An endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma.

Infantile hemangioma (IH) is the most common tumor in children and a paradigm for pathological vasculogenesis, angiogenesis and regression. Propranolol is the mainstay of treatment for IH. It inhibits hemangioma vessel formation via a ß-adrenergic receptor independent off-target effect of its R(+) enantiomer on the endothelial specific transcription factor sex-determining region Y (SRY) box transcription factor 18 (SOX18). Transcriptomic profiling of patient-derived hemangioma stem cells uncovered the mevalonate pathway (MVP) as a target of R(+) propranolol. Loss of SOX18 function confirmed R(+) propranolol mode of action on the MVP. Functional validation in preclinical IH models revealed that statins - targeting the MVP - are potent inhibitors of hemangioma vessel formation. We propose a novel SOX18-MVP-axis as a central regulator of IH pathogenesis and suggest statin repurposing to treat IH. Our findings reveal novel pleiotropic effects of beta-blockers and statins acting on the SOX18-MVP axis to disable an endothelial specific program in IH, which may impact other scenarios involving pathological vasculogenesis and angiogenesis.

Position Statements of the Emerging Trends Committee of the Asian Oceanian Society of Radiology on the Adoption and Implementation of Artificial Intelligence for Radiology

Artificial intelligence (AI) is rapidly gaining recognition in the radiology domain as a greater number of radiologists are becoming AI-literate. However, the adoption and implementation of AI solutions in clinical settings have been slow, with points of contention. A group of AI users comprising mainly clinical radiologists across various Asian countries, including India, Japan, Malaysia, Singapore, Taiwan, Thailand, and Uzbekistan, formed the working group. This study aimed to draft position statements regarding the application and clinical deployment of AI in radiology. The primary aim is to raise awareness among the general public, promote professional interest and discussion, clarify ethical considerations when implementing AI technology, and engage the radiology profession in the ever-changing clinical practice. These position statements highlight pertinent issues that need to be addressed between care providers and care recipients. More importantly, this will help legalize the use of non-human instruments in clinical deployment without compromising ethical considerations, decision-making precision, and clinical professional standards. We base our study on four main principles of medical care—respect for patient autonomy, beneficence, non-maleficence, and justice.

Is non-contrast-enhanced magnetic resonance imaging cost-effective for screening of hepatocellular carcinoma?

INTRODUCTION@#Ultrasonography (US) is the current standard of care for imaging surveillance in patients at risk of hepatocellular carcinoma (HCC). Magnetic resonance imaging (MRI) has been explored as an alternative, given the higher sensitivity of MRI, although this comes at a higher cost. We performed a cost-effective analysis comparing US and dual-sequence non-contrast-enhanced MRI (NCEMRI) for HCC surveillance in the local setting.@*METHODS@#Cost-effectiveness analysis of no surveillance, US surveillance and NCEMRI surveillance was performed using Markov modelling and microsimulation. At-risk patient cohort was simulated and followed up for 40 years to estimate the patients' disease status, direct medical costs and effectiveness. Quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio were calculated.@*RESULTS@#Exactly 482,000 patients with an average age of 40 years were simulated and followed up for 40 years. The average total costs and QALYs for the three scenarios - no surveillance, US surveillance and NCEMRI surveillance - were SGD 1,193/7.460 QALYs, SGD 8,099/11.195 QALYs and SGD 9,720/11.366 QALYs, respectively.@*CONCLUSION@#Despite NCEMRI having a superior diagnostic accuracy, it is a less cost-effective strategy than US for HCC surveillance in the general at-risk population. Future local cost-effectiveness analyses should include stratifying surveillance methods with a variety of imaging techniques (US, NCEMRI, contrast-enhanced MRI) based on patients' risk profiles.

Corynoxine B targets at HMGB1/2 to enhance autophagy for α-synuclein clearance in fly and rodent models of Parkinson's disease.

Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.

Contrastive domain adaptation with consistency match for automated pneumonia diagnosis.

Pneumonia can be difficult to diagnose since its symptoms are too variable, and the radiographic signs are often very similar to those seen in other illnesses such as a cold or influenza. Deep neural networks have shown promising performance in automated pneumonia diagnosis using chest X-ray radiography, allowing mass screening and early intervention to reduce the severe cases and death toll. However, they usually require many well-labelled chest X-ray images for training to achieve high diagnostic accuracy. To reduce the need for training data and annotation resources, we propose a novel method called Contrastive Domain Adaptation with Consistency Match (CDACM). It transfers the knowledge from different but relevant datasets to the unlabelled small-size target dataset and improves the semantic quality of the learnt representations. Specifically, we design a conditional domain adversarial network to exploit discriminative information conveyed in the predictions to mitigate the domain gap between the source and target datasets. Furthermore, due to the small scale of the target dataset, we construct a feature cloud for each target sample and leverage contrastive learning to extract more discriminative features. Lastly, we propose adaptive feature cloud expansion to push the decision boundary to a low-density area. Unlike most existing transfer learning methods that aim only to mitigate the domain gap, our method instead simultaneously considers the domain gap and the data deficiency problem of the target dataset. The conditional domain adaptation and the feature cloud generation of our method are learning jointly to extract discriminative features in an end-to-end manner. Besides, the adaptive feature cloud expansion improves the model's generalisation ability in the target domain. Extensive experiments on pneumonia and COVID-19 diagnosis tasks demonstrate that our method outperforms several state-of-the-art unsupervised domain adaptation approaches, which verifies the effectiveness of CDACM for automated pneumonia diagnosis using chest X-ray imaging.

It is Time to Incorporate Artificial Intelligence in Radiology Residency Programs

With the surge of interest in the development and application of artificial intelligence (AI) in radiology, we propose that know-how on the development and clinical evaluation of AI models needs to be incorporated in radiologist training curricula to prepare our specialty to lead in the new era of radiology practice augmented by AI.

Can we omit systematic biopsies in patients undergoing MRI fusion-targeted prostate biopsies? / 亚洲男科学杂志(英文版)

Magnetic resonance imaging (MRI)-targeted prostate biopsy is the recommended investigation in men with suspicious lesion(s) on MRI. The role of concurrent systematic in addition to targeted biopsies is currently unclear. Using our prospectively maintained database, we identified men with at least one Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesion who underwent targeted and/or systematic biopsies from May 2016 to May 2020. Clinically significant prostate cancer (csPCa) was defined as any Gleason grade group ≥2 cancer. Of 545 patients who underwent MRI fusion-targeted biopsy, 222 (40.7%) were biopsy naïve, 247 (45.3%) had previous prostate biopsy(s), and 76 (13.9%) had known prostate cancer undergoing active surveillance. Prostate cancer was more commonly found in biopsy-naïve men (63.5%) and those on active surveillance (68.4%) compared to those who had previous biopsies (35.2%; both P < 0.001). Systematic biopsies provided an incremental 10.4% detection of csPCa among biopsy-naïve patients, versus an incremental 2.4% among those who had prior negative biopsies. Multivariable regression found age (odds ratio [OR] = 1.03, P = 0.03), prostate-specific antigen (PSA) density ≥0.15 ng ml-2 (OR = 3.24, P < 0.001), prostate health index (PHI) ≥35 (OR = 2.43, P = 0.006), higher PI-RADS score (vs PI-RADS 3; OR = 4.59 for PI-RADS 4, and OR = 9.91 for PI-RADS 5; both P < 0.001) and target lesion volume-to-prostate volume ratio ≥0.10 (OR = 5.26, P = 0.013) were significantly associated with csPCa detection on targeted biopsy. In conclusion, for men undergoing MRI fusion-targeted prostate biopsies, systematic biopsies should not be omitted given its incremental value to targeted biopsies alone. The factors such as PSA density ≥0.15 ng ml-2, PHI ≥35, higher PI-RADS score, and target lesion volume-to-prostate volume ratio ≥0.10 can help identify men at higher risk of csPCa.

Machine learning in medicine: what clinicians should know

With the advent of artificial intelligence (AI), machines are increasingly being used to complete complicated tasks, yielding remarkable results. Machine learning (ML) is the most relevant subset of AI in medicine, which will soon become an integral part of our everyday practice. Therefore, physicians should acquaint themselves with ML and AI, and their role as an enabler rather than a competitor. Herein, we introduce basic concepts and terms used in AI and ML, and aim to demystify commonly used AI/ML algorithms such as learning methods including neural networks/deep learning, decision tree and application domain in computer vision and natural language processing through specific examples. We discuss how machines are already being used to augment the physician's decision-making process, and postulate the potential impact of ML on medical practice and medical research based on its current capabilities and known limitations. Moreover, we discuss the feasibility of full machine autonomy in medicine.

Use of Imaging and Biopsy in Prostate Cancer Diagnosis:A Survey From the Asian Prostate Imaging Working Group

Objective@#To elucidate the use of radiological studies, including nuclear medicine, and biopsy for the diagnosis and staging of prostate cancer (PCA) in clinical practice and understand the current status of PCA in Asian countries via an international survey. @*Materials and Methods@#The Asian Prostate Imaging Working Group designed a survey questionnaire with four domains focused on prostate magnetic resonance imaging (MRI), other prostate imaging, prostate biopsy, and PCA backgrounds. The questionnaire was sent to 111 members of professional affiliations in Korea, Japan, Singapore, and Taiwan who were representatives of their working hospitals, and their responses were analyzed. @*Results@#This survey had a response rate of 97.3% (108/111). The rates of using 3T scanners, antispasmodic agents, laxative drugs, and prostate imaging-reporting and data system reporting for prostate MRI were 21.6%−78.9%, 22.2%−84.2%, 2.3%−26.3%, and 59.5%−100%, respectively. Respondents reported using the highest b-values of 800−2000 sec/mm2 and fields of view of 9−30 cm. The prostate MRI examinations per month ranged from 1 to 600, and they were most commonly indicated for biopsy-naïve patients suspected of PCA in Japan and Singapore and staging of proven PCA in Korea and Taiwan.The most commonly used radiotracers for prostate positron emission tomography are prostate-specific membrane antigen in Singapore and fluorodeoxyglucose in three other countries. The most common timing for prostate MRI was before biopsy (29.9%). Prostate-targeted biopsies were performed in 63.8% of hospitals, usually by MRI-ultrasound fusion approach. The most common presentation was localized PCA in all four countries, and it was usually treated with radical prostatectomy. @*Conclusion@#This survey showed the diverse technical details and the availability of imaging and biopsy in the evaluation of PCA. This suggests the need for an educational program for Asian radiologists to promote standardized evidence-based imaging approaches for the diagnosis and staging of PCA.

Corynoxine B targets at HMGB1/2 to enhance autophagy for α-synuclein clearance in fly and rodent models of Parkinson's disease

Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.

Gadoxetate-Enhanced MRI as a Diagnostic Tool in the Management of Hepatocellular Carcinoma:Report from a 2020 Asia-Pacific Multidisciplinary Expert Meeting

Gadoxetate magnetic resonance imaging (MRI) is widely used in clinical practice for liver imaging. For optimal use, we must understand both its advantages and limitations. This article is the outcome of an online advisory board meeting and subsequent discussions by a multidisciplinary group of experts on liver diseases across the Asia-Pacific region, first held on September 28, 2020. Here, we review the technical considerations for the use of gadoxetate, its current role in the management of patients with hepatocellular carcinoma (HCC), and its relevance in consensus guidelines for HCC imaging diagnosis. In the latter part of this review, we examine recent evidence evaluating the impact of gadoxetate on clinical outcomes on a continuum from diagnosis to treatment decision-making and follow-up. In conclusion, we outline the potential future roles of gadoxetate MRI based on an evolving understanding of the clinical utility of this contrast agent in the management of patients at risk of, or with, HCC.

Evaluation of non-contrast magnetic resonance imaging as an imaging surveillance tool for hepatocellular carcinoma in at-risk patients

INTRODUCTION@#This study aimed to evaluate the potential of non-contrast-enhanced magnetic resonance (MR) imaging as an imaging surveillance tool for detection of hepatocellular carcinoma (HCC) in at-risk patients and to compare the performance of non-contrast MR imaging with ultrasonography (US) as a screening modality for the same.@*METHODS@#In this retrospective study, patients diagnosed with HCC between 1 January 2010 and 31 December 2015 were selected from our institution's cancer registry. Patients who underwent MR imaging and had US performed within three months of the MR imaging were included. For each MR imaging, two non-contrast MR imaging sequences - T2-weighted fat-saturated (T2-W FS) sequence and diffusion-weighted imaging (DWI) - were reviewed for the presence of suspicious lesions. A non-contrast MR image was considered positive if the lesion was seen on both sequences. The performance of non-contrast MR imaging was compared to that of hepatobiliary US for the detection of HCC.@*RESULTS@#A total of 73 patients with 108 HCCs were evaluated. Sensitivity of non-contrast MR imaging for the detection of HCC using T2-W FS and DWI was 93.2%, which was significantly higher than that of US, which was 79.5% (p = 0.02). In a subgroup of 55 patients with imaging features of liver cirrhosis, the sensitivity of non-contrast MR imaging was 90.9%, which was also significantly higher than that of US, which was 74.5% (p = 0.02).@*CONCLUSION@#Our pilot study showed that non-contrast MR imaging, using a combination of T2-W FS and DWI, is a potential alternative to US as a screening tool for surveillance of patients at risk for HCC.

Multiparametric MRI in Active Surveillance of Prostate Cancer: An Overview and a Practical Approach

MRI has become important for the detection of prostate cancer. MRI-guided biopsy is superior to conventional systematic biopsy in patients suspected with prostate cancer. MRI is also increasingly used for monitoring patients with low-risk prostate cancer during active surveillance. It improves patient selection for active surveillance at diagnosis, although its role during follow-up is unclear. We aim to review existing evidence and propose a practical approach for incorporating MRI into active surveillance protocols.

Radiographic features of COVID-19 based on an initial cohort of 96 patients in Singapore

INTRODUCTION@#Chest radiographs (CXRs) are widely used for the screening and management of COVID-19. This article describes the radiographic features of COVID-19 based on an initial national cohort of patients.@*METHODS@#This is a retrospective review of swab-positive patients with COVID-19 who were admitted to four different hospitals in Singapore between 22 January and 9 March 2020. Initial and follow-up CXRs were reviewed by three experienced radiologists to identify the predominant pattern and distribution of lung parenchymal abnormalities.@*RESULTS@#In total, 347 CXRs of 96 patients were reviewed. Initial CXRs were abnormal in 41 (42.7%) out of 96 patients. The mean time from onset of symptoms to CXR abnormality was 5.3 ± 4.7 days. The predominant pattern of lung abnormality was ground-glass opacity on initial CXRs (51.2%) and consolidation on follow-up CXRs (51.0%). Multifocal bilateral abnormalities in mixed central and peripheral distribution were observed in 63.4% and 59.2% of abnormal initial and follow-up CXRs, respectively. The lower zones were involved in 90.2% of initial CXRs and 93.9% of follow-up CXRs.@*CONCLUSION@#In a cohort of swab-positive patients, including those identified from contact tracing, we found a lower incidence of CXR abnormalities than was previously reported. The most common pattern was ground-glass opacity or consolidation, but mixed central and peripheral involvement was more common than peripheral involvement alone.

Multiparametric MRI in Active Surveillance of Prostate Cancer: An Overview and a Practical Approach

MRI has become important for the detection of prostate cancer. MRI-guided biopsy is superior to conventional systematic biopsy in patients suspected with prostate cancer. MRI is also increasingly used for monitoring patients with low-risk prostate cancer during active surveillance. It improves patient selection for active surveillance at diagnosis, although its role during follow-up is unclear. We aim to review existing evidence and propose a practical approach for incorporating MRI into active surveillance protocols.

Variable computed tomography appearances of COVID-19

The coronavirus disease 2019 (COVID-19) is typically diagnosed by specific assays that detect viral nucleic acid from the upper respiratory tract; however, this may miss infections involving only the lower airways. Computed tomography (CT) has been described as a diagnostic modality in the COVID-19 diagnosis and treatment plan. We present a case series with virologically confirmed COVID-19 pneumonia. Variable CT features were observed: consolidation with ground-glass opacities, ground-glass opacities with subpleural reticular bands, and an anterior-posterior gradient of lung abnormalities resembling that of acute respiratory distress syndrome. Evolution of CT findings was observed in one patient, where there was interval resolution of bilateral lung consolidation with development of bronchiolectasis and subpleural fibrotic bands. While sensitive for detecting lung parenchymal abnormalities in COVID-19 pneumonia, the use of CT for initial diagnosis is discouraged and should be reserved for specific clinical indications. Interpretation of chest CT findings should be correlated with duration of symptoms to better determine the disease stage and aid in patient management.

Chest Radiography in Coronavirus Disease 2019 (COVID-19): Correlation with Clinical Course

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 and was declared a global pandemic by the World Health Organization on 11 March 2020. A definitive diagnosis of COVID-19 is made after a positive result is obtained on reverse transcription-polymerase chain reaction assay. In Singapore, rigorous contact tracing was practised to contain the spread of the virus. Nasal swabs and chest radiographs (CXR) were also taken from individuals who were suspected to be infected by COVID-19 upon their arrival at a centralised screening centre. From our experience, about 40% of patients who tested positive for COVID-19 had initial CXR that appeared "normal". In this case series, we described the temporal evolution of COVID-19 in patients with an initial "normal" CXR. Since CXR has limited sensitivity and specificity in COVID-19, it is not suitable as a first-line diagnostic tool. However, when CXR changes become unequivocally abnormal, close monitoring is recommended to manage potentially severe COVID-19 pneumonia.

Epidemiological survey on a family aggregation COVID-19 in Y County, Chenzhou City, Hunan / 上海预防医学

Objective To investigate epidemic characteristics of a family aggregation COVID-19, and to provide scientific basis for prevention and control of family aggregation epidemic. Methods] Field epidemiological methods were used to investigate the cases and close contacts of a family aggregation COVID-19 in Y County, Chenzhou City, Hunan Province. Descriptive statistical analysis was used on epidemiological data . The 2019-nCoV nucleic acid was detected by real-time fluorescence quantitative RT-PCR. Results It was found that Ms. Deng was infected with COVID-19 and became the infectious source of the family aggregation epidemic , who had lived in Wuhan Hubei Province. Her boyfriend Mr. Cao became a second-generation case of COVID-19..Another two asymptomatic but infected persons were family members living with Ms.Deng . Conclusion COVID-19 easily spreads within families. The awareness of family members' protection, the education of new coronavirus pneumonia prevention and control in key groups should be strengthened to avoid the occurrence and spread of family aggregation epidemic.

Artificial Intelligence and Radiology in Singapore: Championing a New Age of Augmented Imaging for Unsurpassed Patient Care

Artificial intelligence (AI) has been positioned as being the most important recent advancement in radiology, if not the most potentially disruptive. Singapore radiologists have been quick to embrace this technology as part of the natural progression of the discipline toward a vision of how clinical medicine, empowered by technology, can achieve our national healthcare objectives of delivering value-based and patient-centric care. In this article, we consider 3 core questions relating to AI in radiology, and review the barriers to the widespread adoption of AI in radiology. We propose solutions and describe a "Centaur" model as a promising avenue for enabling the interfacing between AI and radiologists. Finally, we introduce The Radiological AI, Data Science and Imaging Informatics (RADII) subsection of the Singapore Radiological Society. RADII is an enabling body, which together with key technological and institutional stakeholders, will champion research, development and evaluation of AI for radiology applications.

Synthesis of magnetic Fe3O4 micro/nanospheres in organic solvent.

INTRODUCTION: Micro/nanostructured materials have attracted a great deal of attention, and many strategies have been developed to fabricate micro/nanostructured materials. METHODS: Amine-functionalized micro/nanostructured Fe3O4 with different sizes was synthesized conveniently in organic media. The chemical structures of as-synthesized products were characterized by FTIR, TEM, SEM, and XRD. RESULTS: The ligand binds to the Fe3O4 core by hydrogen bond between the oxygen atom on the surface of Fe3O4 and the hydrogen atom in molecular ethylenediamine. Their magnetic properties were also investigated. CONCLUSIONS: First, there is no need to control the reaction under a nitrogen atmosphere, and just one salt is used as an iron source. The growth and the surface modification of Fe3O4 crystalline nucleation happen at the same time. Second, monodispersed Fe3O4 micro/nanospheres were prepared without additional surfactant or external magnetic fields. Third, this method is preferred compared with the conventional organic phase method, as the reaction condition is milder and less pollutant will be produced.