Alternative splicing in the DBD linker region of p63 modulates binding to DNA and iASPP in vitro.

The transcription factor p63 is expressed in many different isoforms as a result of differential promoter use and splicing. Some of these isoforms have very specific physiological functions in the development and maintenance of epithelial tissues and surveillance of genetic integrity in oocytes. The ASPP family of proteins is involved in modulating the transcriptional activity of the p53 protein family members, including p63.

Regulatory evolution tuning pigmentation intensity quantitatively in .

Quantitative variation in attributes such as color, texture, or stiffness dominates morphological diversification. It results from combinations of alleles at many Mendelian loci. Here, we identify an additional source of quantitative variation among species, continuous evolution in a gene regulatory region.

A Simple Preoperative Score Predicting Failure Following Decompression Surgery for Degenerative Lumbar Spinal Stenosis.

Background Context: Proper patient selection is crucial for the outcome of surgically treated degenerative lumbar spinal stenosis (DLSS). Nevertheless, there is still not a clear consensus regarding the optimal treatment option for patients with DLSS.

Purpose: To investigate the treatment failure rate and introduce a simple, preoperative score to aid surgical decision-making.

No Difference in Risk of Amputation or Frequency of Surgical Interventions Between Patients With Diabetic and Nondiabetic Charcot Arthropathy.

Background: The cause of Charcot neuro-osteoarthropathy (CN) is diabetes in approximately 75% of patients. Most reports on the clinical course and complications of CN focus on diabetic CN, and reports on nondiabetic CN are scarce. No study, to our knowledge, has compared the clinical course of patients initially treated nonoperatively for diabetic and nondiabetic CN.

Phenotypic Discovery of Triazolo[1,5-]quinazolines as a First-In-Class Bone Morphogenetic Protein Amplifier Chemotype.

Phenotypic drug discovery (PDD) continues to fuel the research and development pipelines with first-in-class therapeutic modalities, but success rates critically depend on the quality of the underlying model system. Here, we employed a stem cell-based approach for the target-agnostic, yet pathway-centric discovery of small-molecule cytokine signaling activators to act as morphogens during development and regeneration. Unbiased screening identified triazolo[1,5-]quinazolines as a new-in-class in vitro and in vivo active amplifier of the bone morphogenetic protein (BMP) pathway.

The effect of lumbar spinal fusion on native acetabular anteinclination in standing position.

Purpose: The complex and dynamic spinopelvic interplay is not well understood. The aims of the present study were to investigate the following: (1) whether native acetabular anteinclination (AI) in standing position changes following lumbar spinal fusion (LSF); (2) potential correlations between AI change (ΔAI) and several spinopelvic parameters such as the change in lumbar lordosis (ΔLL), pelvic tilt (ΔPT), and anterior pelvic plane angle (ΔaPP).

Methods: A total of 485 patients (Males: 262, Females: 223) with an average age of 64 ± 13 years who underwent a primary LSF were identified from our institutional database.

Shoulder arthroplasty for proximal humeral fracture treatment: a retrospective functional outcome analysis.

Purpose: Following proximal humeral fractures hemiarthroplasty (HA) or reversed total shoulder arthroplasty (rTSA) are performed if osteosynthesis or conservative treatment is not possible. HA has been reported to result in decreased functional outcomes compared with rTSA. Secondary shoulder arthroplasty, performed after a different initial treatment, has also been associated with inferior outcomes.

Pelvic fixation in surgical correction of neuromuscular scoliosis.

Background: Surgical correction of neuromuscular scoliosis can be associated with high complication rates, including such associated with pelvic fixation. Up to now it is debated whether and when to include the pelvis into the fusion construct. Therefore, we aimed to illuminate when pelvic fixation is beneficial in surgical correction of neuromuscular scoliosis.

Proximal humeral fracture-dislocation: Outcome analysis in osteosynthesis and arthroplasties.

Purpose: Proximal humeral fracture-dislocations (PHFD) are challenging to treat. In older patients, usually arthroplasty is performed. In younger patients, osteosynthesis is chosen.

Dynamic Changes of Circulating Tumor DNA Predict Clinical Outcome in Patients With Advanced Non-Small-Cell Lung Cancer Treated With Immune Checkpoint Inhibitors.

Purpose: Immune checkpoint inhibitors (ICIs) are increasingly being used in non-small-cell lung cancer (NSCLC), yet biomarkers predicting their benefit are lacking. We evaluated if on-treatment changes of circulating tumor DNA (ctDNA) from ICI start (t) to after two cycles (t) assessed with a commercial panel could identify patients with NSCLC who would benefit from ICI.

Patients And Methods: The molecular ctDNA response was evaluated as a predictor of radiographic tumor response and long-term survival benefit of ICI.

Persistence of ctDNA in Patients with Breast Cancer During Neoadjuvant Treatment Is a Significant Predictor of Poor Tumor Response.

Purpose: Accurate response assessment during neoadjuvant systemic treatment (NST) poses a clinical challenge. Therefore, a minimally invasive assessment of tumor response based on cell-free circulating tumor DNA (ctDNA) may be beneficial to guide treatment decisions.

Experimental Design: We profiled 93 genes in tissue from 193 patients with early breast cancer.

Lumbar spinal fusion does not increase early dislocation risk in primary total hip arthroplasty through the direct anterior approach.

Introduction: Patients with total hip arthroplasty (THA) and a concomitant lumbar spinal fusion (LSF) might have an increased incidence of revision surgery and postoperative complications such as early THA dislocation. The direct anterior approach (DAA) has gained popularity in THA due to its soft tissue-preserving nature and the relatively low dislocation risk. The purpose of the present study was to examine whether LSF patients undergoing minimally invasive THA through the DAA might have an increased risk of prosthetic-related complications compared to matched-control patients without a LSF.

Somatic Copy-Number Alterations in Plasma Circulating Tumor DNA from Advanced EGFR-Mutated Lung Adenocarcinoma Patients.

Background: To assess the clinical relevance of genome-wide somatic copy-number alterations (SCNAs) in plasma circulating tumor DNA (ctDNA) from advanced epidermal growth factor receptor ()-mutated lung adenocarcinoma patients.

Methods: We included 43 patients with advanced T790M-positive lung adenocarcinoma who were treated with osimertinib after progression under previous EGFR-TKI therapy. We performed genomic profiling of ctDNA in plasma samples from each patient obtained pre-osimertinib and after patients developed resistance to osimertinib.

A case series of a rare tendon rupture.

The distal triceps tendon rupture is a rare finding. Only 1% of tendon ruptures are related to it. The triceps brachii muscle has three parts.

On-treatment measurements of circulating tumor DNA during FOLFOX therapy in patients with colorectal cancer.

We addressed a significant unknown feature of circulating tumor DNA (ctDNA), i.e., how ctDNA levels change during chemotherapy, by serially monitoring ctDNA in patients with colorectal cancer during the 48-h application of FOLFOX.

Haemophilus haemolyticus: an atypical pathogen of septic arthritis of the knee joint.

Septic knee arthritis is a common disease, mostly due to bacterial infections. We describe a rare case of Haemophilus haemolyticus causing unilateral septic arthritis of a native knee. The affected patient presented with persistent severe knee pain after repeated intra-articular injections.

Comparison of three commercial decision support platforms for matching of next-generation sequencing results with therapies in patients with cancer.

Objective: Precision oncology depends on translating molecular data into therapy recommendations. However, with the growing complexity of next-generation sequencing-based tests, clinical interpretation of somatic genomic mutations has evolved into a formidable task. Here, we compared the performance of three commercial clinical decision support tools, that is, NAVIFY Mutation Profiler (NAVIFY; Roche), QIAGEN Clinical Insight (QCI) Interpret (QIAGEN) and CureMatch Bionov (CureMatch).

Bio-Derived Apatite As a Bone Graft for Vertebral Trauma.

Introduction: Traumatic spinal injury presents the potential for significant morbidity and mortality, and posterior fixation and fusion with bone grafts is a primary treatment for many vertebral fractures. While iliac crest autograft (ICBG) is considered the gold standard in bone grafting, this carries risks of morbidity at the donor site as well as prolonging surgery time. Bone graft substitutes (BGS) may provide a viable alternative to autograft but there is little published data concerning its use in trauma.

Technical Evaluation of Commercial Mutation Analysis Platforms and Reference Materials for Liquid Biopsy Profiling.

Molecular profiling from liquid biopsy, in particular cell-free DNA (cfDNA), represents an attractive alternative to tissue biopsies for the detection of actionable targets and tumor monitoring. In addition to PCR-based assays, Next Generation Sequencing (NGS)-based cfDNA assays are now commercially available and are being increasingly adopted in clinical practice. However, the validity of these products as well as the clinical utility of cfDNA in the management of patients with cancer has yet to be proven.

Multicenter Evaluation of Circulating Cell-Free DNA Extraction and Downstream Analyses for the Development of Standardized (Pre)analytical Work Flows.

Background: In cancer patients, circulating cell-free DNA (ccfDNA) can contain tumor-derived DNA (ctDNA), which enables noninvasive diagnosis, real-time monitoring, and treatment susceptibility testing. However, ctDNA fractions are highly variable, which challenges downstream applications. Therefore, established preanalytical work flows in combination with cost-efficient and reproducible reference materials for ccfDNA analyses are crucial for analytical validity and subsequently for clinical decision-making.

Expression of adiponectin receptors in the brain of adult zebrafish and mouse: Links with neurogenic niches and brain repair.

Adiponectin and its receptors (adipor) have been initially characterized for their role in lipid and glucose metabolism. More recently, adiponectin signaling was shown to display anti-inflammatory effects and to participate in brain homeostasis and neuroprotection. In this study, we investigated adipor gene expression and its regulation under inflammatory conditions in two complementary models: mouse and zebrafish.

Single tube liquid biopsy for advanced non-small cell lung cancer.

The need for a liquid biopsy in non-small cell lung cancer (NSCLC) patients is rapidly increasing. We studied the relation between overall survival (OS) and the presence of four cancer biomarkers from a single blood draw in advanced NSCLC patients: EpCAM circulating tumor cells (CTC), EpCAM CTC, tumor-derived extracellular vesicles (tdEV) and cell-free circulating tumor DNA (ctDNA). EpCAM CTC were detected with CellSearch, tdEV in the CellSearch images and EpCAM CTC with filtration after CellSearch.

Itraconazole-loaded nanostructured lipid carriers (NLC) for pulmonary treatment of aspergillosis in falcons.

Aspergillosis is the most common and most lethal disease in captive falcons, which is most effectively treated with the poorly soluble drug Itraconazole. To obtain a high drug concentration at the side of infection, the falcon's respiratory system, an isotonic, sterile, non-toxic NLC formulation loaded with Itraconazole was developed for pulmonary application. Itraconazole-loaded NLC had a particle size well in the nanometer range and possessed a narrow particle size distribution.

Filopodia-based Wnt transport during vertebrate tissue patterning.

Paracrine Wnt/β-catenin signalling is important during developmental processes, tissue regeneration and stem cell regulation. Wnt proteins are morphogens, which form concentration gradients across responsive tissues. Little is known about the transport mechanism for these lipid-modified signalling proteins in vertebrates.

In vivo analysis of formation and endocytosis of the Wnt/β-catenin signaling complex in zebrafish embryos.

After activation by Wnt/β-Catenin ligands, a multi-protein complex assembles at the plasma membrane as membrane-bound receptors and intracellular signal transducers are clustered into the so-called Lrp6-signalosome [Corrected]. However, the mechanism of signalosome formation and dissolution is yet not clear. Our imaging studies of live zebrafish embryos show that the signalosome is a highly dynamic structure.