A Semi-Virtual Trier Social Stress Test (SV-TSST).

The Trier Social Stress Test (TSST) is a strategy for inducing acute psychological stress and increases in glucocorticoid levels. Here we describe the methodology and implementation of a Semi-Virtual Trier Social Stress Test (SV-TSST) which combines the control of a laboratory environment with reduced need for in-person logistical support and enhanced social distancing without the need for specialized equipment. During the SV-TSST, the participant is guided through the baseline, anticipatory, challenge, and recovery phases of the test by an in-person experimenter.

A functional screen for ubiquitin regulation identifies an E3 ligase secreted by .

Ubiquitin signaling controls many aspects of eukaryotic biology, including targeted protein degradation and immune defense. Remarkably, invading bacterial pathogens have adapted secreted effector proteins that hijack host ubiquitination to gain control over host responses. These ubiquitin-targeted effectors can exhibit, for example, E3 ligase or deubiquitinase activities, often without any sequence or structural homology to eukaryotic ubiquitin regulators.

Interplay between septins and ubiquitin-mediated xenophagy during entrapment.

Septins are cytoskeletal proteins implicated in numerous cellular processes including cytokinesis and morphogenesis. In the case of infection by , septins assemble into cage-like structures that entrap cytosolic bacteria targeted by autophagy. The interplay between septin cage entrapment and bacterial autophagy is poorly understood.

Quantification of intratumoural heterogeneity in mice and patients via machine-learning models trained on PET-MRI data.

In oncology, intratumoural heterogeneity is closely linked with the efficacy of therapy, and can be partially characterized via tumour biopsies. Here we show that intratumoural heterogeneity can be characterized spatially via phenotype-specific, multi-view learning classifiers trained with data from dynamic positron emission tomography (PET) and multiparametric magnetic resonance imaging (MRI). Classifiers trained with PET-MRI data from mice with subcutaneous colon cancer quantified phenotypic changes resulting from an apoptosis-inducing targeted therapeutic and provided biologically relevant probability maps of tumour-tissue subtypes.

Septins and K63 ubiquitin chains are present in separate bacterial microdomains during autophagy of entrapped Shigella.

During host cell invasion, Shigella escapes to the cytosol and polymerizes actin for cell-to-cell spread. To restrict cell-to-cell spread, host cells employ cell-autonomous immune responses including antibacterial autophagy and septin cage entrapment. How septins interact with the autophagy process to target Shigella for destruction is poorly understood.

Neglected simultaneous bilateral asymmetric traumatic hip dislocation in a young male managed by closed reduction manoeuvres in a resource-limited setting: A case report.

Background: Asymmetric bilateral hip dislocations are rare, representing approximately 0.01 %-0.02 % of all joint dislocations.

Driving Impairment Cases Involving Flualprazolam.

Flualprazolam is a novel psychoactive substance in the benzodiazepine class that is increasing in prevalence in the USA. This study describes 19 cases of drivers stopped for impaired driving where flualprazolam was detected. This represents ∼9% of the total cases submitted to the Sedgwick County Regional Forensic Science Center toxicology laboratory between July 2019 and May 2020.

ClinVAP: a reporting strategy from variants to therapeutic options.

Motivation: Next-generation sequencing has become routine in oncology and opens up new avenues of therapies, particularly in personalized oncology setting. An increasing number of cases also implies a need for a more robust, automated and reproducible processing of long lists of variants for cancer diagnosis and therapy. While solutions for the large-scale analysis of somatic variants have been implemented, existing solutions often have issues with reproducibility, scalability and interoperability.

Spectral Clustering Predicts Tumor Tissue Heterogeneity Using Dynamic F-FDG PET: A Complement to the Standard Compartmental Modeling Approach.

In this study, we described and validated an unsupervised segmentation algorithm for the assessment of tumor heterogeneity using dynamic F-FDG PET. The aim of our study was to objectively evaluate the proposed method and make comparisons with compartmental modeling parametric maps and SUV segmentations using simulations of clinically relevant tumor tissue types. An irreversible 2-tissue-compartmental model was implemented to simulate clinical and preclinical F-FDG PET time-activity curves using population-based arterial input functions (80 clinical and 12 preclinical) and the kinetic parameter values of 3 tumor tissue types.

A Novel Unsupervised Segmentation Approach Quantifies Tumor Tissue Populations Using Multiparametric MRI: First Results with Histological Validation.

Purpose: We aimed to precisely estimate intra-tumoral heterogeneity using spatially regularized spectral clustering (SRSC) on multiparametric MRI data and compare the efficacy of SRSC with the previously reported segmentation techniques in MRI studies.

Procedures: Six NMRI nu/nu mice bearing subcutaneous human glioblastoma U87 MG tumors were scanned using a dedicated small animal 7T magnetic resonance imaging (MRI) scanner. The data consisted of T2 weighted images, apparent diffusion coefficient maps, and pre- and post-contrast T2 and T2* maps.

Clinical research and methodology: What usage and what hierarchical order for secondary endpoints?

In a randomised clinical trial, when the result of the primary endpoint shows a significant benefit, the secondary endpoints are scrutinised to identify additional effects of the treatment. However, this approach entails a risk of concluding that there is a benefit for one of these endpoints when such benefit does not exist (inflation of type I error risk). There are mainly two methods used to control the risk of drawing erroneous conclusions for secondary endpoints.

A Population-Based Gaussian Mixture Model Incorporating 18F-FDG PET and Diffusion-Weighted MRI Quantifies Tumor Tissue Classes.

Unlabelled: The aim of our study was to create a novel Gaussian mixture modeling (GMM) pipeline to model the complementary information derived from(18)F-FDG PET and diffusion-weighted MRI (DW-MRI) to separate the tumor microenvironment into relevant tissue compartments and follow the development of these compartments longitudinally.

Methods: Serial (18)F-FDG PET and apparent diffusion coefficient (ADC) maps derived from DW-MR images of NCI-H460 xenograft tumors were coregistered, and a population-based GMM was implemented on the complementary imaging data. The tumor microenvironment was segmented into 3 distinct regions and correlated with histology.

Translational research: precision medicine, personalized medicine, targeted therapies: marketing or science?

Personalized medicine is based on: 1) improved clinical or non-clinical methods (including biomarkers) for a more discriminating and precise diagnosis of diseases; 2) targeted therapies of the choice or the best drug for each patient among those available; 3) dose adjustment methods to optimize the benefit-risk ratio of the drugs chosen; 4) biomarkers of efficacy, toxicity, treatment discontinuation, relapse, etc. Unfortunately, it is still too often a theoretical concept because of the lack of convenient diagnostic methods or treatments, particularly of drugs corresponding to each subtype of pathology, hence to each patient. Stratified medicine is a component of personalized medicine employing biomarkers and companion diagnostics to target the patients likely to present the best benefit-risk balance for a given active compound.

Combined PET/MR: a technology becomes mature.

The combination of PET and MR imaging forms a powerful new imaging modality, PET/MR. The major advantages of concurrent PET/MR acquisitions range from patient comfort and increased throughput to multiparametric imaging and are evaluated and reviewed in this paper specifically with respect to their applications in research and diagnostics. Alongside the use of PET/MR in the field of preclinical research, this paper illuminates the impact of this new modality in the clinical field in such areas as neurology, oncology, and cardiology.

Image-derived biomarkers and multimodal imaging strategies for lung cancer management.

Non-small-cell lung cancer is the most common type of lung cancer and one of the leading causes of cancer-related death worldwide. For this reason, advances in diagnosis and treatment are urgently needed. With the introduction of new, highly innovative hybrid imaging technologies such as PET/CT, staging and therapy response monitoring in lung cancer patients have substantially evolved.

Preclinical and Translational PET/MR Imaging.

Combined PET and MR imaging (PET/MR imaging) has progressed tremendously in recent years. The focus of current research has shifted from technologic challenges to the application of this new multimodal imaging technology in the areas of oncology, cardiology, neurology, and infectious diseases. This article reviews studies in preclinical and clinical translation.

Monoclonal Antibodies for Therapeutic Use: Specific Characteristics of Clinical Development, Evaluation by the Agencies, and Long-term Monitoring of Safety.

Monoclonal antibodies (MoAb) are very different from other drugs. The Round Table aimed to determine whether the specific characteristics of MoAb have repercussions on their clinical development, evaluation by the health authorities, and long-term monitoring. As regards the structure-activity relationship of MoAb, classification according to mechanism of action (neutralising or agonist MoAb, cytolytic MoAb) is more relevant than to their degree of humanisation.

Autologous stem cell transplantation as a first-line treatment strategy for chronic lymphocytic leukemia: a multicenter, randomized, controlled trial from the SFGM-TC and GFLLC.

Long-term responses have been reported after autologous stem cell transplantation (ASCT) for chronic lymphocytic leukemia (CLL). We conducted a prospective, randomized trial of ASCT in previously untreated CLL patients. We enrolled 241 patients < 66 years of age with Binet stage B or C CLL.

Nodular, lymphocyte-predominant Hodgkin lymphoma: a long-term study and analysis of transformation to diffuse large B-cell lymphoma in a cohort of 164 patients from the Adult Lymphoma Study Group.

Background: Nodular, lymphocyte-predominant Hodgkin lymphoma (NLPHL) represents a rare entity.

Methods: A clinical registry was launched from 1973 to 2003 in France. To determine the histologic transformation (HT) rate to diffuse large B-cell lymphoma (DLBCL) and long-term outcomes, 164 patients were selected after histologic review.