Utilization of primary tumor samples for cancer neoantigen discovery.

Background: The use of tumor-infiltrating T lymphocytes (TIL) that recognize cancer neoantigens has led to lasting remissions in metastatic melanoma and certain cases of metastatic epithelial cancer. For the treatment of the latter, selecting cells for therapy typically involves laborious screening of TIL for recognition of autologous tumor-specific mutations, detected through next-generation sequencing of freshly resected metastatic tumors. Our study explored the feasibility of using archived formalin-fixed, paraffin-embedded (FFPE) primary tumor samples for cancer neoantigen discovery, to potentially expedite this process and reduce the need for resections normally required for tumor sequencing.

Personality traits predict the need for cognitive closure in advanced undergraduate medical students.

Background: Uncertainty in medical decision-making is a significant challenge influenced by various patient- and physician-related factors. They include physicians' clinical reasoning skills and their tolerance for uncertainty. Medical students are trained in clinical reasoning and have to learn to manage uncertainty.

Unnecessary diagnostic imaging requested by medical students during a first day of residency simulation: an explorative study.

Background: Physicians' choice of appropriate tests in the diagnostic process is crucial for patient safety. The increased use of medical imaging has raised concerns about its potential overuse. How appropriately medical students order diagnostic tests is unknown.

Acute stress promotes effort mobilization for safety-related goals.

Although the acute stress response is a highly adaptive survival mechanism, much remains unknown about how its activation impacts our decisions and actions. Based on its resource-mobilizing function, here we hypothesize that this intricate psychophysiological process may increase the willingness (motivation) to engage in effortful, energy-consuming, actions. Across two experiments (n = 80, n = 84), participants exposed to a validated stress-induction protocol, compared to a no-stress control condition, exhibited an increased willingness to exert physical effort (grip force) in the service of avoiding the possibility of experiencing aversive electrical stimulation (threat-of-shock), but not for the acquisition of rewards (money).

Adoptive transfer of personalized neoantigen-reactive TCR-transduced T cells in metastatic colorectal cancer: phase 2 trial interim results.

Adoptive cell transfer (ACT) with neoantigen-reactive T lymphocytes can mediate cancer regression. Here we isolated unique, personalized, neoantigen-reactive T cell receptors (TCRs) from tumor-infiltrating lymphocytes of patients with metastatic gastrointestinal cancers and incorporated the TCR α and β chains into gamma retroviral vectors. We transduced autologous peripheral blood lymphocytes and adoptively transferred these cells into patients after lymphodepleting chemotherapy.

Neoantigen-specific stimulation of tumor-infiltrating lymphocytes enables effective TCR isolation and expansion while preserving stem-like memory phenotypes.

Background: Tumor-infiltrating lymphocytes (TILs) targeting neoantigens can effectively treat a selected set of metastatic solid cancers. However, harnessing TILs for cancer treatments remains challenging because neoantigen-reactive T cells are often rare and exhausted, and ex vivo expansion can further reduce their frequencies. This complicates the identification of neoantigen-reactive T-cell receptors (TCRs) and the development of TIL products with high reactivity for patient treatment.

Intersectoral health interventions to improve the well-being of people living with type 2 diabetes: a scoping review protocol.

Introduction: Intersectoral collaboration is a collaborative approach between the health sectors and other sectors to address the interdependent nature of the social determinants of health associated with chronic diseases such as diabetes. This scoping review aims to identify intersectoral health interventions implemented in primary care and community settings to improve the well-being and health of people living with type 2 diabetes.

Methods And Analysis: This protocol is developed by the Arksey and O'Malley (2005) framework for scoping reviews and the Levac methodological enhancement.

Long term follow-up in GAMT deficiency - Correlation of therapy regimen, biochemical and brain proton MR spectroscopy data.

GAMT deficiency is a rare autosomal recessive disease within the group of cerebral creatine deficiency syndromes. Cerebral creatine depletion and accumulation of guanidinoacetate (GAA) lead to clinical presentation with intellectual disability, seizures, speech disturbances and movement disorders. Treatment consists of daily creatine supplementation to increase cerebral creatine, reduction of arginine intake and supplementation of ornithine for reduction of toxic GAA levels.

CSF and venous blood flow from childhood to adulthood studied by real-time phase-contrast MRI.

Purpose: In vivo measurements of CSF and venous flow using real-time phase-contrast (RT-PC) MRI facilitate new insights into the dynamics and physiology of both fluid systems. In clinical practice, however, use of RT-PC MRI is still limited. Because many forms of hydrocephalus manifest in infancy and childhood, it is a prerequisite to investigate normal flow parameters during this period to assess pathologies of CSF circulation.

Folate receptor α deficiency - Myelin-sensitive MRI as a reliable biomarker to monitor the efficacy and long-term outcome of a new therapeutic approach.

Cerebral folate transport deficiency, caused by a genetic defect in folate receptor α, is a devastating neurometabolic disorder that, if untreated, leads to epileptic encephalopathy, psychomotor decline and hypomyelination. Currently, there are limited data on effective dosage and duration of treatment, though early diagnosis and therapy with folinic acid appears critical. The aim of this long-term study was to identify new therapeutic approaches and novel biomarkers for assessing efficacy, focusing on myelin-sensitive MRI.

Phenotypic signatures of circulating neoantigen-reactive CD8 T cells in patients with metastatic cancers.

Circulating T cells from peripheral blood (PBL) can provide a rich and noninvasive source for antitumor T cells. By single-cell transcriptomic profiling of 36 neoantigen-specific T cell clones from 6 metastatic cancer patients, we report the transcriptional and cell surface signatures of antitumor PBL-derived CD8 T cells (NeoTCR). Comparison of tumor-infiltrating lymphocyte (TIL)- and PBL-neoantigen-specific T cells revealed that NeoTCR T cells are low in frequency and display less-dysfunctional memory phenotypes relative to their TIL counterparts.

Optimization of Care Pathways Through Technological, Clinical, Organizational and Social Innovations: A Qualitative Study.

Numerous calls at national and international level are leading some countries to seek to redesign the provision of healthcare and services. Care pathways have the potential to improve outcomes by providing a mechanism to coordinate care and reduce fragmentation and ultimately costs. However, their implementation still shows variable results, resulting in them being considered as complex interventions in complex systems.

Implementation model for a national learning health system (IMPLEMENT-National LHS): a concept analysis and systematic review protocol.

Introduction: Despite efforts and repeated calls to improve the organisation and quality of healthcare and services, and in view of the many challenges facing health systems, the results and capacity to adapt and integrate innovations and new knowledge remain suboptimal. Learning health systems (LHS) may be an effective model to accelerate the application of research for real quality improvement in healthcare. However, while recognising the enormous potential of LHS, the literature suggests the model remains more of an aspiration than a reality.

Pretreatment Neurofilament Light Chain Serum Levels, Early Disease Severity, and Treatment Response in Pediatric Multiple Sclerosis.

Background And Objectives: High disease activity and frequent therapy failure in pediatric multiple sclerosis (MS) make prognostic biomarkers urgently needed. We investigated whether serum neurofilament light chain (sNfL) levels in treatment-naive pediatric patients with MS are associated with early disease severity and indicate treatment outcomes.

Methods: A retrospective cohort study of patients seen in the Göttingen Center for MS in Childhood and Adolescence, Germany.

Clinical Integration of Digital Patient-Reported Outcome Measures in Primary Health Care for Chronic Disease Management: Protocol for a Systematic Review.

Background: Health measurement guides policies and health care decisions are necessary to describe and attain the quintuple aim of improving patient experience, population health, care team well-being, health care costs, and equity. In the primary care setting, patient-reported outcome measurement allows outcome comparisons within and across settings and helps improve the clinical management of patients. However, these digital patient-reported outcome measures (PROMs) are still not adapted to the clinical context of primary health care, which is an indication of the complexity of integrating these tools in this context.

Three-dimensional nuclear architecture distinguishes thyroid cancer histotypes.

Molecular markers can serve as diagnostic tools to support pathological analysis in thyroid neoplasms. However, because the same markers can be observed in some benign thyroid lesions, additional approaches are necessary to differentiate thyroid tumor subtypes, prevent overtreatment and tailor specific clinical management. This applies particularly to the recently described variant of thyroid cancer referred to as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

Evaluation of Novel Enhancer Compounds in Gentamicin-Mediated Readthrough of Nonsense Mutations in Rett Syndrome.

Rett syndrome (RTT), a severe X-linked neurodevelopmental disorder, is primarily caused by mutations in the methyl CpG binding protein 2 gene (). Over 35% RTT patients carry nonsense mutation in , making it a suitable candidate disease for nonsense suppression therapy. In our previous study, gentamicin was found to induce readthrough of nonsense mutations with modest efficiency.

Using patient-derived tumor organoids from common epithelial cancers to analyze personalized T-cell responses to neoantigens.

Adoptive cell transfer of tumor-infiltrating lymphocytes (TIL) can mediate durable complete responses in some patients with common epithelial cancers but does so infrequently. A better understanding of T-cell responses to neoantigens and tumor-related immune evasion mechanisms requires having the autologous tumor as a reagent. We investigated the ability of patient-derived tumor organoids (PDTO) to fulfill this need and evaluated their utility as a tool for selecting T-cells for adoptive cell therapy.

"Fit for the finals" - project report on a telemedical training with simulated patients, peers, and assessors for the licensing exam.

Background: Undergraduate medical students take the licensing exam (M3) as a two-day oral-practical examination. The main requirements are to demonstrate history taking skills and coherent case presentations. The aim of this project was to establish a training in which students can test their communication skills during history taking and their clinical reasoning skills in focused case presentations.