Unlocking the Potential of Secondary Data for Public Health Research: Retrospective Study With a Novel Clinical Platform.

Background: Clinical routine data derived from university hospitals hold immense value for health-related research on large cohorts. However, using secondary data for hypothesis testing necessitates adherence to scientific, legal (such as the General Data Protection Regulation, federal and state protection legislations), technical, and administrative requirements. This process is intricate, time-consuming, and susceptible to errors.

Integration of Trusted Third Party Software into an EDC System for Data Protection - Compliant Identity Management, Consent Management and Pseudonymization in Medical Research Studies.

Introduction: Medical research studies which involve electronic data capture of sensitive data about human subjects need to manage medical and identifying participant data in a secure manner. To protect the identity of data subjects, an independent trusted third party should be responsible for pseudonymization and management of the identifying data.

Methods: We have developed a web-based integrated solution that combines REDCap as an electronic data capture system with the trusted third party software tools of the University Medicine Greifswald, which provides study personnel with a single user interface for both clinical data entry and management of identities, pseudonyms and informed consents.

HarmonizR enables data harmonization across independent proteomic datasets with appropriate handling of missing values.

Dataset integration is common practice to overcome limitations in statistically underpowered omics datasets. Proteome datasets display high technical variability and frequent missing values. Sophisticated strategies for batch effect reduction are lacking or rely on error-prone data imputation.

Circulating Cellular Communication Network Factor 1 Protein as a Sensitive Liquid Biopsy Marker for Early Detection of Breast Cancer.

Background: Despite recent progress in liquid biopsy technologies, early blood-based detection of breast cancer is still a challenge.

Methods: We analyzed secretion of the protein cellular communication network factor 1 (CCN1, formerly cysteine-rich angiogenic inducer 61) in breast cancer cell lines by an enzyme-linked immunosorbent assay (ELISA). Soluble CCN1 in the plasma (2.

Differential regulation of extracellular matrix proteins in three recurrent liver metastases of a single patient with colorectal cancer.

Colorectal cancer (CRC) patients suffer from the second highest mortality among all cancer entities. In half of all CRC patients, colorectal cancer liver metastases (CRLM) can be observed. Metastatic colorectal cancer is associated with poor overall survival and limited treatment options.

Mass Spectrometric Comparison of HPV-Positive and HPV-Negative Oropharyngeal Cancer.

Squamous cell carcinoma of the head and neck (HNSCC) consist of two distinct biological entities. While the numbers of classical, tobacco-induced HNSCC are declining, tumors caused by human papillomavirus (HPV) infection are increasing in many countries. HPV-positive HNSCC mostly arise in the oropharynx and are characterized by an enhanced sensitivity towards radiotherapy and a favorable prognosis.

Mass Spectrometric Lipid Profiles of Picosecond Infrared Laser-Generated Tissue Aerosols Discriminate Different Brain Tissues.

Background And Objectives: A picosecond infrared laser (PIRL) has recently been demonstrated to cut biological tissue without scar formation based on the minimal destructive action on the surrounding cells. During cutting with PIRL, the irradiated tissue is ablated by a cold vaporization process termed desorption by impulsive vibrational excitation. In the resulting aerosol, all molecules are dissolved in small droplets and even labile biomolecules like proteins remain intact after ablation.

Proteome analysis of human mesenchymal stem cells undergoing chondrogenesis when exposed to the products of various magnesium-based materials degradation.

Treatment of physeal fractures (15%-30% of all paediatric fractures) remains a challenge as in approximately 10% of the cases, significant growth disturbance may occur. Bioresorbable Magnesium-based implants represent a strategy to minimize damage (., load support until bone healing without second surgery).

Understanding Protein Networks Using Vester's Sensitivity Model.

Magnesium-based biomaterials belong to the third generation of biomaterials that are also bioactive. These smart materials combine bioactivity and biodegradability, and elicit specific cellular responses at the molecular level. In fact, osteoinductive properties have been observed in mesenchymal stem cells in the presence of Magnesium.

Differential Proteome Analysis of Human Neuroblastoma Xenograft Primary Tumors and Matched Spontaneous Distant Metastases.

Metastasis formation is the major cause for cancer-related deaths and the underlying mechanisms remain poorly understood. In this study we describe spontaneous metastasis xenograft mouse models of human neuroblastoma used for unbiased identification of metastasis-related proteins by applying an infrared laser (IR) for sampling primary tumor and metastatic tissues, followed by mass spectrometric proteome analysis. IR aerosol samples were obtained from ovarian and liver metastases, which were indicated by bioluminescence imaging (BLI), and matched subcutaneous primary tumors.

Application of Displacement Chromatography to Online Two-Dimensional Liquid Chromatography Coupled to Tandem Mass Spectrometry Improves Peptide Separation Efficiency and Detectability for the Analysis of Complex Proteomes.

The complexity of mammalian proteomes is a challenge in bottom-up proteomics. For a comprehensive proteome analysis, multidimensional separation strategies are necessary. Online two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) combining strong cation exchange (SCX) in the first dimension with reversed-phase (RP) chromatography in the second dimension provides a powerful approach to analyze complex proteomes.

Quantitative Lipid Droplet Proteome Analysis Identifies Annexin A3 as a Cofactor for HCV Particle Production.

Lipid droplets are vital to hepatitis C virus (HCV) infection as the putative sites of virion assembly, but morphogenesis and egress of virions remain ill defined. We performed quantitative lipid droplet proteome analysis of HCV-infected cells to identify co-factors of that process. Our results demonstrate that HCV disconnects lipid droplets from their metabolic function.

Quantitative proteomics unveiled: Regulation of DNA double strand break repair by EGFR involves PARP1.

Background: EGFR inhibition blocks DNA double strand break (DSB) repair but the detailed mechanisms are still unclear. We asked whether EGFR inhibition blocks DSB repair by reducing the X-ray-induced phosphorylation of repair proteins using a phosphoproteomic approach.

Materials And Methods: Using UT-SCC5 and SAS head and neck cancer cells we established a differential phosphoproteomic approach for quantitative analysis of DNA repair proteins by stable isotope labeling with amino acids.

Ultrafast extraction of proteins from tissues using desorption by impulsive vibrational excitation.

A picosecond IR laser (PIRL) can be used to blast proteins out of tissues through desorption by impulsive excitation (DIVE) of intramolecular vibrational states of water molecules in the cell in less than a millisecond. With PIRL-DIVE proteins covering a range of a few kDa up to several MDa are extracted in high quantities compared to conventional approaches. The chemical composition of extracted proteins remains unaltered and even enzymatic activities are maintained.

MALDI imaging-based identification of prognostically relevant signals in bladder cancer using large-scale tissue microarrays.

Objective: Although most patients with urinary bladder cancer present with noninvasive and low-malignant stages of the disease, about 20% eventually develop life-threatening metastatic tumors. This study was designed to evaluate the potential of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to identify molecular markers predicting the clinical course of bladder cancer.

Materials And Methods: We employed MALDI-MSI to a bladder cancer tissue microarray including paraffin-embedded tissue samples from 697 patients with clinical follow-up data to search for prognostically relevant associations.

MALDI imaging on large-scale tissue microarrays identifies molecular features associated with tumour phenotype in oesophageal cancer.

Aims: Matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) and tissue microarray (TMA) technologies were jointly utilized to search for molecular features associated with clinicopathological parameters in oesophageal cancer.

Methods And Results: Two TMAs from formalin-fixed tissue samples, including 300 adenocarcinomas and 177 squamous cell carcinomas with clinical follow-up data, were analysed. MALDI-MSI analysis revealed 72 distinct mass per charge (m/z) signals associated with tumour cells, 48 of which were found in squamous cell carcinomas only, and 12 of which were specific for adenocarcinomas.

MALDI mass spectrometric imaging based identification of clinically relevant signals in prostate cancer using large-scale tissue microarrays.

To identify molecular features associated with clinico-pathological parameters and TMPRSS2-ERG fusion status in prostate cancer, we employed MALDI mass spectrometric imaging (MSI) to a prostate cancer tissue microarray (TMA) containing formalin-fixed, paraffin-embedded tissues samples from 1,044 patients for which clinical follow-up data were available. MSI analysis revealed 15 distinct mass per charge (m/z)-signals associated to epithelial structures. A comparison of these signals with clinico-pathological features revealed statistical association with favorable tumor phenotype such as low Gleason grade, early pT stage or low Ki67 labeling Index (LI) for four signals (m/z 700, m/z 1,502, m/z 1,199 and m/z 3,577), a link between high Ki67LI for one signal (m/z 1,013) and a relationship with prolonged time to PSA recurrence for one signal (m/z 1,502; p = 0.