Clinical impact of an explainable machine learning with amino acid PET imaging: application to the diagnosis of aggressive glioma.

Purpose: Radiomics-based machine learning (ML) models of amino acid positron emission tomography (PET) images have shown efficiency in glioma prediction tasks. However, their clinical impact on physician interpretation remains limited. This study investigated whether an explainable radiomics model modifies nuclear physicians' assessment of glioma aggressiveness at diagnosis.

Performance and Clinical Impact of Radiomics and 3D-CNN Models for the Diagnosis of Neurodegenerative Parkinsonian Syndromes on 18 F-FDOPA PET.

Purpose: The aim of this study was to compare the performance and added clinical value of a semiautomated radiomics model and an automated 3-dimensinal convolutional neural network (3D-CNN) model for diagnosing neurodegenerative parkinsonian syndromes on 18 F-FDOPA PET images.

Patients And Methods: This 2-center retrospective study included 687 patients with motor symptoms consistent with parkinsonian syndrome. All patients underwent 18 F-FDOPA brain PET scans, acquired on 3 PET systems from 2 different hospitals, and classified as pathological or nonpathological (by an expert nuclear physician).

Plasmatic Inactive IL-18 Predicts a Worse Overall Survival for Advanced Non-Small-Cell Lung Cancer with Early Metabolic Progression after Immunotherapy Initiation.

Unlabelled: The aim of this study was to assess the potential value of circulating active and inactive IL-18 levels in distinguishing pseudo and true tumor progression among NSCLC patients receiving immune checkpoint inhibitor treatments (ICIs).

Methods: This ancillary study includes 195 patients with metastatic non-small-cell lung cancer (NSCLC) treated with ICI in monotherapy, either pembrolizumab or nivolumab. Plasmatic levels of IL-18-related compounds, comprising the inhibitor IL-18 binding protein (IL-18BP), the inactive IL-18 (corresponding to IL-18/IL-18BP complex), and the active free IL-18, were assayed by ELISA.

[F]FDG-PET/CT atypical response patterns to immunotherapy in non-small cell lung cancer patients: long term prognosis assessment and clinical management proposal.

Aim: To determine the long-term prognosis of immune-related response profiles (pseudoprogression and dissociated response), not covered by conventional PERCIST criteria, in patients with non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPIs).

Methods: 109 patients were prospectively included and underwent [F]FDG-PET/CT at baseline, after 7 weeks (PET1), and 3 months (PET2) of treatment. On PET1, tumor response was assessed using standard PERCIST criteria.

Total metabolic tumor volume on F-FDG PET/CT is a game-changer for patients with metastatic lung cancer treated with immunotherapy.

Purpose: Because of atypical response imaging patterns in patients with metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPIs), new biomarkers are needed for a better monitoring of treatment efficacy. The aim of this prospective study was to evaluate the prognostic value of volume-derived positron-emission tomography (PET) parameters on baseline and follow-up F-fluoro-deoxy-glucose PET (F-FDG-PET) scans and compare it with the conventional PET Response Criteria in Solid Tumors (PERCIST).

Methods: Patients with metastatic NSCLC were included in two different single-center prospective trials.

Privacy preserving image registration.

Image registration is a key task in medical imaging applications, allowing to represent medical images in a common spatial reference frame. Current approaches to image registration are generally based on the assumption that the content of the images is usually accessible in clear form, from which the spatial transformation is subsequently estimated. This common assumption may not be met in practical applications, since the sensitive nature of medical images may ultimately require their analysis under privacy constraints, preventing to openly share the image content.

Efficient long-term multilineage engraftment of CD33-edited hematopoietic stem/progenitor cells in nonhuman primates.

Current immunotherapeutic targets are often shared between neoplastic and normal hematopoietic stem and progenitor cells (HSPCs), leading to unwanted on-target, off-tumor toxicities. Deletion or modification of such targets to protect normal HSPCs is, therefore, of great interest. Although HSPC modifications commonly aim to mimic naturally occurring phenotypes, the long-term persistence and safety of gene-edited cells need to be evaluated.

Metabolomic Signatures of Scarff-Bloom-Richardson (SBR) Grade in Non-Metastatic Breast Cancer.

Purpose: Identification of metabolomic biomarkers of high SBR grade in non-metastatic breast cancer.

Methods: This retrospective bicentric metabolomic analysis included a training set ( = 51) and a validation set ( = 49) of breast cancer tumors, all classified as high-grade (grade III) or low-grade (grade I-II). Metabolomes of tissue samples were studied by liquid chromatography coupled with mass spectrometry.

Radiomics, a Promising New Discipline: Example of Hepatocellular Carcinoma.

Radiomics is a discipline that involves studying medical images through their digital data. Using "artificial intelligence" algorithms, radiomics utilizes quantitative and high-throughput analysis of an image's textural richness to obtain relevant information for clinicians, from diagnosis assistance to therapeutic guidance. Exploitation of these data could allow for a more detailed characterization of each phenotype, for each patient, making radiomics a new biomarker of interest, highly promising in the era of precision medicine.

Multiplex Base Editing to Protect from CD33-Directed Therapy: Implications for Immune and Gene Therapy.

On-target toxicity to normal cells is a major safety concern with targeted immune and gene therapies. Here, we developed a base editing (BE) approach exploiting a naturally occurring CD33 single nucleotide polymorphism leading to removal of full-length CD33 surface expression on edited cells. CD33 editing in human and nonhuman primate (NHP) hematopoietic stem and progenitor cells (HSPCs) protects from CD33-targeted therapeutics without affecting normal hematopoiesis , thus demonstrating potential for novel immunotherapies with reduced off-leukemia toxicity.

The Terminal Extensions of Dbp7 Influence Growth and 60S Ribosomal Subunit Biogenesis in .

Ribosome synthesis is a complex process that involves a large set of protein -acting factors, among them DEx(D/H)-box helicases. These are enzymes that carry out remodelling activities onto RNAs by hydrolysing ATP. The nucleolar DEGD-box protein Dbp7 is required for the biogenesis of large 60S ribosomal subunits.

The DEAD-box protein Dbp6 is an ATPase and RNA annealase interacting with the peptidyl transferase center (PTC) of the ribosome.

Ribosomes are ribozymes, hence correct folding of the rRNAs during ribosome biogenesis is crucial to ensure catalytic activity. RNA helicases, which can modulate RNA-RNA and RNA/protein interactions, are proposed to participate in rRNA tridimensional folding. Here, we analyze the biochemical properties of Dbp6, a DEAD-box RNA helicase required for the conversion of the initial 90S pre-ribosomal particle into the first pre-60S particle.

Perspectives on joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards for [F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors.

Response assessment in the context of immunomodulatory treatments represents a major challenge for the medical imaging community and requires a multidisciplinary approach with involvement of oncologists, radiologists, and nuclear medicine specialists. There is evolving evidence that [F]FDG PET/CT is a useful diagnostic modality for this purpose. The clinical indications for, and the principal aspects of its standardization in this context have been detailed in the recently published "Joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards on recommended use of [F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors version 1.

Learning a confidence score and the latent space of a new supervised autoencoder for diagnosis and prognosis in clinical metabolomic studies.

Background: Presently, there is a wide variety of classification methods and deep neural network approaches in bioinformatics. Deep neural networks have proven their effectiveness for classification tasks, and have outperformed classical methods, but they suffer from a lack of interpretability. Therefore, these innovative methods are not appropriate for decision support systems in healthcare.

Development and validation of a radiomic model for the diagnosis of dopaminergic denervation on [18F]FDOPA PET/CT.

Purpose: FDOPA PET shows good performance for the diagnosis of striatal dopaminergic denervation, making it a valuable tool for the differential diagnosis of Parkinsonism. Textural features are image biomarkers that could potentially improve the early diagnosis and monitoring of neurodegenerative parkinsonian syndromes. We explored the performances of textural features for binary classification of FDOPA scans.

Prognostic value of immunotherapy-induced organ inflammation assessed on FDG PET in patients with metastatic non-small cell lung cancer.

Purpose: We evaluated the prognostic value of immunotherapy-induced organ inflammation observed on FDG PET in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPIs).

Methods: Data from patients with IIIB/IV NSCLC included in two different prospective trials were analyzed. FDG PET/CT exams were performed at baseline (PET) and repeated after 7-8 weeks (PET1) and 12-16 weeks (PET2) of treatment, using iPERCIST for tumor response evaluation.

Joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards on recommended use of [F]FDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors version 1.0.

Purpose: The goal of this guideline/procedure standard is to assist nuclear medicine physicians, other nuclear medicine professionals, oncologists or other medical specialists for recommended use of [F]FDG PET/CT in oncological patients undergoing immunotherapy, with special focus on response assessment in solid tumors.

Methods: In a cooperative effort between the EANM, the SNMMI and the ANZSNM, clinical indications, recommended imaging procedures and reporting standards have been agreed upon and summarized in this joint guideline/procedure standard.

Conclusions: The field of immuno-oncology is rapidly evolving, and this guideline/procedure standard should not be seen as definitive, but rather as a guidance document standardizing the use and interpretation of [F]FDG PET/CT during immunotherapy.

Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells.

Many cancers carry recurrent, change-of-function mutations affecting RNA splicing factors. Here, we describe a method to harness this abnormal splicing activity to drive splicing factor mutation-dependent gene expression to selectively eliminate tumor cells. We engineered synthetic introns that were efficiently spliced in cancer cells bearing SF3B1 mutations, but unspliced in otherwise isogenic wild-type cells, to yield mutation-dependent protein production.

Efficient polymer nanoparticle-mediated delivery of gene editing reagents into human hematopoietic stem and progenitor cells.

Clinical applications of hematopoietic stem cell (HSC) gene editing are limited due to their complex and expensive logistics. HSC editing is commonly performed ex vivo using electroporation and requires good manufacturing practice (GMP) facilities, similar to bone marrow transplant centers. In vivo gene editing could overcome this limitation; however, electroporation is unsuitable for systemic in vivo applications to HSCs.

Intracellular RNase activity dampens zinc finger nuclease-mediated gene editing in hematopoietic stem and progenitor cells.

Over the past decade, numerous gene-editing platforms which alter host DNA in a highly specific and targeted fashion have been described. Two notable examples are zinc finger nucleases (ZFNs), the first gene-editing platform to be tested in clinical trials, and more recently, CRISPR/Cas9. Although CRISPR/Cas9 approaches have become arguably the most popular platform in the field, the therapeutic advantages and disadvantages of each strategy are only beginning to emerge.

Primal-dual for classification with rejection (PD-CR): a novel method for classification and feature selection-an application in metabolomics studies.

Background: Supervised classification methods have been used for many years for feature selection in metabolomics and other omics studies. We developed a novel primal-dual based classification method (PD-CR) that can perform classification with rejection and feature selection on high dimensional datasets. PD-CR projects data onto a low dimension space and performs classification by minimizing an appropriate quadratic cost.

Multiplex CRISPR/Cas9 genome editing in hematopoietic stem cells for fetal hemoglobin reinduction generates chromosomal translocations.

Sickle cell disease and β-thalassemia are common monogenic disorders that cause significant morbidity and mortality globally. The only curative treatment currently is allogeneic hematopoietic stem cell transplantation, which is unavailable to many patients due to a lack of matched donors and carries risks including graft-versus-host disease. Genome editing therapies targeting either the erythroid enhancer or the promoter are already demonstrating success in reinducing fetal hemoglobin.

Association of snR190 snoRNA chaperone with early pre-60S particles is regulated by the RNA helicase Dbp7 in yeast.

Synthesis of eukaryotic ribosomes involves the assembly and maturation of precursor particles (pre-ribosomal particles) containing ribosomal RNA (rRNA) precursors, ribosomal proteins (RPs) and a plethora of assembly factors (AFs). Formation of the earliest precursors of the 60S ribosomal subunit (pre-60S r-particle) is among the least understood stages of ribosome biogenesis. It involves the Npa1 complex, a protein module suggested to play a key role in the early structuring of the pre-rRNA.