'Without the Data You're Not Going to Know If It's Important or Not': A Mixed Methods Study on What Dysphagia Intervention Outcomes are Important to People with Parkinson's Disease and Family Members.

The lack of patient and public involvement in oropharyngeal dysphagia (OD) intervention studies in Parkinson's disease (PD) can bias the choice of outcomes to be measured in these studies. This study aimed to obtain perspectives of individuals living with OD in PD and family members/caregivers on OD intervention outcomes that are important to them. This is part of a larger Core Outcome Set project.

Epoxytiglianes induce keratinocyte wound healing responses via classical protein kinase C activation to promote skin re-epithelialization.

Epoxytiglianes are a novel class of diterpene esters. The prototype epoxytigliane, EBC-46 (tigilanol tiglate), is a potent anti-cancer agent in clinical development for local treatment of a range of human and animal tumors. EBC-46 also consistently promotes wound re-epithelialization at the treatment sites, mediated via activation of classical protein kinase C (PKC) isoforms.

Alpibectir: Early Qualitative and Quantitative Metabolic Profiling from a First-Time-in-Human Study by Combining F-NMR (Nuclear Magnetic Resonance), H-NMR, and High-Resolution Mass Spectrometric Analyses.

Alpibectir (also known as BVL-GSK098 and GSK3729098) is a new chemical entity (NCE) with a novel mechanism for the treatment of tuberculosis. The disposition of alpibectir was determined in subjects from a first-time-in-human trial after a single oral dose of 40 mg and after 7 days repeat dosing at 30 mg. Here we present a combined approach of F-NMR (nuclear magnetic resonance), H-NMR, and high-resolution mass spectrometry (HRMS) to confidently determine the human metabolic fate of alpibectir.

Tigilanol tiglate is an oncolytic small molecule that induces immunogenic cell death and enhances the response of both target and non-injected tumors to immune checkpoint blockade.

Background: Tigilanol tiglate (TT) is a protein kinase C (PKC)/C1 domain activator currently being developed as an intralesional agent for the treatment of various (sub)cutaneous malignancies. Previous work has shown that intratumoral (I.T.

First-in-human study of alpibectir (BVL-GSK098), a novel potent anti-TB drug.

Background: The clinical candidate alpibectir augments the activity of, and overcomes resistance to, the anti-TB drug ethionamide in vitro and in vivo.

Objectives: A Phase 1, double-blind, randomized, placebo-controlled study to investigate the safety, tolerability, pharmacokinetics (PK) and food effect of alpibectir administered as single and multiple oral doses in healthy volunteers (NCT04654143).

Methods: Eighty participants were randomized.

Pacybara: accurate long-read sequencing for barcoded mutagenized allelic libraries.

Motivation: Long-read sequencing technologies, an attractive solution for many applications, often suffer from higher error rates. Alignment of multiple reads can improve base-calling accuracy, but some applications, e.g.

Development of a Core Outcome Set for Dysphagia Interventions in Parkinson's disease (COS-DIP): study protocol.

Introduction: Current clinical trials on swallowing disorders (dysphagia) in Parkinson's disease (PD) apply a high variety of outcomes and different outcome measures making comparative effectiveness research challenging. Furthermore, views of patients and dysphagia clinicians when selecting trial outcomes have not been considered in the past, thus study results may have little importance to them. This study aims to develop an agreed standardised Core Outcome Set for Dysphagia Interventions in Parkinson's disease (COS-DIP), systematically measured and reported as a minimum for all clinical trials.

-1-Azacubane-2-carboxylic Acid: Derivative Scope and Comparative Biological Evaluation.

The unusual and sterically constrained amino acid, -1-azacubane-2-carboxylic acid, was incorporated into a range of bioactive chemical templates, including enalaprilat, perindoprilat, endomorphin-2 and isoniazid, and subjected to biological testing. The endomorphin-2 derivative displayed increased activity at the δ opioid receptor, but a loss in activity was observed in the other cases, although human normal cell line evaluation suggests limited cytotoxic effects.

G1 length dictates H3K27me3 landscapes.

Stem cells have lower facultative heterochromatin as defined by trimethylation of histone H3 lysine 27 (H3K27me3) compared to differentiated cells. However, the mechanisms underlying these differential H3K27me3 levels remain elusive. Because H3K27me3 levels are diluted two-fold in every round of replication and then restored through the rest of the cell cycle, we reasoned that the cell cycle length could be a key regulator of total H3K27me3 levels.

Uncertain benefit of statins in pediatric heart transplant recipients: A PHTS analysis.

Background: Cardiac allograft vasculopathy (CAV) is a leading cause of graft failure in pediatric heart transplant recipients (HTRs). Early statin use has been shown to reduce CAV incidence and all-cause mortality in adult HTRs. We sought to evaluate the contemporary prevalence and trends of statin use in pediatric HTRs and the association between statin use with CAV development and graft failure.

Development of an murine model of perineural invasion and spread of cutaneous squamous cell carcinoma of the head and neck.

Introduction: Cutaneous squamous cell carcinoma of the head and neck (cSCCHN) can metastasize by invading nerves and spread toward the central nervous system. This metastatic process is called perineural invasion (PNI) and spread (PNS). An sciatic nerve mouse model is used for cSCCHN PNI/PNS.

Boltzmann's equation at 150: Traditional and modern solution techniques for charged particles in neutral gases.

Seminal gas discharge experiments of the late 19th and early 20th centuries laid the foundations of modern physics, and the influence of this "golden era" continues to resonate well into the 21st century through modern technologies, medical applications, and fundamental scientific investigations. Key to this continuing success story has been the kinetic equation formulated by Ludwig Boltzmann in 1872, which provides the theoretical foundations necessary for analyzing such highly non-equilibrium situations. However, as discussed here, the full potential of Boltzmann's equation has been realized only in the past 50 years or so, with modern computing power and analytical techniques facilitating accurate solutions for various types of charged particles (ions, electrons, positrons, and muons) in gases.

Therapeutic targeting of anoikis resistance in cutaneous melanoma metastasis.

The acquisition of resistance to anoikis, the cell death induced by loss of adhesion to the extracellular matrix, is an absolute requirement for the survival of disseminating and circulating tumour cells (CTCs), and for the seeding of metastatic lesions. In melanoma, a range of intracellular signalling cascades have been identified as potential drivers of anoikis resistance, however a full understanding of the process is yet to be attained. Mechanisms of anoikis resistance pose an attractive target for the therapeutic treatment of disseminating and circulating melanoma cells.

Exploring Mycosporine-like Amino Acid UV-Absorbing Natural Products for a New Generation of Environmentally Friendly Sunscreens.

Human skin needs additional protection from damaging ultraviolet radiation (UVR: 280-400 nm). Harmful UVR exposure leads to DNA damage and the development of skin cancer. Available sunscreens offer chemical protection from detrimental sun radiation to a certain extent.

Expanding the muscle imaging spectrum in dysferlinopathy: description of an outlier population from the classical MRI pattern.

Dysferlinopathy is a muscle disease characterized by a variable clinical presentation and is caused by mutations in the DYSF gene. The Jain Clinical Outcome Study for Dysferlinopathy (COS) followed the largest cohort of patients (n=187) with genetically confirmed dysferlinopathy throughout a three-year natural history study, in which the patients underwent muscle function tests and muscle magnetic resonance imaging (MRI). We previously described the pattern of muscle pathology in this population and established a series of imaging criteria for diagnosis.

Pacybara: Accurate long-read sequencing for barcoded mutagenized allelic libraries.

Long read sequencing technologies, an attractive solution for many applications, often suffer from higher error rates. Alignment of multiple reads can improve base-calling accuracy, but some applications, e.g.

-Pregnane Glycosides from Australian Caustic Vine ( subsp. ).

subsp. , more commonly known as caustic vine, is a leafless succulent that grows in the northern arid zone of Australia. Toxicity toward livestock has been reported for this species, along with use in traditional medicine and its potential anticancer activity.

Remotely Delivered Cardiac Rehabilitation Exercise for Coronary Heart Disease: Nonrandomized Feasibility Study.

Background: Exercise-based cardiac rehabilitation (CR) is recommended for coronary heart disease (CHD). However, poor uptake of and poor adherence to CR exercise programs have been reported globally. Delivering CR exercise classes remotely may remove some of the barriers associated with traditional hospital- or center-based CR.

Nursing Workforce Optimization Study: A Multi-method Evaluation and Process Improvement Intervention for HIV Service Delivery in Tanzania and Zambia.

Nurses are often suboptimally used in HIV care, due to misalignment of training and practice, workflow inefficiencies, and management challenges. We sought to understand nursing workforce capacity and support implementation of process improvement strategies to improve efficiency of HIV service delivery in Tanzania and Zambia. We conducted time and motion observations and task analyses at 16 facilities followed by process improvement workshops.

SNCA genetic lowering reveals differential cognitive function of alpha-synuclein dependent on sex.

Antisense oligonucleotide (ASO) therapy for neurological disease has been successful in clinical settings and its potential has generated hope for Alzheimer's disease (AD). We previously described that ablating SNCA encoding for α-synuclein (αSyn) in a mouse model of AD was beneficial. Here, we sought to demonstrate whether transient reduction of αSyn expression using ASO could be therapeutic in a mouse model of AD.

Cytokine/Chemokine assessment as a complementary diagnostic tool for inflammatory skin diseases.

Inflammatory skin conditions are the 4 leading cause of non-fatal health burden in the general population worldwide. The diagnosis of skin lesions due to systemic drug reactions, viral or bacterial exanthems, or in patients with psoriasis, atopic dermatitis or contact dermatitis is often difficult and relies heavily upon conventional histopathologic examination. Conversely, it is widely accepted that the cutaneous profile of inflammatory markers, or 'inflammatory signature', is differentially expressed in various skin conditions.