qEEG Neuromarkers of Complex Childhood Trauma in Adolescents.

Complex childhood trauma (CCT) involves prolonged exposure to severe interpersonal stressors, leading to deficits in executive functioning and self-regulation during adolescence, a critical period for neurodevelopment. While qEEG parameters, particularly alpha oscillations, have been proposed as potential biomarkers for trauma, empirical documentation in developmental samples is limited. .

Music, body, and machine: gesture-based synchronization in human-robot musical interaction.

Musical performance relies on nonverbal cues for conveying information among musicians. Human musicians use bodily gestures to communicate their interpretation and intentions to their collaborators, from mood and expression to anticipatory cues regarding structure and tempo. Robotic Musicians can use their physical bodies in a similar way when interacting with fellow musicians.

SMARCA5-mediated chromatin remodeling is required for germinal center formation.

The establishment of long-lasting immunity against pathogens is facilitated by the germinal center (GC) reaction, during which B cells increase their antibody affinity and differentiate into antibody-secreting cells (ASC) and memory cells. These events involve modifications in chromatin packaging that orchestrate the profound restructuring of gene expression networks that determine cell fate. While several chromatin remodelers were implicated in lymphocyte functions, less is known about SMARCA5.

Fcγ receptor binding is required for maximal immunostimulation by CD70-Fc.

Introduction: T cell expressed CD27 provides costimulation upon binding to inducible membrane expressed trimeric CD70 and is required for protective CD8 T cell responses. CD27 agonists could therefore be used to bolster cellular vaccines and anti-tumour immune responses. To date, clinical development of CD27 agonists has focussed on anti-CD27 antibodies with little attention given to alternative approaches.

Response to Tsuda et al. "demonstrating the undermining of science and health policy after the Fukushima nuclear accident by applying the toolkit for detecting misused epidemiological methods".

Background: The SHAMISEN (Nuclear Emergency Situations - Improvement of Medical And Health Surveillance) European project was conducted in 2015-2017 to review the lessons learned from the experience of past nuclear accidents and develop recommendations for preparedness and health surveillance of populations affected by a nuclear accident. Using a toolkit approach, Tsuda et al. recently published a critical review of the article by Cléro et al.

Sulfamate Acetamides as Self-Immolative Electrophiles for Covalent Ligand-Directed Release Chemistry.

Electrophiles for covalent inhibitors that are suitable for in vivo administration are rare. While acrylamides are prevalent in FDA-approved covalent drugs, chloroacetamides are considered too reactive for such purposes. We report sulfamate-based electrophiles that maintain chloroacetamide-like geometry with tunable reactivity.

Coverage rate of opportunistic and organised breast cancer screening in France: Department-level estimation.

Objective: In France, the national breast cancer screening programme (NBCSP), targeting women aged 50-74 years was rolled out nationwide in 2004. It aims at reducing breast cancer mortality. In addition to the NBCSP, the use of opportunistic screening is permitted in France.

Fcγ receptor-mediated cross-linking codefines the immunostimulatory activity of anti-human CD96 antibodies.

New strategies that augment T cell responses are required to broaden the therapeutic arsenal against cancer. CD96, TIGIT, and CD226 are receptors that bind to a communal ligand, CD155, and transduce either inhibitory or activating signals. The function of TIGIT and CD226 is established, whereas the role of CD96 remains ambiguous.

Care pathway of women with interval breast cancer in 2016, based on medico-administrative data.

Background: Since 2004, an organised screening programme (OS) for breast cancer has been in place for 50-74 years women who are not at an increased risk. Despite this, 17% of cancers diagnosed within 24 months following an OS mammogram are interval cancers (IC), diagnosed even though the OS had not reported cancer. After identifying IC from the French administrative healthcare database (SNDS), our objective was to describe the care pathways of women with IC in 2016.

Site-Specific Labeling of Endogenous Proteins Using CoLDR Chemistry.

Chemical modifications of native proteins can affect their stability, activity, interactions, localization, and more. However, there are few nongenetic methods for the installation of chemical modifications at a specific protein site in cells. Here we report a covalent ligand directed release (CoLDR) site-specific labeling strategy, which enables the installation of a variety of functional tags on a target protein while releasing the directing ligand.

Intracellular Protein-Drug Interactions Probed by Direct Mass Spectrometry of Cell Lysates.

Understanding protein-ligand interactions in a cellular context is an important goal in molecular biology and biochemistry, and particularly for drug development. Investigators must demonstrate that drugs penetrate cells and specifically bind their targets. Towards that end, we present a native mass spectrometry (MS)-based method for analyzing drug uptake and target engagement in eukaryotic cells.

Sulfopin is a covalent inhibitor of Pin1 that blocks Myc-driven tumors in vivo.

The peptidyl-prolyl isomerase, Pin1, is exploited in cancer to activate oncogenes and inactivate tumor suppressors. However, despite considerable efforts, Pin1 has remained an elusive drug target. Here, we screened an electrophilic fragment library to identify covalent inhibitors targeting Pin1's active site Cys113, leading to the development of Sulfopin, a nanomolar Pin1 inhibitor.

Tunable Methacrylamides for Covalent Ligand Directed Release Chemistry.

Targeted covalent inhibitors are an important class of drugs and chemical probes. However, relatively few electrophiles meet the criteria for successful covalent inhibitor design. Here we describe α-substituted methacrylamides as a new class of electrophiles suitable for targeted covalent inhibitors.

Lessons learned from Chernobyl and Fukushima on thyroid cancer screening and recommendations in case of a future nuclear accident.

Exposure of the thyroid gland to ionizing radiation at a young age is the main recognized risk factor for differentiated thyroid cancer. After the Chernobyl and Fukushima nuclear accidents, thyroid cancer screening was implemented mainly for children, leading to case over-diagnosis as seen in South Korea after the implementation of opportunistic screening (where subjects are recruited at healthcare sites). The aim of cancer screening is to reduce morbidity and mortality, but screening can also cause negative effects on health (with unnecessary treatment if over-diagnosis) and on quality of life.

The impact of neurofeedback training on children with developmental trauma: A randomized controlled study.

Objective: Developmental trauma or chronic early childhood exposure to abuse and neglect by caregivers has been shown to have a long-lasting pervasive impact on mental and neural development, including problems with attention, impulse control, self-regulation, and executive functioning. Its long-term effects are arguably the costliest public health challenge in the United States. Children with developmental trauma rarely have a satisfactory response to currently available evidence-based psychotherapeutic and pharmacological treatments.

The risk of cancer attributable to diagnostic medical radiation: Estimation for France in 2015.

Although medical ionizing radiation (IR) has clear clinical benefits, it is an established carcinogen. Our study estimates the number of new cancer cases in France in 2015 attributable to IR exposure from medical procedures. Exposures from external (X-rays, CT scans, interventional radiology) and internal (nuclear medicine) sources were considered.

Antibodies to Costimulatory Receptor 4-1BB Enhance Anti-tumor Immunity via T Regulatory Cell Depletion and Promotion of CD8 T Cell Effector Function.

The costimulatory receptor 4-1BB is expressed on activated immune cells, including activated T cells. Antibodies targeting 4-1BB enhance the proliferation and survival of antigen-stimulated T cells in vitro and promote CD8 T cell-dependent anti-tumor immunity in pre-clinical cancer models. We found that T regulatory (Treg) cells infiltrating human or murine tumors expressed high amounts of 4-1BB.

Cancers related to lifestyle and environmental factors in France in 2015.

Background: Cancer is a major cause of premature illness and death in France. To quantify how cancer prevention could reduce the burden, we present estimates of the contribution of lifestyle and environmental risk factors to cancer incidence in France in 2015, comparing these with other high-income countries.

Method: Prevalences of, and relative risks for tobacco smoking, alcohol consumption, inadequate diet, overweight and obesity, physical inactivity, exogenous hormones, suboptimal breastfeeding, infectious agents, ionising radiation, air pollution, ultraviolet exposure, occupational exposures, arsenic in drinking water and indoor benzene were obtained to estimate the population attributable fraction (PAF) and the number of attributable cancers by the cancer site and sex.

Breast cancer screening programme participation and socioeconomic deprivation in France.

The objective was to quantify the relationship between deprivation and national breast cancer screening programme (NBCSP) participation at an ecological level in mainland France. Data from 4,805,390 women-living in 36,209 municipalities within 95 departments-participating in the 2013-2014 NBCSP were analysed using the French Deprivation Index (FDep). FDep population quintiles by municipality were computed to describe NBCSP participation according to deprivation.

PD-1 Blockade and CD27 Stimulation Activate Distinct Transcriptional Programs That Synergize for CD8 T-Cell-Driven Antitumor Immunity.

PD-1 checkpoint blockade has revolutionized the field of cancer immunotherapy, yet the frequency of responding patients is limited by inadequate T-cell priming secondary to a paucity of activatory dendritic cells (DC). DC signals can be bypassed by CD27 agonists, and we therefore investigated if the effectiveness of anti-PD-1/L1 could be improved by combining with agonist anti-CD27 monoclonal antibodies (mAb). The efficacy of PD-1/L1 blockade or agonist anti-CD27 mAb was compared with a dual-therapy approach in multiple tumor models.

The impact of historical breastfeeding practices on the incidence of cancer in France in 2015.

Purpose: The purpose of the study was to estimate the number of new breast cancer cases in France in 2015 attributable to breastfeeding for durations below recommendations (at least 6 months per child), and cases prevented through historical breastfeeding. As a secondary analysis, the corresponding numbers for ovarian cancer were estimated.

Methods: Historical breastfeeding data were obtained from population surveys.

The immunobiology of CD27 and OX40 and their potential as targets for cancer immunotherapy.

In recent years, monoclonal antibodies (mAbs) able to reinvigorate antitumor T-cell immunity have heralded a paradigm shift in cancer treatment. The most high profile of these mAbs block the inhibitory checkpoint receptors PD-1 and CTLA-4 and have improved life expectancy for patients across a range of tumor types. However, it is becoming increasingly clear that failure of some patients to respond to checkpoint inhibition is attributable to inadequate T-cell priming.

Akt signaling is critical for memory CD8 T-cell development and tumor immune surveillance.

Memory CD8 T cells confer long-term immunity against tumors, and anticancer vaccines therefore should maximize their generation. Multiple memory CD8 T-cell subsets with distinct functional and homing characteristics exist, but the signaling pathways that regulate their development are ill defined. Here we examined the role of the serine/threonine kinase Akt in the generation of protective immunity by CD8 T cells.