Publications by authors named "HOLDEN D"

Purpose: The sphingosine-1-phosphate receptor-1 (S1PR) is involved in regulating responses to neuroimmune stimuli. There is a need for S1PR-specific radioligands with clinically suitable brain pharmcokinetic properties to complement existing radiotracers. This work evaluated a promising S1PR radiotracer, [F]TZ4877, in nonhuman primates.

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Intrathecal nicardipine (ITN) is an investigational therapy for cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH). The objective of this scoping review was to characterize the current state of the literature and map the current available evidence, examine research methodology, clarify key concepts and definitions in the literature, report procedural characteristics, identify and analyze knowledge gaps, and serve as a precursor for future systematic reviews, meta-analyses, and randomized controlled trials. An electronic search for studies on ITN for the treatment of CVS and DCI in patients with aSAH was conducted in accordance with published standards.

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Introduction: Cladribine is a deoxyadenosine analogue that can penetrate the blood-brain barrier. It is used to treat multiple sclerosis (MS). However, the mechanistic understanding of the effect of this highly effective therapy on B cells and plasma cells in the central nervous system compartment is limited.

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Introduction: Cancer multi-disciplinary team meetings (MDTM) assemble clinical experts to make diagnostic and treatment recommendations. MDTMs can take place in person, virtually, or in a hybrid format. Virtual and hybrid MDTMs have been in use for over two decades.

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Recent studies demonstrate the efficacy of B cell-targeting therapies in managing multiple sclerosis (MS) activity, emphasizing the critical role of B cells in MS pathogenesis. CladB study aimed to quantify the temporal changes in peripheral immune cells and their activity over 96 weeks of Cladribine tablets (CladT) treatment in relapsing-remitting MS (RRMS). Ten participants (3 males, 7 females) had blood samples collected at multiple intervals (Day 0, 1, 5, then weekly for 8 weeks, biweekly for up to 24 weeks, and monthly for up to 96 weeks) for immune cell analysis, compared to a historical alemtuzumab-treated cohort.

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Introduction: Acute kidney injury (AKI) following burns is associated with increased mortality and morbidity. Some patients require renal replacement therapy. There is limited large-scale data to sufficiently validate risk factors influencing the incidence and severity of early AKI, defined as AKI within the first 72 h since admission to a burn center following burn injury.

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Thoracic outlet syndrome is a complex syndrome that manifests with symptoms based on the presumed injury or impairment of the neurovascular structures in the thoracic outlet space with its intricate anatomy and pathophysiology. The thoracic outlet is a specific anatomical region with three distinct anatomical spaces - interscalene triangle, the costoclavicular space, and the retro-pectoralis minor space. Thoracic outlet syndrome is classified into neurogenic, venous, and arterial thoracic outlet syndrome and often poses diagnostic challenge to implicate a specific condition or cause.

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Neurofilaments (NFs), major cytoskeletal constituents of neurons, have emerged as universal biomarkers of neuronal injury. Neuroaxonal damage underlies permanent disability in various neurological conditions. It is crucial to accurately quantify and longitudinally monitor this damage to evaluate disease progression, evaluate treatment effectiveness, contribute to novel treatment development, and offer prognostic insights.

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Chemical reactions in micrometer-sized droplets can be accelerated by up to six orders of magnitude. However, this acceleration factor (ratio of rate constants relative to bulk) drops to less than 10 for millimeter-sized droplets due to the reduction in surface/volume ratio. To enhance the acceleration in millimeter-sized droplets, we use a new synthesis platform that directly doses reagent vapor onto the reaction droplet surface from a second levitated droplet.

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Unlabelled: The injectisome encoded by pathogenicity island 2 (SPI-2) had been thought to translocate 28 effectors. Here, we used a proteomic approach to characterize the secretome of a clinical strain of invasive non-typhoidal serovar Enteritidis that had been mutated to cause hyper-secretion of the SPI-2 injectisome effectors. Along with many known effectors, we discovered the novel SseM protein.

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Purpose: The sphingosine-1-phosphate receptor-1 (S1PR) is involved in regulating responses to neuroimmune stimuli. There is a need for S1PR-specific radioligands with clinically suitable brain pharmcokinetic properties to complement existing radiotracers. This work evaluated a promising S1PR radiotracer, [F]TZ4877, in nonhuman primates.

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Charged microdroplets accelerate mineral disintegration.

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On September 20-22 September 2023, the international conference 'Microbiology 2023: from single cell to microbiome and host' convened microbiologists from across the globe for a very successful symposium, showcasing cutting-edge research in the field. Invited lecturers delivered exceptional presentations covering a wide range of topics, with a major emphasis on phages and microbiomes, on the relevant bacteria within these ecosystems, and their multifaceted roles in diverse environments. Discussions also spanned the intricate analysis of fundamental bacterial processes, such as cell division, stress resistance, and interactions with phages.

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Background: Despite increasing evidence that Epstein-Barr virus (EBV) plays a causal role in MS, no treatments have been shown to reduce EBV turnover. We studied the effect of famciclovir on salivary EBV shedding in people with MS (NCT05283551) in a pilot, proof-of-concept study.

Methods: People with MS receiving natalizumab provided weekly saliva samples for 12 weeks before starting famciclovir 500 mg twice daily for 12 weeks.

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Biopolymer analysis, including proteomics and glycomics, relies heavily on the use of mass spectrometry for structural elucidation, including sequence determination. Novel methods to improve sample workup, instrument performance, and data analysis continue to be developed to address shortcomings associated with sample preparation, analysis time, data quality, and data interpretation. Here, we present a new method that couples in-source collision-induced dissociation (IS-CID) with two-dimensional tandem mass spectrometry (2D MS/MS) as a way to simplify proteomics and glycomics workflows while also providing additional insight into analyte structures over traditional MS/MS experiments.

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Per- and polyfluoroalkyl substances (PFAS), nicknamed "forever chemicals" due to the strength of their carbon-fluorine bonds, are a class of potent micropollutants that cause deleterious health effects in mammals. The current state-of-the-art detection method requires the collection and transport of water samples to a centralized facility where chromatography and mass spectrometry are performed for the separation, identification, and quantification of PFAS. However, for efficient remediation efforts to be properly informed, a more rapid in-field testing method is required.

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The sigma-2 receptor (σ2R), recently identified as transmembrane protein 97, is expressed in many cell types and mediates important functions in both the peripheral and central nervous systems. Over the years, σ2R has emerged as a potential therapeutic target for cancer and neurological disorders such as Alzheimer's disease (AD). The currently available σ2R radiotracers have been developed primarily for cancer imaging with limited brain uptake.

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Objectives: Systematic reviews have revealed that up to 50% of patients with brain death have residual hypothalamic/pituitary activity based on the absence of central diabetes insipidus (DI). We hypothesized that different degrees of renal dysfunction may impact the presence of DI in patients with brain death.

Design: Single-center prospective data collection.

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Background: Cladribine is an effective immunotherapy for people with multiple sclerosis (pwMS). Whilst most pwMS do not require re-treatment following standard dosing (two treatment courses), disease activity re-emerges in others. The characteristics of pwMS developing re-emerging disease activity remain incompletely understood.

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Objective: Direct oral anticoagulants (DOACs) are first-line therapy for stroke prevention for 1.4 million atrial fibrillation (AF) patients in the UK. However, the rates of DOAC dosing below evidence-based recommendations are estimated between 9% and 22%.

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Article Synopsis
  • Current methods for treating sporadic Alzheimer's mainly target amyloid beta and tau but overlook the critical issue of calcium dysregulation, which is significant in the disease's earlier stages.
  • The study explores the effects of a GCPII inhibitor, 2-MPPA, on aged macaques to see if it can enhance calcium signaling and reduce tau hyperphosphorylation.
  • Results indicated that 2-MPPA treatment led to lower levels of tau pathology and correlated with cognitive improvements, suggesting that targeting GCPII may be a promising strategy for addressing Alzheimer's-related inflammation.*
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The pathogenicity island 2 (SPI-2)-encoded type III secretion system (injectisome) is assembled following uptake of bacteria into vacuoles in mammalian cells. The injectisome translocates virulence proteins (effectors) into infected cells. Numerous studies have established the requirement for a functional SPI-2 injectisome for growth of Typhimurium in mouse macrophages, but the results of similar studies involving Typhi and human-derived macrophages are not consistent.

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Introduction: The Surviving Sepsis Campaign was developed to improve outcomes for all patients with sepsis. Despite sepsis being the primary cause of death after thermal injury, burns have always been excluded from the Surviving Sepsis efforts. To improve sepsis outcomes in burn patients, an international group of burn experts developed the Surviving Sepsis After Burn Campaign (SSABC) as a testable guideline to improve burn sepsis outcomes.

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Background: Emergent neuroendovascular stenting presents challenges for the utilization of antiplatelet agents.

Methods: This was a multicenter, retrospective cohort of patients who underwent emergent neuroendovascular stenting. The primary endpoints were thrombotic and bleeding events in relation to the timing of antiplatelet administration, route of administration, and choice of intravenous (IV) agent and the study investigated practice variability in antiplatelet utilization.

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Background/aim: NovoSorb Biodegradable Temporizing Matrix (BTM) is a relatively novel, biodegradable polyurethane-based dermal regeneration template. The aim of this study was to evaluate the long-term scarring outcomes and safety of BTM in patients who underwent dermal reconstruction involving ≥5% of the total body surface area.

Methods: This was a postmarket, multicenter, observational cohort study involving evaluation of long-term outcomes in patients treated with BTM.

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