, Immune Checkpoint Inhibitors therapeutic use, Immune Checkpoint Inhibitors pharmacology, Neoplasms genetics, Neoplasms immunology, Neoplasms drug therapy, Transcriptome
Abstract

Immune checkpoint therapy (ICB) has conferred significant and durable clinical benefit to some patients with cancer. However, most patients do not respond to ICB, and reliable biomarkers of ICB response are needed to improve patient stratification. Here, we performed a transcriptome-wide meta-analysis across 1,486 tumors from ICB-treated patients and tumors with expected ICB outcomes based on microsatellite status. Using a robust transcriptome deconvolution approach, we inferred cancer- and stroma-specific gene expression differences and identified cell-type specific features of ICB response across cancer types. Consistent with current knowledge, stromal expression of CXCL9, CXCL13, and IFNG were the top determinants of favorable ICB response. In addition, we identified a group of potential immune-suppressive genes, including FCER1A, associated with poor response to ICB. Strikingly, PD-L1 expression in stromal cells, but not cancer cells, is correlated with ICB response across cancer types. Furthermore, the unbiased transcriptome-wide analysis failed to identify cancer-cell intrinsic expression signatures of ICB response conserved across tumor types, suggesting that cancer cells lack tissue-agnostic transcriptomic features of ICB response., Significance: Our results challenge the prevailing dogma that cancer cells present tissue-agnostic molecular markers that modulate immune activity and ICB response, which has implications on the development of improved ICB diagnostics and treatments., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Published
2024
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40. Oncogene-Driven Non-Small Cell Lung Cancers in Patients with a History of Smoking Lack Smoking-Induced Mutations.

Author

Huang CY, Jiang N, Shen M, Lai GG, Tan AC, Jain A, Saw SP, Ang MK, Ng QS, Lim DW, Kanesvaran R, Tan EH, Tan WL, Ong BH, Chua KL, Anantham D, Takano AM, Lim KH, Tam WL, Sim NL, Skanderup AJ, Tan DS, and Rozen SG

Subjects
Humans, Male, Female, Middle Aged, Aged, Adult, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms genetics, Lung Neoplasms pathology, Mutation, Oncogenes genetics, Smoking adverse effects, Smoking genetics
Abstract

Non-small cell lung cancers (NSCLC) in nonsmokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in nonsmokers, alterations in these "nonsmoking-related oncogenes" (NSRO) also occur in smokers. To better understand the clonal architecture and genomic landscape of NSRO-driven tumors in smokers compared with typical-smoking NSCLCs, we investigated genomic and transcriptomic alterations in 173 tumor sectors from 48 NSCLC patients. NSRO-driven NSCLCs in smokers and nonsmokers had similar genomic landscapes. Surprisingly, even in patients with prominent smoking histories, the mutational signature caused by tobacco smoking was essentially absent in NSRO-driven NSCLCs, which was confirmed in two large NSCLC data sets from other geographic regions. However, NSRO-driven NSCLCs in smokers had higher transcriptomic activities related to the regulation of the cell cycle. These findings suggest that, whereas the genomic landscape is similar between NSRO-driven NSCLC in smokers and nonsmokers, smoking still affects the tumor phenotype independently of genomic alterations., Significance: Non-small cell lung cancers driven by nonsmoking-related oncogenes do not harbor genomic scars caused by smoking regardless of smoking history, indicating that the impact of smoking on these tumors is mainly nongenomic., (©2024 American Association for Cancer Research.)

Published
2024
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41. [Relationship between serum 1, 5-anhydroglucitol level and insulin resistance, microvascular complications in type 2 diabetes mellitus].

Author

Tan AC, Zhang Q, Cheng J, and Yan XH

Subjects
Humans, Cross-Sectional Studies, Retrospective Studies, Blood Glucose, Male, Female, Insulin blood, Middle Aged, Diabetic Angiopathies blood, Diabetes Mellitus, Type 2 blood, Diabetes Mellitus, Type 2 complications, Insulin Resistance, Deoxyglucose blood, Deoxyglucose analogs & derivatives
Abstract

Objective: To explore the relationship between serum 1, 5-dehydratoglucitol (1, 5-AG) level and insulin resistance, microvascular complications in patients with type 2 diabetes mellitus (T2DM). Methods: The clinical data of 836 patients with T2DM admitted to the Changsha Central Hospital Affiliated to University of South China from May to December 2023 were retrospectively and cross-sectionally analyzed. Serum 1, 5-AG levels were detected by pyranose oxidase method. According to the microvascular complications (diabetic peripheral neuropathy, diabetic nephropathy, diabetic retinopathy), the patients were divided into simple group (no microvascular complications, n =490), complication group 1 (1 microvascular complications, n =217), and complication group 2 (2 or more microvascular complications, n =129). The relationship between serum 1, 5-AG level and the related indicators of insulin resistance in T2DM patients were explored by Spearman correlation analysis, and the influencing factors of microvascular complications in T2DM patients were explored by multiple ordered logistic regression analysis. Results: The levels of FBG(fasting blood glucose) [(7.37±0.56) mmol/L], FINS(fasting insulin) [(11.34±1.86) mU/L] and HOMA-IR(homeostatic model assessment of insulin resistance) (0.96±0.31) in simple group were lower than those in complication group 1 [(8.37±1.02) mmol/L, (16.26±2.32) mU/L, (1.32±0.41)], complication group 2 [(10.25±2.13) mmol/L, (18.53±2.67) mU/L, (1.54±0.44)], and FBG, FINS and HOMA-IR in complication group 1 were lower than those in complication group 2, and the differences were statistically significant ( F =537.470, 791.690, 136.340, P <0.001). Serum 1, 5-AG level in simple group [77.16 (16.30, 128.07) μg/ml] was higher than that in complication group 1 [51.05 (14.67, 63.18) μg/ml] and complication group 2 [30.42 (12.53, 47.26) μg/ml], and the serum level of 1, 5-AG in complication group 1 was higher than that in complication group 2, and the difference was statistically significant ( H =210.020, P <0.001). The results of Spearman correlation analysis showed that serum 1, 5-AG level was negatively correlated with FBG, FINS and HOMA-IR in T2DM patients ( r =-0.431, -0.372, -0.546, P <0.001). The results of multiple ordered logistic regression analysis showed that Longer duration of diabetes ( OR =2.261, 95% CI : 1.564-3.269), increased HbA1c ( OR =2.040, 95% CI : 1.456-2.858), and increased HOMA-IR ( OR =2.158, 95% CI : 1.484-3.137) and decreased 1, 5-AG ( OR =2.512, 95% CI : 1.691-3.732) were independent risk factors for microvascular complications in T2DM patients ( P <0.05). The results of ROC curve analysis showed that the area under the curve of serum 1, 5-AG in the identification of one microvascular complication was 0.763 (95% CI : 0.731-0.795), and the area under the curve of serum 1, 5-AG in the identification of two or more microvascular complications was 0.730 (95% CI : 0.692-0.767). Conclusion: Serum 1, 5-AG level is negatively correlated with insulin resistance in T2DM patients. Low serum 1, 5-AG level may be an independent risk factor for microvascular complications in T2DM patients.

Published
2024
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42. SASH1 S519N Variant Links Skin Hyperpigmentation and Premature Hair Graying to Dysfunction of Melanocyte Lineage.

Author

Lambert KA, Clements CM, Mukherjee N, Pacheco TR, Shellman SX, Henen MA, Vögeli B, Goldstein NB, Birlea S, Hintzsche J, Caryotakis G, Tan AC, Zhao R, Norris DA, Robinson WA, Wang Y, VanTreeck JG, and Shellman YG

Abstract

A better understanding of human melanocyte (MC) and MC stem cell biology is essential for treating MC-related diseases. This study employed an inherited pigmentation disorder carrying the SASH1 S519N variant in a Hispanic family to investigate SASH1 function in the MC lineage and the underlying mechanism for this disorder. We used a multidisciplinary approach, including clinical examinations, human cell assays, yeast 2-hybrid screening, and biochemical techniques. Results linked early hair graying to the SASH1 S519N variant, a previously unrecognized clinical phenotype in hyperpigmentation disorders. In vitro, we identified SASH1 as a regulator in MC stem cell maintenance and discovered that TNKS2 is crucial for SASH1's role. In addition, the S519N variant is located in one of multiple tankyrase-binding motifs and alters the binding kinetics and affinity of the interaction. In summary, this disorder links both gain and loss of pigmentation in the same individual, hinting to accelerated aging in human MC stem cells. The findings offer insights into the roles of SASH1 and TNKS2 in MC stem cell maintenance and the molecular mechanisms of pigmentation disorders. We propose that a comprehensive clinical evaluation of patients with MC-related disorders should include an assessment and history of hair pigmentation loss., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2024
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43. Detection of circulating tumor DNA with ultradeep sequencing of plasma cell-free DNA for monitoring minimal residual disease and early detection of recurrence in early-stage lung cancer.

Author

Tan AC, Lai GGY, Saw SPL, Chua KLM, Takano A, Ong BH, Koh TPT, Jain A, Tan WL, Ng QS, Kanesvaran R, Rajasekaran T, Kalashnikova E, Renner D, Sudhaman S, Malhotra M, Sethi H, Liu MC, Aleshin A, Lim WT, Tan EH, Skanderup AJ, Ang MK, and Tan DSW

Subjects
Humans, Male, Female, Middle Aged, Aged, Retrospective Studies, Early Detection of Cancer methods, Biomarkers, Tumor genetics, Biomarkers, Tumor blood, Adult, Aged, 80 and over, Multiplex Polymerase Chain Reaction methods, Lung Neoplasms genetics, Lung Neoplasms blood, Lung Neoplasms pathology, Circulating Tumor DNA blood, Circulating Tumor DNA genetics, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local diagnosis, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung blood, Carcinoma, Non-Small-Cell Lung pathology, High-Throughput Nucleotide Sequencing methods, Neoplasm, Residual genetics, Neoplasm, Residual diagnosis, Neoplasm Staging
Abstract

Background: In early-stage non-small cell lung cancer (NSCLC), recurrence is frequently observed. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool to risk stratify patients for recurrence after curative intent therapy. This study aimed to risk stratify patients with early-stage NSCLC via a personalized, tumor-informed multiplex polymerase chain reaction (mPCR) next-generation sequencing assay., Methods: This retrospective cohort study included patients with stage I-III NSCLC. Recruited patients received standard-of-care management (surgical resection with or without adjuvant chemotherapy, followed by surveillance). Whole-exome sequencing of NSCLC resected tissue and matched germline DNA was used to design patient-specific mPCR assays (Signatera, Natera, Inc) to track up to 16 single-nucleotide variants in plasma samples., Results: The overall cohort with analyzed plasma samples consisted of 57 patients. Stage distribution was 68% for stage I and 16% each for stages II and III. Presurgery (i.e., at baseline), ctDNA was detected in 15 of 57 patients (26%). ctDNA detection presurgery was significantly associated with shorter recurrence-free survival (RFS; hazard ratio [HR], 3.54; 95% confidence interval [CI], 1.00-12.62; p = .009). In the postsurgery setting, ctDNA was detected in seven patients, of whom 100% experienced radiological recurrence. ctDNA positivity preceded radiological findings by a median lead time of 2.8 months (range, 0-12.9 months). Longitudinally, ctDNA detection at any time point was associated with shorter RFS (HR, 16.1; 95% CI, 1.63-158.9; p < .0001)., Conclusions: ctDNA detection before surgical resection was strongly associated with a high risk of relapse in early-stage NSCLC in a large unique Asian cohort. Prospective studies are needed to assess the clinical utility of ctDNA status in this setting., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Published
2024
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44. Exploring the Landscape of Immune Checkpoint Inhibitor-Induced Adverse Events Through Big Data Mining of Pan-Cancer Clinical Trials.

Author

Fadlullah MZH, Lin CN, Coleman S, Young A, Naqash AR, Hu-Lieskovan S, and Tan AC

Subjects
Humans, Big Data, Databases, Factual statistics & numerical data, Immune Checkpoint Inhibitors adverse effects, Immune Checkpoint Inhibitors therapeutic use, Data Mining, Neoplasms drug therapy, Clinical Trials as Topic, Drug-Related Side Effects and Adverse Reactions epidemiology
Abstract

Purpose: Immune checkpoint inhibitors (ICIs) have significantly improved the survival of patients with cancer and provided long-term durable benefit. However, ICI-treated patients develop a range of toxicities known as immune-related adverse events (irAEs), which could compromise clinical benefits from these treatments. As the incidence and spectrum of irAEs differs across cancer types and ICI agents, it is imperative to characterize the incidence and spectrum of irAEs in a pan-cancer cohort to aid clinical management., Design: We queried >400 000 trials registered at ClinicalTrials.gov and retrieved a comprehensive pan-cancer database of 71 087 ICI-treated participants from 19 cancer types and 7 ICI agents. We performed data harmonization and cleaning of these trial results into 293 harmonized adverse event categories using Medical Dictionary for Regulatory Activities., Results: We developed irAExplorer (https://irae.tanlab.org), an interactive database that focuses on adverse events in patients administered with ICIs from big data mining. irAExplorer encompasses 71 087 distinct clinical trial participants from 343 clinical trials across 19 cancer types with well-annotated ICI treatment regimens and harmonized adverse event categories. We demonstrated a few of the irAE analyses through irAExplorer and highlighted some associations between treatment- or cancer-specific irAEs., Conclusion: The irAExplorer is a user-friendly resource that offers exploration, validation, and discovery of treatment- or cancer-specific irAEs across pan-cancer cohorts. We envision that irAExplorer can serve as a valuable resource to cross-validate users' internal datasets to increase the robustness of their findings., (© The Author(s) 2024. Published by Oxford University Press.)

Published
2024
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45. The cost-effectiveness of including liquid biopsy into molecular profiling strategies for newly diagnosed advanced non-squamous non-small cell lung cancer in an Asian population.

Author

Liu S, Graves N, and Tan AC

Subjects
Humans, Asian People genetics, Biomarkers, Tumor genetics, Decision Trees, High-Throughput Nucleotide Sequencing, Quality-Adjusted Life Years, Singapore, Carcinoma, Non-Small-Cell Lung diagnosis, Carcinoma, Non-Small-Cell Lung genetics, Cost-Benefit Analysis, Liquid Biopsy economics, Lung Neoplasms diagnosis, Lung Neoplasms genetics
Abstract

Objectives: Liquid biopsy is complementary to tissue biopsy for lung cancer profiling, yet evidence of the cost-effectiveness is limited. This could retard implementation and reimbursement in clinical practice. The aim of this study is to estimate the cost-effectiveness of profiling strategies that include liquid biopsy and to identify the optimal profiling approach for newly diagnosed advanced non-squamous non-small cell lung cancer (NSCLC) in an Asian population using Singapore as an example., Materials and Methods: A decision tree and partitioned-survival model was developed from the Singapore healthcare system's perspective to evaluate the cost-effectiveness of five molecular profiling strategies: either tissue or plasma next-generation sequencing (NGS) alone, a concurrent, and two sequential approaches. Model inputs were informed by local data or published literature. Sensitivity analyses and scenario analyses were undertaken to understand the robustness of the conclusions for decision making. The optimal strategy at different willingness-to-pay (WTP) thresholds was presented by cost-effectiveness acceptability frontier and the expected loss curve., Results: The sequential tissue-plasma NGS approach revealed an additional 0.0981 quality adjusted life years (QALYs) for an extra cost of S$3,074 over a 20-year time horizon compared to tissue NGS alone, resulting in an incremental cost-effectiveness ratio (ICER) of S$31,318/QALY and an incremental net monetary benefit of S$1,343 per patient. The findings were sensitive to the costs of pembrolizumab and osimertinib and the probabilities of re-biopsy after tissue NGS. Sequential plasma-tissue NGS and plasma NGS alone were more costly and less effective than alternatives., Conclusion: The sequential tissue-plasma NGS approach generated the highest net monetary benefit and was the optimal testing strategy when WTP was S$45,000/QALY. It retained superiority but understandably with a higher ICER when expensive, non-first line treatments were included. Overall, its routine clinical practice should be proactively considered for newly diagnosed advanced non-squamous NSCLC in an Asian population., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr A. Tan reported receiving personal fees from Amgen, Bayer, Pfizer, outside the submitted work. The remaining authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2024
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46. Soluble immune-checkpoint factors: a potential immunotherapy biomarker.

Author

Tan AC, Cook SL, and Khasraw M

Subjects
Humans, B7-H1 Antigen, Biomarkers, Immunologic Factors, Immunotherapy, Biomarkers, Tumor, Carcinoma, Non-Small-Cell Lung therapy, Lung Neoplasms therapy
Abstract

There is unmet need for additional biomarkers to better select patients with non-small cell lung cancer (NSCLC) that are likely to benefit from immunotherapy in order to improve patient outcomes, reduce patient toxicity, and relieve the growing burden of healthcare costs. In this issue of the JCI, Hayashi and colleagues evaluated soluble forms of the immune checkpoint molecules PD-L1, PD-1, and CTLA-4 in the plasma of patients with advanced NSCLC who had been treated with anti-PD-1/L1 therapy. The findings suggest that these soluble immune-checkpoint factors may provide a complementary biomarker to PD-L1 IHC, although application into the clinic may not be straightforward.

Published
2024
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47. An Epigenomic fingerprint of human cancers by landscape interrogation of super enhancers at the constituent level.

Author

Liu X, Gillis N, Jiang C, McCofie A, Shaw TI, Tan AC, Zhao B, Wan L, Duckett DR, and Teng M

Subjects
Humans, Epigenomics, Enhancer Elements, Genetic genetics, Gene Expression Regulation, Super Enhancers, Neoplasms genetics
Abstract

Super enhancers (SE), large genomic elements that activate transcription and drive cell identity, have been found with cancer-specific gene regulation in human cancers. Recent studies reported the importance of understanding the cooperation and function of SE internal components, i.e., the constituent enhancers (CE). However, there are no pan-cancer studies to identify cancer-specific SE signatures at the constituent level. Here, by revisiting pan-cancer SE activities with H3K27Ac ChIP-seq datasets, we report fingerprint SE signatures for 28 cancer types in the NCI-60 cell panel. We implement a mixture model to discriminate active CEs from inactive CEs by taking into consideration ChIP-seq variabilities between cancer samples and across CEs. We demonstrate that the model-based estimation of CE states provides improved functional interpretation of SE-associated regulation. We identify cancer-specific CEs by balancing their active prevalence with their capability of encoding cancer type identities. We further demonstrate that cancer-specific CEs have the strongest per-base enhancer activities in independent enhancer sequencing assays, suggesting their importance in understanding critical SE signatures. We summarize fingerprint SEs based on the cancer-specific statuses of their component CEs and build an easy-to-use R package to facilitate the query, exploration, and visualization of fingerprint SEs across cancers., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2024
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48. A Bioinformatics Tool for Identifying Intratumoral Microbes from the ORIEN Dataset.

Author

Wang C, Ma A, Li Y, McNutt ME, Zhang S, Zhu J, Hoyd R, Wheeler CE, Robinson LA, Chan CHF, Zakharia Y, Dodd RD, Ulrich CM, Hardikar S, Churchman ML, Tarhini AA, Singer EA, Ikeguchi AP, McCarter MD, Denko N, Tinoco G, Husain M, Jin N, Osman AEG, Eljilany I, Tan AC, Coleman SS, Denko L, Riedlinger G, Schneider BP, Spakowicz D, and Ma Q

Subjects
Humans, Phylogeny, Computational Biology, High-Throughput Nucleotide Sequencing, Microbiota genetics
Abstract

Evidence supports significant interactions among microbes, immune cells, and tumor cells in at least 10%-20% of human cancers, emphasizing the importance of further investigating these complex relationships. However, the implications and significance of tumor-related microbes remain largely unknown. Studies have demonstrated the critical roles of host microbes in cancer prevention and treatment responses. Understanding interactions between host microbes and cancer can drive cancer diagnosis and microbial therapeutics (bugs as drugs). Computational identification of cancer-specific microbes and their associations is still challenging due to the high dimensionality and high sparsity of intratumoral microbiome data, which requires large datasets containing sufficient event observations to identify relationships, and the interactions within microbial communities, the heterogeneity in microbial composition, and other confounding effects that can lead to spurious associations. To solve these issues, we present a bioinformatics tool, microbial graph attention (MEGA), to identify the microbes most strongly associated with 12 cancer types. We demonstrate its utility on a dataset from a consortium of nine cancer centers in the Oncology Research Information Exchange Network. This package has three unique features: species-sample relations are represented in a heterogeneous graph and learned by a graph attention network; it incorporates metabolic and phylogenetic information to reflect intricate relationships within microbial communities; and it provides multiple functionalities for association interpretations and visualizations. We analyzed 2,704 tumor RNA sequencing samples and MEGA interpreted the tissue-resident microbial signatures of each of 12 cancer types. MEGA can effectively identify cancer-associated microbial signatures and refine their interactions with tumors., Significance: Studying the tumor microbiome in high-throughput sequencing data is challenging because of the extremely sparse data matrices, heterogeneity, and high likelihood of contamination. We present a new deep learning tool, MEGA, to refine the organisms that interact with tumors., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Published
2024
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49. Association of Baseline Tumor-Specific Neoantigens and CD8 + T-Cell Infiltration With Immune-Related Adverse Events Secondary to Immune Checkpoint Inhibitors.

Author

Kerepesi C, Abushukair HM, Ricciuti B, Nassar AH, Adib E, Alessi JV, Pecci F, Rakaee M, Fadlullah MZH, Tőkés AM, Rodig SJ, Awad MM, Tan AC, Bakacs T, and Naqash AR

Subjects
Humans, Immune Checkpoint Inhibitors adverse effects, CD8-Positive T-Lymphocytes pathology, Retrospective Studies, Tumor Microenvironment, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms drug therapy, Lung Neoplasms pathology
Abstract

Purpose: Recent evidence has shown that higher tumor mutational burden strongly correlates with an increased risk of immune-related adverse events (irAEs). By using an integrated multiomics approach, we further studied the association between relevant tumor immune microenvironment (TIME) features and irAEs., Methods: Leveraging the US Food and Drug Administration Adverse Event Reporting System, we extracted cases of suspected irAEs to calculate the reporting odds ratios (RORs) of irAEs for cancers treated with immune checkpoint inhibitors (ICIs). TIME features for 32 cancer types were calculated on the basis of the cancer genomic atlas cohorts and indirectly correlated with each cancer's ROR for irAEs. A separate ICI-treated cohort of non-small-cell lung cancer (NSCLC) was used to evaluate the correlation between tissue-based immune markers (CD8 + , PD-1/L1+, FOXP3+, tumor-infiltrating lymphocytes [TILs]) and irAE occurrence., Results: The analysis of 32 cancers and 33 TIME features demonstrated a significant association between irAE RORs and the median number of base insertions and deletions (INDEL), neoantigens (r = 0.72), single-nucleotide variant neoantigens (r = 0.67), and CD8 + T-cell fraction (r = 0.51). A bivariate model using the median number of INDEL neoantigens and CD8 T-cell fraction had the highest accuracy in predicting RORs (adjusted r 2 = 0.52, P = .002). Immunoprofile assessment of 156 patients with NSCLC revealed a strong trend for higher baseline median CD8 + T cells within patients' tumors who experienced any grade irAEs. Using machine learning, an expanded ICI-treated NSCLC cohort (n = 378) further showed a treatment duration-independent association of an increased proportion of high TIL (>median) in patients with irAEs (59.7% v 44%, P = .005). This was confirmed by using the Fine-Gray competing risk approach, demonstrating higher baseline TIL density (>median) associated with a higher cumulative incidence of irAEs ( P = .028)., Conclusion: Our findings highlight a potential role for TIME features, specifically INDEL neoantigens and baseline-immune infiltration, in enabling optimal irAE risk stratification of patients.

Published
2024
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50. Immune landscape in molecular subtypes of human papillomavirus-negative head and neck cancer.

Author

Xie M, Chaudhary R, Slebos RJC, Lee K, Song F, Poole MI, Hoening DS, Noel LC, Hernandez-Prera JC, Conejo-Garcia JR, Chung CH, and Tan AC

Subjects
Humans, Squamous Cell Carcinoma of Head and Neck genetics, Human Papillomavirus Viruses, Immunotherapy, Tumor Microenvironment, Papillomavirus Infections complications, Papillomavirus Infections genetics, Head and Neck Neoplasms genetics
Abstract

Head and neck squamous cell carcinomas (HNSCC) remain a poorly understood disease clinically and immunologically. HPV is a known risk factor of HNSCC associated with better outcome, whereas HPV-negative HNSCC are more heterogeneous in outcome. Gene expression signatures have been developed to classify HNSCC into four molecular subtypes (classical, basal, mesenchymal, and atypical). However, the molecular underpinnings of treatment response and the immune landscape for these molecular subtypes are largely unknown. Herein, we described a comprehensive immune landscape analysis in three independent HNSCC cohorts (>700 patients) using transcriptomics data. We assigned the HPV - HNSCC patients into these four molecular subtypes and characterized the tumor microenvironment using deconvolution method. We determined that atypical and mesenchymal subtypes have greater immune enrichment and exhibit a T-cell exhaustion phenotype, compared to classical and basal subtypes. Further analyses revealed different B cell maturation and antibody isotypes enrichment patterns, and distinct immune microenvironment crosstalk in the atypical and mesenchymal subtypes. Taken together, our study suggests that treatments that enhances B cell activity may benefit patients with HNSCC of the atypical subtypes. The rationale can be utilized in the design of future precision immunotherapy trials based on the molecular subtypes of HPV - HNSCC., (© 2023 The Authors. Molecular Carcinogenesis published by Wiley Periodicals LLC.)

Published
2024
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