A Comprehensive Functional Investigation of the Human Translocator Protein 18 kDa (TSPO) in a Novel Human Neuronal Cell Knockout Model.

The translocator protein 18 kDa (TSPO) is a multifunctional outer mitochondrial membrane protein associated with various aspects of mitochondrial physiology and multiple roles in health and disease. Here, we aimed to analyse the role of TSPO in the regulation of mitochondrial and cellular functions in a human neuronal cell model. We used the CRISPR/Cas9 technology and generated TSPO knockout (KO) and control (CTRL) variants of human-induced pluripotent stem cells (hiPSCs).

Histologic Characterization of Tumor-Adjacent Mammary Adipose Tissue in Normal-Weight and Overweight/Obese Patients with Triple-Negative Breast Cancer.

Obesity is a risk factor of several types of cancer, including breast cancer. In this study, we aimed to histologically characterize the adipose tissue of the tumor microenvironment (TME) of triple-negative breast cancer (TNBC) in overweight/obese versus normal-weight patients. TNBC tissue sections from normal-weight (BMI) and overweight/obese patients (BMI) were stained with antibodies against CD68, CD163, CD31, CD34, and vimentin.

Nuclei Detection and Segmentation of Histopathological Images Using a Feature Pyramidal Network Variant of a Mask R-CNN.

Cell nuclei interpretation is crucial in pathological diagnostics, especially in tumor specimens. A critical step in computational pathology is to detect and analyze individual nuclear properties using segmentation algorithms. Conventionally, a semantic segmentation network is used, where individual nuclear properties are derived after post-processing a segmentation mask.

Metformin Treatment Is Not Associated with Altered PD-L1 Expression in Diabetic Patients with Oral Squamous Cell Carcinoma.

: The anti-neoplastic activity of metformin is a subject of current debate. Preclinical data have suggested that metformin enhances PD-L1 anti-tumor effects in various cancer entities by decreasing insulin levels and inducing energetic stress. However, its impact on PD-L1 expression remains unclear in a clinical setting.

Multidisciplinary Teams in Musculoskeletal Infection - From a Pathologist's Perspective.

Multidisciplinary team (MDT) meetings have emerged as a promising approach for the treatment of cancer patients. These meetings involve a team of healthcare professionals from different disciplines working together to develop a holistic, patient-centered treatment. Although MDT meetings are well established in oncology, they play a minor role in other diseases.

Sarcopenia influences usage of reperfusion treatment in patients with pulmonary embolism aged 75 years and older.

Background: Although pulmonary embolism (PE) and sarcopenia are common diseases, only a few studies have assessed the impact of sarcopenia in PE on usage of reperfusion treatments in PE.

Methods: All hospitalizations of PE patients aged ≥75 years 2005-2020 in Germany were included in this study and stratified for sarcopenia. Impact of sarcopenia on treatment procedures and adverse in-hospital events were investigated.

Comparative Analysis of Mitochondria Surrounding the Intercalated Discs in Heart Diseases-An Ultrastructural Pilot Study.

Background: Mitochondria play a crucial role in adapting to fluctuating energy demands, particularly in various heart diseases. This study investigates mitochondrial morphology near intercalated discs in left ventricular (LV) heart tissues, comparing samples from patients with sinus rhythm (SR), atrial fibrillation (AF), dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM).

Methods: Transmission electron microscopy was used to analyze mitochondria within 0-3.

Diagnostic accuracy of Afirma gene expression classifier, Afirma gene sequencing classifier, ThyroSeq v2 and ThyroSeq v3 for indeterminate (Bethesda III and IV) thyroid nodules: a meta-analysis.

Objective: The management of thyroid nodules with indeterminate cytology (ITN) is still a challenge. To evaluate the performance of commercial molecular tests for ITN, we performed this comprehensive meta-analysis.

Methods: We performed an electronic search using PubMed/Medline, Embase, and the Cochrane Library.

Clinical impact of panel gene sequencing on therapy of advanced cancers of the digestive system: a retrospective, single center study.

Background: Panel gene sequencing is an established diagnostic tool for precision oncology of solid tumors, but its utility for the treatment of cancers of the digestive system in clinical routine is less well documented.

Methods: We retrospectively identified patients with advanced or metastatic gastrointestinal, pancreaticobiliary or hepatic cancers who received panel gene sequencing at a tertiary university hospital from 2015 to 2022. For these cases, we determined the spectrum of genetic alterations, clinicopathological parameters and treatment courses.

Risk factors for immune-related adverse effects during CPI therapy in patients with head and neck malignancies - a single center study.

Introduction: Checkpoint inhibitors, such as PD1 inhibitors, represent an important pillar in the therapy of advanced malignancies of the head and neck region. The most relevant complications are immune-related adverse effects (irAEs), which represent an immense burden for patients. Currently, no sufficient stratification measures are available to identify patients at increased risk of irAEs.

D-2-hydroxyglutarate supports a tolerogenic phenotype with lowered major histocompatibility class II expression in non-malignant dendritic cells and acute myeloid leukemia cells.

D-2-hydroxyglutarate (D-2-HG) accumulates in patients with acute myeloid leukemia (AML) with mutated isocitrate dehydrogenase (IDH) and in other malignancies. D-2-HG suppresses antitumor T-cell immunity but little is known about potential effects on non-malignant myeloid cells. Here we show that D-2-HG impairs human but not murine dendritic cell differentiation, resulting in a tolerogenic phenotype with low major histocompatibility class II expression.

Fracture related Infection - Challenges in definition and diagnosis.

In the field of orthopedics and trauma surgery, the rise of periprosthetic joint infections following joint replacement and fracture-related infections (FRI) has become a growing concern. The recent establishment of a definitive definition for FRI aimed to standardize diagnosis and treatment approaches while considering unique aspects of implant-associated infections in the presence of concomitant bone fractures. Diagnosing FRI can be challenging due to the varied clinical symptoms, and confirmatory criteria may not always be evident, necessitating additional diagnostic measures.

Imaging-based characterization of tumoral heterogeneity for personalized cancer treatment.

With personalized tumor therapy, understanding and addressing the heterogeneity of malignant tumors is becoming increasingly important. Heterogeneity can be found within one lesion (intralesional) and between several tumor lesions emerging from one primary tumor (interlesional). The heterogeneous tumor cells may show a different response to treatment due to their biology, which in turn influences the outcome of the affected patients and the choice of therapeutic agents.

Immunohistochemical Assessment of Microvessel Density in OSCC: Spatial Heterogeneity of Angiogenesis and Its Impact on Survival.

(1) Background Oral squamous cell carcinomas (OSCC) are a common malignancy of the oral cavity and are often diagnosed when they have already spread to the regional lymph nodes. Advanced stages of cancer are characterized by the development of distant metastases. Angiogenesis, a hallmark of cancer, is known to contribute to cancer progression and metastasis.

Deep learning to predict breast cancer sentinel lymph node status on INSEMA histological images.

Background: Sentinel lymph node (SLN) status is a clinically important prognostic biomarker in breast cancer and is used to guide therapy, especially for hormone receptor-positive, HER2-negative cases. However, invasive lymph node staging is increasingly omitted before therapy, and studies such as the randomised Intergroup Sentinel Mamma (INSEMA) trial address the potential for further de-escalation of axillary surgery. Therefore, it would be helpful to accurately predict the pretherapeutic sentinel status using medical images.

Scorpionfish BPI is highly active against multiple drug-resistant isolates from people with cystic fibrosis.

Chronic pulmonary infection is a hallmark of cystic fibrosis (CF) and requires continuous antibiotic treatment. In this context, () is of special concern since colonizing strains frequently acquire multiple drug resistance (MDR). Bactericidal/permeability-increasing protein (BPI) is a neutrophil-derived, endogenous protein with high bactericidal potency against Gram-negative bacteria.

Prediction of heart transplant rejection from routine pathology slides with self-supervised deep learning.

Aims: One of the most important complications of heart transplantation is organ rejection, which is diagnosed on endomyocardial biopsies by pathologists. Computer-based systems could assist in the diagnostic process and potentially improve reproducibility. Here, we evaluated the feasibility of using deep learning in predicting the degree of cellular rejection from pathology slides as defined by the International Society for Heart and Lung Transplantation (ISHLT) grading system.

3D Visualization, Skeletonization and Branching Analysis of Blood Vessels in Angiogenesis.

Angiogenesis is the process of new blood vessels growing from existing vasculature. Visualizing them as a three-dimensional (3D) model is a challenging, yet relevant, task as it would be of great help to researchers, pathologists, and medical doctors. A branching analysis on the 3D model would further facilitate research and diagnostic purposes.

Ultrastructural Evidence of Mitochondrial Dysfunction in Osteomyelitis Patients.

Osteomyelitis is a difficult-to-treat disease with high chronification rates. First studies suggest increases in mitochondrial fission and mitochondrial dysfunction as possible contributors to the accumulation of intracellular reactive oxygen species and thereby to the cell death of infected bone cells. The aim of the present study is to analyze the ultrastructural impact of bacterial infection on osteocytic and osteoblastic mitochondria.

Expression of pH-Sensitive GPCRs in Peritoneal Carcinomatosis of Colorectal Cancer-First Results.

Solid tumors have an altered metabolism with a so-called inside-out pH gradient (decreased pH < increased pH). This also signals back to tumor cells via proton-sensitive ion channels or G protein-coupled receptors (pH-GPCRs) to alter migration and proliferation. Nothing, however, is known about the expression of pH-GPCRs in the rare form of peritoneal carcinomatosis.