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General General

A public-private partnership for the express development of antiviral leads: a perspective view.

In Expert opinion on drug discovery ; h5-index 34.0

INTRODUCTION : The COVID-19 pandemic raises the question of strategic readiness for emergent pathogens. The current case illustrates that the cost of inaction can be higher in the future. The perspective article proposes a dedicated, government-sponsored agency developing anti-viral leads against all potentially dangerous pathogen species.

AREAS COVERED : The author explores the methods of computational drug screening and in-silico synthesis and proposes a specialized government-sponsored agency focusing on leads and functioning in collaboration with a network of labs, pharma, biotech firms, and academia, in order to test each lead against multiple viral species. The agency will employ artificial intelligence and machine learning tools to cut the costs further. The algorithms are expected to receive continuous feedback from the network of partners conducting the tests.

EXPERT OPINION : The author proposes a bionic principle, emulating antibody response by producing a combinatorial diversity of high q uality generic antiviral leads, suitable for multiple potentially emerging species. The availability of multiple pre-tested agents and an even greater number of combinations would reduce the impact of the next outbreak. The methodologies developed in this effort are likely to find utility in the design of chronic disease therapeutics.

Mayburd Anatoly

2020-Sep-02

COVID-19, anti-virals, artificial intelligence, docking, emergent pathogens

Radiology Radiology

T1 and T2 MR fingerprinting measurements of prostate cancer and prostatitis correlate with deep learning-derived estimates of epithelium, lumen, and stromal composition on corresponding whole mount histopathology.

In European radiology ; h5-index 62.0

OBJECTIVES : To explore the associations between T1 and T2 magnetic resonance fingerprinting (MRF) measurements and corresponding tissue compartment ratios (TCRs) on whole mount histopathology of prostate cancer (PCa) and prostatitis.

MATERIALS AND METHODS : A retrospective, IRB-approved, HIPAA-compliant cohort consisting of 14 PCa patients who underwent 3 T multiparametric MRI along with T1 and T2 MRF maps prior to radical prostatectomy was used. Correspondences between whole mount specimens and MRI and MRF were manually established. Prostatitis, PCa, and normal peripheral zone (PZ) regions of interest (ROIs) on pathology were segmented for TCRs of epithelium, lumen, and stroma using two U-net deep learning models. Corresponding ROIs were mapped to T2-weighted MRI (T2w), apparent diffusion coefficient (ADC), and T1 and T2 MRF maps. Their correlations with TCRs were computed using Pearson's correlation coefficient (R). Statistically significant differences in means were assessed using one-way ANOVA.

RESULTS : Statistically significant differences (p < 0.01) in means of TCRs and T1 and T2 MRF were observed between PCa, prostatitis, and normal PZ. A negative correlation was observed between T1 and T2 MRF and epithelium (R = - 0.38, - 0.44, p < 0.05) of PCa. T1 MRF was correlated in opposite directions with stroma of PCa and prostatitis (R = 0.35, - 0.44, p < 0.05). T2 MRF was positively correlated with lumen of PCa and prostatitis (R = 0.57, 0.46, p < 0.01). Mean T2 MRF showed significant differences (p < 0.01) between PCa and prostatitis across both transition zone (TZ) and PZ, while mean T1 MRF was significant (p = 0.02) in TZ.

CONCLUSION : Significant associations between MRF (T1 in the TZ and T2 in the PZ) and tissue compartments on corresponding histopathology were observed.

KEY POINTS : • Mean T2 MRF measurements and ADC within cancerous regions of interest dropped with increasing ISUP prognostic groups (IPG). • Mean T1 and T2 MRF measurements were significantly different (p < 0.001) across IPGs, prostatitis, and normal peripheral zone (NPZ). • T2 MRF showed stronger correlations in the peripheral zone, while T1 MRF showed stronger correlations in the transition zone with histopathology for prostate cancer.

Shiradkar Rakesh, Panda Ananya, Leo Patrick, Janowczyk Andrew, Farre Xavier, Janaki Nafiseh, Li Lin, Pahwa Shivani, Mahran Amr, Buzzy Christina, Fu Ping, Elliott Robin, MacLennan Gregory, Ponsky Lee, Gulani Vikas, Madabhushi Anant

2020-Sep-02

Deep learning, Magnetic resonance imaging, Prostatectomy, Prostatic neoplasms, Prostatitis

Radiology Radiology

A systematic review of radiomics in osteosarcoma: utilizing radiomics quality score as a tool promoting clinical translation.

In European radiology ; h5-index 62.0

OBJECTIVES : To assess the methodological quality and risk of bias in radiomics studies investigating diagnosis, therapy response, and survival of patients with osteosarcoma.

METHODS : In this systematic review, literatures on radiomics in osteosarcoma were included and assessed for methodological quality through the radiomics quality score (RQS). The risk of bias and concern of application was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. A meta-analysis of studies focusing on predicting osteosarcoma response to neoadjuvant chemotherapy was performed.

RESULTS : Twelve radiomics studies exploring osteosarcoma were identified, and five were included in meta-analysis. The RQS reached an average of 20.4% (6.92 of 36) with good inter-rater agreement (ICC 0.95, 95% CI 0.85-0.99). Four studies validated results with an internal dataset, none of which used external dataset; one study was prospectively designed, and another one shared part of the dataset. The risk of bias and concern of application were mainly related to index test aspect. The meta-analysis showed a diagnostic odds ratio of 43.68 (95%CI 13.5-141.31) for predicting response to neoadjuvant chemotherapy with high heterogeneity and low methodological quality.

CONCLUSIONS : The overall scientific quality of included studies is insufficient; however, radiomics remains a promising technology for predicting treatment response, which might guide therapeutic decision-making and related to prognosis. Improvements in study design, validation, and open science needs to be made to demonstrate the generalizability of findings and to achieve clinical applications. Widespread application of RQS, pre-trained RQS scoring procedure, and modification of RQS in response to clinical needs are necessary.

KEY POINTS : • Limited radiomics studies were established in osteosarcoma with mean RQS of 20.4%, commonly due to unvalidated results, retrospective study design, and absence of open science. • Meta-analysis of radiomics studies predicting osteosarcoma response to neoadjuvant chemotherapy showed high diagnostic odds ratio 43.68, while high heterogeneity and low methodological quality were the main concerns. • A previously trained data extraction instrument allowed reaching moderate inter-rater agreement in RQS applications, while RQS still needs improvement to become a wide adaptive tool in reviews of radiomics studies, in routine self-check before manuscript submitting and in study design.

Zhong Jingyu, Hu Yangfan, Si Liping, Jia Geng, Xing Yue, Zhang Huan, Yao Weiwu

2020-Sep-02

Machine learning, Neoadjuvant therapy, Osteosarcoma, Quality improvement, Systematic review

General General

Through Predictive Personalized Medicine.

In Brain sciences

Neuroblastoma (NBM) is a deadly form of solid tumor mostly observed in the pediatric age. Although survival rates largely differ depending on host factors and tumor-related features, treatment for clinically aggressive forms of NBM remains challenging. Scientific advances are paving the way to improved and safer therapeutic protocols, and immunotherapy is quickly rising as a promising treatment that is potentially safer and complementary to traditionally adopted surgical procedures, chemotherapy and radiotherapy. Improving therapeutic outcomes requires new approaches to be explored and validated. In-silico predictive models based on analysis of a plethora of data have been proposed by Lombardo et al. as an innovative tool for more efficacious immunotherapy against NBM. In particular, knowledge gained on intracellular signaling pathways linked to the development of NBM was used to predict how the different phenotypes could be modulated to respond to anti-programmed cell death-ligand-1 (PD-L1)/programmed cell death-1 (PD-1) immunotherapy. Prediction or forecasting are important targets of artificial intelligence and machine learning. Hopefully, similar systems could provide a reliable opportunity for a more targeted approach in the near future.

Giglia Giuseppe, Gambino Giuditta, Sardo Pierangelo

2020-Aug-28

PD-L1, computational modelling, immunotherapy, neuroblastoma

General General

A public-private partnership for the express development of antiviral leads: a perspective view.

In Expert opinion on drug discovery ; h5-index 34.0

INTRODUCTION : The COVID-19 pandemic raises the question of strategic readiness for emergent pathogens. The current case illustrates that the cost of inaction can be higher in the future. The perspective article proposes a dedicated, government-sponsored agency developing anti-viral leads against all potentially dangerous pathogen species.

AREAS COVERED : The author explores the methods of computational drug screening and in-silico synthesis and proposes a specialized government-sponsored agency focusing on leads and functioning in collaboration with a network of labs, pharma, biotech firms, and academia, in order to test each lead against multiple viral species. The agency will employ artificial intelligence and machine learning tools to cut the costs further. The algorithms are expected to receive continuous feedback from the network of partners conducting the tests.

EXPERT OPINION : The author proposes a bionic principle, emulating antibody response by producing a combinatorial diversity of high q uality generic antiviral leads, suitable for multiple potentially emerging species. The availability of multiple pre-tested agents and an even greater number of combinations would reduce the impact of the next outbreak. The methodologies developed in this effort are likely to find utility in the design of chronic disease therapeutics.

Mayburd Anatoly

2020-Sep-02

COVID-19, anti-virals, artificial intelligence, docking, emergent pathogens

Radiology Radiology

Identifying normal mammograms in a large screening population using artificial intelligence.

In European radiology ; h5-index 62.0

OBJECTIVES : To evaluate the potential of artificial intelligence (AI) to identify normal mammograms in a screening population.

METHODS : In this retrospective study, 9581 double-read mammography screening exams including 68 screen-detected cancers and 187 false positives, a subcohort of the prospective population-based Malmö Breast Tomosynthesis Screening Trial, were analysed with a deep learning-based AI system. The AI system categorises mammograms with a cancer risk score increasing from 1 to 10. The effect on cancer detection and false positives of excluding mammograms below different AI risk thresholds from reading by radiologists was investigated. A panel of three breast radiologists assessed the radiographic appearance, type, and visibility of screen-detected cancers assigned low-risk scores (≤ 5). The reduction of normal exams, cancers, and false positives for the different thresholds was presented with 95% confidence intervals (CI).

RESULTS : If mammograms scored 1 and 2 were excluded from screen-reading, 1829 (19.1%; 95% CI 18.3-19.9) exams could be removed, including 10 (5.3%; 95% CI 2.1-8.6) false positives but no cancers. In total, 5082 (53.0%; 95% CI 52.0-54.0) exams, including 7 (10.3%; 95% CI 3.1-17.5) cancers and 52 (27.8%; 95% CI 21.4-34.2) false positives, had low-risk scores. All, except one, of the seven screen-detected cancers with low-risk scores were judged to be clearly visible.

CONCLUSIONS : The evaluated AI system can correctly identify a proportion of a screening population as cancer-free and also reduce false positives. Thus, AI has the potential to improve mammography screening efficiency.

KEY POINTS : • Retrospective study showed that AI can identify a proportion of mammograms as normal in a screening population. • Excluding normal exams from screening using AI can reduce false positives.

Lång Kristina, Dustler Magnus, Dahlblom Victor, Åkesson Anna, Andersson Ingvar, Zackrisson Sophia

2020-Sep-02

Artificial intelligence, Breast cancer, Mammography, Mass screening