Publications by authors named "Jiali Han"

229 Publications

Urban Scene LOD Vectorized Modeling From Photogrammetry Meshes.

IEEE Trans Image Process 2021 1;30:7458-7471. Epub 2021 Sep 1.

Urban scene modeling is a challenging task for the photogrammetry and computer vision community due to its large scale, structural complexity, and topological delicacy. This paper presents an efficient multistep modeling framework for large-scale urban scenes from aerial images. It takes aerial images and a textured 3D mesh model generated by an image-based modeling system as the input and outputs compact polygon models with semantics at different levels of detail (LODs). Based on the key observation that urban buildings usually have piecewise planar rooftops and vertical walls, we propose a segment-based modeling method, which consists of three major stages: scene segmentation, roof contour extraction, and building modeling. By combining the deep neural network predictions with geometric constraints of the 3D mesh, the scene is first segmented into three classes. Then, for each building mesh, the 2D line segments are detected and used to slice the ground into polygon cells, followed by assigning each cell a roof plane via a MRF optimization. Finally, the LOD model is obtained by extruding cells to their corresponding planes. Compared with direct modeling in 3D space, we transform the mesh into a uniform 2D image grid representation and most of the modeling work is performed in 2D space, which has the advantages of low computational complexity and high robustness. In addition, our method doesn't require any global prior, such as the Manhattan or Atlanta world assumption, making it flexible to model scenes with different characteristics and complexity. Experiments on both single buildings and large-scale urban scenes demonstrate that by combining 2D photometric with 3D geometric information, the proposed algorithm is robust and efficient in urban scene LOD vectorized modeling compared with the state-of-the-art approaches.
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http://dx.doi.org/10.1109/TIP.2021.3106811DOI Listing
September 2021

Citrus Consumption and Risk of Non-Melanoma Skin Cancer in the UK Biobank.

Nutr Cancer 2021 Jul 20:1-6. Epub 2021 Jul 20.

Department of Epidemiology, Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, Indiana, USA.

Non-melanoma skin cancer (NMSC) incidence has been dramatically increasing worldwide. Psoralen, a known photocarcinogen, is naturally abundant in citrus products, leading to the hypothesis that high citrus consumption may increase NMSC risk. We fitted age- and multivariable-adjusted logistic regression models to evaluate the association between citrus consumption and NMSC risk among 197,372 UKBB participants. A total of 9,613 NMSC cases were identified using International Classification of Disease 10 codes. Citrus consumption data were collected via five rounds of 24-hour recall questionnaires. We found no association between high total citrus consumption and NMSC risk, although a slightly elevated NMSC risk was observed among participants who consumed >0 to half a serving of total citrus per day (OR [95% CI] = 1.08 [1.01-1.16]). There was no association between individual citrus products and NMSC risk. High citrus consumption was not associated with an increased risk of NMSC in our UKBB sample. Further studies are needed to clarify these associations.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1952439 .
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http://dx.doi.org/10.1080/01635581.2021.1952439DOI Listing
July 2021

Genetic variants of and in myeloid cell-related pathway genes independently predict cutaneous melanoma-specific survival.

Am J Cancer Res 2021 15;11(6):3252-3262. Epub 2021 Jun 15.

Duke Cancer Institute, Duke University Medical Center Durham, NC 27710, USA.

Both and evidence has supported a key role of myeloid cells in immune suppression in melanoma and in promoting melanocytic metastases. Some single-nucleotide polymorphisms (SNPs) have been shown to predict cutaneous melanoma-specific survival (CMSS), but the association between genetic variation in myeloid cell-related genes and cutaneous melanoma (CM) patient survival remains unknown.

Methods: we investigated associations between SNPs in myeloid cell-related pathway genes and CMSS in a discovery dataset of 850 CM patients and replicated the findings in another dataset of 409 CM patients.

Results: we identified two SNPs ( rs10151787 A>G and rs2069018 T>C) as independent prognostic factors for CMSS, with adjusted allelic hazards ratios of 1.56 (95% confidence interval =1.19-2.05, =0.001) and 1.66 (1.22-2.26, =0.001), respectively; so were their combined unfavorable alleles in a dose-response manner in both discovery and replication datasets ( <0.001 and 0.002, respectively). Additional functional analysis revealed that both rs10151787 G and rs2069018 C alleles were associated with elevated mRNA expression levels in normal tissues.

Conclusions: Our findings suggest that rs10151787 A>G and rs2069018 T>C are independent prognostic biomarkers for CMSS.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263692PMC
June 2021

Identifying Susceptibility Loci for Cutaneous Squamous Cell Carcinoma Using a Fast Sequence Kernel Association Test.

Front Genet 2021 10;12:657499. Epub 2021 May 10.

Department of Epidemiology and Biostatistics, School of Public Health, Indiana University at Bloomington, Bloomington, IN, United States.

Cutaneous squamous cell carcinoma (cSCC) accounts for about 20% of all skin cancers, the most common type of malignancy in the United States. Genome-wide association studies (GWAS) have successfully identified multiple genetic variants associated with the risk of cSCC. Most of these studies were single-locus-based, testing genetic variants one-at-a-time. In this article, we performed gene-based association tests to evaluate the joint effect of multiple variants, especially rare variants, on the risk of cSCC by using a fast sequence kernel association test (fastSKAT). The study included 1,710 cSCC cases and 24,304 cancer-free controls from the Nurses' Health Study, the Nurses' Health Study II and the Health Professionals Follow-up Study. We used UCSC Genome Browser to define gene units as candidate loci, and further evaluated the association between all variants within each gene unit and disease outcome. Four genes , and were identified using Bonferroni adjusted significance level. Our study is complementary to the existing GWASs, and our findings may provide additional insights into the etiology of cSCC. Further studies are needed to validate these findings.
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http://dx.doi.org/10.3389/fgene.2021.657499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141858PMC
May 2021

Agent-based automated persuasion with adaptive concessions tuned by emotions.

J Ambient Intell Humaniz Comput 2021 Mar 18:1-15. Epub 2021 Mar 18.

School of Management, China University of Mining and Technology (Beijing), Beijing, China.

Human-to-agent automated negotiation has many potentials in a variety of applications. How to design an agent with equivalent persuasion capabilities with its human rivals is the key to the success of such systems but the research on this problem is still at its early stage. With the aim of improving agents' persuasion ability, this paper proposes to construct emotional agents and emotion-dependent persuasion actions in automated negotiation with multiple issues. First, a multi-issue evaluation function adjusted by the rival's reputation is constructed to determine whether emotional persuasion is needed. Then, by applying the Weber-Fechner Law, this paper proposes a method to measure an agent's emotion generated by evaluating the rival's proposal. Persuasion is categorized into four types and an emotion-based method is proposed for an agent to select a persuasion type. The selected persuasion type is further related to updating concessions, so that an agent can make concessions adaptive to both the rival's proposal and the focal agent's emotional state. Moreover, a series of numerical experiments on bilateral negotiation between agents are conducted to illustrate the proposed model and validate its effectiveness in improving negotiation efficiency. Theoretical and practical implications as well as limitations are discussed in the end.
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http://dx.doi.org/10.1007/s12652-021-03089-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971364PMC
March 2021

Common genetic polymorphisms contribute to the association between chronic lymphocytic leukaemia and non-melanoma skin cancer.

Int J Epidemiol 2021 08;50(4):1325-1334

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

Background: Epidemiological studies have demonstrated a positive association between chronic lymphocytic leukaemia (CLL) and non-melanoma skin cancer (NMSC). We hypothesized that shared genetic risk factors between CLL and NMSC could contribute to the association observed between these diseases.

Methods: We examined the association between (i) established NMSC susceptibility loci and CLL risk in a meta-analysis including 3100 CLL cases and 7667 controls and (ii) established CLL loci and NMSC risk in a study of 4242 basal cell carcinoma (BCC) cases, 825 squamous cell carcinoma (SCC) cases and 12802 controls. Polygenic risk scores (PRS) for CLL, BCC and SCC were constructed using established loci. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: Higher CLL-PRS was associated with increased BCC risk (OR4th-quartile-vs-1st-quartile = 1.13, 95% CI: 1.02-1.24, Ptrend = 0.009), even after removing the shared 6p25.3 locus. No association was observed with BCC-PRS and CLL risk (Ptrend = 0.68). These findings support a contributory role for CLL in BCC risk, but not for BCC in CLL risk. Increased CLL risk was observed with higher SCC-PRS (OR4th-quartile-vs-1st-quartile = 1.22, 95% CI: 1.08-1.38, Ptrend = 1.36 × 10-5), which was driven by shared genetic susceptibility at the 6p25.3 locus.

Conclusion: These findings highlight the role of pleiotropy regarding the pathogenesis of CLL and NMSC and shows that a single pleiotropic locus, 6p25.3, drives the observed association between genetic susceptibility to SCC and increased CLL risk. The study also provides evidence that genetic susceptibility for CLL increases BCC risk.
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http://dx.doi.org/10.1093/ije/dyab042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521875PMC
August 2021

Genome-wide association study in almost 195,000 individuals identifies 50 previously unidentified genetic loci for eye color.

Sci Adv 2021 Mar 10;7(11). Epub 2021 Mar 10.

Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.

Human eye color is highly heritable, but its genetic architecture is not yet fully understood. We report the results of the largest genome-wide association study for eye color to date, involving up to 192,986 European participants from 10 populations. We identify 124 independent associations arising from 61 discrete genomic regions, including 50 previously unidentified. We find evidence for genes involved in melanin pigmentation, but we also find associations with genes involved in iris morphology and structure. Further analyses in 1636 Asian participants from two populations suggest that iris pigmentation variation in Asians is genetically similar to Europeans, albeit with smaller effect sizes. Our findings collectively explain 53.2% (95% confidence interval, 45.4 to 61.0%) of eye color variation using common single-nucleotide polymorphisms. Overall, our study outcomes demonstrate that the genetic complexity of human eye color considerably exceeds previous knowledge and expectations, highlighting eye color as a genetically highly complex human trait.
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http://dx.doi.org/10.1126/sciadv.abd1239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946369PMC
March 2021

Recreational and residential sun exposure and risk of endometriosis: a prospective cohort study.

Hum Reprod 2021 01;36(1):199-210

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Study Question: Is recreational and residential sun exposure associated with risk of endometriosis?

Summary Answer: Tanning bed use in early adulthood, sunscreen use and history of sunburns were associated with a greater risk of endometriosis; however, higher residential UV exposure was associated with a lower endometriosis risk.

What Is Known Already: Previous research has reported an association between endometriosis and skin cancer, with evidence of shared risk factors between the two diseases. We investigated the potential associations between ultraviolet radiation and endometriosis risk.

Study Design, Size, Duration: The Nurses' Health Study II is a prospective cohort of 116 429 female US nurses aged 25-42 years at enrolment in 1989. Participants completed self-administered biennial questionnaires through June 2015.

Participants/materials, Settings, Methods: We investigated self-reported measures of recreational sun-exposure and geocoded residential UV exposure in childhood and adulthood in relation to risk of laparoscopically confirmed endometriosis among premenopausal white women. We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% CIs.

Main Results And The Role Of Chance: During follow-up, 4791 incident cases of laparoscopically confirmed endometriosis were reported among 1 252  248 person-years. Tanning bed use during high school/college (≥6 times per year vs. never use: HR = 1.19, 95% CI = 1.01-1.40; Ptrend = 0.04) and at ages 25-35 (HR = 1.24, 95% CI = 1.12-1.39; Ptrend ≤ 0.0001), number of sunburns during adolescence (Ptrend = 0.03) and percentage of time using sunscreen in adulthood (Ptrend = 0.002) were positively associated with risk of endometriosis. In contrast, residential UV level at birth (highest vs. lowest quintile: HR = 0.81, 95% CI = 0.72-0.92; Ptrend = 0.0001), at age 15 (HR = 0.79, 95% CI = 0.70-0.88; Ptrend ≤ 0.0001) and at age 30 (HR = 0.90, 95% CI = 0.82-0.99; Ptrend = 0.21) were associated with a decreased risk of endometriosis.

Limitations, Reasons For Caution: Self-reported endometriosis diagnosis may be prone to misclassification; however, we restricted our definition to laparoscopically confirmed endometriosis, which has been shown to have high validity compared to medical records.

Wider Implications Of The Findings: Our results suggest that tanning bed use in early adulthood increases endometriosis risk, potentially through a harmful effect of ultraviolet A wavelengths, and that residential UV exposure reduces risk, possibly via optimal vitamin D synthesis. These findings should be investigated further to enhance our understanding of endometriosis aetiology.

Study Funding/competing Interest(s): This project was supported by NICHD grants HD48544 and HD52473, HD57210, NIH grant CA50385, CA176726. M.K. was supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme (#PIOF-GA-2011-302078) and is grateful to the Philippe Foundation and the Bettencourt-Schueller Foundation for their financial support. H.R.H. is supported by the National Cancer Institute, National Institutes of Health (K22 CA193860). The authors have nothing to disclose.

Trial Registration Number: N/A.
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http://dx.doi.org/10.1093/humrep/deaa280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801789PMC
January 2021

Novel genetic variants of and of the endosome-related pathway predict cutaneous melanoma-specific survival.

Am J Cancer Res 2020 1;10(10):3382-3394. Epub 2020 Oct 1.

Duke Cancer Institute, Duke University Medical Center Durham, NC 27710, USA.

Endosomes regulate cell polarity, adhesion, signaling, immunity, and tumor progression, which may influence cancer outcomes. Here we evaluated associations between 36,068 genetic variants of 228 endosome-related pathway genes and cutaneous melanoma disease-specific survival (CMSS) using genotyping data from two previously published genome-wide association studies. The discovery dataset included 858 CM patients with 95 deaths from The University of Texas MD Anderson Cancer Center, and the replication dataset included 409 CM patients with 48 deaths from the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). In multivariate Cox proportional hazards regression analysis, we found that two novel SNPs ( rs11666894 A>C and rs12376285 C>T) predicted CMSS, with adjusted hazards ratios of 1.47 (95% confidence interval = 1.15-1.89 and = 0.002) and 1.73 (1.30-2.31 and 0.0002), respectively. Combined analysis of risk genotypes of these two SNPs revealed a dose-dependent decrease in CMSS associated with an increased number of risk genotypes ( = 0.0002). Subsequent expression quantitative trait loci (eQTL) analysis revealed that rs11666894 was associated with mRNA expression levels in lymphoblastoid cell lines from 373 European descendants (<0.0001) and that rs12376285 was associated with mRNA expression levels in cultured fibroblasts from 605 European-Americans (<0.0001). Our findings suggest that novel genetic variants of and in the endosome-related pathway genes may be promising prognostic biomarkers for CMSS, but these results need to be validated in future larger studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642651PMC
October 2020

Genome-wide association study identifies 48 common genetic variants associated with handedness.

Nat Hum Behav 2021 01 28;5(1):59-70. Epub 2020 Sep 28.

Institute of Biological Psychiatry, Mental Health Services of Copenhagen, Copenhagen, Denmark.

Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (r = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.
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http://dx.doi.org/10.1038/s41562-020-00956-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116623PMC
January 2021

Looking for Sunshine: Genetic Predisposition to Sun Seeking in 265,000 Individuals of European Ancestry.

J Invest Dermatol 2021 04 10;141(4):779-786. Epub 2020 Sep 10.

Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, United Kingdom. Electronic address:

Despite growing public awareness of the adverse consequences of excessive sun exposure, modifying sun-seeking behavior is challenging because it appears to be driven by addictive mechanisms. This can have effects on health because sun exposure, although beneficial, when prolonged and repeated shows a causal relationship with skin cancer risk. Using data from 2,500 United Kingdom twins, we observed sun seeking to be significantly heritable (h2 ≥ 58%). In a GWAS meta-analysis of sun-seeking behavior in 261,915 subjects of European ancestry, we identified five GWAS-significant loci previously associated with addiction, behavioral and personality traits, cognitive function, and educational attainment and enriched for CNS gene expression: MIR2113 (P = 2.08 × 10), FAM76B/MTMR2/CEP57 (P = 3.70 × 10), CADM2 (P = 9.36 × 10), TMEM182 (P = 1.64 × 10), and PLCL1/LINC01923/SATB2 (P = 3.93 × 10). These findings imply that the behavior concerning UV exposure is complicated by a genetic predisposition shared with neuropsychological traits. This should be taken into consideration when designing awareness campaigns and may help improve people's attitudes toward sun exposure.
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http://dx.doi.org/10.1016/j.jid.2020.08.014DOI Listing
April 2021

Personal use of permanent hair dyes and cancer risk and mortality in US women: prospective cohort study.

BMJ 2020 09 2;370:m2942. Epub 2020 Sep 2.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA

Objective: To evaluate the associations between personal use of permanent hair dyes and cancer risk and mortality.

Design: Prospective cohort study.

Setting And Participants: 117 200 women enrolled in the Nurses' Health Study, an ongoing prospective cohort study of female nurses in the United States. The women were free of cancer at baseline, reported information on personal use of permanent hair dyes, and were followed for 36 years.

Exposure: Status, duration, frequency, and integral use (cumulative dose calculated from duration and frequency) of permanent hair dyes. Age at first use and time since first use of permanent hair dyes.

Main Outcome Measures: Associations of personal use of permanent hair dyes with risk of overall cancer and specific cancers, and cancer related death. Age and multivariable adjusted hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazard models.

Results: Ever users of permanent hair dyes had no significant increases in risk of solid cancers (n=20 805, excluding non-melanoma skin cancers; hazard ratio 0.98, 95% confidence interval 0.96 to 1.01) or hematopoietic cancers overall (n=1807; 1.00, 0.91 to 1.10) compared with non-users. Additionally, ever users did not have an increased risk of most specific cancers (cutaneous squamous cell carcinoma, bladder cancer, melanoma, estrogen receptor positive breast cancer, progesterone receptor positive breast cancer, hormone receptor positive breast cancer, brain cancer, colorectal cancer, kidney cancer, lung cancer, and most of the major subclasses and histological subtypes of hematopoietic cancer) or cancer related death (n=4860; 0.96, 0.91 to 1.02). Basal cell carcinoma risk was slightly increased for ever users (n=22 560; 1.05, 1.02 to 1.08). Cumulative dose was positively associated with risk of estrogen receptor negative breast cancer, progesterone receptor negative breast cancer, hormone receptor negative breast cancer, and ovarian cancer. An increased risk of Hodgkin lymphoma was observed only for women with naturally dark hair (based on 70 women, 24 with dark hair), and a higher risk of basal cell carcinoma was observed for women with naturally light hair.

Conclusion: No positive association was found between personal use of permanent hair dye and risk of most cancers and cancer related mortality. The increased risk of basal cell carcinoma, breast cancer (estrogen receptor negative, progesterone receptor negative, hormone receptor negative) and ovarian cancer, and the mixed findings in analyses stratified by natural hair color warrant further investigation.
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http://dx.doi.org/10.1136/bmj.m2942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463170PMC
September 2020

Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility.

Nat Genet 2020 05 27;52(5):494-504. Epub 2020 Apr 27.

Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain.

Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 × 10) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis.
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http://dx.doi.org/10.1038/s41588-020-0611-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255059PMC
May 2020

Scalable point cloud meshing for image-based large-scale 3D modeling.

Vis Comput Ind Biomed Art 2019 Aug 7;2(1):10. Epub 2019 Aug 7.

National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China.

Image-based 3D modeling is an effective method for reconstructing large-scale scenes, especially city-level scenarios. In the image-based modeling pipeline, obtaining a watertight mesh model from a noisy multi-view stereo point cloud is a key step toward ensuring model quality. However, some state-of-the-art methods rely on the global Delaunay-based optimization formed by all the points and cameras; thus, they encounter scaling problems when dealing with large scenes. To circumvent these limitations, this study proposes a scalable point-cloud meshing approach to aid the reconstruction of city-scale scenes with minimal time consumption and memory usage. Firstly, the entire scene is divided along the x and y axes into several overlapping chunks so that each chunk can satisfy the memory limit. Then, the Delaunay-based optimization is performed to extract meshes for each chunk in parallel. Finally, the local meshes are merged together by resolving local inconsistencies in the overlapping areas between the chunks. We test the proposed method on three city-scale scenes with hundreds of millions of points and thousands of images, and demonstrate its scalability, accuracy, and completeness, compared with the state-of-the-art methods.
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http://dx.doi.org/10.1186/s42492-019-0020-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099569PMC
August 2019

On fusion methods for knowledge discovery from multi-omics datasets.

Comput Struct Biotechnol J 2020 5;18:509-517. Epub 2020 Mar 5.

Department of Biosystems Engineering, University of Arizona, United States.

Recent years have witnessed the tendency of measuring a biological sample on multiple omics scales for a comprehensive understanding of how biological activities on varying levels are perturbed by genetic variants, environments, and their interactions. This new trend raises substantial challenges to data integration and fusion, of which the latter is a specific type of integration that applies a uniform method in a scalable manner, to solve biological problems which the multi-omics measurements target. Fusion-based analysis has advanced rapidly in the past decade, thanks to application drivers and theoretical breakthroughs in mathematics, statistics, and computer science. We will briefly address these methods from methodological and mathematical perspectives and categorize them into three types of approaches: data fusion (a narrowed definition as compared to the general data fusion concept), model fusion, and mixed fusion. We will demonstrate at least one typical example in each specific category to exemplify the characteristics, principles, and applications of the methods in general, as well as discuss the gaps and potential issues for future studies.
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http://dx.doi.org/10.1016/j.csbj.2020.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078495PMC
March 2020

Genome-wide meta-analysis identifies eight new susceptibility loci for cutaneous squamous cell carcinoma.

Nat Commun 2020 02 10;11(1):820. Epub 2020 Feb 10.

Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin & Bren Simon Cancer Center, Indiana University, 1050 Wishard Blvd, Indianapolis, IN, 46202, USA.

Cutaneous squamous cell carcinoma (SCC) is one of the most common cancers in the United States. Previous genome-wide association studies (GWAS) have identified 14 single nucleotide polymorphisms (SNPs) associated with cutaneous SCC. Here, we report the largest cutaneous SCC meta-analysis to date, representing six international cohorts and totaling 19,149 SCC cases and 680,049 controls. We discover eight novel loci associated with SCC, confirm all previously associated loci, and perform fine mapping of causal variants. The novel SNPs occur within skin-specific regulatory elements and implicate loci involved in cancer development, immune regulation, and keratinocyte differentiation in SCC susceptibility.
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http://dx.doi.org/10.1038/s41467-020-14594-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7010741PMC
February 2020

Pancreatic safety of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

Pharmacoepidemiol Drug Saf 2020 02;29(2):161-172

Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indiana.

Purpose: This study aimed to systematically evaluate the association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and pancreatic safety in patients with type 2 diabetes mellitus (T2DM).

Methods: Electronic databases were searched before September 2019 to include randomized controlled trials (RCTs) of SGLT2 inhibitors that reported any event on pancreatitis or pancreatic cancer among patients with T2DM. Peto odds ratio (OR) with 95% confidence interval (CI) was used to pool the data. The GRADE framework was introduced to assess the quality of evidence.

Results: Of the 35 trials involving 44 912 patients with T2DM included, 41 events of acute pancreatitis (19 trials; 32 932 patients), 72 events of overall pancreatitis (including acute pancreatitis, chronic pancreatitis, or nonspecific pancreatitis; 26 trials; 36 688 patients), and 40 events of pancreatic cancer (18 trials; 27 806 patients) were reported during a median follow-up of 52 weeks. SGLT2 inhibitors were not associated with an increased risk of acute pancreatitis compared to controls (placebo or other active drugs; Peto OR, 1.13; 95% CI, 0.60-2.13; moderate quality evidence). A similar result was found for risk of overall pancreatitis (Peto OR, 1.08; 95% CI, 0.67-1.75; moderate quality evidence) and pancreatic cancer (Peto OR, 1.34; 95% CI, 0.71-2.54; very low-quality evidence).

Conclusions: Moderate quality evidence from RCTs shows no significantly increased risk of acute pancreatitis associated with SGLT2 inhibitors, while there is very low-quality evidence suggesting no significant association between SGLT2 inhibitors and pancreatic cancer among patients with T2DM.
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http://dx.doi.org/10.1002/pds.4943DOI Listing
February 2020

Rare Earth Doped Optical Fibers with Multi-section Core.

iScience 2019 Dec 15;22:423-429. Epub 2019 Nov 15.

AdValue Photonics Inc., Tucson, AZ 85706, USA. Electronic address:

The gain bandwidth of a single-mode fiber is limited by the atomic transitions of one rare earth gain element. Here we overcome this long-standing challenge by designing a new single-mode fiber with multi-section core, where each section is doped with different gain element. We theoretically propose and experimentally demonstrate that this configuration provides a gain bandwidth well beyond the capability of conventional design, whereas the inclusion of multiple sections does not compromise single-mode operation or the quality of the transverse modal profile. This new fiber will be beneficial in realizing all fiber laser systems with few-cycle pulse duration or octave tunability.
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http://dx.doi.org/10.1016/j.isci.2019.11.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909000PMC
December 2019

Distinct transcriptomic landscapes of cutaneous basal cell carcinomas and squamous cell carcinomas.

Genes Dis 2021 Mar 19;8(2):181-192. Epub 2019 Oct 19.

Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.

The majority of non-melanoma skin cancer (NMSC) is cutaneous basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), which are also called keratinocyte carcinomas, as both of them originate from keratinocytes. The incidence of keratinocyte carcinomas is over 5 million per year in the US, three-fold higher than the total incidence of all other types of cancer combined. While there are several reports on gene expression profiling of BCC and SCC, there are significant variations in the reported gene expression changes in different studies. One reason is that tumor-adjacent normal skin specimens were not included in many studies as matched controls. Furthermore, while numerous studies of skin stem cells in mouse models have been reported, their relevance to human skin cancer remains unknown. In this report, we analyzed gene expression profiles of paired specimens of keratinocyte carcinomas with their matched normal skin tissues as the control. Among several novel findings, we discovered a significant number of zinc finger encoding genes up-regulated in human BCC. In BCC, a novel link was found between hedgehog signaling, Wnt signaling, and the cilium. While the SCC cancer-stem-cell gene signature is shared between human and mouse SCCs, the hair follicle stem-cell signature of mice was not highly represented in human SCC. Differential gene expression (DEG) in human BCC shares gene signature with both bulge and epidermal stem cells. We have also determined that human BCCs and SCCs have distinct gene expression patterns, and some of them are not fully reflected in current mouse models.
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http://dx.doi.org/10.1016/j.gendis.2019.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099692PMC
March 2021

Cutaneous nevi and internal cancer risk: Results from two large prospective cohorts of US women.

Int J Cancer 2020 07 22;147(1):14-20. Epub 2019 Oct 22.

Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN.

Elevated cutaneous nevus number has been linked to longer telomeres. Recently, a large systematic Mendelian randomization study identified a significant positive association between telomere length and risk of cancer. Here, we hypothesized that higher nevus count, as a phenotypic marker of longer telomere, may be associated with increased risk of internal cancer, and prospectively examined the association between nevus count and total as well as site-specific cancer risk among participants in the Nurses' Health Study (NHS, 1986-2012) and the Nurses' Health Study 2 (NHS2, 1989-2013) using Cox proportional hazards models. During 3,900,264 person-years of follow-up, we documented a total of 23,004 internal cancer cases (15,484 in the NHS and 7,520 in the NHS2). Compared to participants who had no nevi, the multivariate hazard ratios of total cancer (excluding skin cancer) were 1.06 (95% confidence interval [CI], 1.03-1.09) for women with 1-5 nevi, 1.08 (95% CI, 1.03-1.15) for those who had 6-14 nevi and 1.19 (95% CI, 1.05-1.35) for those with 15 or more nevi (p trend <0.0001). Moreover, because nevus count has been associated with risk of breast cancer previously, we conducted a secondary analysis by excluding breast cancer from the outcomes of interest. The results were very similar to those of our primary analysis. For individual cancer, most of the associations with nevus count were positive but not statistically significant. In conclusion, we identified the number of cutaneous nevi as a phenotypic marker associated with internal cancer risk, which may be explained by telomere biology.
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http://dx.doi.org/10.1002/ijc.32703DOI Listing
July 2020

A Prospective Study of Leukocyte Telomere Length and Risk of Gestational Diabetes in a Multiracial Cohort.

Epidemiology 2019 11;30 Suppl 2:S10-S16

From the Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.

Background: Short telomere length (TL), an indicator of cellular aging and oxidative stress, has been implicated in glucose homeostasis. Additionally, studies have illustrated that the association of TL with health outcomes may vary by age. Yet, data on the association between TL and gestational diabetes mellitus (GDM) are sparse and the potential effect modification by age remains unknown.

Methods: We prospectively investigated TL in early pregnancy in relation to the subsequent GDM risk in a case-control study of 93 women with GDM and 186 randomly selected controls matched on age, race/ethnicity, and gestational weeks at blood collection. TL was measured using blood samples collected at 10-14 gestational weeks and reported as the T/S ratio, a ratio of telomere repeat length T to copy number of a single copy gene S. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression adjusted for major risk factors.

Results: Overall, TL was not significantly associated with GDM risk. The TL-GDM association was significantly modified by age (Pinteraction = 0.02). Shorter TL in early pregnancy was associated with an increased GDM risk among women <30 years old (adjusted OR comparing the shortest vs. longest tertile: 3.1, 95% CI = 1.2, 8.1), but not associated with GDM risk among women ≥30 years.

Conclusion: Our findings suggest that TL in early pregnancy may be implicated in GDM development, particularly among younger women.
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http://dx.doi.org/10.1097/EDE.0000000000001081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276843PMC
November 2019

Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3).

Int J Cancer 2020 05 22;146(9):2394-2405. Epub 2019 Jul 22.

Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN.

Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all p < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.
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http://dx.doi.org/10.1002/ijc.32555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960354PMC
May 2020

Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development.

Oncotarget 2019 Mar 5;10(19):1760-1774. Epub 2019 Mar 5.

Department of Epidemiology and Prevention, N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation.

The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in (OR=0.44, value=3.27x10 in overall lung cancer and OR=0.41, value=9.71x10 in non-small cell lung cancer), (OR=0.73, value=1.01x10 in adenocarcinoma) and (OR=1.82, value=7.62x10 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.
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http://dx.doi.org/10.18632/oncotarget.26678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442994PMC
March 2019

Publisher Correction: Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways.

Nat Commun 2019 01 14;10(1):299. Epub 2019 Jan 14.

Dermatology Research Centre, University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.

The original version of this Article contained errors in the spelling of the authors Fan Liu and M. Arfan Ikram, which were incorrectly given as Fan Lui and Arfan M. Ikram. In addition, the original version of this Article also contained errors in the author affiliations which are detailed in the associated Publisher Correction.
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http://dx.doi.org/10.1038/s41467-018-08078-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331636PMC
January 2019

Circulating high sensitivity C reactive protein concentrations and risk of lung cancer: nested case-control study within Lung Cancer Cohort Consortium.

BMJ 2019 01 3;364:k4981. Epub 2019 Jan 3.

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer, Vanderbilt University School of Medicine, Nashville, TN, USA.

Objectives: To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type.

Design: Nested case-control study.

Setting: 20 population based cohort studies in Asia, Europe, Australia, and the United States.

Participants: 5299 patients with incident lung cancer, with individually incidence density matched controls.

Exposure: Circulating hsCRP concentrations in prediagnostic serum or plasma samples.

Main Outcome Measure: Incident lung cancer diagnosis.

Results: A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up.

Conclusions: Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315896PMC
http://dx.doi.org/10.1136/bmj.k4981DOI Listing
January 2019

Novel disease syndromes unveiled by integrative multiscale network analysis of diseases sharing molecular effectors and comorbidities.

BMC Med Genomics 2018 Dec 31;11(Suppl 6):112. Epub 2018 Dec 31.

Center for Biomedical Informatics and Biostatistics, The University of Arizona, Tucson, AZ, 85721, USA.

Background: Forty-two percent of patients experience disease comorbidity, contributing substantially to mortality rates and increased healthcare costs. Yet, the possibility of underlying shared mechanisms for diseases remains not well established, and few studies have confirmed their molecular predictions with clinical datasets.

Methods: In this work, we integrated genome-wide association study (GWAS) associating diseases and single nucleotide polymorphisms (SNPs) with transcript regulatory activity from expression quantitative trait loci (eQTL). This allowed novel mechanistic insights for noncoding and intergenic regions. We then analyzed pairs of SNPs across diseases to identify shared molecular effectors robust to multiple test correction (False Discovery Rate FDR < 0.05). We hypothesized that disease pairs found to be molecularly convergent would also be significantly overrepresented among comorbidities in clinical datasets. To assess our hypothesis, we used clinical claims datasets from the Healthcare Cost and Utilization Project (HCUP) and calculated significant disease comorbidities (FDR < 0.05). We finally verified if disease pairs resulting molecularly convergent were also statistically comorbid more than by chance using the Fisher's Exact Test.

Results: Our approach integrates: (i) 6175 SNPs associated with 238 diseases from ~ 1000 GWAS, (ii) eQTL associations from 19 tissues, and (iii) claims data for 35 million patients from HCUP. Logistic regression (controlled for age, gender, and race) identified comorbidities in HCUP, while enrichment analyses identified cis- and trans-eQTL downstream effectors of GWAS-identified variants. Among ~ 16,000 combinations of diseases, 398 disease-pairs were prioritized by both convergent eQTL-genetics (RNA overlap enrichment, FDR < 0.05) and clinical comorbidities (OR > 1.5, FDR < 0.05). Case studies of comorbidities illustrate specific convergent noncoding regulatory elements. An intergenic architecture of disease comorbidity was unveiled due to GWAS and eQTL-derived convergent mechanisms between distinct diseases being overrepresented among observed comorbidities in clinical datasets (OR = 8.6, p-value = 6.4 × 10 FET).

Conclusions: These comorbid diseases with convergent eQTL genetic mechanisms suggest clinical syndromes. While it took over a decade to confirm the genetic underpinning of the metabolic syndrome, this study is likely highlighting hundreds of new ones. Further, this knowledge may improve the clinical management of comorbidities with precision and shed light on novel approaches of drug repositioning or SNP-guided precision molecular therapy inclusive of intergenic risks.
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http://dx.doi.org/10.1186/s12920-018-0428-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311938PMC
December 2018

Association Between Health Maintenance Practices and Skin Cancer Risk as a Possible Source of Detection Bias.

JAMA Dermatol 2019 03;155(3):353-357

Department of Dermatology, Warren Alpert Medical School of Brown University, Providence, Rhode Island.

Importance: Detection bias may influence the results of epidemiologic studies of skin cancer risk. An individual's degree of contact with the health care system, and, specifically, undergoing routine screening practices, may be a source of such bias. More intensive screening practices may be associated with increased diagnoses of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma.

Objective: To assess a possible association between health care screening practices and skin cancer risk.

Design, Setting, And Participants: The cohort of participants for this study was drawn from the Nurses' Health Study (121 700 women) and Health Professionals Follow-up Study (51 529 men). Participants in the Nurses' Health Study were followed up from June 1, 1990, to June 1, 2012, and participants in the Health Professionals Follow-up Study were followed up from January 1, 1990, to January 1, 2012. Statistical analysis was performed from April 4, 2017, to May 16, 2018.

Exposures: During cohort follow-up, Nurses' Health Study and Health Professionals Follow-up Study participants were asked whether they had undergone various health care screening practices including physical examination by a physician, sigmoidoscopy or colonoscopy, eye examination, serum cholesterol test, mammography, breast examination and pelvic examination, and prostate-specific antigen test and rectal examination.

Main Outcomes And Measures: Incident BCC, SCC, and invasive melanoma. Cases of SCC and melanoma were confirmed with histopathologic findings. Hazard ratios (HRs) with 95% CIs were calculated for the association between screening practices and the various types of skin cancer.

Results: This study included 77 736 women from the Nurses' Health Study (mean [SD] age at baseline, 56 [7] years) who were followed up for 1 388 523 person-years and 39 756 men from the Health Professionals Follow-up Study (mean [SD] age at baseline, 58 [10] years) who were followed up for 635 319 person-years. A total of 14 319 incident BCCs, 1517 SCCs, and 506 melanomas were identified in the Nurses' Health Study cohort and 8741 incident BCCs, 1191 SCCs, and 469 melanomas were identified in the Health Professionals Follow-up Study cohort. Positive associations were seen between various screening practices and diagnoses of BCC and SCC, with similar directions of associations seen with melanoma for some screening practices. In the Nurses' Health Study, the multivariable HR associated with undergoing a physical examination was 1.46 (95% CI, 1.30-1.64) for BCC, 2.32 (95% CI, 1.41-3.80) for SCC, and 1.66 (95% CI, 0.85-3.22) for melanoma. Similar results were seen in the Health Professionals Follow-up Study, with a multivariable HR associated with undergoing a physical examination of 1.43 (95% CI, 1.26-1.63) for BCC and 1.85 (95% CI, 1.17-2.92) for SCC, with an attenuated HR for melanoma of 1.04 (95% CI, 0.64-1.69).

Conclusions And Relevance: Undergoing health care screening practices increases the likelihood of being diagnosed with skin cancer. Researchers should be aware of this association and, where appropriate and possible, condition analyses of skin cancer risk on measures of health care use, including screening, to address confounding associated with detection bias.
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http://dx.doi.org/10.1001/jamadermatol.2018.4216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439894PMC
March 2019

Interaction of body mass index or waist-to-hip ratio and sun exposure associated with nonmelanoma skin cancer: A prospective study from the Women's Health Initiative.

Cancer 2019 04 11;125(7):1133-1142. Epub 2018 Dec 11.

Division of Dermatology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.

Background: The incidence of nonmelanoma skin cancer (NMSC) exceeds the incidence of all other types of cancers combined. Cumulative sun exposure and intermittent sun exposure are known risk factors for the development of NMSC. Because obesity has been shown to decrease the risk of NMSC incidence, this study investigated whether the risk of NMSC with sun exposure was consistent across different levels of body size.

Methods: Body size was assessed with the body mass index (BMI) and the waist-to-hip ratio (WHR). Sun exposure was assessed in watts and langleys and by the amount of time spent outdoors per day in the summer during a person's 30s.

Results: Among 71,645 postmenopausal women eligible for inclusion in this study, 13,351 participants (18.6%) developed NMSC. A BMI ≥ 25 kg/m or a WHR ≥ 0.80 was associated with lower NMSC hazard rates (hazard ratio for BMI, 0.78; hazard ratio for WHR, 0.89); however, the association between higher levels of sun exposure and a higher risk of NMSC was more apparent among women with a BMI ≥ 25 kg/m or a WHR ≥ 0.80 in comparison with those of a normal weight (P for interaction for BMI < .001; P for interaction for WHR = .022).

Conclusions: Although most studies have considered sun exposure as a covariate, none have addressed the potential interaction of body size with sun exposure; therefore, the effect size of being overweight or obese may have been overestimated. In comparison to the normal-weight group, those in the overweight group had increasingly higher hazard rates with increasing sun exposure. Further studies are warranted to investigate how increased weight interacts with sun exposure to influence skin cancer pathogenesis.
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http://dx.doi.org/10.1002/cncr.31810DOI Listing
April 2019

Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways.

Nat Commun 2018 11 14;9(1):4774. Epub 2018 Nov 14.

Dermatology Research Centre, University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.

The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analysis combining the nevus results with a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1, PPARGC1B, HDAC4, FAM208B, DOCK8, and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk (KITLG an exception), while many melanoma risk loci do not alter nevus count. For example, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis.
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http://dx.doi.org/10.1038/s41467-018-06649-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235897PMC
November 2018

Voriconazole exposure and risk of cutaneous squamous cell carcinoma among lung or hematopoietic cell transplant patients: A systematic review and meta-analysis.

J Am Acad Dermatol 2019 Feb 18;80(2):500-507.e10. Epub 2018 Aug 18.

Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana; Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana. Electronic address:

Background: Current evidence about the association between voriconazole and risk of cutaneous squamous cell carcinoma (SCC) remains inconsistent.

Objective: To assess the association between voriconazole use and risk of SCC.

Methods: We systematically searched PubMed and Embase and performed a random effects model meta-analysis to calculate the pooled relative risk (RR) with a 95% confidence interval (CI).

Results: Of the 8 studies involving a total of 3710 individuals with a lung transplant or hematopoietic cell transplant that were included in the qualitative analysis, 5 were included in the meta-analysis. Use of voriconazole was significantly associated with increased risk of SCC (RR, 1.86; 95% CI, 1.36-2.55). The increased risk did not differ according to type of transplantation or adjustment for sun exposure. Longer duration of voriconazole use was found to be positively associated with risk of SCC (RR, 1.72; 95% CI, 1.09-2.72). Voriconazole use was not associated with increased risk of basal cell carcinoma (RR, 0.84; 95% CI, 0.41-1.71).

Limitations: There were some heterogeneities in the retrospective observational studies.

Conclusions: Our findings support an increased risk of SCC associated with voriconazole in individuals with a lung transplant or hematopoietic cell transplant. Routine dermatologic surveillance should be performed, especially among individuals at high risk of developing SCC.
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http://dx.doi.org/10.1016/j.jaad.2018.08.010DOI Listing
February 2019
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