AXL-TBK1 driven AKT3 activation promotes metastasis.

The receptor tyrosine kinase AXL promotes tumor progression, metastasis, and therapy resistance through the induction of epithelial-mesenchymal transition (EMT). Here, we found that activation of AXL resulted in the phosphorylation of TANK-binding kinase 1 (TBK1) and the downstream activation of AKT3 and Snail, a transcription factor critical for EMT. Mechanistically, we showed that TBK1 directly bound to and phosphorylated AKT3 in a manner dependent on the multiprotein complex mTORC1.

Multi-Zone Visco-Node-Pore Sensing: A Microfluidic Platform for Multi-Frequency Viscoelastic Phenotyping of Single Cells.

This study introduces multi-zone visco-Node-Pore Sensing (mz-visco-NPS), an electronic-based microfluidic platform for single-cell viscoelastic phenotyping. mz-visco-NPS implements a series of sinusoidal-shaped contraction zones that periodically deform a cell at specific strain frequencies, leading to changes in resistance across the zones that correspond to the cell's frequency-dependent elastic G' and viscous G″ moduli. mz-visco-NPS is validated by measuring the viscoelastic changes of MCF-7 cells when their cytoskeleton is disrupted.

ctDNA responds to neoadjuvant treatment in locally advanced rectal cancer.

Background: Liquid biopsy is a minimally invasive procedure investigating tumor mutations.

Methods: In our retrospective study, we investigated whether molecular therapy monitoring of patients receiving neoadjuvant radio(chemo)therapy on a daily routine is possible in 17 patients with locally advanced rectal cancer. Six patients received short-course radiotherapy (5 × 5 Gy) with subsequent surgery, six patients were treated according RAPIDO protocol with short-course radiotherapy followed by chemotherapy (FOLFOX4) and subsequent surgery and five patients received conventional neoadjuvant radiochemotherapy with 5-FU followed by surgery.

Dynamic changes in extracellular vesicle-associated miRNAs elicited by ultrasound in inflammatory bowel disease patients.

Blood-based biomarkers that reliably indicate disease activity in the intestinal tract are an important unmet need in the management of patients with IBD. Extracellular vesicles (EVs) are cell-derived membranous microparticles, which reflect the cellular and functional state of their site of site of origin. As ultrasound waves may lead to molecular shifts of EV contents, we hypothesized that application of ultrasound waves on inflamed intestinal tissue in IBD may amplify the inflammation-specific molecular shifts in EVs like altered EV-miRNA expression, which in turn can be detected in the peripheral blood.

Oral Health Status of Healthcare Workers in Ilembula/Tanzania during the COVID-19 Condition.

The challenge of reduced dental treatment and education infrastructure in the Tanzanian highlands affects the oral health situation of both the general population and local healthcare workers. The aim of this study was to investigate the oral health status of healthcare workers at Ilembula Lutheran Hospital (ILH), Tanzania, during the COVID-19 pandemic. In total, 134 healthcare workers (62 women, 72 men; mean age 36.

Diagnostic Utility of Artificial Intelligence-assisted Transperineal Biopsy Planning in Prostate Cancer Suspected Men: A Prospective Cohort Study.

Background And Objective: Accurate magnetic resonance imaging (MRI) reporting is essential for transperineal prostate biopsy (TPB) planning. Although approved computer-aided diagnosis (CAD) tools may assist urologists in this task, evidence of improved clinically significant prostate cancer (csPCa) detection is lacking. Therefore, we aimed to document the diagnostic utility of using Prostate Imaging Reporting and Data System (PI-RADS) and CAD for biopsy planning compared with PI-RADS alone.

Reliability and interobserver variability of a grading system of ventricular distension in dogs.

Introduction: Internal hydrocephalus is the most common malformation of the central nervous system in dogs. Although the grades of ventricular distension have importance for long-term prognosis, there is no standard classification scheme describing the grade of the ventricular distension in dogs.

Materials And Methods: Magnetic resonance imaging (MRI) scans from 147 dogs of various breed, sex, skull conformation, and weight were reviewed retrospectively and blinded between three observers.

Selection of cross-reactive T cells by commensal and food-derived yeasts drives cytotoxic T1 cell responses in Crohn's disease.

Aberrant CD4 T cell reactivity against intestinal microorganisms is considered to drive mucosal inflammation in inflammatory bowel diseases. The disease-relevant microbial species and the corresponding microorganism-specific, pathogenic T cell phenotypes remain largely unknown. In the present study, we identified common gut commensal and food-derived yeasts, as direct activators of altered CD4 T cell reactions in patients with Crohn's disease (CD).

S1 Guideline: Impairment of gonadal function After Cancer in Childhood and Adolescence.

A possible negative consequence of cancer treatment is the fertility impairment of young cancer survivors. However, most former patients express the wish to have biological children. Fertility-preserving measures are available and are - under certain circumstances - financed by health insurance.

Cell Line Development Using Targeted Gene Integration into MAR-Rich Landing Pads for Stable Expression of Transgenes.

Integration of a gene of interest (GOI) into the genome of mammalian cells is the first step of cell line development campaigns for the production of biotherapeutics. Besides random integration methods, targeted gene integration approaches have emerged as promising tools over the last few years. In addition to reducing heterogeneity within a pool of recombinant transfectants, this process can also facilitate shorter timelines of the current cell line development process.

A critical spotlight on the paradigms of FFPE-DNA sequencing.

In the late 19th century, formalin fixation with paraffin-embedding (FFPE) of tissues was developed as a fixation and conservation method and is still used to this day in routine clinical and pathological practice. The implementation of state-of-the-art nucleic acid sequencing technologies has sparked much interest for using historical FFPE samples stored in biobanks as they hold promise in extracting new information from these valuable samples. However, formalin fixation chemically modifies DNA, which potentially leads to incorrect sequences or misinterpretations in downstream processing and data analysis.

Cumulative 10-year performance of endodontically treated teeth with prosthetic restorations of base metal alloy double crowns with friction pins-a retrospective study.

Objectives: This 120-month follow-up study aimed to investigate the complication rate of abutment teeth after endodontic pretreatment with base metal alloy double crowns with friction pins.

Materials And Methods: A total of 158 participants (n = 71, 44.9% women) aged 62.

Sustained postconfluent culture of human mammary epithelial cells enriches for luminal and c-Kit+ subtypes.

Background: A challenge in human mammary epithelial cell (HMEC) culture is sustaining the representation of competing luminal, myoepithelial, and progenitor lineages over time. As cells replicate in culture, myoepithelial cells come to dominate the composition of the culture with serial passaging. This drift in composition presents a challenge for studying luminal and progenitor cells, which are prospective cells of origin for most breast cancer subtypes.

Ten-year clinical performance of non-precious metal double crowns with friction pins in severely reduced dentitions-a retrospective study.

Objectives: This follow-up study aimed at collecting long-term data for removable partial dentures (RPDs) retained by double crowns with spark-eroded friction pins (DCP) and comparing them in the presence of severely reduced dentition (SRD) and non-SRD (NSRD, i.e. residual dentition with more than three abutment teeth) after a 10-year wearing period.

An Extremely Rare Cause of an Obstructive Jaundice in Adults: Limited Langerhans Cell Histiocytosis of the Extrahepatic Bile Duct.

Langerhans cell histiocytosis (LCH) is a rare group of idiopathic disorders (previously termed "histiocytosis X") which is characterized by the presence of cells with characteristics similar to bone marrow-derived Langerhans cells which infiltrate various tissues and organs. Like Langerhans cells located in the skin, they express histiocytic markers such as S100, CD1a, and CD68 and contain Birbeck granules, which are rod-shaped intracytoplasmic organelles best demonstrated in electron microscopy. LCH primarily affects the skeleton, but lung, skin, liver, and lymph node involvement may occur alike.

The impact of inosine on hippocampal synaptic transmission and plasticity involves the release of adenosine through equilibrative nucleoside transporters rather than the direct activation of adenosine receptors.

Inosine has robust neuroprotective effects, but it is unclear if inosine acts as direct ligand of adenosine receptors or if it triggers metabolic effects indirectly modifying the activity of adenosine receptors. We now combined radioligand binding studies with electrophysiological recordings in hippocampal slices to test how inosine controls synaptic transmission and plasticity. Inosine was without effect at 30 μM and decreased field excitatory post-synaptic potentials by 14% and 33% at 100 and 300 μM, respectively.

Nitric oxide metabolites: associations with cardiovascular biomarkers and clinical parameters in patients with HFpEF.

Aims: Heart failure with preserved ejection fraction (HFpEF) is one of the most rapidly growing cardiovascular health burden worldwide, but there is still a lack of understanding about the HFpEF pathophysiology. The nitric oxide (NO) signalling pathway has been identified as a potential key element. The aim of our study was to investigate markers of NO metabolism [l-arginine (l-Arg), homoarginine (hArg), and asymmetric and symmetric dimethylarginine (ADMA and SDMA)], additional biomarkers [N-terminal pro-B-type natriuretic peptide (NT-proBNP), endothelin-1 (ET-1), mid-regional pro-adrenomedullin (MR-proADM), copeptin, and high-sensitivity C-reactive protein (hsCRP)], and the endothelial function in an integrated approach focusing on associations with clinical characteristics in patients with HFpEF.

Evaluation of systematic prostate biopsies when performing transperineal MRI/TRUS fusion biopsy with needle tracking-what is the additional value?

Purpose: To evaluate the additional value of systematic biopsies (SB) when performing transperineal MRI/TRUS fusion biopsies (MRI/TRUS TPBx) with needle tracking.

Methods: From January 2019 to March 2021 969 Patients after a MRI/TRUS TPBx were evaluated separately for target biopsies (TB) and systematic biopsies regarding PCa detection and PCa risk evaluation. Needle tracking in the axial sequences of multiparametric MRI was used to assess the localisation of the detected PCa in the biopsy cores related to the reported PI-RADS lesions.

Antibiotic prophylaxis versus no antibiotic prophylaxis in transperineal prostate biopsies (NORAPP): a randomised, open-label, non-inferiority trial.

Background: The benefit of antibiotic prophylaxis is uncertain when performing transperineal prostate biopsies. Judicious use of antibiotics is required as antimicrobial resistance increases worldwide. We aimed to assess whether antibiotic prophylaxis can be omitted when performing transperineal prostate biopsies under local anaesthesia as an outpatient procedure.

Pediatric Cardiac Magnetic Resonance Reference Values for Biventricular Volumes Derived From Different Contouring Techniques.

Background: Measurement of ventricular volumes and function using MRI is an important tool in pediatric congenital heart disease. However, normal values for children are sparce and analysis methods are inconsistent.

Purpose: To propose biventricular reference values in children for two MRI postprocessing (contouring) techniques.

Full-Spectrum InP-Based Quantum Dots with Near-Unity Photoluminescence Quantum Efficiency.

Photoluminescent color conversion by quantum dots (QDs) makes possible the formation of spectrum-on-demand light sources by combining blue LEDs with the light generated by a specific blend of QDs. Such applications, however, require a near-unity photoluminescence quantum efficiency since self-absorption magnifies disproportionally the impact of photon losses on the overall conversion efficiency. Here, we present a synthesis protocol for forming InP-based QDs with +90% quantum efficiency across the full visible spectrum from blue/cyan to red.