Experience of primary dental care teams in managing the oral health of oncology patients.

Background: Estimates suggest that one in two people will experience cancer in their lifetime. Cancer and the treatment of cancer can have several impacts on oral health. It is therefore important that dental teams are supported in managing this group of patients especially in primary care dental settings, where most of these patients will first present to dental services.

Targeted protein degradation of PDE4 shortforms by a novel proteolysis targeting chimera.

Cyclic AMP (cAMP) has a crucial role in many vital cellular processes and there has been much effort expended in the discovery of inhibitors against the enzyme superfamily that degrades this second messenger, namely phosphodiesterases (PDEs). The journey of competitive PDE inhibitors to the clinic has been hampered by side effects profiles that have resulted from a lack of selectivity for subfamilies and individual isoforms because of high conservation of catalytic site sequences and structures. Here we introduce a proteolysis targeting chimera (PROTAC) that can specifically target a small subset of isoforms from the PDE4 family to send the enzyme for degradation at the proteasome by recruiting a ubiquitin E3 ligase into proximity with the PDE.

A postdoctoral training program in bioimage analysis.

We herein describe a postdoctoral training program designed to train biologists with microscopy experience in bioimage analysis. We detail the rationale behind the program, the various components of the training program, and outcomes in terms of works produced and the career effects on past participants. We analyze the results of an anonymous survey distributed to past and present participants, indicating overall high value of all 12 rated aspects of the program, but significant heterogeneity in which aspects were most important to each participant.

Effectiveness of intracuff alkalinized lidocaine associated with intravenous dexamethasone in reducing laryngotracheal morbidity in children undergoing general anesthesia for tonsillectomy: a randomized controlled trial.

Background: Postoperative sore throat is one of the main postoperative complaints in patients undergoing tonsillectomy. As the primary outcome, we aimed to determine whether endotracheal tube cuffs filled with alkalinized lidocaine are associated with a lower incidence of postoperative sore throat and anesthesia emergence phenomena in children undergoing tonsillectomy or adenotonsillectomy. We also assessed the potential additional benefits of IV dexamethasone in reducing postoperative laryngotracheal morbidity.

NKCC1 inhibition reduces periaxonal swelling, increases white matter sparing, and improves neurological recovery after contusive SCI.

Ultrastructural studies of contusive spinal cord injury (SCI) in mammals have shown that the most prominent acute changes in white matter are periaxonal swelling and separation of myelin away from their axon, axonal swelling, and axonal spheroid formation. However, the underlying cellular and molecular mechanisms that cause periaxonal swelling and the functional consequences are poorly understood. We hypothesized that periaxonal swelling and loss of connectivity between the axo-myelinic interface impedes neurological recovery by disrupting conduction velocity, and glial to axonal trophic support resulting in axonal swelling and spheroid formation.

Piximi - An Images to Discovery web tool for bioimages and beyond.

Deep learning has greatly accelerated research in biological image analysis yet it often requires programming skills and specialized tool installation. Here we present Piximi, a modern, no-programming image analysis tool leveraging deep learning. Implemented as a web application at Piximi.

Sustainable oral healthcare: what is it and how do we achieve it?

In recent years, there has been an increase in interest in what environmental sustainability means for healthcare, including oral health and dentistry. To help facilitate discussions among key stakeholders in this area, the Scottish Dental Clinical Effectiveness Programme held a workshop in November 2022. The purpose of this workshop was to explore current thinking on the subject of sustainability as it relates to oral health and to help stakeholders identify how to engage with the sustainability agenda.

A Postdoctoral Training Program in Bioimage Analysis.

We herein describe a postdoctoral training program designed to train biologists with microscopy experience in bioimage analysis. We detail the rationale behind the program, the various components of the training program, and outcomes in terms of works produced and the career effects on past participants. We analyze the results of an anonymous survey distributed to past and present participants, indicating overall high value of all 12 rated aspects of the program, but significant heterogeneity in which aspects were most important to each participant.

Optimizing a linear 'Doggybone' DNA vaccine for influenza virus through the incorporation of DNA targeting sequences and neuraminidase antigen.

Influenza virus represents a challenge for traditional vaccine approaches due to its seasonal changes and potential for zoonotic transmission. Nucleic acid vaccines can overcome some of these challenges, especially through the inclusion of multiple antigens to increase the breadth of response. RNA vaccines were an important part of the response to the COVID-19 pandemic, but for future outbreaks DNA vaccines may have some advantages in terms of stability and manufacturing cost that warrant continuing investigation to fully realize their potential.

Citizen science to improve patient and public involvement in GUideline Implementation in oral health and DEntistry (the GUIDE platform).

Background: Citizen science is a way to democratise science by involving groups of citizens in the research process. Clinical guidelines are used to improve practice, but their implementation can be limited. Involving patients and the public can enhance guideline implementation, but there is uncertainty about the best approaches to achieve this.

Reducing cell intrinsic immunity to mRNA vaccine alters adaptive immune responses in mice.

The response to mRNA vaccines needs to be sufficient for immune cell activation and recruitment, but moderate enough to ensure efficacious antigen expression. The choice of the cap structure and use of N1-methylpseudouridine (m1Ψ) instead of uridine, which have been shown to reduce RNA sensing by the cellular innate immune system, has led to improved efficacy of mRNA vaccine platforms. Understanding how RNA modifications influence the cell intrinsic immune response may help in the development of more effective mRNA vaccines.

High-content microscopy reveals a morphological signature of bortezomib resistance.

Drug resistance is a challenge in anticancer therapy. In many cases, cancers can be resistant to the drug prior to exposure, that is, possess intrinsic drug resistance. However, we lack target-independent methods to anticipate resistance in cancer cell lines or characterize intrinsic drug resistance without a priori knowledge of its cause.

CellProfiler plugins - An easy image analysis platform integration for containers and Python tools.

CellProfiler is a widely used software for creating reproducible, reusable image analysis workflows without needing to code. In addition to the >90 modules that make up the main CellProfiler program, CellProfiler has a plugins system that allows for the creation of new modules which integrate with other Python tools or tools that are packaged in software containers. The CellProfiler-plugins repository contains a number of these CellProfiler modules, especially modules that are experimental and/or dependency-heavy.

CellProfiler plugins -- an easy image analysis platform integration for containers and Python tools.

CellProfiler is a widely used software for creating reproducible, reusable image analysis workflows without needing to code. In addition to the >90 modules that make up the main CellProfiler program, CellProfiler has a plugins system that allows for the creation of new modules which integrate with other Python tools or tools that are packaged in software containers. The CellProfiler-plugins repository contains a number of these CellProfiler modules, especially modules that are experimental and/or dependency-heavy.

Discovering cellular programs of intrinsic and extrinsic drivers of metabolic traits using LipocyteProfiler.

A primary obstacle in translating genetic associations with disease into therapeutic strategies is elucidating the cellular programs affected by genetic risk variants and effector genes. Here, we introduce LipocyteProfiler, a cardiometabolic-disease-oriented high-content image-based profiling tool that enables evaluation of thousands of morphological and cellular profiles that can be systematically linked to genes and genetic variants relevant to cardiometabolic disease. We show that LipocyteProfiler allows surveillance of diverse cellular programs by generating rich context- and process-specific cellular profiles across hepatocyte and adipocyte cell-state transitions.

Ca-induced myelin pathology precedes axonal spheroid formation and is mediated in part by store-operated Ca entry after spinal cord injury.

The formation of axonal spheroid is a common feature following spinal cord injury. To further understand the source of Ca that mediates axonal spheroid formation, we used our previously characterized ex vivo mouse spinal cord model that allows precise perturbation of extracellular Ca. We performed two-photon excitation imaging of spinal cords isolated from Thy1 transgenic mice and applied the lipophilic dye, Nile red, to record dynamic changes in dorsal column axons and their myelin sheaths respectively.

OME-Zarr: a cloud-optimized bioimaging file format with international community support.

A growing community is constructing a next-generation file format (NGFF) for bioimaging to overcome problems of scalability and heterogeneity. Organized by the Open Microscopy Environment (OME), individuals and institutes across diverse modalities facing these problems have designed a format specification process (OME-NGFF) to address these needs. This paper brings together a wide range of those community members to describe the cloud-optimized format itself-OME-Zarr-along with tools and data resources available today to increase FAIR access and remove barriers in the scientific process.

High-content microscopy reveals a morphological signature of bortezomib resistance.

Drug resistance is a challenge in anticancer therapy, particularly with targeted therapeutics and cytotoxic compounds. In many cases, cancers can be resistant to the drug prior to exposure, i.e.

Systematic Review of Tumor Segmentation Strategies for Bone Metastases.

Purpose: To investigate the segmentation approaches for bone metastases in differentiating benign from malignant bone lesions and characterizing malignant bone lesions.

Method: The literature search was conducted in Scopus, PubMed, IEEE and MedLine, and Web of Science electronic databases following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of 77 original articles, 24 review articles, and 1 comparison paper published between January 2010 and March 2022 were included in the review.

OME-Zarr: a cloud-optimized bioimaging file format with international community support.

A growing community is constructing a next-generation file format (NGFF) for bioimaging to overcome problems of scalability and heterogeneity. Organized by the Open Microscopy Environment (OME), individuals and institutes across diverse modalities facing these problems have designed a format specification process (OME-NGFF) to address these needs. This paper brings together a wide range of those community members to describe the cloud-optimized format itself -- OME-Zarr -- along with tools and data resources available today to increase FAIR access and remove barriers in the scientific process.

The practices and beliefs of dental professionals regarding the management of patients taking anticoagulant and antiplatelet drugs.

Aim: This study aimed to inform the implementation of the updated Scottish Dental Clinical Effectiveness Programme (SDCEP) guidance, 'Management of Dental Patients taking Anticoagulant or Antiplatelet Drugs', and to determine training needs by investigating dental professionals' current practice and beliefs regarding management of patients taking these medications.

Methods: Dental professionals were recruited via the NHS Education for Scotland Portal. The online questionnaire collected demographic information, data on current practice and information about beliefs regarding behaviours related to the management of patients on anticoagulant or antiplatelet medication.

Formulation, inflammation, and RNA sensing impact the immunogenicity of self-amplifying RNA vaccines.

To be effective, RNA vaccines require both translation and the induction of an immune response to recruit cells to the site of immunization. These factors can pull in opposite directions with the inflammation reducing expression of the vaccine antigen. We investigated how formulation affects the acute systemic cytokine response to a self-amplifying RNA (saRNA) vaccine.

Direct Ryanodine Receptor-2 Knockout in Primary Afferent Fibers Modestly Affects Neurological Recovery after Contusive Spinal Cord Injury.

Neuronal ryanodine receptors (RyR) release calcium from internal stores and play a key role in synaptic plasticity, learning, and memory. Dysregulation of RyR function contributes to neurodegeneration and negatively impacts neurological recovery after spinal cord injury (SCI). However, the individual role of RyR isoforms and the underlying mechanisms remain poorly understood.

Potential physiological and pathological roles for axonal ryanodine receptors.

Clinical disability following trauma or disease to the spinal cord often involves the loss of vital white matter elements including axons and glia. Although excessive Ca is an established driver of axonal degeneration, therapeutically targeting externally sourced Ca to date has had limited success in both basic and clinical studies. Contributing factors that may underlie this limited success include the complexity of the many potential sources of Ca entry and the discovery that axons also contain substantial amounts of stored Ca that if inappropriately released could contribute to axonal demise.