Pub Date : 2023-09-01DOI: 10.1053/j.semnuclmed.2023.06.006
Aage Kristian Olsen Alstrup DVM, PhD , Morten Busk PhD , Anita Dittrich MS , Kasper Hansen PhD , Tobias Wang PhD , Mads Damkjær PhD , Johnnie Bremholm Andersen PhD , Henrik Lauridsen PhD
The bulk of biomedical positron emission tomography (PET)-scanning experiments are performed on mammals (ie, rodents, pigs, and dogs), and the technique is only infrequently applied to answer research questions in ectothermic vertebrates such as fish, amphibians, and reptiles. Nevertheless, many unique and interesting physiological characteristics in these ectothermic vertebrates could be addressed in detail through PET. The low metabolic rate of ectothermic animals, however, may compromise the validity of physiological and biochemical parameters derived from the images created by PET and other scanning modalities. Here, we review some of the considerations that should be taken into account when PET scanning fish, amphibians, and reptiles. We present specific results from our own experiments, many of which remain previously unpublished, and we draw on examples from the literature. We conclude that knowledge on the natural history and physiology of the species studied and an understanding of the limitations of the PET scanning techniques are necessary to avoid the design of faulty experiments and erroneous conclusions.
{"title":"Special Challenges in PET Imaging of Ectothermic Vertebrates","authors":"Aage Kristian Olsen Alstrup DVM, PhD , Morten Busk PhD , Anita Dittrich MS , Kasper Hansen PhD , Tobias Wang PhD , Mads Damkjær PhD , Johnnie Bremholm Andersen PhD , Henrik Lauridsen PhD","doi":"10.1053/j.semnuclmed.2023.06.006","DOIUrl":"10.1053/j.semnuclmed.2023.06.006","url":null,"abstract":"<div><p>The bulk of biomedical positron emission tomography (PET)-scanning experiments are performed on mammals (ie, rodents, pigs, and dogs), and the technique is only infrequently applied to answer research questions in ectothermic vertebrates such as fish, amphibians, and reptiles. Nevertheless, many unique and interesting physiological characteristics in these ectothermic vertebrates could be addressed in detail through PET. The low metabolic rate of ectothermic animals, however, may compromise the validity of physiological and biochemical parameters derived from the images created by PET and other scanning modalities. Here, we review some of the considerations that should be taken into account when PET scanning fish, amphibians, and reptiles. We present specific results from our own experiments, many of which remain previously unpublished, and we draw on examples from the literature. We conclude that knowledge on the natural history and physiology of the species studied and an understanding of the limitations of the PET scanning techniques are necessary to avoid the design of faulty experiments and erroneous conclusions.</p></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9974539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1053/j.semnuclmed.2023.04.007
Morten Busk PhD , Steffen Sinning PhD , Aage K.O. Alstrup DVM, PhD, Dr.Vet.Sci , Ole L. Munk PhD , Mikkel H. Vendelbo MD, PhD
Cell lines are essential in biomedical research due to their adaptability and precise simulation of physiological and pathophysiological conditions. Cell culture techniques have greatly advanced our understanding of biology in various fields and are widely regarded as a reliable and durable tool. Their diverse applications make them indispensable in scientific research. Radiation-emitting compounds are commonly used in cell culture research to investigate biological processes. Radiolabeled compounds are utilized to study cell function, metabolism, molecular markers, receptor density, drug binding and kinetics, as well as to analyze the direct interaction of radiotracers with target organ cells. This allows for the examination of normal physiology and disease states. The In Vitro system simplifies the study and filters out nonspecific signals from the In Vivo environment, leading to more specific results. Moreover, cell cultures offer ethical advantages when evaluating new tracers and drugs in preclinical studies. While cell experiments cannot entirely replace animal experiments, they reduce the need for live animals in experimentation.
{"title":"Nuclear Medicine Preclinical Research: The Role of Cell Cultures","authors":"Morten Busk PhD , Steffen Sinning PhD , Aage K.O. Alstrup DVM, PhD, Dr.Vet.Sci , Ole L. Munk PhD , Mikkel H. Vendelbo MD, PhD","doi":"10.1053/j.semnuclmed.2023.04.007","DOIUrl":"10.1053/j.semnuclmed.2023.04.007","url":null,"abstract":"<div><p>Cell lines are essential in biomedical research due to their adaptability and precise simulation of physiological and pathophysiological conditions. Cell culture techniques have greatly advanced our understanding of biology in various fields and are widely regarded as a reliable and durable tool. Their diverse applications make them indispensable in scientific research. Radiation-emitting compounds are commonly used in cell culture research to investigate biological processes. Radiolabeled compounds are utilized to study cell function, metabolism, molecular markers, receptor density, drug binding and kinetics, as well as to analyze the direct interaction of radiotracers with target organ cells. This allows for the examination of normal physiology and disease states. The In Vitro system simplifies the study and filters out nonspecific signals from the In Vivo environment, leading to more specific results. Moreover, cell cultures offer ethical advantages when evaluating new tracers and drugs in preclinical studies. While cell experiments cannot entirely replace animal experiments, they reduce the need for live animals in experimentation.</p></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.1053/j.semnuclmed.2023.02.002
Colleen Olkowski BS , Bruna Fernandes PhD , Gary L. Griffiths PhD , Frank Lin MD , Peter L. Choyke MD
Prostate cancer remains a major cause of mortality and morbidity, affecting millions of men, with a large percentage expected to develop the disease as they reach advanced ages. Treatment and management advances have been dramatic over the past 50 years or so, and one aspect of these improvements is reflected in the multiple advances in diagnostic imaging techniques. Much attention has been focused on molecular imaging techniques that offer high sensitivity and specificity and can now more accurately assess disease status and detect recurrence earlier. During development of molecular imaging probes, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) must be evaluated in preclinical models of the disease. If such agents are to be translated to the clinic, where patients undergoing these imaging modalities are injected with a molecular imaging probe, these agents must first be approved by the FDA and other regulatory agencies prior to their adoption in clinical practice. Scientists have worked assiduously to develop preclinical models of prostate cancer that are relevant to the human disease to enable testing of these probes and related targeted drugs. Challenges in developing reproducible and robust models of human disease in animals are beset with practical issues such as the lack of natural occurrence of prostate cancer in mature male animals, the difficulty of initiating disease in immune-competent animals and the sheer size differences between humans and conveniently smaller animals such as rodents. Thus, compromises in what is ideal and what can be achieved have had to be made. The workhorse of preclinical animal models has been, and remains, the investigation of human xenograft tumor models in athymic immunocompromised mice. Later models have used other immunocompromised models as they have been found and developed, including the use of directly derived patient tumor tissues, completely immunocompromised mice, orthotopic methods for inducing prostate cancer within the mouse prostate itself and metastatic models of advanced disease. These models have been developed in close parallel with advances in imaging agent chemistries, radionuclide developments, computer electronics advances, radiometric dosimetry, biotechnologies, organoid technologies, advances in in vitro diagnostics, and overall deeper understandings of disease initiation, development, immunology, and genetics. The combination of molecular models of prostatic disease with radiometric-based studies in small animals will always remain spatially limited due to the inherent resolution sensitivity limits of PET and SPECT decay processes, fundamentally set at around a 0.5 cm resolution limit. Nevertheless, it is central to researcher's efforts and to successful clinical translation that the best animal models are adopted, accepted, and scientifically verified as part of this truly interdisciplinary approach to addressing this important disea
{"title":"Preclinical Imaging of Prostate Cancer","authors":"Colleen Olkowski BS , Bruna Fernandes PhD , Gary L. Griffiths PhD , Frank Lin MD , Peter L. Choyke MD","doi":"10.1053/j.semnuclmed.2023.02.002","DOIUrl":"10.1053/j.semnuclmed.2023.02.002","url":null,"abstract":"<div><p>Prostate cancer remains a major cause of mortality and morbidity, affecting millions of men, with a large percentage expected to develop the disease as they reach advanced ages. Treatment and management advances have been dramatic over the past 50 years or so, and one aspect of these improvements is reflected in the multiple advances in diagnostic imaging techniques. Much attention has been focused on molecular imaging techniques that offer high sensitivity and specificity and can now more accurately assess disease status and detect recurrence earlier. During development of molecular imaging probes, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) must be evaluated in preclinical models of the disease. If such agents are to be translated to the clinic, where patients undergoing these imaging modalities are injected with a molecular imaging probe, these agents must first be approved by the FDA and other regulatory agencies prior to their adoption in clinical practice. Scientists have worked assiduously to develop preclinical models of prostate cancer that are relevant to the human disease to enable testing of these probes and related targeted drugs. Challenges in developing reproducible and robust models of human disease in animals are beset with practical issues such as the lack of natural occurrence of prostate cancer in mature male animals, the difficulty of initiating disease in immune-competent animals and the sheer size differences between humans and conveniently smaller animals such as rodents. Thus, compromises in what is ideal and what can be achieved have had to be made. The workhorse of preclinical animal models has been, and remains, the investigation of human xenograft tumor models in athymic immunocompromised mice. Later models have used other immunocompromised models as they have been found and developed, including the use of directly derived patient tumor tissues, completely immunocompromised mice, orthotopic methods for inducing prostate cancer within the mouse prostate itself and metastatic models of advanced disease. These models have been developed in close parallel with advances in imaging agent chemistries, radionuclide developments, computer electronics advances, radiometric dosimetry, biotechnologies, organoid technologies, advances in in vitro diagnostics, and overall deeper understandings of disease initiation, development, immunology, and genetics. The combination of molecular models of prostatic disease with radiometric-based studies in small animals will always remain spatially limited due to the inherent resolution sensitivity limits of PET and SPECT decay processes, fundamentally set at around a 0.5 cm resolution limit. Nevertheless, it is central to researcher's efforts and to successful clinical translation that the best animal models are adopted, accepted, and scientifically verified as part of this truly interdisciplinary approach to addressing this important disea","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10440231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10399333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01DOI: 10.4274/nts.galenos.2023.0016
Elif Özdemir
{"title":"Radium-223 for the Treatment of Painful Bone Metastates in Castration-resistant Prostate Cancer","authors":"Elif Özdemir","doi":"10.4274/nts.galenos.2023.0016","DOIUrl":"https://doi.org/10.4274/nts.galenos.2023.0016","url":null,"abstract":"","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88476831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-29DOI: 10.1053/j.semnuclmed.2023.08.001
Michael C.M. Gammel MD, Esteban L. Solari PhD, Matthias Eiber MD, Isabel Rauscher MD, Stephan G. Nekolla PhD
PET/MRI is a relevant application field for prostate cancer management, offering advantages in early diagnosis, staging, and therapy planning. Despite drawbacks such as higher costs, longer acquisition time, and the need for skilled personnel, the technical integration of PET and MRI provides valuable information for detecting primary tumors, identifying metastases, and characterizing the disease, leading to more accurate staging and personalized treatment strategies. However, PET/MRI adoption has been slow, but ongoing technological advancements and AI integration might overcome challenges and improve clinical utility. As precision medicine gains importance in oncology, PET/MRI's multiparametric data can tailor treatment plans to individual patients, providing a comprehensive assessment of tumor biology and aggressiveness for more effective therapeutic strategies.
{"title":"A Clinical Role of PET-MRI in Prostate Cancer?","authors":"Michael C.M. Gammel MD, Esteban L. Solari PhD, Matthias Eiber MD, Isabel Rauscher MD, Stephan G. Nekolla PhD","doi":"10.1053/j.semnuclmed.2023.08.001","DOIUrl":"10.1053/j.semnuclmed.2023.08.001","url":null,"abstract":"<div><p>PET/MRI is a relevant application field for prostate cancer<span> management, offering advantages in early diagnosis, staging, and therapy planning. Despite drawbacks such as higher costs, longer acquisition time, and the need for skilled personnel, the technical integration of PET<span> and MRI provides valuable information for detecting primary tumors, identifying metastases<span><span>, and characterizing the disease, leading to more accurate staging and personalized treatment strategies. However, PET/MRI adoption has been slow, but ongoing technological advancements and AI integration might overcome challenges and improve clinical utility. As precision medicine gains importance in </span>oncology, PET/MRI's multiparametric data can tailor treatment plans to individual patients, providing a comprehensive assessment of tumor biology and aggressiveness for more effective therapeutic strategies.</span></span></span></p></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10185224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-26DOI: 10.1053/j.semnuclmed.2023.08.002
Imaging water pathways in the human body provides an excellent way of measuring accurately the blood flow directed to different organs. This makes it a powerful diagnostic tool for a wide range of diseases that are related to perfusion and oxygenation. Although water PET has a long history, its true potential has not made it into regular clinical practice. The article highlights the potential of water PET in molecular imaging and suggests its prospective role in becoming an essential tool for the 21st century precision medicine in different domains ranging from preclinical to clinical research and practice. The recent technical advances in high-sensitivity PET imaging can play a key accelerating role in empowering this technique, though there are still several challenges to overcome.
人体水路成像是精确测量流向不同器官的血流量的绝佳方法。这使其成为一种强大的诊断工具,可用于治疗与血流灌注和氧合有关的多种疾病。虽然水 PET 的历史悠久,但其真正的潜力尚未进入常规临床实践。这篇文章强调了水 PET 在分子成像方面的潜力,并指出它有望成为 21 世纪精准医学从临床前研究到临床研究和实践等不同领域的重要工具。最近在高灵敏度 PET 成像方面取得的技术进步可以为这项技术的发展起到关键的加速作用,尽管仍有一些挑战需要克服。
{"title":"[15O]H2O PET: Potential or Essential for Molecular Imaging?","authors":"","doi":"10.1053/j.semnuclmed.2023.08.002","DOIUrl":"10.1053/j.semnuclmed.2023.08.002","url":null,"abstract":"<div><p>Imaging water pathways in the human body provides an excellent way of measuring accurately the blood flow directed to different organs. This makes it a powerful diagnostic tool for a wide range of diseases that are related to perfusion and oxygenation. Although water PET has a long history, its true potential has not made it into regular clinical practice. The article highlights the potential of water PET in molecular imaging and suggests its prospective role in becoming an essential tool for the 21st century precision medicine in different domains ranging from preclinical to clinical research and practice. The recent technical advances in high-sensitivity PET imaging can play a key accelerating role in empowering this technique, though there are still several challenges to overcome.</p></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2023-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0001299823000703/pdfft?md5=4120c30c7a2c89788378b09cd48488fa&pid=1-s2.0-S0001299823000703-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10110885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
While RECIST 1.1 is well established in radiological response assessment, it is of limited use in prostate cancer (PCa) considering that the disease is often seen only as sclerotic bone changes on conventional imaging. Therefore, a molecular imaging-based response assessment including bone scans has been proposed and used in clinical trials, however, due to the flare phenomenon on bone scans this assessment leads to substantial delays in the detection of progression. Indeed, a robust and reliable imaging tool to assess response to chemotherapy in PCa is still warranted. Whether Positron Emission Tomography (PET) targeting the Prostate-Specific Membrane Antigen (PSMA) could achieve this, is still controversial. In this review, we summarized the available data on cytotoxic agents and their impact on PSMA expression, as well as the available data on PSMA PET imaging for response assessment.
{"title":"Is There a Role of Interim PSMA PET in Chemotherapy of Prostate Cancer?","authors":"Riccardo Laudicella PhD , Matteo Bauckneht PhD , Irene A. Burger","doi":"10.1053/j.semnuclmed.2023.07.006","DOIUrl":"10.1053/j.semnuclmed.2023.07.006","url":null,"abstract":"<div><p>While RECIST 1.1 is well established in radiological response assessment, it is of limited use in prostate cancer (PCa) considering that the disease is often seen only as sclerotic bone changes on conventional imaging. Therefore, a molecular imaging-based response assessment including bone scans has been proposed and used in clinical trials, however, due to the flare phenomenon on bone scans this assessment leads to substantial delays in the detection of progression. Indeed, a robust and reliable imaging tool to assess response to chemotherapy in PCa is still warranted. Whether Positron Emission Tomography (PET) targeting the Prostate-Specific Membrane Antigen (PSMA) could achieve this, is still controversial. In this review, we summarized the available data on cytotoxic agents and their impact on PSMA expression, as well as the available data on PSMA PET imaging for response assessment.</p></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0001299823000600/pdfft?md5=28c3f4df4137beca5605769e183d9f7c&pid=1-s2.0-S0001299823000600-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10088961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Prostate cancer is the second most common cause of malignancy among men, with bone metastasis being a significant source of morbidity and mortality in advanced cases. Detecting and treating bone metastasis at an early stage is crucial to improve the quality of life and survival of prostate cancer patients. This objective strongly relies on imaging studies. While CT and MRI have their specific utilities, they also possess certain drawbacks. Bone scintigraphy, although cost-effective and widely available, presents high false-positive rates. The emergence of PET/CT and PET/MRI, with their ability to overcome the limitations of standard imaging methods, offers promising alternatives for the detection of bone metastasis. Various radiotracers targeting cell division activity or cancer-specific membrane proteins, as well as bone seeking agents, have been developed and tested. The use of positron-emitting isotopes such as fluorine-18 and gallium-68 for labeling allows for a reduced radiation dose and unaffected biological properties. Furthermore, the integration of artificial intelligence (AI) and radiomics techniques in medical imaging has shown significant advancements in reducing interobserver variability, improving accuracy, and saving time. This article provides an overview of the advantages and limitations of bone scan using SPECT and SPECT/CT and PET imaging methods with different radiopharmaceuticals and highlights recent developments in hybrid scanners, AI, and radiomics for the identification of prostate cancer bone metastasis using molecular imaging.
{"title":"Bone Metastasis in Prostate Cancer: Bone Scan Versus PET Imaging","authors":"Nasibeh Mohseninia MD , Nazanin Zamani-Siahkali MD , Sara Harsini MD, PHD , Ghasemali Divband MD , Christian Pirich MD, PHD , Mohsen Beheshti MD","doi":"10.1053/j.semnuclmed.2023.07.004","DOIUrl":"10.1053/j.semnuclmed.2023.07.004","url":null,"abstract":"<div><p>Prostate cancer is the second most common cause of malignancy among men, with bone metastasis being a significant source of morbidity and mortality in advanced cases. Detecting and treating bone metastasis at an early stage is crucial to improve the quality of life and survival of prostate cancer patients. This objective strongly relies on imaging studies. While CT and MRI have their specific utilities, they also possess certain drawbacks. Bone scintigraphy, although cost-effective and widely available, presents high false-positive rates. The emergence of PET/CT and PET/MRI, with their ability to overcome the limitations of standard imaging methods, offers promising alternatives for the detection of bone metastasis. Various radiotracers targeting cell division activity or cancer-specific membrane proteins, as well as bone seeking agents, have been developed and tested. The use of positron-emitting isotopes such as fluorine-18 and gallium-68 for labeling allows for a reduced radiation dose and unaffected biological properties. Furthermore, the integration of artificial intelligence (AI) and radiomics techniques in medical imaging has shown significant advancements in reducing interobserver variability, improving accuracy, and saving time. This article provides an overview of the advantages and limitations of bone scan using SPECT and SPECT/CT and PET imaging methods with different radiopharmaceuticals and highlights recent developments in hybrid scanners, AI, and radiomics for the identification of prostate cancer bone metastasis using molecular imaging.</p></div>","PeriodicalId":21643,"journal":{"name":"Seminars in nuclear medicine","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0001299823000570/pdfft?md5=4ed2f0e3ff816233b324e320ea4f406b&pid=1-s2.0-S0001299823000570-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10017057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}