99 results on '"Betz-Stablein, B."'
Search Results
2. A systematic review of changes in melanocytic naevi during immune checkpoint inhibition and targeted therapy
- Author
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Bruijn, T.V.M., primary, Dinh, S.T., additional, Elshot, Y.S., additional, van der Mierden, S., additional, Soyer, P.H., additional, Olsen, C.M., additional, Betz-Stablein, B., additional, Bekkenk, M.W., additional, Rustemeyer, T., additional, and Plasmeijer, E.I., additional
- Published
- 2024
- Full Text
- View/download PDF
3. A-405 - A systematic review of changes in melanocytic naevi during immune checkpoint inhibition and targeted therapy
- Author
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Bruijn, T.V.M., Dinh, S.T., Elshot, Y.S., van der Mierden, S., Soyer, P.H., Olsen, C.M., Betz-Stablein, B., Bekkenk, M.W., Rustemeyer, T., and Plasmeijer, E.I.
- Published
- 2024
- Full Text
- View/download PDF
4. Breast cancer polygenic risk scores: A 12-month prospective study of patient reported outcomes and risk management behavior.
- Author
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Yanes T., Meiser B., Kaur R., Young M.-A., Mitchell P.B., Scheepers-Joynt M., McInerny S., Taylor S., Barlow-Stewart K., Antill Y., Salmon L., Smyth C., Betz-Stablein B., James P.A., Yanes T., Meiser B., Kaur R., Young M.-A., Mitchell P.B., Scheepers-Joynt M., McInerny S., Taylor S., Barlow-Stewart K., Antill Y., Salmon L., Smyth C., Betz-Stablein B., and James P.A.
- Abstract
Introduction: Polygenic risk scores (PRS) for breast cancer risk have emerged as a potential tool for informing disease risk management. However, little is known about women's responses to receiving this information. This study aimed to prospectively assess patient reported outcomes and risk management behavior of women choosing to receive (receivers) or decline (decliners) their breast cancer PRS. Method(s): Women either unaffected or affected by breast cancer and from families with no identified pathogenic variant in a breast cancer risk gene were invited to receive their PRS. Genotyping for 62 common variants was performed, from which a PRS and relative risk were calculated. All participants completed a questionnaire at study enrollment. Receivers completed questionnaires at two-weeks and 12- months after receiving their PRS, and decliners a second questionnaire at 12-months post study enrollment. Result(s): Of the 208 participants, 165 (79%) received their PRS. Among receivers there were no changes in anxiety or distress following testing. Receiving a low PRS was associated with reduced perceived breast cancer risk at 12-months (p = 0.030). At 12-months, breast screening and uptake of risk-reducing strategies were consistent with current Australian guidelines of breast cancer risk management. Compared to receivers, decliners reported significantly higher decisional regret regarding receipt of their PRS (p<0.001). Reasons for declining PRS included being unable to attend the appointment in person and concerns over potential emotional response. Conclusion(s): Our findings provide additional support for the suitability of PRS in clinical practice, while highlighting the issues that need to be addressed when providing this information.
- Published
- 2022
5. Ongoing incident hepatitis C virus infection among people with a history of injecting drug use in an Australian prison setting, 2005‐2014: The HITS‐p study
- Author
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Cunningham, E. B., Hajarizadeh, B., Bretana, N. A., Amin, J., Betz‐Stablein, B., Dore, G. J., Luciani, F., Teutsch, S., Dolan, K., Lloyd, A. R., Grebely, J., Haber, Paul, Rawlinson, William, Treloar, Carla, and Maher, Lisa
- Published
- 2017
- Full Text
- View/download PDF
6. High variability in anatomic patterns of cutaneous photodamage: a population‐based study
- Author
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Betz‐Stablein, B., primary, Llewellyn, S., additional, Bearzi, P., additional, Grochulska, K., additional, Rutjes, C., additional, Aitken, J.F., additional, Janda, M., additional, O’Rouke, P., additional, Soyer, H.P., additional, and Green, A.C., additional
- Published
- 2021
- Full Text
- View/download PDF
7. Peer Review #1 of "Sunburns among beachgoers in the northern coast of Peru: frequency and factors associated (v0.1)"
- Author
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Betz-Stablein, B, additional
- Published
- 2021
- Full Text
- View/download PDF
8. Breast cancer polygenic risk scores: a 12-month prospective study of patient reported outcomes and risk management behavior.
- Author
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Yanes T., Meiser B., Kaur R., Young M.-A., Mitchell P.B., Scheepers-Joynt M., McInerny S., Taylor S., Barlow-Stewart K., Antill Y., Salmon L., Smyth C., Betz-Stablein B., James P.A., Yanes T., Meiser B., Kaur R., Young M.-A., Mitchell P.B., Scheepers-Joynt M., McInerny S., Taylor S., Barlow-Stewart K., Antill Y., Salmon L., Smyth C., Betz-Stablein B., and James P.A.
- Abstract
Purpose: To prospectively assess patient reported outcomes and risk management behavior of women choosing to receive (receivers) or decline (decliners) their breast cancer polygenic risk score (PRS). Method(s): Women either unaffected or affected by breast cancer and from families with no identified pathogenic variant in a breast cancer risk gene were invited to receive their PRS. All participants completed a questionnaire at study enrollment. Receivers completed questionnaires at two weeks and 12 months after receiving their PRS, and decliners a second questionnaire at 12 months post study enrollment. Result(s): Of the 208 participants, 165 (79%) received their PRS. Among receivers, there were no changes in anxiety or distress following testing. However, compared to women with a low PRS, those with a high PRS reported greater genetic testing-specific distress, perceived risk, decisional regret, and less genetic testing-positive response. At 12 months, breast screening and uptake of risk-reducing strategies were consistent with current Australian guidelines of breast cancer risk management. Reasons for declining PRS included being unable to attend the appointment in person and concerns over potential emotional response. Conclusion(s): The outcomes of the study provide insight into women's responses to receiving PRS and highlight the issues that need to be addressed in the associated model of genetic counseling.Copyright © 2021, Crown.
- Published
- 2021
9. Breast cancer polygenic risk scores: a 12-month prospective study of patient reported outcomes and risk management behavior
- Author
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Yanes, T, Meiser, B, Kaur, R, Young, MA, Mitchell, PB, Scheepers-Joynt, M, McInerny, S, Taylor, S, Barlow-Stewart, K, Antill, Y, Salmon, L, Smyth, C, Betz-Stablein, B, James, PA, Yanes, T, Meiser, B, Kaur, R, Young, MA, Mitchell, PB, Scheepers-Joynt, M, McInerny, S, Taylor, S, Barlow-Stewart, K, Antill, Y, Salmon, L, Smyth, C, Betz-Stablein, B, and James, PA
- Abstract
Purpose: To prospectively assess patient reported outcomes and risk management behavior of women choosing to receive (receivers) or decline (decliners) their breast cancer polygenic risk score (PRS). Methods: Women either unaffected or affected by breast cancer and from families with no identified pathogenic variant in a breast cancer risk gene were invited to receive their PRS. All participants completed a questionnaire at study enrollment. Receivers completed questionnaires at two weeks and 12 months after receiving their PRS, and decliners a second questionnaire at 12 months post study enrollment. Results: Of the 208 participants, 165 (79%) received their PRS. Among receivers, there were no changes in anxiety or distress following testing. However, compared to women with a low PRS, those with a high PRS reported greater genetic testing–specific distress, perceived risk, decisional regret, and less genetic testing–positive response. At 12 months, breast screening and uptake of risk-reducing strategies were consistent with current Australian guidelines of breast cancer risk management. Reasons for declining PRS included being unable to attend the appointment in person and concerns over potential emotional response. Conclusion: The outcomes of the study provide insight into women’s responses to receiving PRS and highlight the issues that need to be addressed in the associated model of genetic counseling.
- Published
- 2021
10. Quantitative analysis of the splice variants expressed by the major hepatitis B virus genotypes
- Author
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Lim, CS, Sozzi, V, Littlejohn, M, Yuen, LKW, Warner, N, Betz-Stablein, B, Luciani, F, Revill, PA, Brown, CM, Lim, CS, Sozzi, V, Littlejohn, M, Yuen, LKW, Warner, N, Betz-Stablein, B, Luciani, F, Revill, PA, and Brown, CM
- Abstract
Hepatitis B virus (HBV) is a major human pathogen that causes liver diseases. The main HBV RNAs are unspliced transcripts that encode the key viral proteins. Recent studies have shown that some of the HBV spliced transcript isoforms are predictive of liver cancer, yet the roles of these spliced transcripts remain elusive. Furthermore, there are nine major HBV genotypes common in different regions of the world, these genotypes may express different spliced transcript isoforms. To systematically study the HBV splice variants, we transfected human hepatoma cells, Huh7, with four HBV genotypes (A2, B2, C2 and D3), followed by deep RNA-sequencing. We found that 13-28 % of HBV RNAs were splice variants, which were reproducibly detected across independent biological replicates. These comprised 6 novel and 10 previously identified splice variants. In particular, a novel, singly spliced transcript was detected in genotypes A2 and D3 at high levels. The biological relevance of these splice variants was supported by their identification in HBV-positive liver biopsy and serum samples, and in HBV-infected primary human hepatocytes. Interestingly the levels of HBV splice variants varied across the genotypes, but the spliced pregenomic RNA SP1 and SP9 were the two most abundant splice variants. Counterintuitively, these singly spliced SP1 and SP9 variants had a suboptimal 5' splice site, supporting the idea that splicing of HBV RNAs is tightly controlled by the viral post-transcriptional regulatory RNA element.
- Published
- 2021
11. Self‐reported naevus density may lead to misclassification of melanoma risk
- Author
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Betz‐Stablein, B., primary, Koh, U., additional, Plasmeijer, E.I., additional, Janda, M., additional, Aitken, J.F., additional, Soyer, H.P., additional, and Green, A.C., additional
- Published
- 2020
- Full Text
- View/download PDF
12. Epidemic surveillance in a low resource setting: Lessons from an evaluation of the Solomon Islands syndromic surveillance system, 2017
- Author
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Craig, AT, Joshua, CA, Sio, AR, Donoghoe, M, Betz-Stablein, B, Bainivalu, N, Dalipanda, T, Kaldor, J, Rosewell, AE, Schierhout, G, Craig, AT, Joshua, CA, Sio, AR, Donoghoe, M, Betz-Stablein, B, Bainivalu, N, Dalipanda, T, Kaldor, J, Rosewell, AE, and Schierhout, G
- Abstract
Background: Solomon Islands is one of the least developed countries in the world. Recognising that timely detection of outbreaks is needed to enable early and effective response to disease outbreaks, the Solomon Islands government introduced a simple syndromic surveillance system in 2011. We conducted the first evaluation of the system and the first exploration of a national experience within the broader multi-country Pacific Syndromic Surveillance System to determine if it is meeting its objectives and to identify opportunities for improvement. Methods: We used a multi-method approach involving retrospective data collection and statistical analysis, modelling, qualitative research and observational methods. Results: We found that the system was well accepted, highly relied upon and designed to account for contextual limitations. We found the syndromic algorithm used to identify outbreaks was moderately sensitive, detecting 11.8% (IQR: 6.3-25.0%), 21.3% (IQR: 10.3-36.8%), 27.5% (IQR: 12.8-52.3%) and 40.5% (IQR: 13.5-65.7%) of outbreaks that caused small, moderate, large and very large increases in case presentations to health facilities, respectively. The false alert rate was 10.8% (IQR: 4.8-24.5%). Rural coverage of the system was poor. Limited workforce, surveillance resourcing and other 'upstream' health system factors constrained performance. Conclusions: The system has made a significant contribution to public health security in Solomon Islands, but remains insufficiently sensitive to detect small-moderate sized outbreaks and hence should not be relied upon as a stand-alone surveillance strategy. Rather, the system should sit within a complementary suite of early warning surveillance activities including event-based, in-patient- and laboratory-based surveillance methods. Future investments need to find a balance between actions to address the technical and systems issues that constrain performance while maintaining simplicity and hence sustainability.
- Published
- 2018
13. A161 ONGOING INCIDENT HEPATITIC C VIRUS INFECTION AMONG PEOPLE WITH A HISTORY OF INJECTING DRUG USE IN AN AUSTRALIAN PRISON SETTING
- Author
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Cunningham, E B, primary, Hajarizadeh, B, additional, Amin, J, additional, Betz-Stablein, B, additional, Dore, G J, additional, Luciani, F, additional, Teutsch, S, additional, Bretana, N A, additional, Dolan, K, additional, Lloyd, A R, additional, and Grebely, J, additional
- Published
- 2018
- Full Text
- View/download PDF
14. Ongoing incident hepatitis C virus infection among people with a history of injecting drug use in an Australian prison setting, 2005-2014: The HITS-p study
- Author
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Cunningham, EB, Hajarizadeh, B, Bretana, NA, Amin, J, Betz-Stablein, B, Dore, GJ, Luciani, F, Teutsch, S, Dolan, K, Lloyd, AR, Grebely, J, Haber, P, Rawlinson, W, Treloar, C, Maher, L, Cunningham, EB, Hajarizadeh, B, Bretana, NA, Amin, J, Betz-Stablein, B, Dore, GJ, Luciani, F, Teutsch, S, Dolan, K, Lloyd, AR, Grebely, J, Haber, P, Rawlinson, W, Treloar, C, and Maher, L
- Abstract
Hepatitis C virus (HCV) transmission is high in prisons. This study investigated trends in HCV incidence and associated factors among a cohort of prisoners with a history of injecting drug use in New South Wales, Australia. Data were available from the Hepatitis C Incidence and Transmission Study—prisons (HITS-p) from 2005 to 2014. Temporal trends in HCV incidence were evaluated. Factors associated with time to HCV seroconversion among people with ongoing injecting was assessed using Cox proportional hazards. Among 320 antibody-negative participants with a history of injecting drug use (mean age 26; 72% male), 62% (n=197) reported injecting drug use during follow-up. Overall, 93 infections were observed. HCV incidence was 11.4/100 person-years in the overall population and 6.3/100 person-years among the continually imprisoned population. A stable trend in HCV incidence was observed. Among the overall population with ongoing injecting during follow-up, ≥weekly injecting drug use frequency was independently associated with time to HCV seroconversion. Among continuously imprisoned injectors with ongoing injecting during follow-up, needle/syringe sharing was independently associated with time to HCV seroconversion. This study demonstrates that prison is a high-risk environment for acquisition of HCV infection. Needle and syringe sharing was associated with HCV infection among continually imprisoned participants, irrespective of frequency of injecting or the type of drug injected. These findings highlight the need for the evaluation of improved HCV prevention strategies in prison, including needle/syringe programmes and HCV treatment.
- Published
- 2017
15. Analysis of resistance-associated substitutions in acute hepatitis C virus infection by deep sequencing across six genotypes and three continents
- Author
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Eltahla, AA, Rodrigo, C, Betz-Stablein, B, Grebely, J, Applegate, T, Luciani, F, Schinkel, J, Dore, GJ, Page, K, Bruneau, J, Morris, MD, Cox, AL, Kim, AY, Shoukry, NH, Lauer, GM, Maher, L, Hellard, M, Prins, M, Lloyd, AR, Bull, RA, Eltahla, AA, Rodrigo, C, Betz-Stablein, B, Grebely, J, Applegate, T, Luciani, F, Schinkel, J, Dore, GJ, Page, K, Bruneau, J, Morris, MD, Cox, AL, Kim, AY, Shoukry, NH, Lauer, GM, Maher, L, Hellard, M, Prins, M, Lloyd, AR, and Bull, RA
- Abstract
Several direct-acting antivirals (DAAs) have been approved for the treatment of chronic hepatitis C virus (HCV) infections, opening the door to highly effective interferon-free treatment regimens. Resistance-associated substitutions (RASs) have been reported both in treatment-naïve patients and following treatment with protease (NS3), phosphoprotein (NS5A) and polymerase (NS5B) inhibitors. The prevalence of naturally occurring RASs in untreated HCV-infected individuals has mostly been analysed in those infected with genotype 1 (GT1), in the late phase of infection, and only within limited regions of the genome. Furthermore, the geographic distribution of RASs remains poorly characterized. In this study, we used next-generation sequencing to analyse full-length HCV genomes for the prevalence of RASs in acute HCV infections identified in nine international prospective cohorts. RASs were analysed in 179 participants infected with all six major HCV genotypes (GT1-GT6), and the geographic distribution of RASs was assessed in 107 GT1a and GT3a samples. While RASs were detected at varied frequencies across the three genomic regions, and between genotypes, RASs relevant to multiple DAAs in the leading IFN-free regimens were rarely detected in combination. Low-frequency RASs (<10% of the viral population) were also shown to have a GT-specific distribution. The main RASs with geographic associations were NS3 Q80K in GT1a samples and NS5B N142T in GT3a. These data provide the backdrop for prospective surveillance of RASs during DAA treatment scale-up.
- Published
- 2017
16. Incident hepatitis c virus genotype distribution and multiple infection in australian prisons
- Author
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Walker, MR, Li, H, Teutsch, S, Betz-Stablein, B, Luciani, F, Lloyd, AR, Bull, RA, Walker, MR, Li, H, Teutsch, S, Betz-Stablein, B, Luciani, F, Lloyd, AR, and Bull, RA
- Abstract
Hepatitis C virus (HCV) is a highly diverse pathogen that is classified into seven distinct genotypes. Simultaneous or sequential reinfection with multiple HCV genotypes is recognized in high-risk populations, such as injecting drug users (IDUs). Multiple infection is of clinical concern as different genotypes have various sensitivities to current antiviral therapies. Therefore, a better understanding of the frequency of multiple infection and of the genotypes currently being transmitted is clinically relevant. An Australian cohort of IDUs (n123), identified with primary incident infection, was followed for multiple infection by regular HCV RNA testing between 2005 and 2013. A total of 354 samples were tested. Sequencing of primary incident infections revealed that genotype 3a was the most common circulating genotype, followed by genotype 1a. Examination of longitudinally collected samples identified complex patterns of multiple infection, including reinfection and superinfection. In those with multiple infection, there was no apparent evidence of homotypic immunity conferring protection against reinfection of the same subtype. This study revealed frequent multiple infection in a high-risk prisoner cohort, illustrating the complex nature of HCV infection and reinfection and highlighting the need for pan-genotypic antiviral therapies.
- Published
- 2016
17. HCV RNA traffic and association with NS5A in living cells
- Author
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Fiches, GN, Eyre, NS, Aloia, AL, Van Der Hoek, K, Betz-Stablein, B, Luciani, F, Chopra, A, Beard, MR, Fiches, GN, Eyre, NS, Aloia, AL, Van Der Hoek, K, Betz-Stablein, B, Luciani, F, Chopra, A, and Beard, MR
- Abstract
The spatiotemporal dynamics of Hepatitis C Virus (HCV) RNA localisation are poorly understood. To address this we engineered HCV genomes harbouring MS2 bacteriophage RNA stem-loops within the 3'-untranslated region to allow tracking of HCV RNA via specific interaction with a MS2-Coat-mCherry fusion protein. Despite the impact of these insertions on viral fitness, live imaging revealed that replication of tagged-HCV genomes induced specific redistribution of the mCherry-tagged-MS2-Coat protein to motile and static foci. Further analysis showed that HCV RNA was associated with NS5A in both static and motile structures while a subset of motile NS5A structures was devoid of HCV RNA. Further investigation of viral RNA traffic with respect to lipid droplets (LDs) revealed HCV RNA-positive structures in close association with LDs. These studies provide new insights into the dynamics of HCV RNA traffic with NS5A and LDs and provide a platform for future investigations of HCV replication and assembly.
- Published
- 2016
18. A method for near full-length amplification and sequencing for six hepatitis C virus genotypes
- Author
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Bull, RA, Eltahla, AA, Rodrigo, C, Koekkoek, SM, Walker, M, Pirozyan, MR, Betz-Stablein, B, Toepfer, A, Laird, M, Oh, S, Heiner, C, Maher, L, Schinkel, J, Lloyd, AR, Luciani, F, Bull, RA, Eltahla, AA, Rodrigo, C, Koekkoek, SM, Walker, M, Pirozyan, MR, Betz-Stablein, B, Toepfer, A, Laird, M, Oh, S, Heiner, C, Maher, L, Schinkel, J, Lloyd, AR, and Luciani, F
- Abstract
Background: Hepatitis C virus (HCV) is a rapidly evolving RNA virus that has been classified into seven genotypes. All HCV genotypes cause chronic hepatitis, which ultimately leads to liver diseases such as cirrhosis. The genotypes are unevenly distributed across the globe, with genotypes 1 and 3 being the most prevalent. Until recently, molecular epidemiological studies of HCV evolution within the host and at the population level have been limited to the analyses of partial viral genome segments, as it has been technically challenging to amplify and sequence the full-length of the 9.6 kb HCV genome. Although recent improvements have been made in full genome sequencing methodologies, these protocols are still either limited to a specific genotype or cost-inefficient. Results: In this study we describe a genotype-specific protocol for the amplification and sequencing of the near-full length genome of all six major HCV genotypes. We applied this protocol to 122 HCV positive clinical samples, and had a successful genome amplification rate of 90 %, when the viral load was greater than 15,000 IU/ml. The assay was shown to have a detection limit of 1-3 cDNA copies per reaction. The method was tested with both Illumina and PacBio single molecule, real-time (SMRT) sequencing technologies. Illumina sequencing resulted in deep coverage and allowed detection of rare variants as well as HCV co-infection with multiple genotypes. The application of the method with PacBio RS resulted in sequence reads greater than 9 kb that covered the near full-length HCV amplicon in a single read and enabled analysis of the near full-length quasispecies. Conclusions: The protocol described herein can be utilised for rapid amplification and sequencing of the near-full length HCV genome in a cost efficient manner suitable for a wide range of applications.
- Published
- 2016
19. HCV RNA traffic and association with NS5A in living cells
- Author
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Fiches, G.N., Eyre, N.S., Aloia, A.L., Van Der Hoek, K., Betz-Stablein, B., Luciani, F., Chopra, A., Beard, M.R., Fiches, G.N., Eyre, N.S., Aloia, A.L., Van Der Hoek, K., Betz-Stablein, B., Luciani, F., Chopra, A., and Beard, M.R.
- Abstract
The spatiotemporal dynamics of Hepatitis C Virus (HCV) RNA localisation are poorly understood. To address this we engineered HCV genomes harbouring MS2 bacteriophage RNA stem-loops within the 3′-untranslated region to allow tracking of HCV RNA via specific interaction with a MS2-Coat-mCherry fusion protein. Despite the impact of these insertions on viral fitness, live imaging revealed that replication of tagged-HCV genomes induced specific redistribution of the mCherry-tagged-MS2-Coat protein to motile and static foci. Further analysis showed that HCV RNA was associated with NS5A in both static and motile structures while a subset of motile NS5A structures was devoid of HCV RNA. Further investigation of viral RNA traffic with respect to lipid droplets (LDs) revealed HCV RNA-positive structures in close association with LDs. These studies provide new insights into the dynamics of HCV RNA traffic with NS5A and LDs and provide a platform for future investigations of HCV replication and assembly.
- Published
- 2016
20. Single-Molecule Sequencing Reveals Complex Genome Variation of Hepatitis B Virus during 15 Years of Chronic Infection following Liver Transplantation
- Author
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Betz-Stablein, B. D., primary, Töpfer, A., additional, Littlejohn, M., additional, Yuen, L., additional, Colledge, D., additional, Sozzi, V., additional, Angus, P., additional, Thompson, A., additional, Revill, P., additional, Beerenwinkel, N., additional, Warner, N., additional, and Luciani, F., additional
- Published
- 2016
- Full Text
- View/download PDF
21. Stable Incidence of Hepatitis C Virus Infection among People with a History of Injecting Drug Use in an Australian Prison Setting, 2005–2014: The Hits-P Study
- Author
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Cunningham, E.B., primary, Luciani, F., additional, Hajarizadeh, B., additional, Betz-Stablein, B., additional, Bretana, N.A., additional, Teutsch, S., additional, Dore, G.J., additional, Grebely, J., additional, and Lloyd, A.R., additional
- Published
- 2016
- Full Text
- View/download PDF
22. Analysis of resistance-associated substitutions in acute hepatitis C virus infection by deep sequencing across six genotypes and three continents.
- Author
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Eltahla, A. A., Rodrigo, C., Betz‐Stablein, B., Grebely, J., Applegate, T., Luciani, F., Schinkel, J., Dore, G. J., Page, K., Bruneau, J., Morris, M. D., Cox, A. L., Kim, A. Y., Shoukry, N. H., Lauer, G. M., Maher, L., Hellard, M., Prins, M., Lloyd, A. R., and Bull, R. A.
- Subjects
ANTIVIRAL agents ,HEPATITIS C treatment ,PHOSPHOPROTEINS ,POLYMERASES ,GENOTYPES - Abstract
Several direct-acting antivirals ( DAAs) have been approved for the treatment of chronic hepatitis C virus ( HCV) infections, opening the door to highly effective interferon-free treatment regimens. Resistance-associated substitutions ( RASs) have been reported both in treatment-naïve patients and following treatment with protease ( NS3), phosphoprotein ( NS5A) and polymerase ( NS5B) inhibitors. The prevalence of naturally occurring RASs in untreated HCV-infected individuals has mostly been analysed in those infected with genotype 1 ( GT1), in the late phase of infection, and only within limited regions of the genome. Furthermore, the geographic distribution of RASs remains poorly characterized. In this study, we used next-generation sequencing to analyse full-length HCV genomes for the prevalence of RASs in acute HCV infections identified in nine international prospective cohorts. RASs were analysed in 179 participants infected with all six major HCV genotypes ( GT1- GT6), and the geographic distribution of RASs was assessed in 107 GT1a and GT3a samples. While RASs were detected at varied frequencies across the three genomic regions, and between genotypes, RASs relevant to multiple DAAs in the leading IFN-free regimens were rarely detected in combination. Low-frequency RASs (<10% of the viral population) were also shown to have a GT-specific distribution. The main RASs with geographic associations were NS3 Q80K in GT1a samples and NS5B N142T in GT3a. These data provide the backdrop for prospective surveillance of RASs during DAA treatment scale-up. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
23. FRI-170 - Stable Incidence of Hepatitis C Virus Infection among People with a History of Injecting Drug Use in an Australian Prison Setting, 2005–2014: The Hits-P Study
- Author
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Cunningham, E.B., Luciani, F., Hajarizadeh, B., Betz-Stablein, B., Bretana, N.A., Teutsch, S., Dore, G.J., Grebely, J., and Lloyd, A.R.
- Published
- 2016
- Full Text
- View/download PDF
24. Outcomes of Unrelated Umbilical Cord Blood Transplantation In Pediatric Patients With Primary and Secondary Myelodysplastic Syndromes
- Author
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Parikh, S.H., primary, Mendizabal, A., additional, Betz-Stablein, B., additional, Martin, P.L., additional, Szabolcs, P., additional, Prasad, V.K., additional, Driscoll, T.A., additional, and Kurtzberg, J., additional
- Published
- 2009
- Full Text
- View/download PDF
25. Relationships Among Commonly Used Measures of Cord Blood Potency, Aldhbr Cell Content, and Colony Forming Cell Content in Cord Blood Units Prior to Cryopreservation: Towards an Improved Metric for Potency of Banked Cord Blood
- Author
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Page, K., Betz-Stablein, B., Mendizabal, A., Wease, S., Shoulars, K., Gentry, T., Balber, A.E., and Kurtzberg, J.
- Published
- 2012
- Full Text
- View/download PDF
26. A161 ONGOING INCIDENT HEPATITIC C VIRUS INFECTION AMONG PEOPLE WITH A HISTORY OF INJECTING DRUG USE IN AN AUSTRALIAN PRISON SETTING
- Author
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Cunningham, EB, Hajarizadeh, B, Amin, J, Betz-Stablein, B, Dore, GJ, Luciani, F, Teutsch, S, Bretana, NA, Dolan, K, Lloyd, AR, Grebely, J, Cunningham, EB, Hajarizadeh, B, Amin, J, Betz-Stablein, B, Dore, GJ, Luciani, F, Teutsch, S, Bretana, NA, Dolan, K, Lloyd, AR, and Grebely, J
27. Ongoing incident hepatitis C virus infection among people with a history of injecting drug use in an Australian prison setting, 2005-2014: The HITS-p study
- Author
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Behzad Hajarizadeh, Neil Arvin Bretaña, Suzy Teutsch, Andrew R. Lloyd, Kate Dolan, Jason Grebely, Evan B Cunningham, Brigid Betz-Stablein, Gregory J. Dore, Janaki Amin, Fabio Luciani, Cunningham, EB, Hajarizadeh, B, Bretana, NA, Amin, J, Betz-Stablein, B, Dore, GJ, Luciani, F, Teutsch, S, Dolan, K, Lloyd, AR, and Grebely, J
- Subjects
hepatitis C virus ,Adult ,Male ,medicine.medical_specialty ,Hepatitis C virus ,Population ,030508 substance abuse ,medicine.disease_cause ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Virology ,Internal medicine ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Seroconversion ,PWID ,Substance Abuse, Intravenous ,education ,Syringe ,education.field_of_study ,Hepatology ,Transmission (medicine) ,business.industry ,Incidence ,Incidence (epidemiology) ,Australia ,virus diseases ,Hepatitis C ,medicine.disease ,digestive system diseases ,Infectious Diseases ,Prisons ,Immunology ,Cohort ,incidence ,Female ,prison ,New South Wales ,0305 other medical science ,business - Abstract
usc Hepatitis C virus (HCV) transmission is high in prisons. This study investigated trends in HCV incidence and associated factors among a cohort of prisoners with a history of injecting drug use in New South Wales, Australia. Data were available from the Hepatitis C Incidence and Transmission Study—prisons (HITS-p) from 2005 to 2014. Temporal trends in HCV incidence were evaluated. Factors associated with time to HCV seroconversion among people with ongoing injecting was assessed using Cox proportional hazards. Among 320 antibody-negative participants with a history of injecting drug use (mean age 26; 72% male), 62% (n=197) reported injecting drug use during follow-up. Overall, 93 infections were observed. HCV incidence was 11.4/100 person-years in the overall population and 6.3/100 person-years among the continually imprisoned population. A stable trend in HCV incidence was observed. Among the overall population with ongoing injecting during follow-up, ≥weekly injecting drug use frequency was independently associated with time to HCV seroconversion. Among continuously imprisoned injectors with ongoing injecting during follow-up, needle/syringe sharing was independently associated with time to HCV seroconversion. This study demonstrates that prison is a high-risk environment for acquisition of HCV infection. Needle and syringe sharing was associated with HCV infection among continually imprisoned participants, irrespective of frequency of injecting or the type of drug injected. These findings highlight the need for the evaluation of improved HCV prevention strategies in prison, including needle/syringe programmes and HCV treatment. Refereed/Peer-reviewed
- Published
- 2017
28. A161 ONGOING INCIDENT HEPATITIC C VIRUS INFECTION AMONG PEOPLE WITH A HISTORY OF INJECTING DRUG USE IN AN AUSTRALIAN PRISON SETTING
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Andrew R. Lloyd, Evan B Cunningham, Janaki Amin, Behzad Hajarizadeh, Gregory J. Dore, Neil Arvin Bretaña, Fabio Luciani, Suzy Teutsch, Kate Dolan, Jason Grebely, Brigid Betz-Stablein, Cunningham, EB, Hajarizadeh, B, Amin, J, Betz-Stablein, B, Dore, GJ, Luciani, F, Teutsch, S, Bretana, NA, Dolan, K, Lloyd, AR, and Grebely, J
- Subjects
medicine.medical_specialty ,Hepatitis C virus ,medicine.disease_cause ,behavioral disciplines and activities ,survival analysis ,mental disorders ,follow-up ,medicine ,harm reduction ,hepatitis c ,Seroconversion ,Psychiatry ,Imprisonment ,crime ,Needle sharing ,Harm reduction ,business.industry ,Transmission (medicine) ,Incidence (epidemiology) ,Australia ,virus diseases ,social sciences ,Hepatitis C ,medicine.disease ,interferons ,Poster Presentations ,population characteristics ,business - Abstract
usc Background: There are close ties between injecting drug use and incarceration as a result of imprisonment for drug-related crimes and therefore Hepatitis C virus (HCV) transmission in prisons is high. The most effective strategies to prevent HCV transmission, including needle-syringe exchange (NSP) and opiate substitution therapies (OST) are commonly unavailable in the prisons. Understanding trends in incidence and associated factors in prisons is crucial for developing and improving HCV prevention and treatment programs in the prison setting. Aims: This study investigated trends in HCV incidence and associated factors among a cohort of prisoners in New South Wales (NSW), Australia. Methods: Data were available from the Hepatitis C Incidence and Transmission Study in prisons (HITS-p) from 2005–2014. Temporal trends in HCV incidence were evaluated. Factors associated with time to HCV seroconversion were assessed using Cox proportional hazards regression. Results: Among 590 participants enrolled, 320 were eligible for inclusion (≥1 follow-up visit, lifetime history of injecting drugs, and HCV antibody/RNA negative at enrolment). The mean age was 26 years, 72% (n=229) were male, 33% (n=104) reported recent injecting drug use, 11% (n=35) reported greater than or equal to weekly injecting since entering prison, and 25% (n=81) reported syringe sharing during follow-up. 93 seroconversions were observed in the overall sample [815 person-years (py) of follow-up] while 32 seroconversions were seen in the continuously imprisoned population (507 py of follow-up). HCV incidence was 11.4/100 p-yrs (95% CI: 9.3–14.0/100 p-yrs) in the overall sample and 6.3/100 p-yrs (95% CI: 4.5–8.9/100 p-yrs) among the continually imprisoned sample. A stable trend in incidence was observed over the study period (Figure 1). In adjusted analyses among the overall sample, greater than or equal to weekly injecting was independently associated with time to HCV seroconversion. In adjusted analyses among the continuously imprisoned population, syringe sharing was independently associated with time to HCV seroconversion. Conclusions: This study demonstrates that current prevention strategies have failed to reduce the incidence of HCV in the Australian prison setting between 2005 and 2014. This study also highlights the need for clean injecting equipment in prison given that needle and syringe sharing was associated with HCV infection among continually imprisoned participants, irrespective of frequency of injecting or the type of drug injected. Prison remains a high risk environment for acquisition of HCV infection and highlights the need for improved harm reduction strategies including NSP and evaluation of interferon-free HCV treatment as prevention strategies in prisons. Refereed/Peer-reviewed
- Published
- 2018
29. Development and Validation of a Total Body Photo-Numeric Freckling Density Scale.
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Susinna M, Mothershaw A, Ghahari N, Kahler S, Primiero C, Dillon H, Fischer C, Janda M, Soyer HP, and Betz-Stablein B
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- Adult, Female, Humans, Male, Young Adult, Reproducibility of Results, Skin Pigmentation physiology, Photography
- Published
- 2024
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30. Estimation of Body Mass Index (BMI) from 3D total body photography.
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Kahler S, Betz-Stablein B, Lee F, Torrano J, Janda M, Primiero C, Soyer HP, and Jayasinghe D
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- 2024
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31. Combining Automated Lesion Risk and Change Assessment Improves Melanoma Detection: A Retrospective Accuracy Study.
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Rutjes C, Mothershaw A, D'Alessandro BM, Primiero CA, McInerney-Leo A, Soyer HP, Janda M, and Betz-Stablein B
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- 2024
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32. POT1 and multiple primary melanomas: the dermatological phenotype.
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Maas EJ, DeBortoli E, Nathan V, Freeman NP, Mothershaw A, Smit DJ, Betz-Stablein B, Aoude LG, Stark MS, Sturm RA, Soyer HP, and McInerney-Leo AM
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- Humans, Female, Male, Middle Aged, Adult, Genetic Predisposition to Disease, Aged, Neoplasms, Multiple Primary genetics, Neoplasms, Multiple Primary pathology, Melanoma genetics, Melanoma pathology, Phenotype, Skin Neoplasms genetics, Skin Neoplasms pathology, Telomere-Binding Proteins genetics, Shelterin Complex
- Abstract
POT1 is the second most frequently reported gene (after CDKN2A ) in familial melanoma. Pathogenic variants are associated with earlier onset and/or multiple primary melanomas (MPMs). To date, POT1 phenotypical reports have been largely restricted to associated malignancies, and description of the dermatological landscape has been limited. We identified 10 variants in n=18 of 384 (4.7%) unrelated individuals (n=13 MPMs; n=5 single primary melanomas) of European ancestry. Five variants were rare (minor allele frequency <0.001) or novel (two loss-of-function (LOF), one splice acceptor and two missense) and were predicted to be functionally significant, in five unrelated probands with MPMs (≥3 melanomas). We performed three-dimensional total body photography on both individuals with confirmed pathogenic LOF variants to characterise the dermatological phenotype. Total body naevus counts (≥2 mm diameter) were significantly higher (p=7.72
×10-12 ) in carriers compared with a control population. Majority of naevi were on the probands' back and lower limb regions, where only mild to moderate ultraviolet (UV) damage was observed. Conversely, the head/neck region, where both probands exhibited severe UV damage, had comparably fewer naevi. We hypothesise that carriage of functionally significant POT1 variants is associated with increased naevus counts generally, and naevi >5 mm in diameter specifically and the location of these are independent of UV damage., Competing Interests: Competing interests: PS is a shareholder of MoleMap Limited and e-derm consult and undertakes regular teledermatological reporting for both companies. PS is a medical consultant for Canfield Scientific and Blaze Bioscience MoleMap Australia Limited, and a medical advisor for First Derm. No other authors have conflicts to declare., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2024
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33. The SLICE-3D dataset: 400,000 skin lesion image crops extracted from 3D TBP for skin cancer detection.
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Kurtansky NR, D'Alessandro BM, Gillis MC, Betz-Stablein B, Cerminara SE, Garcia R, Girundi MA, Goessinger EV, Gottfrois P, Guitera P, Halpern AC, Jakrot V, Kittler H, Kose K, Liopyris K, Malvehy J, Mar VJ, Martin LK, Mathew T, Maul LV, Mothershaw A, Mueller AM, Mueller C, Navarini AA, Rajeswaran T, Rajeswaran V, Saha A, Sashindranath M, Serra-García L, Soyer HP, Theocharis G, Vos A, Weber J, and Rotemberg V
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- Humans, Algorithms, Imaging, Three-Dimensional, Skin diagnostic imaging, Skin Neoplasms diagnostic imaging
- Abstract
AI image classification algorithms have shown promising results when applied to skin cancer detection. Most public skin cancer image datasets are comprised of dermoscopic photos and are limited by selection bias, lack of standardization, and lend themselves to development of algorithms that can only be used by skilled clinicians. The SLICE-3D ("Skin Lesion Image Crops Extracted from 3D TBP") dataset described here addresses those concerns and contains images of over 400,000 distinct skin lesions from seven dermatologic centers from around the world. De-identified images were systematically extracted from sensitive 3D Total Body Photographs and are comparable in optical resolution to smartphone images. Algorithms trained on lower quality images could improve clinical workflows and detect skin cancers earlier if deployed in primary care or non-clinical settings, where photos are captured by non-expert physicians or patients. Such a tool could prompt individuals to visit a specialized dermatologist. This dataset circumvents many inherent limitations of prior datasets and may be used to build upon previous applications of skin imaging for cancer detection., (© 2024. The Author(s).)
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- 2024
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34. Prompt-driven Latent Domain Generalization for Medical Image Classification.
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Yan S, Yu Z, Liu C, Ju L, Mahapatra D, Betz-Stablein B, Mar V, Janda M, Soyer P, and Ge Z
- Abstract
Deep learning models for medical image analysis easily suffer from distribution shifts caused by dataset artifact bias, camera variations, differences in the imaging station, etc., leading to unreliable diagnoses in real-world clinical settings. Domain generalization (DG) methods, which aim to train models on multiple domains to perform well on unseen domains, offer a promising direction to solve the problem. However, existing DG methods assume domain labels of each image are available and accurate, which is typically feasible for only a limited number of medical datasets. To address these challenges, we propose a unified DG framework for medical image classification without relying on domain labels, called Prompt-driven Latent Domain Generalization (PLDG). PLDG consists of unsupervised domain discovery and prompt learning. This framework first discovers pseudo domain labels by clustering the bias-associated style features, then leverages collaborative domain prompts to guide a Vision Transformer to learn knowledge from discovered diverse domains. To facilitate cross-domain knowledge learning between different prompts, we introduce a domain prompt generator that enables knowledge sharing between domain prompts and a shared prompt. A domain mixup strategy is additionally employed for more flexible decision margins and mitigates the risk of incorrect domain assignments. Extensive experiments on three medical image classification tasks and one debiasing task demonstrate that our method can achieve comparable or even superior performance than conventional DG algorithms without relying on domain labels. Our code is publicly available at https://github.com/SiyuanYan1/PLDG/tree/main.
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- 2024
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35. Diversifying dermatology: Improving skin of colour representation.
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Susanto A, Nathan V, Janda M, Khosrotehrani K, McMeniman E, Soyer HP, and Betz-Stablein B
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- 2024
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36. Automated Detection of Pigmented Iris Freckles Using a Deep Neural Network for Cutaneous Melanoma Risk.
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Naranpanawa N, Jayasinghe D, Sturm RA, Betz-Stablein B, Janda M, Eriksson A, Soyer HP, and Chandra SS
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- 2024
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37. A protocol for annotation of total body photography for machine learning to analyze skin phenotype and lesion classification.
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Primiero CA, Betz-Stablein B, Ascott N, D'Alessandro B, Gaborit S, Fricker P, Goldsteen A, González-Villà S, Lee K, Nazari S, Nguyen H, Ntouskos V, Pahde F, Pataki BE, Quintana J, Puig S, Rezze GG, Garcia R, Soyer HP, and Malvehy J
- Abstract
Introduction: Artificial Intelligence (AI) has proven effective in classifying skin cancers using dermoscopy images. In experimental settings, algorithms have outperformed expert dermatologists in classifying melanoma and keratinocyte cancers. However, clinical application is limited when algorithms are presented with 'untrained' or out-of-distribution lesion categories, often misclassifying benign lesions as malignant, or misclassifying malignant lesions as benign. Another limitation often raised is the lack of clinical context (e.g., medical history) used as input for the AI decision process. The increasing use of Total Body Photography (TBP) in clinical examinations presents new opportunities for AI to perform holistic analysis of the whole patient, rather than a single lesion. Currently there is a lack of existing literature or standards for image annotation of TBP, or on preserving patient privacy during the machine learning process., Methods: This protocol describes the methods for the acquisition of patient data, including TBP, medical history, and genetic risk factors, to create a comprehensive dataset for machine learning. 500 patients of various risk profiles will be recruited from two clinical sites (Australia and Spain), to undergo temporal total body imaging, complete surveys on sun behaviors and medical history, and provide a DNA sample. This patient-level metadata is applied to image datasets using DICOM labels. Anonymization and masking methods are applied to preserve patient privacy. A two-step annotation process is followed to label skin images for lesion detection and classification using deep learning models. Skin phenotype characteristics are extracted from images, including innate and facultative skin color, nevi distribution, and UV damage. Several algorithms will be developed relating to skin lesion detection, segmentation and classification, 3D mapping, change detection, and risk profiling. Simultaneously, explainable AI (XAI) methods will be incorporated to foster clinician and patient trust. Additionally, a publicly released dataset of anonymized annotated TBP images will be released for an international challenge to advance the development of new algorithms using this type of data., Conclusion: The anticipated results from this protocol are validated AI-based tools to provide holistic risk assessment for individual lesions, and risk stratification of patients to assist clinicians in monitoring for skin cancer., Competing Interests: HS is a shareholder of MoleMap NZ Limited and e-derm consult GmbH and undertakes regular teledermatological reporting for both companies, Medical Consultant for Canfield Scientific Inc., Blaze Bioscience Inc., and a Medical Advisor for First Derm. JM and SP are co-founders of Diagnosis Dermatologica and Athena Care and investors in Dermavision. JM received honorarium from Canfield Scientific for consultancy and Fotofinder for educational activities. NA was employed by V7. BD was employed by Canfield Scientific Inc. SG was employed by ISAHIT. PF and HN were employed by Torus Actions & Belle.ai. AG was employed by IBM Research. SG-V and JQ were employed by Coronis Computing SL. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Primiero, Betz-Stablein, Ascott, D’Alessandro, Gaborit, Fricker, Goldsteen, González-Villà, Lee, Nazari, Nguyen, Ntouskos, Pahde, Pataki, Quintana, Puig, Rezze, Garcia, Soyer and Malvehy.)
- Published
- 2024
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38. Re: Incidence of in situ vs invasive melanoma: testing the "obligate precursor" hypothesis.
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Kahler S, Janda M, Soyer HP, and Betz-Stablein B
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- Humans, Incidence, Melanoma, Cutaneous Malignant, Melanoma epidemiology, Melanoma etiology, Skin Neoplasms diagnosis, Skin Neoplasms epidemiology, Skin Neoplasms etiology
- Published
- 2024
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39. MITF E318K: A rare homozygous case with multiple primary melanoma.
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Wallingford CK, Maas EJ, Howard A, DeBortoli E, Bhanja D, Lee K, Mothershaw A, Jagirdar K, Willett R, Betz-Stablein B, Sturm RA, Soyer HP, and McInerney-Leo AM
- Subjects
- Male, Humans, Adult, Homozygote, Microphthalmia-Associated Transcription Factor genetics, Melanoma genetics, Skin Neoplasms genetics, Nevus genetics, Neoplasms, Multiple Primary
- Abstract
MITF E318K moderates melanoma risk. Only five MITF E318K homozygous cases have been reported to date, one in association with melanoma. This novel report uses 3D total-body-photography (TBP) to describe the dermatological phenotype of a homozygous MITF E318K individual. The case, a 32-year-old male, was diagnosed with his first of six primary melanomas at 26 years of age. Five melanomas were located on the back and one in the groin. Two were superficial spreading. Three arose from pre-existing naevi and one was a rare naevoid melanoma. 3D-TBP revealed a high naevus count (n = 162) with pigmentation varying from light to dark. Most naevi generally (n = 90), and large (>5 mm diameter) and clinically atypical naevi specifically were located on the back where sun damage was mild. In contrast, naevi count was low (n = 25 total) on the head/neck and lower limbs where sun damage was severe. Thus, melanoma location correlated with naevi density, rather than degree of sun damage. In addition to the MITF E318K homozygosity, there was heterozygosity for four other moderate-risk variants, which may contribute to melanoma risk. Further research is warranted to explore whether melanomas in E318K heterozygous and other homozygotes coincide with regions of high naevi density as opposed to sun damage. This could inform future melanoma screening/surveillance., (© 2023 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)
- Published
- 2024
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40. Overdiagnosis in Melanoma Screening: Is It a Real Problem?
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Betz-Stablein B and Soyer HP
- Published
- 2023
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41. GOLM1 : expanding our understanding of melanoma susceptibility.
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Maas EJ, Wallingford CK, DeBortoli E, Smit DJ, Betz-Stablein B, Aoude LG, Stark MS, Sturm RA, Soyer HP, and McInerney-Leo AM
- Subjects
- Humans, Cell Proliferation, Membrane Proteins, Melanoma genetics, Skin Neoplasms genetics
- Abstract
Competing Interests: Competing interests: PS is a shareholder of MoleMap Limited and e-derm consult and undertakes regular teledermatological reporting for both companies. PS is a medical consultant for Canfield Scientific, Blaze Bioscience and MoleMap Australia Limited, and a medical advisor for First Derm.
- Published
- 2023
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42. Improving Artificial Intelligence-Based Diagnosis on Pediatric Skin Lesions.
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Mehta PP, Sun M, Betz-Stablein B, Halpern A, Soyer HP, Weber J, Kose K, and Rotemberg V
- Subjects
- Adult, Humans, Child, Artificial Intelligence, Skin pathology, Skin Neoplasms diagnosis, Skin Neoplasms pathology, Melanoma diagnosis, Melanoma pathology, Skin Diseases pathology
- Abstract
Artificial intelligence algorithms to classify melanoma are dependent on their training data, which limits generalizability. The objective of this study was to compare the performance of an artificial intelligence model trained on a standard adult-predominant dermoscopic dataset before and after the addition of additional pediatric training images. The performances were compared using held-out adult and pediatric test sets of images. We trained two models: one (model A) on an adult-predominant dataset (37,662 images from the International Skin Imaging Collaboration) and the other (model A+P) on an additional 1,536 pediatric images. We compared performance between the two models on adult and pediatric held-out test images separately using the area under the receiver operating characteristic curve. We then used Gradient-weighted Class Activation Maps and background skin masking to understand the contributions of the lesion versus background skin to algorithm decision making. Adding images from a pediatric population with different epidemiological and visual patterns to current reference standard datasets improved algorithm performance on pediatric images without diminishing performance on adult images. This suggests a way that dermatologic artificial intelligence models can be made more generalizable. The presence of background skin was important to the pediatric-specific improvement seen between models. Our study highlights the importance of carefully curated and labeled data from diverse inputs to improve the generalizability of AI models for dermatology, in this case applied to dermoscopic images of adult and pediatric lesions to improve melanoma detection., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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43. Spatial Randomness in the Distribution of Acquired Melanocytic Nevi of the Back in a Population-Based Sample.
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Jayasinghe D, Betz-Stablein B, Stark MS, Soyer HP, and Janda M
- Subjects
- Humans, Nevus, Pigmented epidemiology, Skin Neoplasms epidemiology
- Published
- 2023
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44. The MC1R r allele does not increase melanoma risk in MITF E318K carriers.
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Wallingford CK, Demeshko A, Krishnakripa AK, Smit DJ, Duffy DL, Betz-Stablein B, Pflugfelder A, Jagirdar K, Holland E, Mann GJ, Primiero CA, Yanes T, Malvehy J, Badenas C, Carrera C, Aguilera P, Olsen CM, Ward SV, Haass NK, Sturm RA, Puig S, Whiteman DC, Law MH, Cust AE, Potrony M, Soyer HP, and McInerney-Leo AM
- Subjects
- Humans, Alleles, Receptor, Melanocortin, Type 1 genetics, Microphthalmia-Associated Transcription Factor genetics, Australia epidemiology, Genotype, Genetic Predisposition to Disease genetics, Melanoma genetics, Skin Neoplasms genetics
- Abstract
Background: Population-wide screening for melanoma is not cost-effective, but genetic characterization could facilitate risk stratification and targeted screening. Common Melanocortin-1 receptor (MC1R) red hair colour (RHC) variants and Microphthalmia-associated transcription factor (MITF) E318K separately confer moderate melanoma susceptibility, but their interactive effects are relatively unexplored., Objectives: To evaluate whether MC1R genotypes differentially affect melanoma risk in MITF E318K+ vs. E318K- individuals., Materials and Methods: Melanoma status (affected or unaffected) and genotype data (MC1R and MITF E318K) were collated from research cohorts (five Australian and two European). In addition, RHC genotypes from E318K+ individuals with and without melanoma were extracted from databases (The Cancer Genome Atlas and Medical Genome Research Bank, respectively). χ2 and logistic regression were used to evaluate RHC allele and genotype frequencies within E318K+/- cohorts depending on melanoma status. Replication analysis was conducted on 200 000 general-population exomes (UK Biobank)., Results: The cohort comprised 1165 MITF E318K- and 322 E318K+ individuals. In E318K- cases MC1R R and r alleles increased melanoma risk relative to wild type (wt), P < 0.001 for both. Similarly, each MC1R RHC genotype (R/R, R/r, R/wt, r/r and r/wt) increased melanoma risk relative to wt/wt (P < 0.001 for all). In E318K+ cases, R alleles increased melanoma risk relative to the wt allele [odds ratio (OR) 2.04 (95% confidence interval 1.67-2.49); P = 0.01], while the r allele risk was comparable with the wt allele [OR 0.78 (0.54-1.14) vs. 1.00, respectively]. E318K+ cases with the r/r genotype had a lower but not significant melanoma risk relative to wt/wt [OR 0.52 (0.20-1.38)]. Within the E318K+ cohort, R genotypes (R/R, R/r and R/wt) conferred a significantly higher risk compared with non-R genotypes (r/r, r/wt and wt/wt) (P < 0.001). UK Biobank data supported our findings that r did not increase melanoma risk in E318K+ individuals., Conclusions: RHC alleles/genotypes modify melanoma risk differently in MITF E318K- and E318K+ individuals. Specifically, although all RHC alleles increase risk relative to wt in E318K- individuals, only MC1R R increases melanoma risk in E318K+ individuals. Importantly, in the E318K+ cohort the MC1R r allele risk is comparable with wt. These findings could inform counselling and management for MITF E318K+ individuals., Competing Interests: Conflicts of interest H.P.S. is a shareholder of MoleMap NZ Limited and e-derm consult GmbH, and undertakes regular teledermatological reporting for both companies; he is also a Medical Consultant for Canfield Scientific Inc., Blaze Bioscience Inc., MoleMap Australia Pty Limited, and a Medical Advisor for First Derm and Revenio Research Oy. The other authors state no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists.)
- Published
- 2023
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45. The dynamic nature of naevi in adulthood: prospective population-based study using three-dimensional total-body photography.
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Jayasinghe D, Koh U, Plasmeijer EI, Menzies SW, Aitken JF, Soyer HP, Janda M, Green AC, and Betz-Stablein B
- Subjects
- Humans, Prospective Studies, Research, Photography, Nevus, Pigmented, Skin Neoplasms
- Abstract
Competing Interests: Conflicts of interest H.P.S. is a shareholder of MoleMap NZ Limited and e-derm consult GmbH, and undertakes regular teledermatological reporting for both companies. H.P.S. is a medical consultant for Canfield Scientific Inc., MoleMap Australia Pty Ltd, Blaze Bioscience Inc. and a medical advisor for First Derm.
- Published
- 2023
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46. Can people take high-quality images using mobile dermatoscopes at home on easy-to-see and difficult-to-see body areas?
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Rodriguez-Acevedo AJ, O'Hara M, Koh U, Betz-Stablein B, Horsham C, Soyer HP, and Janda M
- Published
- 2023
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47. Artificial Intelligence for the Classification of Pigmented Skin Lesions in Populations with Skin of Color: A Systematic Review.
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Liu Y, Primiero CA, Kulkarni V, Soyer HP, and Betz-Stablein B
- Subjects
- Humans, Artificial Intelligence, Sensitivity and Specificity, Skin Pigmentation, Racial Groups, Melanoma pathology, Skin Neoplasms diagnosis, Skin Neoplasms pathology
- Abstract
Background: While skin cancers are less prevalent in people with skin of color, they are more often diagnosed at later stages and have a poorer prognosis. The use of artificial intelligence (AI) models can potentially improve early detection of skin cancers; however, the lack of skin color diversity in training datasets may only widen the pre-existing racial discrepancies in dermatology., Objective: The aim of this study was to systematically review the technique, quality, accuracy, and implications of studies using AI models trained or tested in populations with skin of color for classification of pigmented skin lesions., Methods: PubMed was used to identify any studies describing AI models for classification of pigmented skin lesions. Only studies that used training datasets with at least 10% of images from people with skin of color were eligible. Outcomes on study population, design of AI model, accuracy, and quality of the studies were reviewed., Results: Twenty-two eligible articles were identified. The majority of studies were trained on datasets obtained from Chinese (7/22), Korean (5/22), and Japanese populations (3/22). Seven studies used diverse datasets containing Fitzpatrick skin type I-III in combination with at least 10% from black Americans, Native Americans, Pacific Islanders, or Fitzpatrick IV-VI. AI models producing binary outcomes (e.g., benign vs. malignant) reported an accuracy ranging from 70% to 99.7%. Accuracy of AI models reporting multiclass outcomes (e.g., specific lesion diagnosis) was lower, ranging from 43% to 93%. Reader studies, where dermatologists' classification is compared with AI model outcomes, reported similar accuracy in one study, higher AI accuracy in three studies, and higher clinician accuracy in two studies. A quality review revealed that dataset description and variety, benchmarking, public evaluation, and healthcare application were frequently not addressed., Conclusions: While this review provides promising evidence of accurate AI models in populations with skin of color, the majority of the studies reviewed were obtained from East Asian populations and therefore provide insufficient evidence to comment on the overall accuracy of AI models for darker skin types. Large discrepancies remain in the number of AI models developed in populations with skin of color (particularly Fitzpatrick type IV-VI) compared with those of largely European ancestry. A lack of publicly available datasets from diverse populations is likely a contributing factor, as is the inadequate reporting of patient-level metadata relating to skin color in training datasets., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
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- 2023
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48. Unusual suspects in hereditary melanoma: POT1, POLE, BAP1.
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Maas EJ, Betz-Stablein B, Aoude LG, Soyer HP, and McInerney-Leo AM
- Subjects
- Humans, Genetic Predisposition to Disease, Germ-Line Mutation genetics, Telomere-Binding Proteins genetics, Tumor Suppressor Proteins genetics, Ubiquitin Thiolesterase genetics, Melanoma, Cutaneous Malignant, Melanoma genetics, Skin Neoplasms genetics
- Abstract
Systematic literature searches on POT1/POLE/BAP1 found that limited skin phenotypic characteristics have been documented in mutation carriers; 248 variants were annotated, and high-cluster variant regions associated with cutaneous melanoma were found in all three genes. Genotype-phenotype correlations can be used to identify patient disease predisposition based on mutation position and cluster regions., Competing Interests: Declaration of interests H.P.S. is a shareholder of MoleMap NZ Limited and e-derm consult GmbH, and undertakes regular teledermatological reporting for both companies. H.P.S. is also a Medical Consultant for Canfield Scientific Inc, MoleMap Australia Pty Ltd, Blaze Bioscience Inc, Revenio Research Oy and a Medical Advisor for First Derm. The other authors have no conflicts of interest to declare., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2022
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49. Amelanotic/hypopigmented melanoma in a sibship with oculocutaneous albinism.
- Author
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Maas EJ, Wallingford CK, McGuire JJ, Rutjes C, Smit DJ, Betz-Stablein B, Sturm RA, Soyer HP, and McInerney-Leo AM
- Subjects
- Female, Humans, Male, Membrane Transport Proteins genetics, Monophenol Monooxygenase, Mutation, Pedigree, Melanoma, Cutaneous Malignant, Albinism, Oculocutaneous genetics, Melanoma, Amelanotic, Skin Neoplasms genetics
- Abstract
Oculocutaneous albinism (OCA) is a rare condition characterized by hypopigmentation. A female proband and her sister, both with primary amelanotic/hypopigmented melanoma, underwent three-dimensional total-body photography and dermoscopy. Both sisters had exome sequencing along with their brother, who had OCA but no history of melanoma. Imaging analysis was consistent with OCA in terms of individual typology angle scores, degree of sun damage, and high naevus counts. Exome data filtered for variants in known OCA and melanoma/naevi susceptibility genes (n = 98) found all siblings were compound heterozygous for TYR mutations (Arg402Ter and Val275Phe), previously reported as causative OCA variants. A rare missense variant in PARP1 (p.Pro377Ser) was solely present in the melanoma-unaffected brother, which is noteworthy as this was previously reported as potentially protective in a familial melanoma pedigree positive for CDKN2A mutations. Evaluation and confirmation of functional impact in larger cohorts could personalize melanoma screening in OCA., (© 2022 Japanese Dermatological Association.)
- Published
- 2022
- Full Text
- View/download PDF
50. Body Site Distribution of Acquired Melanocytic Naevi and Associated Characteristics in the General Population of Caucasian Adults: A Scoping Review.
- Author
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Jayasinghe D, Nufer KL, Betz-Stablein B, Soyer HP, and Janda M
- Abstract
The number of melanocytic naevi is a major risk factor for melanoma. The divergent pathway hypothesis proposes that the propensity for naevus proliferation and malignant transformation may differ by body site and exposure to ultraviolet (UV) radiation. This scoping review aimed to summarise the evidence on the number and distribution of naevi (≥ 2 mm) on the body overall and by individual anatomical sites in Caucasian adults, and to assess whether studies used the International Agency for Research on Cancer (IARC) protocol to guide naevus counting processes. Systematic searches of Embase and PubMed identified 661 potentially relevant studies, and 12 remained eligible after full-text review. Studies varied widely in their counting protocols, reporting of naevus counts overall and by body sites, and used counting personnel with differing qualifications. Only one study used the IARC protocol. Studies reported that the highest number of naevi was on the trunk in males and on the arms in females. Body sites which receive intermittent exposure to UV radiation had higher density of naevi. Larger naevi (≥ 5 mm) were detected mostly on body sites intermittently exposed to UV radiation, and smaller naevi (< 5 mm) on chronically exposed sites. Studies reported that environmental and behavioural aspects related to UV radiation exposure, as well as genetic factors, all impact body site and size distribution of naevi. This review found that to overcome limitations of the current evidence, future studies should use consistent naevus counting protocols. Skin surface imaging could improve the reliability of findings. An updated IARC protocol is required that integrates these emerging standards and technologies to guide reliable and reproducible naevus counting in the future., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
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