The PARP inhibitor talazoparib synergizes with reovirus to induce cancer killing and tumour control in vivo in mouse models.

Reovirus type 3 Dearing (RT3D) is an oncolytic, double-stranded RNA virus. To identify potential RT3D drug-viral sensitizer, here we use a high-throughput screen of therapeutic agents and find a PARP-1 inhibitor, talazoparib, as a top hit. RT3D interacts with retinoic acid-induced gene-1 (RIG-I) and activates PARP-1, with consequent PARylation of components of the extrinsic apoptosis pathway.

PARP-1 Inhibition Increases Oxidative Stress in Ets-1-Expressing MDA-MB-231 Breast Cancer Cells.

Background: The Ets-1 transcription factor plays a primordial role in regulating the expression of numerous genes implicated in cancer progression. In a previous study, we revealed that poly(ADP-ribose) polymerase-1 (PARP-1) inhibition by PJ-34 results in Ets-1 level increase in cells, which is related with cell death of Ets-1-expressing cancer cells.

Aims: The mechanism of the antitumor effect of PARP-1 inhibition was investigated in the Ets-1-expressing MDA-MB-231 breast cancer cells.

Pooled analysis of oral microbiome profiles defines robust signatures associated with periodontitis.

Unlabelled: Oral microbial dysbiosis has been associated with periodontitis in studies using 16S rRNA gene sequencing analysis. However, this technology is not sufficient to consistently separate the bacterial species to species level, and reproducible oral microbiome signatures are scarce. Obtaining these signatures would significantly enhance our understanding of the underlying pathophysiological processes of this condition and foster the development of improved therapeutic strategies, potentially personalized to individual patients.

A RIPK1-specific PROTAC degrader achieves potent antitumor activity by enhancing immunogenic cell death.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a critical stress sentinel that coordinates cell survival, inflammation, and immunogenic cell death (ICD). Although the catalytic function of RIPK1 is required to trigger cell death, its non-catalytic scaffold function mediates strong pro-survival signaling. Accordingly, cancer cells can hijack RIPK1 to block necroptosis and evade immune detection.

Immunogenic cell death in cancer: targeting necroptosis to induce antitumour immunity.

Most metastatic cancers remain incurable due to the emergence of apoptosis-resistant clones, fuelled by intratumour heterogeneity and tumour evolution. To improve treatment, therapies should not only kill cancer cells but also activate the immune system against the tumour to eliminate any residual cancer cells that survive treatment. While current cancer therapies rely heavily on apoptosis - a largely immunologically silent form of cell death - there is growing interest in harnessing immunogenic forms of cell death such as necroptosis.

Poly(ADP-ribose) Polyremase-1 (PARP-1) Inhibition: A Promising Therapeutic Strategy for ETS-Expressing Tumours.

ETS transcription factors are a highly conserved family of proteins involved in the progression of many cancers, such as breast and prostate carcinomas, Ewing's sarcoma, and leukaemias. This significant involvement can be explained by their roles at all stages of carcinogenesis progression. Generally, their expression in tumours is associated with a poor prognosis and an aggressive phenotype.

Impact of emergency physician-performed ultrasound for the evaluation of patients with acute abdominal pain, prospective randomized dual Centre study: study protocol for a diagnostic trial.

Background: Abdominal pain is frequent in patients consulting in emergency departments. The aim of this study is to determine the diagnosis efficacy of point-of-care ultrasound (POCUS) in patients consulting in the ED for acute abdominal pain by comparing the rate of exact diagnostic between the two arms (with or without POCUS), according to the index diagnostic established by an adjudication committee.

Methods: It is a randomized, controlled, open and interventional study in two emergency departments.

Plasma haemolysis index and interleukine-6 for the early prediction of cardiac surgery-associated acute kidney injury. A proof-of-concept study.

Introduction: Haemolysis and inflammation contribute to cardiac surgery-associated acute kidney injury (CS-AKI). We aimed to assess the performance of plasma haemolysis index (HI) and interleukine-6 (IL-6) for the prediction of all-stage CS-AKI. We also assessed their ability to predict moderate-to-severe CS-AKI and to discriminate persistent from transient CS-AKI.

The NUCKS1-SKP2-p21/p27 axis controls S phase entry.

Efficient entry into S phase of the cell cycle is necessary for embryonic development and tissue homoeostasis. However, unscheduled S phase entry triggers DNA damage and promotes oncogenesis, underlining the requirement for strict control. Here, we identify the NUCKS1-SKP2-p21/p27 axis as a checkpoint pathway for the G1/S transition.

Subgingival Microbiota and Cytokines Profile Changes in Patients with Periodontitis: A Pilot Study Comparing Healthy and Diseased Sites in the Same Oral Cavities.

Periodontitis is a common condition characterized by an exacerbated pro-inflammatory response, which leads to tissue destruction and, ultimately, alveolar bone loss. In this pilot study, we assess the microbiota composition and cytokine profile changes in patients with stage III/IV, grade B/C periodontitis, specifically by comparing healthy and diseased sites in the same oral cavity. Overall, we found that microbiota architecture was significantly disrupted between diseased and healthy sites, and that the clustering was driven, in part, by the increased relative abundances of Synergistetes in diseased sites, as well as the increased abundances of Firmicutes in healthy sites.

Breast milk protein content at week 3 after birth and neurodevelopmental outcome in preterm infants fed fortified breast milk.

Background: Feeding supplemented mother milk during hospital stay improves neurodevelopment in preterm infants. Yet the composition of mother milk varies widely between subjects. The relationship between this variation and outcome is unknown.

Osteopathic manipulative treatment to improve exclusive breast feeding at 1 month.

Objective: Previous studies have assessed breastfeeding-support programmes. Among these, osteopathic manipulative treatment (OMT) is a frequently used approach, although without strong evidence of efficacy.

Methods: A double-blind randomised controlled trial was conducted between July 2013 and March 2016.

Early point-of-care focused echocardiographic asystole as a predictive factor for absence of return of spontaneous circulatory in out-of-hospital cardiac arrests: a study protocol for a prospective, multicentre observational study.

Introduction: Management of out-of-hospital cardiac arrests (OHCAs) in France is performed by a particular prehospital system based on medicalisation of mobile intensive care units composed of an emergency physician and a nurse with all the required devices for advanced care. It follows the European recommendations which advocate for the use of early point-of-care focused echocardiography (EPOCE) in the prehospital setting. An ability of EPOCE may be to predict the absence of return of spontaneous circulation (ROSC) in cases of absence of cardiac motion.

Response to letter to the editor: "comment on unplanned out-of-hospital birth and risk factors of adverse perinatal outcome: findings from a prospective cohort".

The aim of this Letter to the Editor was to respond to a comment highlighting potential statistical biases in an analysis of our recently published article. We therefore specified the method for selecting the model variables in order to limit overfitting, then we used the Firth method to control the sparse data bias, and finally for checking internal validity we used bootstrapping methods. In total, the conclusions of our model were not changed by these new analyses.

Unplanned out-of-hospital birth and risk factors of adverse perinatal outcome: findings from a prospective cohort.

Background: In France, while most babies are delivered at hospital, emergency medical services (EMS) weekly manage calls for unplanned out-of-hospital births. The objective of our study was to describe neonatal morbidity and mortality, defined as death or neonatal intensive care unit hospitalization at Day 7, in a prospective multicentric cohort of unplanned out-of-hospital births.

Methods: We prospectively analyzed out-of-hospital births from 25 prehospital EMS units in France.

RIPK1 and Caspase-8 Ensure Chromosome Stability Independently of Their Role in Cell Death and Inflammation.

Receptor-interacting protein kinase (RIPK) 1 functions as a key mediator of tissue homeostasis via formation of Caspase-8 activating ripoptosome complexes, positively and negatively regulating apoptosis, necroptosis, and inflammation. Here, we report an unanticipated cell-death- and inflammation-independent function of RIPK1 and Caspase-8, promoting faithful chromosome alignment in mitosis and thereby ensuring genome stability. We find that ripoptosome complexes progressively form as cells enter mitosis, peaking at metaphase and disassembling as cells exit mitosis.

Interplay between base excision repair protein XRCC1 and ALDH2 predicts overall survival in lung and liver cancer patients.

Background: To deliver efficacious personalised cancer treatment, it is essential to characterise the cellular metabolism as well as the genetic stability of individual tumours. In this study, we describe a new axis between DNA repair and detoxification of aldehyde derivatives with important implications for patient prognosis and treatment.

Methods: Western blot and qPCR analyses were performed in relevant non-transformed and cancer cell lines from lung and liver tissue origin in combination with bioinformatics data mining of The Cancer Genome Atlas database from lung and hepatocellular cancer patients.

Serotype Distribution and Antimicrobial Resistance of Species in Bangui, Central African Republic, from 2002 to 2013.

is a major cause of severe diarrhea in children less than the age of 5 years in sub-Saharan Africa. The aim of this study was to describe the (sub-)serotype distribution and antimicrobial susceptibility of serogroups from Centrafrican patients with diarrhea between 2002 and 2013. We collected 443 isolates in total.

Persistent DNA strand breaks induce a CAF-like phenotype in normal fibroblasts.

Cancer-associated fibroblasts (CAFs) are an emerging target for cancer therapy as they promote tumour growth and metastatic potential. However, CAF targeting is complicated by the lack of knowledge-based strategies aiming to selectively eliminate these cells. There is a growing body of evidence suggesting that a pro-inflammatory microenvironment (e.