Publications

Advanced Prostate Cancer with ATM Loss: PARP and ATR Inhibitors

HALO AI Publications, Publications

Antje Neeb, et al, European Urology, 2021
Researchers set out to evaluate the role of the ATM kinase in metastatic castration-resistant prostate cancer (mCRPC) with the long-term goal of improving molecular stratification in patients. HALO and HALO AI were used in the analysis of 800 ATM immunohistochemistry samples. Neeb et al detected ATM loss by IHC in 11% of their patient cohort which was associated with increased genomic instability but was not associated with a worse outcome. An in vitro model of ATM loss showed sensitivity to ATR and PARP inhibitors, which may be further investigated in future clinical trials of patients with ATM loss.

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Identification of immune checkpoints in COVID-19

Publications, Spotlight on Covid-19 Research Publications /

Researchers aiming to block excessive lung inflammation in COVID-19 patients found upregulated immune checkpoint biomarkers in patients with a range of COVID-19 symptoms (from paucisymptomatic to acute respiratory distress syndrome). In addition, Carvelli et al found increased expression of C5a, an inflammatory mediator, in serum and the C5aR1 receptor on myeloid cells in COVID-19 patients, which are known to initiate inflammatory responses by recruiting naeutrophils and monocytes to lungs. An In vitro neutrophil migration assay quantified with the CytoNuclear FL Module of HALO software demonstrated that the clinical stage therapeutic monoclonal antibody, avdoralimab, effectively inhibited C5a-induced neutrophil migration. The authors propose use of avdoralimab to limit excessive lung inflammation associated with acute respiratory distress in COVID-19 patients.

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Baricitinib treatment resolves lower airway inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques

Publications, Spotlight on Covid-19 Research Publications

Hoang, T.N., Pino, M., Boddapati, A.K. et al.. Baricitinib treatment resolves lower airway inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques. This article is a

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Acute Respiratory Distress and Cytokine Storm in Aged, SARS-CoV-2 Infected African Green Monkeys, but not in Rhesus Macaques

Publications, Spotlight on Covid-19 Research Publications

Blair, R.V., Vaccari, M., Doyle-Meyers, L.A.. et al. Acute Respiratory Distress and Cytokine Storm in Aged, SARS-CoV-2 Infected African Green Monkeys, but not in Rhesus Macaques. This article is a preprint and has not been certified by peer review.  doi: https://doi.org/10.1101/2020.06.18.157933. SARS-CoV-2 induces a wide range of disease severity ranging from asymptomatic infection, to a life-threating illness, particularly in the elderly and persons with comorbid conditions. Among those persons with serious COVID-19 disease, acute respiratory distress syndrome (ARDS) is a common and often fatal presentation. Animal models of SARS-CoV-2 infection that manifest severe disease are needed to investigate the pathogenesis of COVID-19 induced ARDS and evaluate therapeutic strategies.

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Ad26 vaccine protects against SARS-CoV-2 severe clinical disease in hamsters

Area Quantification, COVID-19, HALO Publications, Infectious Disease, Multiplex IHC, Publications

Lisa H Tostanoski, et al, Nature Medicine, 2020.
In this study led by researchers at Harvard Medical School, they report the first demonstration of prevention of severe clinical disease in a hamster model of SARS-CoV-2 that were provided with a single immunization of the adenovirus serotype 26 (Ad26) vaccine. The Ad26 vaccine utilizes a stabilized spike protein of the SARS-CoV-2 and in the United States this vaccine is commonly known as the Johnson and Johnson vaccine. This study, published in print in November 2020 contributed to the scientific body of evidence in animal models that enabled clinical vaccine trials that in turn led to emergency use approvals in the United States, Canada, and other countries. Researchers leveraged the Multiplex IHC module of HALO for evaluation of the percentage of SAR-N protein positive cells and for Iba-1 quantification. The Area Quantification IHC module was used to determine the percentage of SARS-CoV-2 sense or anti-sense probe or Mx1 protein as a function of area. The Cytonuclear IHC module and Area Quantification IHC modules were used in detection of MPO+ or CD3+ cells expressed as a proportion of total alveolar tissue.

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Two distinct immunopathological profiles in autopsy lungs of COVID-19

HALO AI Publications, Publications

Ronny Nienhold, et al, Nature Communications, 2020
An international consortium of researchers characterized lung tissue from patients with COVID-19 using transcriptomic, histologic, and cellular analyses. Nienhold and colleagues report two phenotypes associated with lethal COVID-19 disease. One showed high levels of interferon stimulated genes in the lungs as well as limited lung damage and high levels of cytokines and viral loads. The second phenotype included severe lung damage with low levels of interferon stimulated genes, low viral loads, and high levels of CD8+ T cells and macrophages. As patients with the first phenotype die sooner, this highlights the need for biomarkers to classify COVID-19 patients and potentially guide treatment. HALO AI was trained using annotations from a pathologist to identify lung tissue and the resulting output was confirmed by pathology review. HALO was also used for quantification of immunohistochemistry analysis of CD3, CD4, CD8, CD20, CD68, CD123, CD163, and PD1.

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