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Background Despite multimodality treatments including neurosurgery, radiotherapy and chemotherapy, glioblastoma (GBM) prognosis remains poor. GBM is classically considered as a radioresistant tumor, because of its high local recurrence rate, inside the irradiation field. The development of new radiosensitizer is crucial to improve the patient outcomes. Pre-clinical data showed that Poly (ADP-ribose) polymerase inhibitors (PARPi) could be considered as a promising class of radiosensitizer. The aim of this study is to evaluate Olaparib, a PARPi, as radiosensitizing agent, combined with the Stupp protocol, namely temozolomide (TMZ) and intensity modulated radiotherapy (IMRT) in first line treatment of partially or non-resected GBM. Methods The OLA-TMZ-RTE-01 study is a multicenter non-randomized phase I/IIa trial including unresectable or partially resectable GBM patients, from 18 to 70 years old. A two-step dose-escalation phase I design will first determine the recommended phase 2 dose (RP2D) of olaparib, delivered concomitantly with TMZ plus conventional irradiation for 6 weeks and as single agent for 4 weeks (radiotherapy period), and second, the RP2D of olaparib combined with adjuvant TMZ (maintenance period). Phase IIa will assess the 18-month overall survival (OS) of this combination. In both phase I and IIa separately considered, the progression-free survival, the objective response rate, the neurocognitive functions of patients, emotional disorders among caregivers, the survival without toxicity, degradation nor progression, the complications onset and the morphologic and functional MRI (magnetic resonance imaging) parameters will be also assessed as secondary objectives. Ancillary objectives will explore alteration of the DNA repair pathways on biopsy tumor, proton magnetic resonance spectroscopy parameters to differentiate tumor relapse and radionecrosis, and an expanded cognition evaluation. Up to 79 patients will be enrolled: 30 patients in the phase I and 49 patients in the phase IIa. Discussion Combining PARP inhibitors, such as olaparib, with radiotherapy and chemotherapy in GBM may improve survival outcomes, while sparing healthy tissue and preserving neurocognitive function, given the replication-dependent efficacy of olaparib, and the increased PARP expression in GBM as compared to non-neoplastic brain tissue. Ancillary studies will help to identify genetic biomarkers predictive of PARPi efficacy as radiosensitizer. Trial registration NCT03212742 , registered June, 7, 2017. Protocol version: Version 2.2 dated from 2017/08/18.

The use of artificial intelligence in education (AIEd) has grown exponentially in the last decade, particularly intelligent tutoring systems (ITSs). Despite the increased use of ITSs and their promise to improve learning, their real educational value remains unclear. This systematic review aims to identify the effects of ITSs on K-12 students’ learning and performance and which experimental designs are currently used to evaluate them. The 28 studies analyzed in this systematic review included a total of 4597 students ( N  = 4597) and used quasi-experimental designs with varying intervention durations. Overall, our findings suggest that the effects of ITSs on learning and performance in K-12 education are generally positive but are found to be mitigated when compared to non-intelligent tutoring systems. However, additional research with longer interventions and increased sample sizes with greater diversity is warranted. Additionally, the ethical implications of using AI for teaching should be investigated.

We hypothesized that a single dose of methylphenidate (MP) would modulate cerebral motor activation and behavior in patients having suffered a subcortical stroke. Eight men with a single stroke on the corticospinal tract resulting in a pure motor hemiparesia were included in a randomized, cross-over, double-blind, placebo-controlled study. Patients were first evaluated 17 days after stroke onset by validated neurological scales, motor tests and fMRI (flexion/extension of the digits) after 20 mg MP or placebo. Seven days later, the patients underwent the same protocol and received the drug they had not taken at the first evaluation. Each patient was his own control. Placebo intake did not change performance. MP compared to placebo elicited a significant improvement in motor performance of the affected hand at the finger tapping test. MP induced: (1) a hyperactivation of the ipsilesional primary sensorimotor cortex including the motor hand and face areas and of the contralesional premotor cortex; (2) a hypoactivation of the ipsilesional anterior cingulum. Hyperactivation in the face motor area correlated positively with the improvement in performance. We demonstrated that the reorganized network may efficiently be targeted by the drug and that the effect of MP might partly rely on an improvement in attention/effort through cingulum modulation.

This longitudinal study analyzed the interactions between the quality of life and the coping strategies of 100 patients treated for breast cancer and their caregivers. Data were collected after diagnosis, at the end of treatment, and 6 months after treatment with the Quality of Life Questionnaire-C30 (QLQ-C30), Duke Health Profile and Ways of Coping Checklist for both patients and caregivers. The theoretical model was tested using a typology of patients and mixed model analyses. The quality of life of patients changed over time and no cluster effect was found. The influence of the sociodemographic characteristics, coping strategies (patients and caregivers) and the quality of life of caregivers on patient’s quality of life were different according to the quality of life dimensions considered. To understand the adaptation of patients to their disease, it is therefore essential to look at whether the caregiver is capable of playing a supporting role.