Moderate levels of folic acid benefit outcomes for cilia based neural tube defects.

Folic acid (FA) supplementation is a potent tool to reduce devastating birth defects known as neural tube defects (NTDs). Though effective, questions remain how FA achieves its protective effect and which gene mutations are sensitive to folic acid levels. We explore the relationship between FA dosage and NTD rates using NTD mouse models.

Accessing Therapeutically-Relevant Multifunctional Antisense Oligonucleotide Conjugates Using Native Chemical Ligation.

Antisense oligonucleotide (ASO) therapies hold significant promise in the realm of molecular medicine. By precisely targeting RNA molecules, ASOs offer an approach to modulate gene expression and protein production, making them valuable tools for treating a wide range of genetic and acquired diseases. As the precise intracellular targeting and delivery of ASOs is challenging, strategies for preparing ASO-ligand conjugates are in exceedingly high demand.

Internet Access and Use by Patients with Gynecologic Malignancies: A Cross-Sectional Study.

The influence of digitalization on information-seeking, decision-making properties of patients, therapy monitoring, and patient-physician interactions has and will change the global health sector tremendously. With this study, we add knowledge on the degree of digitalization, digital device availability, the use and availability of home and mobile internet access, and the willingness to use novel forms of patient-physician interactions in a group of gynecologic cancer patients. From July 2017 to March 2022, 150 women with a diagnosis of gynecologic malignancy at the University Hospital of Cologne participated in this questionnaire-based cohort study.

RSG1 is required for cilia-dependent neural tube closure.

Cilia play a key role in the regulation of signaling pathways required for embryonic development, including the proper formation of the neural tube, the precursor to the brain and spinal cord. Forward genetic screens were used to generate mouse lines that display neural tube defects (NTD) and secondary phenotypes useful in interrogating function. We describe here the L3P mutant line that displays phenotypes of disrupted Sonic hedgehog signaling and affects the initiation of cilia formation.

Dimethyl sulfoxide as a novel therapy in a murine model of acute lung injury.

Introduction: The endothelial glycocalyx on the luminal surface of endothelial cells contributes to the permeability barrier of the pulmonary vasculature. Dimethyl sulfoxide (DMSO) has a disordering effect on plasma membranes, which prevents the formation of ordered membrane domains important in the shedding of the endothelial glycocalyx. We hypothesized that DMSO would protect against protein leak by preserving the endothelial glycocalyx in a murine model of acute respiratory distress syndrome (ARDS).

Short- and Long-Term Outcomes of Patients with Postoperative Arrhythmia after Liver Surgery.

Background: New-onset postoperative arrhythmia (PA) has previously been described as a pivotal risk factor for postoperative morbidity and mortality after visceral surgery. However, there is a lack of data concerning liver surgery. The incidence and impact of new-onset postoperative arrhythmia after liver surgery was, therefore, analyzed in a monocentric study.

Dimethyl malonate protects the lung in a murine model of acute respiratory distress syndrome.

Background: Succinate is a proinflammatory citric acid cycle metabolite that accumulates in tissues during pathophysiological states. Oxidation of succinate after ischemia-reperfusion leads to reversal of the electron transport chain and generation of reactive oxygen species. Dimethyl malonate (DMM) is a competitive inhibitor of succinate dehydrogenase, which has been shown to reduce succinate accumulation.

Genomic virulence features of Beauveria bassiana as a biocontrol agent for the mountain pine beetle population.

Background: The mountain pine beetle, Dendroctonus ponderosae, is an irruptive bark beetle that causes extensive mortality to many pine species within the forests of western North America. Driven by climate change and wildfire suppression, a recent mountain pine beetle (MPB) outbreak has spread across more than 18 million hectares, including areas to the east of the Rocky Mountains that comprise populations and species of pines not previously affected. Despite its impacts, there are few tactics available to control MPB populations.

Succinate metabolism and membrane reorganization drives the endotheliopathy and coagulopathy of traumatic hemorrhage.

Acute hemorrhage commonly leads to coagulopathy and organ dysfunction or failure. Recent evidence suggests that damage to the endothelial glycocalyx contributes to these adverse outcomes. The physiological events mediating acute glycocalyx shedding are undefined, however.

Single-cell heterogeneity of EGFR and CDK4 co-amplification is linked to immune infiltration in glioblastoma.

Glioblastoma (GBM) is the most aggressive brain tumor, with a median survival of ∼15 months. Targeted approaches have not been successful in this tumor type due to the large extent of intratumor heterogeneity. Mosaic amplification of oncogenes suggests that multiple genetically distinct clones are present in each tumor.

The HLA ligandome of oropharyngeal squamous cell carcinomas reveals shared tumour-exclusive peptides for semi-personalised vaccination.

Background: The immune peptidome of OPSCC has not previously been studied. Cancer-antigen specific vaccination may improve clinical outcome and efficacy of immune checkpoint inhibitors such as PD1/PD-L1 antibodies.

Methods: Mapping of the OPSCC HLA ligandome was performed by mass spectrometry (MS) based analysis of naturally presented HLA ligands isolated from tumour tissue samples (n = 40) using immunoaffinity purification.

Incidence and impact of new-onset postoperative arrhythmia after surgery of the lower gastrointestinal tract.

Postoperative arrhythmias (PAs) are common events and have been widely investigated in cardiothoracic surgery. Within visceral surgery, a recent study revealed a significant occurrence of PA in esophageal resections. In contrast, PA in lower gastrointestinal surgery is rarely investigated and has been rudimentary described in the medical literature.

Treatment dependent impact of plasma-derived exosomes from head and neck cancer patients on the epithelial-to-mesenchymal transition.

Background: Epithelial to mesenchymal transition (EMT) is a key process in carcinogenesis of head and neck squamous cell carcinoma (HNSCC), contributing to tumor invasiveness, distant metastasis, and recurrence. Exosomes are known mediators and regulators of EMT. Here, we analyze the impact of exosomes that were primed by conventional therapy on EMT modulation.

Ring-opening reactions for the solid-phase synthesis of nisin lipopeptide analogues.

Three lipopeptide analogues of the lantibiotic nisin A have been synthesised on-resin using Fmoc-SPPS techniques to investigate the structure-activity relationship of the A and B ring of these types of lanthipeptides. Lanthionine and methyllanthionine macrocycles were incorporated using orthogonally protected residues for on-resin cyclisation. Unsaturated dehydroalanine and, for the first time, dehydrobutyrine were synthesised on-resin from their cysteine derivatives.

[Traumatology of the nose].

Isolated nasal bone fractures are the most common injuries of the central midface. They can be divided into different fracture types, depending on the exposure and orientation of violence. It is essential to ensure that there is no septal hematoma or abscess, which would require an emergency surgical intervention.

Cargo and Functional Profile of Saliva-Derived Exosomes Reveal Biomarkers Specific for Head and Neck Cancer.

Background: Exosomes contribute to immunosuppression in head and neck squamous cell carcinoma (HNSCC), a tumor entity which lacks specific tumor biomarkers. Plasma-derived exosomes from HNSCC patients correlate with clinical parameters and have potential as liquid biopsy. Here, we investigate the cargo and functional profile of saliva-derived exosomes from HNSCC patients and their potential as non-invasive biomarkers for disease detection and immunomodulation.

Incidence, Associated Risk Factors, and Outcomes of Postoperative Arrhythmia After Upper Gastrointestinal Surgery.

Importance: New-onset postoperative arrhythmia, which most often presents as postoperative atrial fibrillation (AF), is a frequent complication in patients undergoing visceral surgery of the upper gastrointestinal tract. Its relevance for patients' outcomes is unknown.

Objective: To assess the incidence of arrhythmia after upper gastrointestinal surgery, its risk factors, and its short- and long-term implications for patient outcomes.

Pathogenesis of neural tube defects: The regulation and disruption of cellular processes underlying neural tube closure.

Neural tube closure (NTC) is crucial for proper development of the brain and spinal cord and requires precise morphogenesis from a sheet of cells to an intact three-dimensional structure. NTC is dependent on successful regulation of hundreds of genes, a myriad of signaling pathways, concentration gradients, and is influenced by epigenetic and environmental cues. Failure of NTC is termed a neural tube defect (NTD) and is a leading class of congenital defects in the United States and worldwide.

Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation.

The loci are closely linked to the gene. Mismatches in these loci occur with a frequency of about 8%-12% in otherwise 10/10 HLA-matched transplant pairs. There is preliminary evidence that these disparities may associate with increased acute graft-versus-host disease (GvHD) rates.

Digital Technical and Informal Resources of Breast Cancer Patients From 2012 to 2020: Questionnaire-Based Longitudinal Trend Study.

Background: Digitalization offers enormous potential in medicine. In the era of digitalization, the development of the use of digital, technical, and informal resources of breast cancer patients and factors influencing the degree of digitization of patients has been insufficiently researched.

Objective: The aim of this study was to assess the development of the use of digital technical and informal resources in a well-defined patient cohort.

Methylene Analogues of Neopetrosiamide as Potential Antimetastatic Agents: Solid-Supported Syntheses Using Diamino Diacids for Pre-Stapling of Peptides with Multiple Disulfides.

Neopetrosiamide, a 28-residue peptide from sp., contains three disulfide bonds and hinders mammalian tumor cell invasion. Proper connectivity of disulfide bonds is crucial for activity.

Evaluating mental illness-substance abuse stigmatic perceptions through education: A library-nursing initiative.

In this library-nursing initiative, the goal was to identify any changes in stigmatic perceptions among public library staff regarding mental health and substance abuse, post 3-day educational sessions. A total of n = 37 library staff participated in this project and attended all three educational sessions and completed a pre- and postquestionnaire designed to address common mental health and substance abuse-related stigmatic perceptions among public library staff. Upon analysis of the pre- and postresponses, we identified that there were statistically significant changes in two perceptions, namely; "embarrassed to disclose mental illness" and "commonality of substance abuse" (p ≤ .

Immune-Stimulatory Effects of Curcumin on the Tumor Microenvironment in Head and Neck Squamous Cell Carcinoma.

Curcumin is known to have immune-modulatory and antitumor effects by interacting with more than 30 different proteins. An important feature of curcumin is the inhibition of nuclear factor kappa of activated B-cells (NF-κB). Here, we evaluate the potential of curcumin to reverse the epithelial to mesenchymal transition (EMT) of head and neck squamous cell carcinoma (HNSCC) cells as a part of tumor escape mechanisms.

A Quantitative Paradigm for Decision-Making in Precision Oncology.

The complexity and variability of cancer progression necessitate a quantitative paradigm for therapeutic decision-making that is dynamic, personalized, and capable of identifying optimal treatment strategies for individual patients under substantial uncertainty. Here, we discuss the core components and challenges of such an approach and highlight the need for comprehensive longitudinal clinical and molecular data integration in its development. We describe the complementary and varied roles of mathematical modeling and machine learning in constructing dynamic optimal cancer treatment strategies and highlight the potential of reinforcement learning approaches in this endeavor.