Measuring facial mimicry: Affdex vs. EMG.

Facial mimicry is the automatic imitation of the facial affect expressions of others. It serves as an important component of interpersonal communication and affective co-experience. Facial mimicry has so far been measured by Electromyography (EMG), which requires a complex measuring apparatus.

5-(Trifluoromethyl)-1,2,4-oxadiazole (TFMO)-based highly selective class IIa HDAC inhibitors exhibit synergistic anticancer activity in combination with bortezomib.

Clinically used pan and class I HDACi cause severe side effects, whereas class IIa HDACi are less cytotoxic. Here, we present the synthesis and anticancer effects of a series of 5-(trifluoromethyl)-1,2,4-oxadiazole (TFMO)-based amides and alkoxyamides derived from the previously reported class IIa HDACi YAK540. The most active class IIa inhibitor 1a showed nanomolar inhibition of the class IIa enzymes 4, 5, 7 (IC HDAC4: 12 nM) and high selectivity (selectivity index >318 for HDAC4) over non-class IIa HDACs.

Rivaroxaban attenuates neutrophil maturation in the bone marrow niche.

Pharmacological inhibition of factor Xa by rivaroxaban has been shown to mediate cardioprotection and is frequently used in patients with, e.g., atrial fibrillation.

Psychosocial functioning as a mediator between childhood trauma and symptom severity in patients with schizophrenia.

Background: There is empirical evidence that childhood trauma is associated with symptom severity and psychosocial functioning in schizophrenia.

Objective: The present study aimed to further elucidate these associations by examining which subdomains of schizophrenic symptoms and psychosocial functioning are associated with childhood trauma. In addition, it should be tested whether the association between childhood trauma and schizophrenic symptoms is mediated by psychosocial functioning.

Mesenchymal-epithelial transition in lymph node metastases of oral squamous cell carcinoma is accompanied by ZEB1 expression.

Background: Oral squamous cell carcinoma (OSCC), an HPV-negative head and neck cancer, frequently metastasizes to the regional lymph nodes but only occasionally beyond. Initial phases of metastasis are associated with an epithelial-mesenchymal transition (EMT), while the consolidation phase is associated with mesenchymal-epithelial transition (MET). This dynamic is referred to as epithelial-mesenchymal plasticity (EMP).

Synergistic Interaction of the Class IIa HDAC Inhibitor CHDI0039 with Bortezomib in Head and Neck Cancer Cells.

In contrast to class I/IIb/pan histone deacetylase inhibitors (HDACi), the role of class IIa HDACi as anti-cancer chemosensitizing agents is less well understood. Here, we studied the effects of HDAC4 in particular and the class IIa HDACi CHDI0039 on proliferation and chemosensitivity in Cal27 and cisplatin-resistant Cal27CisR head and neck squamous cell cancer (HNSCC). HDAC4 and HDAC5 overexpression clones were generated.

Dynamics of CXCR4 positive circulating tumor cells in prostate cancer patients during radiotherapy.

Ablative radiotherapy is a highly efficient treatment modality for patients with metastatic prostate cancer (PCa). However, a subset of patients does not respond. Currently, this subgroup with bad prognosis cannot be identified before disease progression.

MacroH2A impedes metastatic growth by enforcing a discrete dormancy program in disseminated cancer cells.

MacroH2A variants have been linked to inhibition of metastasis through incompletely understood mechanisms. Here, we reveal that solitary dormant disseminated cancer cells (DCCs) display increased levels of macroH2A variants in head and neck squamous cell carcinoma PDX in vivo models and patient samples compared to proliferating primary or metastatic lesions. We demonstrate that dormancy-inducing transforming growth factor-β2 and p38α/β pathways up-regulate macroH2A expression and that macroH2A variant overexpression is sufficient to induce DCC dormancy and suppress metastasis in vivo.

Lethal Sepsis in the Course of Medicinal Leech Therapy.

A patient with oral squamous cell carcinoma (OSCC) underwent complex surgical tumor therapy, including the reconstruction of soft tissues using a radial forearm flap. Due to venous congestion that could only partly be resolved by revision surgery, leech therapy was started on the second postoperative day. The patient developed pneumonia and sepsis and died as a result of septic shock, despite having received targeted broad-spectrum antibiotic therapy since day 5.

Association of C-Terminal Pro-Endothelin-1 with Mortality in the Population-Based KORA F4 Study.

Introduction: Endothelin-1 and its prohormone C-terminal pro-endothelin-1 (CT-proET-1) have been linked to metabolic alterations, inflammatory responses and cardiovascular events in selected study populations. We analyzed the association of CT-proET-1 with cardiovascular events and mortality, carotid intima-media-thickness as surrogate for early atherosclerotic lesions, biomarkers of subclinical inflammation and adipokines in a population-based study.

Methods: The cross-sectional and prospective analyses used data from the KORA F4 study with a median follow-up time of 9.

An NR2F1-specific agonist suppresses metastasis by inducing cancer cell dormancy.

We describe the discovery of an agonist of the nuclear receptor NR2F1 that specifically activates dormancy programs in malignant cells. The agonist led to a self-regulated increase in NR2F1 mRNA and protein and downstream transcription of a novel dormancy program. This program led to growth arrest of an HNSCC PDX line, human cell lines, and patient-derived organoids in 3D cultures and in vivo.

The regulatory effect of hyaluronan on human mesenchymal stem cells' fate modulates their interaction with cancer cells in vitro.

Metastatic spread of cancer cells into a pre-metastatic niche is highly dependent on a supporting microenvironment. Human bone marrow-derived mesenchymal stem cells (bmMSCs) contribute to the tumor microenvironment and promote cancer metastasis by inducing epithelial-to-mesenchymal transition and immune evasion. The underlying mechanisms, however, are incompletely understood.

Alexithymia and Facial Mimicry in Response to Infant and Adult Affect-Expressive Faces.

Facial mimicry is the automatic tendency to imitate facial expressions of emotions. Alexithymia is associated with a reduced facial mimicry ability to affect expressions of adults. There is evidence that the baby schema may influence this process.

GLS-driven glutamine catabolism contributes to prostate cancer radiosensitivity by regulating the redox state, stemness and ATG5-mediated autophagy.

Radiotherapy is one of the curative treatment options for localized prostate cancer (PCa). The curative potential of radiotherapy is mediated by irradiation-induced oxidative stress and DNA damage in tumor cells. However, PCa radiocurability can be impeded by tumor resistance mechanisms and normal tissue toxicity.

Is the prediction of one or two ipsilateral positive lymph nodes by computerized tomography and ultrasound reliable enough to restrict therapeutic neck dissection in oral squamous cell carcinoma (OSCC) patients?

Introduction: Proper management of the clinically involved neck in OSCC patients continues to be a matter of debate. Our aim was to analyze the accuracy of computerized tomography (CT) and ultrasound (US) in anticipating the exact location of lymph node (LN) metastases of OSCC patients across the AAO-HNS (American Academy of Otolaryngology-Head and Neck Surgery) levels ipsi- and contralaterally. Furthermore, we wanted to assess the suitability of therapeutic selective neck dissection (SND) in patients with one or two ipsilateral positive nodes upon clinical staging (cN1/cN2a and cN2b(2/x) patients).

Considering the Experimental use of Temozolomide in Glioblastoma Research.

Temozolomide (TMZ) currently remains the only chemotherapeutic component in the approved treatment scheme for Glioblastoma (GB), the most common primary brain tumour with a dismal patient's survival prognosis of only ~15 months. While frequently described as an alkylating agent that causes DNA damage and thus-ultimately-cell death, a recent debate has been initiated to re-evaluate the therapeutic role of TMZ in GB. Here, we discuss the experimental use of TMZ and highlight how it differs from its clinical role.

Genetic characterization of a unique neuroendocrine transdifferentiation prostate circulating tumor cell-derived eXplant model.

Transformation of castration-resistant prostate cancer (CRPC) into an aggressive neuroendocrine disease (CRPC-NE) represents a major clinical challenge and experimental models are lacking. A CTC-derived eXplant (CDX) and a CDX-derived cell line are established using circulating tumor cells (CTCs) obtained by diagnostic leukapheresis from a CRPC patient resistant to enzalutamide. The CDX and the derived-cell line conserve 16% of primary tumor (PT) and 56% of CTC mutations, as well as 83% of PT copy-number aberrations including clonal TMPRSS2-ERG fusion and NKX3.

Evaluation of HER2 expression in urothelial carcinoma cells as a biomarker for circulating tumor cells.

Background: Detection of circulating tumor cells (CTC) by techniques based on epithelial cell adhesion molecule (EpCAM) is suboptimal in urothelial carcinoma (UC). As HER2 is thought to be broadly expressed in UC, we explored its utility for CTC detection.

Methods: HER2 and EpCAM expression was analyzed in 18 UC cell lines (UCCs) by qRT-PCR, western blot and fluorescence-activated cell scanning (FACS) and compared to the strongly HER2-expressing breast cancer cell line SKBR3 and other controls.

Spatiotemporally controlled induction of gene expression in vivo allows tracking the fate of tumor cells that traffic through the lymphatics.

Metastasis is a multistep process, during which circulating tumor cells traffic through diverse anatomical locations. Stable inducible marking of tumor cells in a manner that is tightly spatially and temporally controlled would allow tracking the contribution of cells passing through specific locations to metastatic dissemination. For example, tumor cells enter the lymphatic system and can form metastases in regional lymph nodes, but the relative contribution of tumor cells that traffic through the lymphatic system to the formation of distant metastases remains controversial.

Intra-Patient Heterogeneity of Circulating Tumor Cells and Circulating Tumor DNA in Blood of Melanoma Patients.

Despite remarkable progress in melanoma therapy, the exceptional heterogeneity of the disease has prevented the development of reliable companion biomarkers for the prediction or monitoring of therapy responses. Here, we show that difficulties in detecting blood-based markers, like circulating tumor cells (CTC), might arise from the translation of the mutational heterogeneity of melanoma cells towards their surface marker expression. We provide a unique method, which enables the molecular characterization of clinically relevant CTC subsets, as well as circulating tumor DNA (ctDNA), from a single blood sample.

Minimal Residual Disease in Head and Neck Cancer and Esophageal Cancer.

Malignant epithelial tumors of the upper digestive tract are a major cause of cancer-related death worldwide. The most common of these cancers are head and neck squamous cell carcinomas (HNSCC) and esophageal cancers (EC), which are both characterized by early dissemination and poor prognosis. Although patients with early detected cancers can be subjected to multimodal therapies with curative intention, they are endangered by lethal relapses that frequently occur.

Classification of Cells in CTC-Enriched Samples by Advanced Image Analysis.

In the CellSearch system, blood is immunomagnetically enriched for epithelial cell adhesion molecule (EpCAM) expression and cells are stained with the nucleic acid dye 4'6-diamidino-2-phenylindole (DAPI), Cytokeratin-PE (CK), and CD45-APC. Only DAPI+/CK+ objects are presented to the operator to identify circulating tumor cells (CTC) and the identity of all other cells and potential undetected CTC remains unrevealed. Here, we used the open source imaging program Automatic CTC Classification, Enumeration and PhenoTyping (ACCEPT) to analyze all DAPI+ nuclei in EpCAM-enriched blood samples obtained from 192 metastatic non-small cell lung cancer (NSCLC) patients and 162 controls.