Investigation of linear energy transfer (LET)-dependence behavior and dosimetric response of a flat-panel detector in pencil beam scanning proton therapy.

Purpose: This study aims to elucidate the dependence of the flat-panel detector's response on the linear energy transfer (LET) and evaluate the practical viability of employing flat-panel detectors in proton dosimetry applications through LET-dependent correction factors.

Methods: The study assessed the flat-panel detector's response across varying depths using solid water and distinct 100, 150, and 200 MeV proton beams by comparing the flat-panel readings against reference doses measured with an ionization chamber. A Monte Carlo code was used to derive LET values, and an LET-dependent response correction factor was determined based on the ratio of the uncorrected flat-panel dose to the ionization chamber dose.

Current Practice of Podiatrists in Testing for Diabetic Polyneuropathy and Implementing Foot Care (PROTECT Study Survey 2).

Aims: Podiatrists constitute a key member of a multidisciplinary foot care team, but their services remain underutilized. We sought to gain insights into the daily practice of podiatrists focusing on screening for and monitoring of diabetic sensorimotor polyneuropathy (DSPN) as well as foot management.

Methods: This cross-sectional survey included 125 podiatrists from 12 federal states across Germany who responded to an online questionnaire.

Diagnosis, Treatment and Long-Term Management of Vitamin B12 Deficiency in Adults: A Delphi Expert Consensus.

: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. : We conducted a scoping review of the literature published in PubMed since January 2003.

Assessment of technical and clinical utility of a bead-based flow cytometry platform for multiparametric phenotyping of CNS-derived extracellular vesicles.

Background: Extracellular vesicles (EVs) originating from the central nervous system (CNS) can enter the blood stream and carry molecules characteristic of disease states. Therefore, circulating CNS-derived EVs have the potential to serve as liquid-biopsy markers for early diagnosis and follow-up of neurodegenerative diseases and brain tumors. Monitoring and profiling of CNS-derived EVs using multiparametric analysis would be a major advance for biomarker as well as basic research.

CBCT-Based Dose Monitoring and Adaptive Planning Triggers in Head and Neck PBS Proton Therapy.

Purpose: To investigate the feasibility of using cone-beam computed tomography (CBCT)-derived synthetic CTs to monitor the daily dose and trigger a plan review for adaptive proton therapy (APT) in head and neck cancer (HNC) patients.

Methods: For 84 HNC patients treated with proton pencil-beam scanning (PBS), same-day CBCT and verification CT (vfCT) pairs were retrospectively collected. The ground truth CT (gtCT) was created by deforming the vfCT to the same-day CBCT, and it was then used as a dosimetric baseline and for establishing plan review trigger recommendations.

Association between diabetes and thiamine status - A systematic review and meta-analysis.

Background: Thiamine (vitamin B1) is an essential cofactor in glucose metabolism, but it remains unclear whether thiamine status is lower in individuals with diabetes compared to individuals with normal glucose metabolism.

Aims: We conducted a systematic review and meta-analysis to study whether the circulating concentrations of various thiamine analytes differ between people with and those without diabetes.

Methods: PubMed and the Cochrane Central Register of Controlled Trials were searched according to the study protocol.

Screening and diagnosis of diabetic polyneuropathy in clinical practice: A survey among German physicians (PROTECT Study Survey).

Aims: We sought to obtain detailed information on the procedures and appraisal of screening for and diagnosing diabetic sensorimotor polyneuropathy (DSPN) in clinical practice.

Methods: This cross-sectional survey included 574 physicians from 13 federal states across Germany who responded to a tripartite questionnaire.

Results: The vast majority of the respondents reported to screen for DSPN at least once a year (87 %), while 65 % reported to examine the feet of DSPN patients at least twice a year.

A novel serum extracellular vesicle protein signature to monitor glioblastoma tumor progression.

Detection of tumor progression in patients with glioblastoma remains a major challenge. Extracellular vesicles (EVs) are potential biomarkers and can be detected in the blood of patients with glioblastoma. In our study, we evaluated the potential of serum-derived EVs from glioblastoma patients to serve as biomarker for tumor progression.

Alveolar echinococcosis as a cause of vertebral osteomyelitis and soft tissue infection with recurrent cutaneous fistula formation.

Echinococcus multilocularis is endemic in Germany. However, alveolar echinococcosis is a rare disease. Most commonly the parasite affects the liver, behaving like a malignant tumour.

Extracellular Vesicle Separation Techniques Impact Results from Human Blood Samples: Considerations for Diagnostic Applications.

Extracellular vesicles (EVs) are reminiscent of their cell of origin and thus represent a valuable source of biomarkers. However, for EVs to be used as biomarkers in clinical practice, simple, comparable, and reproducible analytical methods must be applied. Although progress is being made in EV separation methods for human biofluids, the implementation of EV assays for clinical diagnosis and common guidelines are still lacking.

MicroRNA-mediated vascular intercellular communication is altered in chronic kidney disease.

Aims: Chronic kidney disease (CKD) is an independent risk factor for the development of coronary artery disease (CAD). For both, CKD and CAD, the intercellular transfer of microRNAs (miRs) through extracellular vesicles (EVs) is an important factor of disease development. Whether the combination of CAD and CKD affects endothelial function through cellular crosstalk of EV-incorporated miRs is still unknown.

Analysis of Serum miRNA in Glioblastoma Patients: CD44-Based Enrichment of Extracellular Vesicles Enhances Specificity for the Prognostic Signature.

Glioblastoma is a devastating disease, for which biomarkers allowing a prediction of prognosis are urgently needed. microRNAs have been described as potentially valuable biomarkers in cancer. Here, we studied a panel of microRNAs in extracellular vesicles (EVs) from the serum of glioblastoma patients and evaluated their correlation with the prognosis of these patients.

Polyneuropathy is inadequately treated despite increasing symptom intensity in individuals with and without diabetes (PROTECT follow-up study).

Aims/introduction: Despite its major clinical impact, distal symmetric polyneuropathy remains frequently undiagnosed and undertreated in clinical practice. We previously reported in the PROTECT Study that 70% of type 2 diabetes patients with distal symmetric polyneuropathy were unaware of having the latter condition.

Materials And Methods: In the present follow up after 2.

Exosome-dependent immune surveillance at the metastatic niche requires BAG6 and CBP/p300-dependent acetylation of p53.

Extracellular vesicles released by tumor cells contribute to the reprogramming of the tumor microenvironment and interfere with hallmarks of cancer including metastasis. Notably, melanoma cell-derived EVs are able to establish a pre-metastatic niche in distant organs, or on the contrary, exert anti-tumor activity. However, molecular insights into how vesicles are selectively packaged with cargo defining their specific functions remain elusive.

Extracellular vesicle measurements with nanoparticle tracking analysis - An accuracy and repeatability comparison between NanoSight NS300 and ZetaView.

The expanding field of extracellular vesicle (EV) research needs reproducible and accurate methods to characterize single EVs. Nanoparticle Tracking Analysis (NTA) is commonly used to determine EV concentration and diameter. As the EV field is lacking methods to easily confirm and validate NTA data, questioning the reliability of measurements remains highly important.

Circulating innate immune markers and outcomes in treatment-naïve advanced non-small cell lung cancer patients.

Introduction: Innate immunity represents the first step of activation of the immune system and dictates the quality of adaptive immune responses. Studies have reported links between systemic inflammatory or innate immune markers and prognosis in patients with lung cancer. To our knowledge, the prospective and concomitant study of these systemic markers has never been performed.

Hodgkin Lymphoma-Derived Extracellular Vesicles Change the Secretome of Fibroblasts Toward a CAF Phenotype.

Secretion of extracellular vesicles (EVs) is a ubiquitous mechanism of intercellular communication based on the exchange of effector molecules, such as growth factors, cytokines, and nucleic acids. Recent studies identified tumor-derived EVs as central players in tumor progression and the establishment of the tumor microenvironment (TME). However, studies on EVs from classical Hodgkin lymphoma (cHL) are limited.

Painful and painless neuropathies are distinct and largely undiagnosed entities in subjects participating in an educational initiative (PROTECT study).

Aims: We conducted a nationwide educational initiative to determine the prevalence and risk factors of diagnosed and undiagnosed painful and painless distal sensory polyneuropathy (DSPN).

Methods: Among 1850 participants, 781 had no history of diabetes (ND), 126 had type 1 diabetes (T1D), and 943 had type 2 diabetes (T2D). Painful DSPN was defined as polyneuropathy detected by bedside tests with pain and/or burning in the feet, while painless DSPN was defined as polyneuropathy with paresthesias, numbness, or absence of symptoms.

Cancer-derived extracellular vesicles: friend and foe of tumour immunosurveillance.

Extracellular vesicles (EVs) are important players of intercellular signalling mechanisms, including communication with and among immune cells. EVs can affect the surrounding tissue as well as peripheral cells. Recently, EVs have been identified to be involved in the aetiology of several diseases, including cancer.

Soluble NKG2D ligands in the ovarian cancer microenvironment are associated with an adverse clinical outcome and decreased memory effector T cells independent of NKG2D downregulation.

The immune receptor NKG2D is predominantly expressed on NK cells and T cell subsets and confers anti-tumor activity. According to the current paradigm, immune surveillance is counteracted by soluble ligands shed into the microenvironment, which down-regulate NKG2D receptor expression. Here, we analyzed the clinical significance of the soluble NKG2D ligands sMICA and sULBP2 in the malignancy-associated ascites of ovarian cancer.

Nodes of Ranvier in skin biopsies of patients with diabetes mellitus.

Paranodal demyelination has been discussed as a potential mechanism of nerve fiber damage in diabetic neuropathy (DNP). Studies on human tissue are limited, as nerve biopsies are invasive and only rarely performed in patients with confirmed DNP. Skin biopsy has recently been suggested as a tool to analyze paranodal and nodal changes of myelinated fibers.

NKp30 isoforms and NKp30 ligands are predictive biomarkers of response to imatinib mesylate in metastatic GIST patients.

Despite effective targeted therapy acting on and tyrosine kinases, gastrointestinal stromal tumors (GIST) escape treatment by acquiring mutations conveying resistance to imatinib mesylate (IM). Following the identification of NKp30-based immunosurveillance of GIST and the off-target effects of IM on NK cell functions, we investigated the predictive value of NKp30 isoforms and NKp30 soluble ligands in blood for the clinical response to IM. The relative expression and the proportions of NKp30 isoforms markedly impacted both event-free and overall survival, in two independent cohorts of metastatic GIST.

RIG-I activation induces the release of extracellular vesicles with antitumor activity.

Activation of the innate immune receptor retinoic acid-inducible gene I (RIG-I) by its specific ligand 5'-triphosphate-RNA (3pRNA) triggers antitumor immunity predominantly via NK cell activation and direct apoptosis induction in tumor cells. However, how NK cells are mobilized to attack the tumor cells remains elusive. Here, we show that RIG-I activation induced the secretion of extracellular vesicles (EVs) from melanoma cells, which by themselves revealed antitumor activity and .