Increase in EEG functional connectivity and power during wakefulness in self-limited epilepsy with centrotemporal spikes.

Objective: Examine power and functional connectivity (FC) in children with Self-limited Epilepsy with Centrotemporal Spikes (SeLECTS) during resting-state.

Methods: We retrospectively analyzed 37 children with SeLECTS and 34 matched controls. Fifty seconds of awake resting-state source-reconstructed EEG per subject were selected to compare groups using power and weighted phase lag index (wPLI).

Effects of inverse methods and spike phases on interictal high-density EEG source reconstruction.

Objective: To determine the effect of inverse methods and timepoints of interictal epileptic discharges (IEDs) used for high-density electric source imaging (hd-ESI) in pharmacoresistant focal epilepsies.

Methods: We retrospectively evaluated the hd-ESI and [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) of 21 operated patients with pharmacoresistant focal epilepsy (Engel I). Volumetric hd-ESI was performed with three different inverse methods such as the inverse solution linearly constrained minimum variance (LCMV, a beamformer method), standardized low resolution electromagnetic tomography (sLORETA) and weighted minimum-norm estimation (wMNE) and at different IED phases.

Big Field of View MRI T1w and FLAIR Template - NMRI225.

Image templates are a common tool for neuroscience research. Often, they are used for spatial normalization of magnetic resonance imaging (MRI) data, which is a necessary procedure for analyzing brain morphology and function via voxel-based analysis. This allows the researcher to reduce individual shape differences across images and make inferences across multiple subjects.

Feasibility of high-density electric source imaging in the presurgical workflow: Effect of number of spikes and automated spike detection.

Objective: Presurgical high-density electric source imaging (hdESI) of interictal epileptic discharges (IEDs) is only used by few epilepsy centers. One obstacle is the time-consuming workflow both for recording as well as for visual review. Therefore, we analyzed the effect of (a) an automated IED detection and (b) the number of IEDs on the accuracy of hdESI and time-effectiveness.

Energetics and Kinetics of Hydrogen Electrosorption on a Graphene-Covered Pt(111) Electrode.

The Angstrom-scale space between graphene and its substrate provides an attractive playground for scientific exploration and can lead to breakthrough applications. Here, we report the energetics and kinetics of hydrogen electrosorption on a graphene-covered Pt(111) electrode using electrochemical experiments, in situ spectroscopy, and density functional theory calculations. The graphene overlayer influences the hydrogen adsorption on Pt(111) by shielding the ions from the interface and weakening the Pt-H bond energy.

GEP-NET radiomics: a systematic review and radiomics quality score assessment.

Objective: The number of radiomics studies in gastroenteropancreatic neuroendocrine tumours (GEP-NETs) is rapidly increasing. This systematic review aims to provide an overview of the available evidence of radiomics for clinical outcome measures in GEP-NETs, to understand which applications hold the most promise and which areas lack evidence.

Methods: PubMed, Embase, and Wiley/Cochrane Library databases were searched and a forward and backward reference check of the identified studies was executed.

Trastuzumab and pertuzumab combination therapy for advanced pre-treated HER2 exon 20-mutated non-small cell lung cancer.

Introduction: In 1-3% of non-small cell lung cancer (NSCLC) human epidermal growth factor 2 (HER2) mutations are identified as a genomic driver. Nevertheless, no HER2-targeted treatment is approved for NSCLC. In the Drug Rediscovery Protocol (DRUP), patients are treated with off-label drugs based on their molecular profile.

Prognostic value of CT characteristics in GEP-NET: A systematic review.

Aim: A range of CT characteristics with potential prognostic value have previously been identified for gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). Still, there is no widely accepted consensus on which characteristics should be reported as prognostic factors. This systematic review therefore aims to provide an overview of the available literature regarding CT characteristics and their prognostic significance for GEP-NET patients.

Directionality of the injected current targeting the P20/N20 source determines the efficacy of 140 Hz transcranial alternating current stimulation (tACS)-induced aftereffects in the somatosensory cortex.

Interindividual anatomical differences in the human cortex can lead to suboptimal current directions and may result in response variability of transcranial electrical stimulation methods. These differences in brain anatomy require individualized electrode stimulation montages to induce an optimal current density in the targeted area of each individual subject. We aimed to explore the possible modulatory effects of 140 Hz transcranial alternating current stimulation (tACS) on the somatosensory cortex using personalized multi-electrode stimulation montages.

Patients with Rare Cancers in the Drug Rediscovery Protocol (DRUP) Benefit from Genomics-Guided Treatment.

Purpose: Patients with rare cancers (incidence less than 6 cases per 100,000 persons per year) commonly have less treatment opportunities and are understudied at the level of genomic targets. We hypothesized that patients with rare cancer benefit from approved anticancer drugs outside their label similar to common cancers.

Experimental Design: In the Drug Rediscovery Protocol (DRUP), patients with therapy-refractory metastatic cancers harboring an actionable molecular profile are matched to FDA/European Medicines Agency-approved targeted therapy or immunotherapy.

Differential Survival and Therapy Benefit of Patients with Breast Cancer Are Characterized by Distinct Epithelial and Immune Cell Microenvironments.

Purpose: Extensive work in preclinical models has shown that microenvironmental cells influence many aspects of cancer cell behavior, including metastatic potential and their sensitivity to therapeutics. In the human setting, this behavior is mainly correlated with the presence of immune cells. Here, in addition to T cells, B cells, macrophages, and mast cells, we identified the relevance of nonimmune cell types for breast cancer survival and therapy benefit, including fibroblasts, myoepithelial cells, muscle cells, endothelial cells, and seven distinct epithelial cell types.

Patients with Biallelic BRCA1/2 Inactivation Respond to Olaparib Treatment Across Histologic Tumor Types.

Purpose: To assess the efficacy of olaparib, a PARP inhibitor (PARPi) in patients with tumors with mutations, regardless of histologic tumor type.

Patients And Methods: Patients with treatment-refractory mutated cancer were included for treatment with off-label olaparib 300 mg twice daily until disease progression or unacceptable toxicity. In Drug Rediscovery Protocol (DRUP), patients with treatment-refractory solid malignancies receive off-label drugs based on tumor molecular profiles while whole-genome sequencing (WGS) is performed on baseline tumor biopsies.

Local Mast Cell Activation Promotes Neovascularization.

Mast cells have been associated with arteriogenesis and collateral formation. In advanced human atherosclerotic plaques, mast cells have been shown to colocalize with plaque neovessels, and mast cells have also been associated with tumor vascularization. Based on these associations, we hypothesize that mast cells promote angiogenesis during ischemia.

Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients.

There is a clear and unmet clinical need for biomarkers to predict responsiveness to chemotherapy for cancer. We developed an in vitro test based on patient-derived tumor organoids (PDOs) from metastatic lesions to identify nonresponders to standard-of-care chemotherapy in colorectal cancer (CRC). In a prospective clinical study, we show the feasibility of generating and testing PDOs for evaluation of sensitivity to chemotherapy.

The Drug Rediscovery protocol facilitates the expanded use of existing anticancer drugs.

The large-scale genetic profiling of tumours can identify potentially actionable molecular variants for which approved anticancer drugs are available. However, when patients with such variants are treated with drugs outside of their approved label, successes and failures of targeted therapy are not systematically collected or shared. We therefore initiated the Drug Rediscovery protocol, an adaptive, precision-oncology trial that aims to identify signals of activity in cohorts of patients, with defined tumour types and molecular variants, who are being treated with anticancer drugs outside of their approved label.

Moderate alcohol consumption and lower total mortality risk: Justified doubts or established facts?

For almost a century, the scientific community is aware of the J-shaped curve between alcohol consumption and all-cause mortality. Moderate drinkers seem to live longer than both abstainers and heavy drinkers. These epidemiological observations regarding moderate alcohol consumption and beneficial health effects have been incessantly scrutinised for confounding and bias.

Stress-induced mast cell activation contributes to atherosclerotic plaque destabilization.

Mast cells accumulate in the perivascular tissue during atherosclerotic plaque progression and contribute to plaque destabilization. However, the specific triggers for mast cell activation in atherosclerosis remain unresolved. We hypothesized that psychological stress-induced activation of mast cells may contribute to plaque destabilization.

Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids.

Cancer immunotherapies have shown substantial clinical activity for a subset of patients with epithelial cancers. Still, technological platforms to study cancer T-cell interactions for individual patients and understand determinants of responsiveness are presently lacking. Here, we establish and validate a platform to induce and analyze tumor-specific T cell responses to epithelial cancers in a personalized manner.

Detection of endogenously circulating mesenchymal stem cells in human cancer patients.

Mesenchymal stem cells (MSCs) can play a vital role in tumor progression and anticancer therapy response, as demonstrated by various in vitro and in vivo model systems. Their ability to home to developing tumors and modulate the tumor microenvironment, by suppressing T-cell responses and contributing to the tumor stroma, is suggested to have a significant impact on disease progression, metastasis formation, and therapy response. Most evidence, however, is derived from artificial models using exogenously administered MSCs.

Phase I study of combined indomethacin and platinum-based chemotherapy to reduce platinum-induced fatty acids.

Purpose: Chemotherapy-resistance remains a major obstacle to effective anti-cancer treatment. We previously showed that platinum analogs cause the release of two fatty acids. These platinum-induced fatty acids (PIFAs) induced complete chemoresistance in mice, whereas co-administration of a COX-1 inhibitor, indomethacin, prevented PIFA release and significantly enhanced chemosensitivity.

Molecular Tumor Boards: current practice and future needs.

Background: Due to rapid technical advances, steeply declining sequencing costs, and the ever-increasing number of targeted therapies, it can be expected that extensive tumor sequencing such as whole-exome and whole-genome sequencing will soon be applied in standard care. Clinicians will thus be confronted with increasingly complex genetic information and multiple test-platforms to choose from. General medical training, meanwhile, can hardly keep up with the pace of innovation.