Publications by authors named "Es J"
Article Synopsis
- The mammalian pancreas has three key parts: exocrine acini and ducts, along with endocrine islets, all originating from a common progenitor during development.
- Researchers created 18 human fetal pancreas organoid lines from samples between 8-17 weeks of gestation, with four lines showing the ability to produce all three cell types while thriving in culture for over two years.
- Single-cell RNA sequencing revealed LGR5 cells as crucial developmental stem cells, indicating that these organoids are capable of long-term growth and can differentiate into acinar, ductal, and endocrine cells.
Background: Previous research highlights persistent differential attainment by ethnicity in medical education, wherein the perceived inclusiveness significantly influences ethnic minority students' and trainees' outcomes. Biased organizational practices and microaggressions exacerbate the challenges faced by ethnic minorities, leading to lower academic performance and higher dropout rates. Consequently, understanding ethnic minority GP-trainees' experiences and perspectives regarding relevant educational aspects is crucial for addressing these disparities and cultivating a more inclusive environment within medical education.
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- Mitochondrial disease is a rare condition currently lacking approved treatments, with sonlicromanol being a promising candidate that modifies key metabolic and inflammatory pathways.
- A Phase 2b study was conducted to evaluate sonlicromanol's safety and efficacy in adults with a specific genetic mutation, involving both a randomized controlled trial (RCT) and a long-term extension study.
- While the primary endpoint of the RCT didn't show significant results, there were indications of improvement in certain cognitive and emotional assessments among patients who were more affected at baseline.
Carcinogenesis results from the sequential acquisition of oncogenic mutations that convert normal cells into invasive, metastasizing cancer cells. Colorectal cancer exemplifies this process through its well-described adenoma-carcinoma sequence, modeled previously using clustered regularly interspaced short palindromic repeats (CRISPR) to induce four consecutive mutations in wild-type human gut organoids. Here, we demonstrate that long-term culture of mismatch-repair-deficient organoids allows the selection of spontaneous oncogenic mutations through the sequential withdrawal of Wnt agonists, epidermal growth factor (EGF) agonists and the bone morphogenetic protein (BMP) antagonist Noggin, while TP53 mutations were selected through the addition of Nutlin-3.
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- Nuclear receptors (NRs) are important transcription factors in the small intestine that respond to various signals and influence multiple biological processes such as nutrient absorption and drug metabolism.
- This study examines the activation of six different NRs using small molecule agonists in human intestinal organoids, highlighting their roles in lipid, glucose, and amino acid absorption, as well as electrolyte balance.
- Unique target genes associated with specific NRs were identified, providing valuable insights that could lead to enhanced pharmacological and therapeutic applications.
Enteroendocrine cells (EECs) are gut epithelial cells that respond to intestinal contents by secreting hormones, including the incretins glucagon-like peptide 1 (GLP-1) and gastric inhibitory protein (GIP), which regulate multiple physiological processes. Hormone release is controlled through metabolite-sensing proteins. Low expression, interspecies differences, and the existence of multiple EEC subtypes have posed challenges to the study of these sensors.
View Article and Find Full Text PDFIntroduction: Up to 50% of pulmonary embolism (PE) patients have perfusion defects or residual vascular obstruction during follow-up despite adequate anticoagulant treatment, and a similar percentage experience chronic functional limitations and/or dyspnoea post-PE. We aimed to evaluate the association between pulmonary perfusion defects or residual vascular obstruction and functional recovery after PE.
Methods: We performed a systematic review and meta-analysis including studies assessing both the presence of perfusion defects or residual vascular obstruction and functional recovery ( persistent symptoms, quality of life, exercise endurance).
Isogenic disease models, such as genetically engineered organoids, provide insight into the impact of genetic variants on organ function. Here, we present a protocol to create isogenic disease models from adult stem cell-derived organoids using next-generation CRISPR tools. We describe steps for single guide RNA (sgRNA) design and cloning, electroporation, and selecting electroporated cells.
View Article and Find Full Text PDFBackground: A recent study found that ethnic minority General Practice (GP)-trainees receive more negative assessments than their majority peers. Previous qualitative research suggested that learning climate-related factors play a pivotal role in unequal opportunities for trainees in post-graduate medical settings, indicating that insufficient inclusivity had put minority students at risk of failure and dropout.
Study Objectives: We aimed to develop broadly supported strategies for an inclusive learning climate in Dutch GP-specialty training.
Background: The rotational position of the aortic root (AoR) is of substantial clinical interest as it has been associated with severe aortic complications, such as aortic dissections. We described a cardiac magnetic resonance (CMR)-based method for measuring AoR rotation and evaluated the reliability of measurements.
Methods: CMR was used for measuring AoR rotation in 50 consecutive healthy subjects.
Because of the COVID-19 pandemic, several health care services, including cardiac rehabilitation (CR), had to transition to virtual delivery, for which formal evaluations are lacking. In this pilot study, we investigated the implementation of a virtual CR program by surveying 30 patients attending virtual CR. Virtual CR was well received, although patients provided recommendations to improve delivery such as offering individual sessions and changing how education materials were delivered.
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- FBXW7 is a protein that helps break down other proteins, and when it's mutated, it can contribute to cancer.
- Scientists used a special tool called CRISPR to change certain parts of this protein in colon tissue samples, which made the samples grow better without needing as much EGF, a growth factor.
- The research showed that these mutations help keep another protein called EGFR alive longer, making the cancer cells less sensitive to certain treatments.
Background: Focal adhesion signaling involving receptor tyrosine kinases (RTK) and integrins co-controls cancer cell survival and therapy resistance. However, co-dependencies between these receptors and therapeutically exploitable vulnerabilities remain largely elusive in HPV-negative head and neck squamous cell carcinoma (HNSCC).
Methods: The cytotoxic and radiochemosensitizing potential of targeting 10 RTK and β1 integrin was determined in up to 20 3D matrix-grown HNSCC cell models followed by drug screening and patient-derived organoid validation.
Article Synopsis
- The study examines how pulmonary endarterectomy (PEA) affects hemodynamics and exercise capacity in patients with chronic thromboembolic pulmonary hypertension (CTEPH) classified as mild or severe based on their mean pulmonary arterial pressure (mPAP).
- 18 CTEPH patients were evaluated before and 18 months after PEA, revealing that those with mild CTEPH had less impairment in exercise capacity at baseline compared to the severe group.
- Post-surgery, both groups showed improvements in hemodynamics, but only the severe group experienced a significant increase in exercise capacity, suggesting postoperative outcomes were similar despite initial differences in severity.
We examined the potential effects of weed species on the arbuscular mycorrhizal fungi (AMF) in an organic winter wheat () field in Lebanon. In this agroecosystem, the field and its surroundings were covered with spontaneous vegetation corresponding to local weeds. The coexistence between wheat and weeds did not modify AM fungal community diversity and colonization in but changed their composition.
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- The conjunctival epithelium has two key cell types: goblet cells that produce mucus and keratinocytes that secrete water, with keratinocytes presenting mucins on their surface.
- Research involves long-term organoid cultures of human and mouse conjunctiva, revealing essential gene expression and identification of conjunctival stem cells.
- The study also explores viral infections (HSV1, hAdV8, SARS-CoV-2) in conjunctival cultures, demonstrating treatment options for some infections and documenting gene expression changes induced by these viruses, highlighting the potential for organoid transplantation to study conjunctival health and disease.
Background: Bladder cancer is one of the most common cancer types worldwide. Generally, research relies on invasive sampling strategies.
Methods: Here, we generate bladder cancer organoids directly from urine (urinoids).
Enteroendocrine cells (EECs) are hormone-producing cells residing in the epithelium of stomach, small intestine (SI), and colon. EECs regulate aspects of metabolic activity, including insulin levels, satiety, gastrointestinal secretion, and motility. The generation of different EEC lineages is not completely understood.
View Article and Find Full Text PDFIntestinal stem cells (ISCs) maintain the epithelial lining of the intestines, but mechanisms regulating ISCs and their niche after damage remain poorly understood. Utilizing radiation injury to model intestinal pathology, we report here that the Interleukin-33 (IL-33)/ST2 axis, an immunomodulatory pathway monitored clinically as an intestinal injury biomarker, regulates intrinsic epithelial regeneration by inducing production of epidermal growth factor (EGF). Three-dimensional imaging and lineage-specific RiboTag induction within the stem cell compartment indicated that ISCs expressed IL-33 in response to radiation injury.
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- - The study explores the use of advanced CRISPR/Cas9-based base editors for creating intricate tumor models using human organoids derived from adult stem cells (ASC), specifically focusing on liver (hepatocyte) and endometrial organoids.
- - Results demonstrate the effectiveness of cytosine and adenine base editors in inducing specific mutations, such as CTNNB1 mutations in liver organoids and PTEN nonsense mutations in endometrial organoids, which lead to tumor development even with one mutated copy.
- - Additionally, the researchers enhanced base editing capabilities by employing multiple Cas9 variants for targeted mutations and established a method to model colorectal cancer by editing five cancer genes simultaneously in one experiment.
Background: Exact benefits of currently recommended close monitoring in intermediate high risk acute pulmonary embolism (PE) patients are unknown.
Methods: This prospective observational cohort study determined clinical characteristics, and disease course of intermediate high risk acute PE patients in an academic hospital setting . Frequency of hemodynamic deterioration, use of rescue reperfusion therapy and PE related mortality, were outcomes of interest.
Background: Comprehensive data on long COVID across ethnic and migrant groups are lacking. We investigated incidence, nature of symptoms, clinical predictors, and duration of long COVID among COVID-19 hospitalised patients in the Netherlands by migration background (Dutch, Turkish, Moroccan, and Surinamese origin, Others).
Methods: We used COVID-19 admissions and follow up data (January 2021-July 2022) from Amsterdam University Medical Centers.
Background: The COVID-19 pandemic significantly impacted the conduct of clinical trials through delay, interruption or cancellation. Decentralised methods in clinical trials could help to continue trials during a pandemic. This paper presents the results of an exploratory study conducted early in the pandemic to gain insight into and describe the experiences of organisations involved in clinical trials, with regard to the impact of COVID-19 on the conduct of trials, and the adoption of decentralised methods prior to, and as mitigation for the impact, of COVID-19.
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