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Session introduction: Characterizing the importance of environmental exposures, interactions between the environment and genetic architecture, and genetic interactions: New methods for understanding the etiology of complex traits and disease 20

Session introduction: Characterizing the importance of envir...

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20th Pacific Symposium on Biocomputing, PSB 2015

作者： Hall, Molly A. Verma, Shefali Setia Wall, Dennis P. Moore, Jason H. Keating, Brendan Campbell, Daniel B. Gibson, Gregory Asselbergs, Folkert W. Pendergrass, Sarah Center for Systems Genomics Department of Biochemistry and Molecular Biology Pennsylvania State University University ParkPA16802 United States Department of Pediatrics Division of Systems Medicine Program in Biomedical Informatics Stanford University StanfordCA94305 United States Institute for Quantitative Biomedical Sciences Department of Genetics Geisel School of Medicine Dartmouth College HanoverNH03755 United States Center for Applied Genomics Children's Hospital of Philadelphia PhiladelphiaPA19104 United States Department of Psychiatry and the Behavioral Sciences Zilkha Neurogenetic Institute Center for Genomic Psychiatry Neuroscience Graduate Program Keck School of Medicine University of Southern California Los AngelesCA90089 United States Center for Integrative Genomics Department of Biology Georgia Institute of Technology AtlantaGA30332 United States Department of Cardiology Division of Heart and Lungs University Medical Center Ultrecht Netherlands

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Predicting Microsatellite Instability from Histology Images with Dilated Neighborhood Attention Transformer in Colorectal Cancer

Predicting Microsatellite Instability from Histology Images ...

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IEEE Symposium on Bioinformatics and Bioengineering (BIBE)

作者： Yun-Chi Chen Tung Chao Wimaya Nitya Phandita Tzu-Yu Sun Huai-Zhi Wang Yi-Hsien Hsieh Le-Yin Hsu Che Lin Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University (NTU) Taipei Taiwan College of Bioresources and Agriculture NTU Taipei Taiwan Department of Computer Science and Information Engineering National Taiwan University of Science and Technology Taipei Taiwan Graduate Institute of Communication Engineering NTU Taipei Taiwan Data Science Degree Program NTU Taipei Taiwan Department of Electrical Engineering NTU Taipei Taiwan Center for Advanced Computing and Imaging in Biomedicine NTU Taipei Taiwan Smart Medicine and Health Informatics Program NTU Taipei Taiwan

ISBN: (数字)9798331518622

ISBN: (纸本)9798331518639

Microsatellite instability (MSI) is a pivotal genetic marker influencing the efficacy of immunotherapy in colorectal cancer. Traditional MSI examination often requires additional genetic or immunohistochemical tests, whereas histology images, widely available in colorectal cancer diagnosis, offer a valuable alternative for MSI prediction. Although Transformer-based models have demonstrated promising outcomes in predicting MSI from histology images, they are hampered by traditional local attention mechanisms that struggle to capture long-range interdependencies and establish a comprehensive global receptive field. In this study, we introduce DiNAT-MSI, a novel framework for histology-based MSI prediction that incorporates the Dilated Neighborhood Attention Transformer (DiNAT). This model enhances global context recognition and substantially expands receptive fields, all without additional computational burden. Our results demonstrate that DiNAT-MSI achieves a superior patientwise AUROC compared to ResNet18 and Swin Transformer, along with commendable explainability. Our work not only illustrates a more accessible diagnostic tool for leveraging histological data but also underscores the potential of Transformerbased models with sophisticated attention designs in advancing precision medicine for colorectal cancer patients.

关键词： Attention mechanisms Histopathology Computational modeling Precision medicine Small satellites Immunotherapy Colorectal cancer Predictive models Transformers Genetics

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Dose Optimization of rhIL-7-hyFc for Patients With Lymphopenia Using a Neonatal Fc Receptor-Mediated Recycling-Based and Target-Mediated Drug Disposition Pharmacokinetic Model

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Clinical and translational science 2025年第5期18卷 e70252页

作者： Hye Seon Jeon Sang Won Lee Woojin Jung Heeyoon Jung Donghoon Choi Mi-Sun Byun Hwi-Yeol Yun Soyoung Lee Anhye Kim Jung-Woo Chae Howard Lee College of Pharmacy Chungnam National University Daejeon Republic of Korea. Department of Pharmacology Hanyang University College of Medicine Seoul Republic of Korea. Department of Clinical Pharmacology and Therapeutics Hanyang University Seoul Hospital Seoul Republic of Korea. Population Health Sciences Program Department of Population and Quantitative Health Sciences University of Massachusetts Chan Medical School Worcester Massachusetts USA. Research Institute of NeoImmuneTech Inc. Pohang Republic of Korea. Clinical Development Department Genexine Inc. Seoul Republic of Korea. Department of Bio-AI Convergence Chungnam National University Daejeon Republic of Korea. Department of Clinical Pharmacology and Therapeutics CHA University Bundang Medical Center Seongnam Republic of Korea. Department of Pharmacology CHA University School of Medicine CHA University Seongnam Republic of Korea. Institute for Biomedical Informatics CHA University School of Medicine CHA University Seongnam Republic of Korea. Department of Clinical Pharmacology and Therapeutics Seoul National University Hospital Seoul Republic of Korea. Department of Molecular Medicine and Biopharmaceutical Sciences Graduate School of Convergence Science and Technology Seoul National University Seoul Republic of Korea. Advanced Institute of Convergence Technology Suwon Republic of Korea.

Recombinant human interleukin-7 hybrid Fc (rhIL-7-hyFc) is a homodimer of rhIL-7 fused to a hyFc. Exogenous IL-7 promotes T cell proliferation and increases lymphocyte count, making it a potential treatment option for lymphopenia and cancer. To improve therapeutic efficacy, rhIL-7-hyFc was developed as a long-acting IL-7. This study aimed to create a pharmacokinetic model for rhIL-7-hyFc by incorporating neonatal Fc receptor (FcRn)-mediated recycling and target-mediated drug disposition (TMDD) of the IL-7 receptor. Data were collected from a randomized, double-blind, placebo-controlled phase 1 trial involving 30 healthy volunteers who received single doses of rhIL-7-hyFc. Volunteers received 20 or 60 mg/kg subcutaneously, 60 mg/kg intramuscularly (IM), or a placebo. Clinical data were provided by Genexine Inc. (Seoul, Republic of Korea). A TMDD-FcRn-mediated recycling pharmacokinetic model was developed using NONMEM 7.5 software, assisted by PsN 5.3.1 software. A quasi-steady-state approximation was used to describe drug-receptor and drug-FcRn interactions. The model evaluation included goodness of fit, visual predictive checks, and bootstrap analysis. Based on the pharmacokinetic parameters of the final model, a simulation was conducted to select the dosage regimen, ensuring a probability of at least 0.8 for meeting both safety and efficacy criteria. The model successfully described the pharmacokinetic profiles of 24 patients administered rhIL-7-hyFc. Based on the simulation results, 670-800 μg/kg every 3 weeks, 1010-1530 μg/kg every 6 weeks, and 1510-2190 μg/kg every 9 weeks IM were proposed. These results may help further understand rhIL-7-hyFc characteristics and, moreover, provide guidance for selecting the appropriate dosing regimen in future clinical trials.

关键词： lymphopenia optimal dosing for clinical trials rhIL‐7‐hyFc semi‐mechanistic model

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The role of input imaging combination and ADC threshold on segmentation of acute ischemic stroke lesion using U-Net

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European Radiology 2023年第9期33卷 6157-6167页

作者： Li, Ya-Hui Lin, Shao-Chieh Chung, Hsiao-Wen Chang, Chia-Ching Peng, Hsu-Hsia Huang, Teng-Yi Shen, Wu-Chung Tsai, Chon-Haw Lo, Yu-Chien Lee, Tung-Yang Juan, Cheng-Hsuan Juan, Cheng-En Chang, Hing-Chiu Liu, Yi-Jui Juan, Chun-Jung Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taipei Taiwan Department of Medical Imaging China Medical University Hsinchu Hospital No. 199 Sec. 1 Xinglong Rd. Zhubei City Hsinchu County 302 Hsinchu Taiwan Ph.D. Program in Electrical and Communication Engineering Feng Chia University Taichung Taiwan Department of Electrical Engineering National Taiwan University Taipei Taiwan Department of Management Science National Yang Ming Chiao Tung University Hsinchu Taiwan Department of Biomedical Engineering and Environmental Sciences National Tsing Hua University Hsinchu Taiwan Department of Electrical Engineering National Taiwan University of Science and Technology Taipei Taiwan Department of Radiology School of Medicine College of Medicine China Medical University Taichung Taiwan Department of Medical Imaging Medical University Hospital Taichung Taiwan Department of Neurology China Medical University Hospital Taichung Taiwan Cheng Ching Hospital Taichung Taiwan Master’s Program of Biomedical Informatics and Biomedical Engineering Feng Chia University Taichung Taiwan Department of Automatic Control Engineering Feng Chia University No. 100 Wenhwa Rd. Seatwen Taichung 40724 Taiwan Department of Biomedical Engineering The Chinese University of Hong Kong ERB1112 11/F William M.W. Mong Engineering Building N.T Shatin Hong Kong Multi-Scale Medical Robotics Center The Chinese University of Hong Kong N.T Shatin Hong Kong Department of Biomedical Engineering National Defense Medical Center Taipei Taiwan Department of Computer Science and Information Engineering National Taiwan University Taipei Taiwan

Background: To evaluate the effect of the weighting of input imaging combo and ADC threshold on the performance of the U-Net and to find an optimized input imaging combo and ADC threshold in segmenting acute ischemic stroke (AIS) lesion. Methods: This study retrospectively enrolled a total of 212 patients having AIS. Four combos, including ADC-ADC-ADC (AAA), DWI-ADC-ADC (DAA), DWI-DWI-ADC (DDA), and DWI-DWI-DWI (DDD), were used as input images, respectively. Three ADC thresholds including 0.6, 0.8 and 1.8 × 10^–3 mm²/s were applied. Dice similarity coefficient (DSC) was used to evaluate the segmentation performance of U-Nets. Nonparametric Kruskal–Wallis test with Tukey–Kramer post-hoc tests were used for comparison. A p <.05 was considered statistically significant. Results: The DSC significantly varied among different combos of images and different ADC thresholds. Hybrid U-Nets outperformed uniform U-Nets at ADC thresholds of 0.6 × 10^–3 mm²/s and 0.8 × 10^–3 mm²/s (p <.001). The U-Net with imaging combo of DDD had segmentation performance similar to hybrid U-Nets at an ADC threshold of 1.8 × 10^–3 mm²/s (p =.062 to 1). The U-Net using the imaging combo of DAA at the ADC threshold of 0.6 × 10^–3 mm²/s achieved the highest DSC in the segmentation of AIS lesion. Conclusions: The segmentation performance of U-Net for AIS varies among the input imaging combos and ADC thresholds. The U-Net is optimized by choosing the imaging combo of DAA at an ADC threshold of 0.6 × 10^–3 mm²/s in segmentating AIS lesion with highest DSC. Key Points: • Segmentation performance of U-Net for AIS differs among input imaging combos. • Segmentation performance of U-Net for AIS differs among ADC thresholds. • U-Net is optimized using DAA with ADC = 0.6 × 10^–3mm²/s. © 2023, The Author(s), under exclusive licence to European Society of Radiology.

关键词： Deep Learning Diffusion Magnetic Resonance Imaging Ischemic Stroke Neural Networks, Computer Retrospective Study

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Physician Compliance With a Computerized Clinical Decision Support System for Anemia Management of Patients With End-stage Kidney Disease on Hemodialysis: Retrospective Electronic Health Record Observational Study

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JMIR Formative Research 2023年 7卷 e44373页

作者： Yang, Ju-Yeh Shu, Kai-Hsiang Peng, Yu-Sen Hsu, Shih-Ping Chiu, Yen-Ling Pai, Mei-Fen Wu, Hon-Yen Tsai, Wan-Chuan Tung, Kuei-Ting Kuo, Raymond N. Institute of Health Policy and Management College of Public Health National Taiwan University Taipei Taiwan Division of Nephrology Department of Internal Medicine Far Eastern Memorial Hospital New Taipei City Taiwan Center for General Education Lee-Ming Institute of Technology New Taipei City Taiwan Graduate Institute of Medicine Yuan Ze University Taoyuan Taiwan Graduate Program in Biomedical Informatics Yuan Ze University Taoyuan Taiwan

Background: Previous studies on clinical decision support systems (CDSSs) for the management of renal anemia in patients with end-stage kidney disease undergoing hemodialysis have previously focused solely on the effects of the CDSS. However, the role of physician compliance in the efficacy of the CDSS remains ill-defined. Objective: We aimed to investigate whether physician compliance was an intermediate variable between the CDSS and the management outcomes of renal anemia. Methods: We extracted the electronic health records of patients with end-stage kidney disease on hemodialysis at the Far Eastern Memorial Hospital Hemodialysis Center (FEMHHC) from 2016 to 2020. FEMHHC implemented a rule-based CDSS for the management of renal anemia in 2019. We compared the clinical outcomes of renal anemia between the pre- and post-CDSS periods using random intercept models. Hemoglobin levels of 10 to 12 g/dL were defined as the on-target range. Physician compliance was defined as the concordance of adjustments of the erythropoietin-stimulating agent (ESA) between the CDSS recommendations and the actual physician prescriptions. Results: We included 717 eligible patients on hemodialysis (mean age 62.9, SD 11.6 years;male n=430, 59.9%) with a total of 36, 091 hemoglobin measurements (average hemoglobin and on-target rate were 11.1, SD 1.4, g/dL and 59.9%, respectively). The on-target rate decreased from 61.3% (pre-CDSS) to 56.2% (post-CDSS) owing to a high hemoglobin percentage of >12 g/dL (pre: 21.5%;post: 29%). The failure rate (hemoglobin <10 g/dL) decreased from 17.2% (pre-CDSS) to 14.8% (post-CDSS). The average weekly ESA use of 5848 (SD 4211) units per week did not differ between phases. The overall concordance between CDSS recommendations and physician prescriptions was 62.3%. The CDSS concordance increased from 56.2% to 78.6%. In the adjusted random intercept model, the post-CDSS phase showed increased hemoglobin by 0.17 (95% CI 0.14-0.21) g/dL, weekly ESA by 264 (95% CI

关键词： anemia management clinical decision support clinical decision support system decision support electronic health records end-stage kidney disease erythropoietin-stimulating agent hemodialysis kidney disease patient outcome physician compliance

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COWID: an efficient cloud-based genomics workflow for scalable identification of SARS-COV-2

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Briefings in Bioinformatics 2023年第5期24卷 bbad280-bbad280页

作者： Lim, Hendrick Gao-Min Fann, Yang C Lee, Yuan-Chii Gladys Graduate Institute of Biomedical Informatics College of Medical Science and Technology Taipei Medical University Taipei 11031 Taiwan Department of Medical Research Tzu Chi Hospital Indonesia Pantai Indah Kapuk Greater Jakarta 14470 Indonesia It and Bioinformatics Program Division of Intramural National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda 20892 MD United States

Implementing a specific cloud resource to analyze extensive genomic data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a challenge when resources are limited. To overcome this, we repurposed a cloud platform initially designed for use in research on cancer genomics (https://***) to enable its use in research on SARS-CoV-2 to build Cloud Workflow for Viral and Variant Identification (COWID). COWID is a workflow based on the Common Workflow Language that realizes the full potential of sequencing technology for use in reliable SARS-CoV-2 identification and leverages cloud computing to achieve efficient parallelization. COWID outperformed other contemporary methods for identification by offering scalable identification and reliable variant findings with no false-positive results. COWID typically processed each sample of raw sequencing data within 5 min at a cost of only US$0.01. The COWID source code is publicly available (https://***/hendrick0403/COWID) and can be accessed on any computer with Internet access. COWID is designed to be user-friendly;it can be implemented without prior programming knowledge. Therefore, COWID is a time-efficient tool that can be used during a pandemic. © 2023 Published by Oxford University Press.

关键词： cloud repurposing cloud workflow COVID-19 Illumina sequencing parallel computation SARS-CoV-2

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Improving quantitation accuracy in isobaric-labeling mass spectrometry experiments with spectral library searching and feature-based peptide-spectrum match filter

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Scientific Reports 2023年第1期13卷 1-10页

作者： Kuo, Tzu-Yun Wang, Jen-Hung Huang, Yung-Wen Sung, Ting-Yi Chen, Ching-Tai Department of Biochemical Science and Technology National Taiwan University Taipei 10617 Taiwan Bioinformatics Program Taiwan International Graduate Program Institute of Statistical Science Academia Sinica Taipei 11529 Taiwan Institute of Information Science Academia Sinica Taipei 11529 Taiwan Institute of Biomedical Informatics National Yang Ming Chiao Tung University Taipei 11221 Taiwan Department of Computer Science and Information Engineering National Taiwan University Taipei 10617 Taiwan Department of Bioinformatics and Biomedical Engineering Asia University Taichung 41354 Taiwan Center for Precision Health Research Asia University Taichung 41354 Taiwan

Isobaric labeling relative quantitation is one of the dominating proteomic quantitation technologies. Traditional quantitation pipelines for isobaric-labeled mass spectrometry data are based on sequence database searching. In this study, we present a novel quantitation pipeline that integrates sequence database searching, spectral library searching, and a feature-based peptide-spectrum-match (PSM) filter using various spectral features for filtering. The combined database and spectral library searching results in larger quantitation coverage, and the filter removes PSMs with larger quantitation errors, retaining those with higher quantitation accuracy. Quantitation results show that the proposed pipeline can improve the overall quantitation accuracy at the PSM and protein levels. To our knowledge, this is the first study that utilizes spectral library searching to improve isobaric labeling-based quantitation. For users to conveniently perform the proposed pipeline, we have implemented the feature-based filter being executable on both Windows and Linux platforms;its executable files, user manual, and sample data sets are freely available at https://***/comics/Software_*** . Furthermore, with the developed filter, the proposed pipeline is fully compatible with the Trans-Proteomic Pipeline. © 2023, Springer Nature Limited.

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New Tools for Lineage Tracing in Cancer In Vivo

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Cancer Biology 1000年第1期7卷 111-129页

作者： Matthew G. Jones Dian Yang Jonathan S. Weissman 2Department of Cellular and Molecular Pharmacology University of California San Francisco San Francisco California USA 1Whitehead Institute for Biomedical Research Howard Hughes Medical Institute David H. Koch Institute for Integrative Cancer Research and Department of Biology Massachusetts Institute of Technology Cambridge Massachusetts USA email: weissman@wi.mit.edudyang@wi.mit.edu 4Center for Computational Biology University of California Berkeley Berkeley California USA 5Center for Personal Dynamic Regulomes Stanford University School of Medicine Stanford California USA 3Biological and Medical Informatics Graduate Program and Integrative Program in Quantitative Biology University of California San Francisco San Francisco California USA

During tumor evolution, cancer cells can acquire the ability to proliferate, invade neighboring tissues, evade the immune system, and spread systemically. Tracking this process remains challenging, as many key events occur stochastically and over long times, which could be addressed by studying the phylogenetic relationships among cancer cells. Several lineage tracing approaches have been developed and employed in many tumor models and contexts, providing critical insights into tumor evolution. Recent advances in single-cell lineage tracing have greatly expanded the resolution, scale, and readout of lineage tracing toolkits. In this review, we provide an overview of static lineage tracing methods, and then focus on evolving lineage tracing technologies that enable reconstruction of tumor phylogenies at unprecedented resolution. We also discuss in vivo applications of these technologies to profile subclonal dynamics, quantify tumor plasticity, and track metastasis. Finally, we highlight outstanding questions and emerging technologies for building comprehensive cancer evolution roadmaps.

关键词： cancer biology lineage tracing single-cell analysis tumor evolution cancer metastasis cell barcoding

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Kidney multiome-based genetic scorecard reveals convergent coding and regulatory variants

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Science (New York, N.Y.) 2025年第6734期387卷 eadp4753页

作者： Liu, Hongbo Abedini, Amin Ha, Eunji Ma, Ziyuan Sheng, Xin Dumoulin, Bernhard Qiu, Chengxiang Aranyi, Tamas Li, Shen Dittrich, Nicole Chen, Hua-Chang Tao, Ran Tarng, Der-Cherng Hsieh, Feng-Jen Chen, Shih-Ann Yang, Shun-Fa Lee, Mei-Yueh Kwok, Pui-Yan Wu, Jer-Yuarn Chen, Chien-Hsiun Khan, Atlas Limdi, Nita A. Wei, Wei-Qi Walunas, Theresa L. Karlson, Elizabeth W. Kenny, Eimear E. Luo, Yuan Kottyan, Leah Connolly, John J. Jarvik, Gail P. Weng, Chunhua Shang, Ning Cole, Joanne B. Mercader, Josep M. Mandla, Ravi Majarian, Timothy D. Florez, Jose C. Haas, Mary E. Lotta, Luca A. Drivas, Theodore G. Vy, Ha My T Nadkarni, Girish N. Wiley, Laura K. Wilson, Melissa P. Gignoux, Christopher R. Rasheed, Humaira Thomas, Laurent F. Åsvold, Bjørn Olav Brumpton, Ben M. Hallan, Stein I. Hveem, Kristian Zheng, Jie Hellwege, Jacklyn N. Zawistowski, Matthew Zöllner, Sebastian Franceschini, Nora Hu, Hailong Zhou, Jianfu Kiryluk, Krzysztof Ritchie, Marylyn D. Palmer, Matthew Edwards, Todd L. Voight, Benjamin F. Hung, Adriana M. Susztak, Katalin Department of Medicine Renal Electrolyte and Hypertension Division University of Pennsylvania Philadelphia PA United States Institute of Diabetes Obesity and Metabolism University of Pennsylvania Philadelphia PA United States Department of Genetics University of Pennsylvania Philadelphia PA United States Penn-CHOP Kidney Innovation Center University of Pennsylvania Philadelphia PA United States Liangzhu Laboratory Zhejiang University 1369 West Wenyi Road Hangzhou Zhejiang China Department of Nephrology Children' Hospital Zhejiang University School of Medicine National Clinical Research Center for Child Health Hangzhou Zhejiang China Institute of Molecular Life Sciences HUN-REN Research Center for Natural Sciences Budapest Hungary Department of Molecular Biology Semmelweis University Budapest Hungary Department of Medicine Federal University of São Paulo São Paulo Brazil Department of Biostatistics Vanderbilt University Medical Center Nashville TN United States Vanderbilt Genetics Institute Vanderbilt University Medical Center Nashville TN United States Institute of Clinical Medicine School of Medicine National Yang Ming Chiao Tung University ROC Taipei Taiwan Division of Nephrology Department of Medicine Taipei Veterans General Hospital ROC Taipei Taiwan Institute of Biomedical Sciences Academia Sinica ROC Taipei Taiwan Cardiovascular Center Taichung Veterans General Hospital Taichung Taiwan ROC National Chung Hsing University Taichung Taiwan ROC Heart Rhythm Center Division of Cardiology Department of Medicine Taipei Veterans General Hospital ROC Taipei Taiwan Department of Internal Medicine College of Medicine National Yang Ming Chiao Tung University ROC Taipei Taiwan Institute of Medicine Chung Shan Medical University Taichung Taiwan ROC Department of Medical Research Chung Shan Medical University Hospital Taichung Taiwan ROC Division of Endocrinology and Metabolism Department of Internal Medicine Kaohsiung Medical Universit

Kidney dysfunction is a major cause of mortality, but its genetic architecture remains elusive. In this study, we conducted a multiancestry genome-wide association study in 2.2 million individuals and identified 1026 (97 previously unknown) independent loci. Ancestry-specific analysis indicated an attenuation of newly identified signals on common variants in European ancestry populations and the power of population diversity for further discoveries. We defined genotype effects on allele-specific gene expression and regulatory circuitries in more than 700 human kidneys and 237,000 cells. We found 1363 coding variants disrupting 782 genes, with 601 genes also targeted by regulatory variants and convergence in 161 genes. Integrating 32 types of genetic information, we present the "Kidney Disease Genetic Scorecard" for prioritizing potentially causal genes, cell types, and druggable targets for kidney disease.

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Nuclear cardiology image enhancement using wavelet transform analysis

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Physica Medica 2014年 30卷 e30-e30页

作者： A. Poulakis S. Angelakis G. Fountos G.S. Panagiotakis I. Asteriadis I. Valais Department of Biomedical Engineering Technological Educational Institute of Athens 12210 Athens Greece Biomedical Informatics and Technology Graduate Program School of Computer Science University of Crete Department of Medical Physics Medical School University of Patras 265 00 Patras Greece Department of Nuclear Medicine General Hospital of Kavala 65 500 Kavala Greece

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