Level I and II deficits-A clinical survey on international practice of awake craniotomy and definitions of postoperative "major" and "minor" deficits.

Background: Awake craniotomy (AC) is a technique that balances maximum resection and minimal postoperative deficits in patients with intracranial tumors. To aid in the comparability of functional outcomes after awake surgery, this study investigated its international practice and aimed to define categories of postoperative deficits.

Methods: A survey was distributed via neurosurgical networks in Europe (European Association of Neurosurgical Societies, EANS), the Netherlands (Nederlandse Vereniging voor Neurochirurgie, NVVN), Belgium (Belgian Society of Neurosurgery, BSN), and the United States (Congress of Neurological Surgeons, CNS) between April 2022 and April 2023.

Sertraline/chloroquine combination therapy to target hypoxic and immunosuppressive serine/glycine synthesis-dependent glioblastomas.

The serine/glycine (ser/gly) synthesis pathway branches from glycolysis and is hyperactivated in approximately 30% of cancers. In ~13% of glioblastoma cases, we observed frequent amplifications and rare mutations in the gene encoding the enzyme PSPH, which catalyzes the last step in the synthesis of serine. This urged us to unveil the relevance of PSPH genetic alterations and subsequent ser/gly metabolism deregulation in the pathogenesis of glioblastoma.

A novel lineage-tracing tool reveals that hypoxic tumor cells drive tumor relapse after radiotherapy.

Purpose: Tumor hypoxia imposes a main obstacle to the efficacy of anti-cancer therapy. Understanding the cellular dynamics of individual hypoxic cells before, during and post-treatment has been hampered by the technical inability to identify and trace these cells over time.

Methods And Materials: Here, we present a novel lineage-tracing reporter for hypoxic cells based on the conditional expression of a HIF1a-CreER-UnaG biosensor that can visualize hypoxic cells in a time-dependent manner and trace the fate of hypoxic cells over time.

Opportunities and Challenges of Small Molecule Inhibitors in Glioblastoma Treatment: Lessons Learned from Clinical Trials.

Glioblastoma (GBM) is the most prevalent central nervous system tumour (CNS). Patients with GBM have a dismal prognosis of 15 months, despite an intensive treatment schedule consisting of surgery, chemoradiation and concurrent chemotherapy. In the last decades, many trials have been performed investigating small molecule inhibitors, which target specific genes involved in tumorigenesis.

Enhanced radiation sensitivity, decreased DNA damage repair, and differentiation defects in airway stem cells derived from patients with chronic obstructive pulmonary disease.

Radiation therapy (RT) is a common treatment for lung cancer. Still, it can lead to irreversible loss of pulmonary function and a significant reduction in quality of life for one-third of patients. Preexisting comorbidities, such as chronic obstructive pulmonary disease (COPD), are frequent in patients with lung cancer and further increase the risk of complications.

Vulnerability profiles of workers and the relation with burnout symptoms: results from the Netherlands working conditions survey.

Introduction: Unfavorable working conditions may place workers in a vulnerable position in the labour market, but studies on the clustering of these factors and their relation to burnout symptoms are lacking. This study aims to identify subgroups of workers in potentially vulnerable positions in the labour market and examine whether burnout symptoms differ across the established subgroups.

Methods: This study utilizes cross-sectional data from 2019 of the Netherlands Working Conditions Survey (n = 55,283).

Treating chronic wounds in an acute care setting: the forgotten diagnosis.

Background: Chronic wounds include lower extremity ulcers, diabetic foot ulcers, and pressure injuries, and can take months or years to heal. Wounds place a high burden on outpatient and inpatient care settings. This burden is expected to increase markedly in the United States as the population ages and with increased rates of diabetes, obesity, and COVID-19.

The DMT1 isoform lacking the iron-response element regulates normal and malignant hematopoiesis via NOTCH pathway activation.

Natural resistance-associated macrophage protein 2 (NRAMP 2; also known as DMT1 and encoded by SLC11A2) is mainly known for its iron transport activity. Recently, the DMT1 isoform lacking the iron-response element (nonIRE) was associated with aberrant NOTCH pathway activity. In this report, we investigated the function of DMT1 nonIRE in normal and malignant hematopoiesis.

Targeting serine/glycine metabolism improves radiotherapy response in non-small cell lung cancer.

Background: Lung cancer is the most lethal cancer, and 85% of cases are classified as non-small cell lung cancer (NSCLC). Metabolic rewiring is a cancer hallmark that causes treatment resistance, and lacks insights into serine/glycine pathway adaptations upon radiotherapy.

Methods: We analyzed radiotherapy responses using mass-spectrometry-based metabolomics in NSCLC patient's plasma and cell lines.

Iron-responsive element of Divalent metal transporter 1 (Dmt1) controls Notch-mediated cell fates.

Notch receptor activation is regulated by the intramembrane protease γ-secretase, which cleaves and liberates the Notch intracellular domain (Nicd) that regulates gene transcription. While γ-secretase cleavage is necessary, we demonstrate it is insufficient for Notch activation and requires vesicular trafficking. Here, we report Divalent metal transporter 1 (Dmt1, Slc11A2) as a novel and essential regulator of Notch signalling.

Applying objective metrics to neurosurgical skill development with simulation and spaced repetition learning.

Objective: Surgical skills laboratories augment educational training by deepening one's understanding of anatomy and allowing the safe practice of technical skills. Novel, high-fidelity, cadaver-free simulators provide an opportunity to increase access to skills laboratory training. The neurosurgical field has historically evaluated skill by subjective assessment or outcome measures, as opposed to process measures with objective, quantitative indicators of technical skill and progression.

Managing Exudate Pooling: A Simplified Practical Guide.

Background: Exudate pooling is the collection of wound fluid in the wound bed. Wounds with irregular depth, pockets, or cavities can create a dead space between the dressing and the wound bed where exudate can accumulate. Exudate pooling could lead to increased risk of infection or biofilm formation, maceration of the periwound skin, and delayed wound healing.

A qualitative study into the perspectives of clients on shared decision-making as a method to support return to work.

Background: Being able to participate in work is an important determinant of health. Therefore, reintegration professionals provide support to clients to return to work (RTW). Since RTW has a significant impact on a client's life, it is preferred that clients are involved in the decision-making process of RTW.

Identification of Potential Prognostic and Predictive Immunological Biomarkers in Patients with Stage I and Stage III Non-Small Cell Lung Cancer (NSCLC): A Prospective Exploratory Study.

Radiotherapy (RT) and chemotherapy can induce immune responses, but not much is known regarding treatment-induced immune changes in patients. This exploratory study aimed to identify potential prognostic and predictive immune-related proteins associated with progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC). In this prospective study, patients with stage I NSCLC treated with stereotactic body radiation therapy ( = 26) and patients with stage III NSCLC treated with concurrent chemoradiotherapy ( = 18) were included.

How to facilitate guideline use? A bottom-up qualitative approach developing a training programme for professionals involved in work participation of people with a chronic disease.

Background: A guideline for occupational health professionals (OHPs) is developed which provides them with knowledge and skills to optimize their guidance to people with a chronic disease.

Objective: Developing a training programme to acquire and apply knowledge and skills provided by the guideline, through a bottom-up approach.

Methods: First, OHPs training needs were explored using focus groups.

The Role of Intracellular Trafficking of Notch Receptors in Ligand-Independent Notch Activation.

Aberrant Notch signaling has been found in a broad range of human malignancies. Consequently, small molecule inhibitors and antibodies targeting Notch signaling in human cancers have been developed and tested; however, these have failed due to limited anti-tumor efficacy because of dose-limiting toxicities in normal tissues. Therefore, there is an unmet need to discover novel regulators of malignant Notch signaling, which do not affect Notch signaling in healthy tissues.

Patient Activation for Self-Management in Patients with Idiopathic Pulmonary Fibrosis or Sarcoidosis.

Background: Self-management is considered important in the management of patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis. However, data about the degree of activation for self-management is lacking.

Objectives: The aim of the study was to determine the degree of activation for self-management in patients with IPF or sarcoidosis using the Patient Activation Measure (PAM) and to evaluate the association between PAM scores, clinical characteristics, and health-related outcomes.

Artificial Intelligence Applications to Improve the Treatment of Locally Advanced Non-Small Cell Lung Cancers.

Locally advanced non-small cell lung cancer patients represent around one third of newly diagnosed lung cancer patients. There remains a large unmet need to find treatment strategies that can improve the survival of these patients while minimizing therapeutical side effects. Increasing the availability of patients' data (imaging, electronic health records, patients' reported outcomes, and genomics) will enable the application of AI algorithms to improve therapy selections.

Biomarkers of Radiotherapy-Induced Immunogenic Cell Death.

Radiation therapy (RT) can induce an immunogenic variant of regulated cell death that can initiate clinically relevant tumor-targeting immune responses. Immunogenic cell death (ICD) is accompanied by the exposure and release of damage-associated molecular patterns (DAMPs), chemokine release, and stimulation of type I interferon (IFN-I) responses. In recent years, intensive research has unraveled major mechanistic aspects of RT-induced ICD and has resulted in the identification of immunogenic factors that are released by irradiated tumor cells.

Patient-Derived Cancer Organoids as Predictors of Treatment Response.

Patient-derived cancer organoids have taken a prominent role in pre-clinical and translational research and have been generated for most common solid tumors. Cancer organoids have been shown to retain key genetic and phenotypic characteristics of their tissue of origin, tumor subtype and maintain intratumoral heterogeneity and therefore have the potential to be used as predictors for individualized treatment response. In this review, we highlight studies that have used cancer organoids to compare the efficacy of standard-of-care and targeted combination treatments with clinical patient response.