The General Movement Assessment (GMA) is a validated evaluation of brain maturation essential to shaping early individual developmental trajectories of preterm infants. To ensure a reliable GMA, preterm infants should be recorded for 30 to 60 min before manually selecting at least three sequences with general movements. This time-consuming task of manually selecting short video sequences from lengthy recordings impedes its implementation within the Neonatal Unit.
View Article and Find Full Text PDFNeoadjuvant immune checkpoint blockade (ICB) has shown unprecedented activity in mismatch repair deficient (MMRd) colorectal cancers, but its effectiveness in MMRd endometrial cancer (EC) remains unknown. In this investigator-driven, phase I, feasibility study (NCT04262089), 10 women with MMRd EC of any grade, planned for primary surgery, received two cycles of neoadjuvant pembrolizumab (200 mg IV) every three weeks. A pathologic response (primary objective) was observed in 5/10 patients, with 2 patients showing a major pathologic response.
View Article and Find Full Text PDFRecent work has shown evidence for the prognostic significance of tumor infiltrating B cells (B-TIL) in high grade serous ovarian carcinoma (HGSOC), the predominant histological subtype of ovarian cancer. However, it remains unknown how the favorable prognosis associated with B-TIL relates to the current standard treatments of primary debulking surgery (PDS) followed by chemotherapy or (neo-)adjuvant chemotherapy (NACT) combined with interval debulking surgery. To address this, we analyzed the prognostic impact of B-TIL in relationship to primary treatment and tumor infiltrating T cell status in a highly homogenous cohort of HGSOC patients.
View Article and Find Full Text PDFPhys Imaging Radiat Oncol
July 2024
Current online adaptive radiotherapy (oART) workflows require dedicated equipment. Our aim was to develop and implement an oART workflow for a C-arm linac which can be performed using standard clinically available tools. A workflow was successfully developed and implemented.
View Article and Find Full Text PDFBackground: Patients with mismatch repair-deficient (MMRd) endometrial cancer (EC) can derive great benefit from immune checkpoint inhibitors (ICI). However not all responses and predictors of primary resistance are lacking.
Methods: We compared the immune tumor microenvironment of MMRd EC ICI-responders (Rs) and ICI non-responders (NRs), using spatial multiplexed immune profiling and unsupervised hierarchical clustering analysis.
Early JWST observations have uncovered a population of red sources that might represent a previously overlooked phase of supermassive black hole growth. One of the most intriguing examples is an extremely red, point-like object that was found to be triply imaged by the strong lensing cluster Abell 2744 (ref. ).
View Article and Find Full Text PDFBackground: CD103 is an integrin specifically expressed on the surface of cancer-reactive T cells. The number of CD103+ T cells significantly increases during successful immunotherapy and might therefore be an attractive biomarker for noninvasive PET imaging of immunotherapy response. Since the long half-life of antibodies preclude repeat imaging of CD103+ T cell dynamics early in therapy, we therefore here explored PET imaging with CD103 Fab fragments radiolabeled with a longer (Zr) and shorter-lived radionuclide (Ga).
View Article and Find Full Text PDFIn search of a potent small molecular PD-L1 inhibitor, we designed and synthesized a compound based on a 2-hydroxy-4-phenylthiophene-3-carbonitrile moiety. Ligand's performance was tested in vitro and compared side-by-side with a known PD-L1 antagonist with a proven bioactivity BMS1166. Subsequently, we modified both compounds to allow F labeling that could be used for PET imaging.
View Article and Find Full Text PDFDespite the high prevalence of late-onset sepsis (LOS) in neonatal intensive care units, a reliable diagnosis remains difficult. This prospective, multicenter cohort study aimed to identify biomarkers early to rule out the diagnosis of LOS in 230 neonates ≥7 days of life with signs of suspected LOS. Blood levels of eleven protein biomarkers (PCT, IL-10, IL-6, NGAL, IP-10, PTX3, CD14, LBP, IL-27, gelsolin, and calprotectin) were measured.
View Article and Find Full Text PDFThe genes that drive development each typically have many different enhancers. Properly coordinating the action of these different enhancers is crucial to correctly specifying cell-fate decisions, yet it remains poorly understood how their activity is choregraphed in time. To shed light on this question, we used recently developed single-cell live imaging tools to dissect the regulation of Fushi tarazu (Ftz) in Drosophila melanogaster embryos.
View Article and Find Full Text PDFPurpose: CD103, an integrin specifically expressed on the surface of cancer-reactive T cells, is significantly increased during successful immunotherapy across human malignancies. In this study, we describe the generation and zirconium-89 (Zr) radiolabeling of monoclonal antibody (mAb) clones that specifically recognize human CD103 for non-invasive immune positron-emission tomography (PET) imaging of T cell infiltration as potential biomarker for effective anticancer immune responses.
Experimental Design: First, to determine the feasibility of anti-CD103 immuno-PET to visualize CD103-positive cells at physiologically and clinically relevant target densities, we developed an Zr-anti-murine CD103 PET tracer.
Reactivation of tumor infiltrating T lymphocytes (TILs) with immune checkpoint inhibitors or co-stimulators has proven to be an effective anti-cancer strategy for a broad range of malignancies. However, epithelial ovarian cancer (EOC) remains largely refractory to current T cell-targeting immunotherapeutics. Therefore, identification of novel immune checkpoint targets and biomarkers with prognostic value for EOC is warranted.
View Article and Find Full Text PDFIdentification of human cancer-reactive CD8+ T cells is crucial for the stratification of patients for immunotherapy and determination of immune-therapeutic effects. To date, these T cells have been identified mainly based on cell surface expression of programmed cell death protein 1 (PD-1) or co-expression of CD103 and CD39. A small subset of CD103- CD39+ CD8+ T cells is also present in tumors, but little is known about these T cells.
View Article and Find Full Text PDFImpaired platelet production is a mechanism of immune thrombocytopenia (ITP). Morphological abnormalities of megakaryocytes (MKs) are sometimes observed in this disease. Two studies have suggested an association between MK abnormalities and response to corticosteroids in primary ITP, but none have investigated this association for thrombopoietin-receptor agonists (TPO-RAs).
View Article and Find Full Text PDFUnlabelled: Cocaine-induced transient hallucinations (CIH) are a frequent complication following cocaine intake that is associated with addiction severity.
Methods: Two hundred and forty-two non-psychotic and Caucasian lifetime cocaine users were included in a French multicentric study. Clinical variables and dopamine pathway genotype data were extracted and tested with CIH scores using a zero-inflated binomial model, which allows for the exploration of factors associated with occurrence and severity separately.
CD103-positive tissue resident memory-like CD8 T cells (CD8CD103 TRM) are associated with improved prognosis across malignancies, including high-grade serous ovarian cancer (HGSOC). However, whether quantification of CD8, CD103 or both is required to improve existing survival prediction and whether all HGSOC patients or only specific subgroups of patients benefit from infiltration, remains unclear. To address this question, we applied image-based quantification of CD8 and CD103 multiplex immunohistochemistry in the intratumoral and stromal compartments of 268 advanced-stage HGSOC patients from two independent clinical institutions.
View Article and Find Full Text PDFMobile phones (MPs) of healthcare workers (HCWs) may represent an important source of transmission of infectious agents. This longitudinal study documents the contamination of these tools. Ten MPs handled by senior pediatricians were sampled once a week during 23 weeks in three pediatric wards of the University Hospital of Saint-Etienne, France.
View Article and Find Full Text PDFThe management of alcohol withdrawal syndrome is a frequent work in both community medicine and hospital wards. One of the most severe complications of alcohol withdrawal is Delirium Tremens (DT). The purpose of this development is to update knowledge on this complication in terms of diagnosis, evaluation and therapeutic approaches.
View Article and Find Full Text PDFDNA-sensing receptor Cyclic GMP-AMP Synthase (cGAS) and its downstream signaling effector STimulator of INterferon Genes (STING) have gained significant interest in the field of tumor immunology, as a dysfunctional cGAS-STING pathway is associated with poor prognosis and worse response to immunotherapy. However, studies so far have not taken into account the polymorphic nature of the STING-encoding STING1 gene. We hypothesized that the presence of allelic variance in STING1 would cause variation between individuals as to their susceptibility to cancer development, cancer progression, and potential response to (immuno)therapy.
View Article and Find Full Text PDFOptimum risk stratification in early-stage endometrial cancer combines clinicopathologic factors and the molecular endometrial cancer classification defined by The Cancer Genome Atlas (TCGA). It is unclear whether analysis of intratumoral immune infiltrate improves this. We developed a machine-learning, image-based algorithm to quantify density of CD8 and CD103 immune cells in tumor epithelium and stroma in 695 stage I endometrioid endometrial cancers from the PORTEC-1 and -2 trials.
View Article and Find Full Text PDFTumor-infiltrating CD8+ T cells (TIL) are of the utmost importance in anti-tumor immunity. CD103 defines tumor-resident memory T cells (T cells) associated with improved survival and response to immune checkpoint blockade (ICB) across human tumors. Co-expression of CD39 and CD103 marks tumor-specific T with enhanced cytolytic potential, suggesting that CD39+CD103+ T could be a suitable biomarker for immunotherapy.
View Article and Find Full Text PDFIntroduction: Clinical guidelines suggest a glycated hemoglobin A1c (HbA1c) target of ≤ 6.5% for type 2 diabetes patients with short duration of disease, few comorbidities and/or long life expectancy-provided this goal can be achieved safely. We explored whether initial combination treatment with the dipeptidyl peptidase-4 inhibitor linagliptin and metformin could provide better glycemic control (HbA1c ≤ 6.
View Article and Find Full Text PDFNeurobiological changes affecting new mothers are known to support the development of the mother-infant relationship (the 'maternal brain'). However, which aspects of parenting are actually mother-specific and which rely on general cognitive abilities remains debated. For example, refuting earlier findings, a recent study demonstrated that fathers identify their own baby from their cries just as well as mothers.
View Article and Find Full Text PDF