Publications by authors named "Thomas Whittaker"

The United States (US) is experiencing a maternal health crisis, with high rates of maternal morbidity and mortality. The US has the highest rates of pregnancy-related mortality among industrialized nations. Maternal mortality has more than quadrupled over the last decades.

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Geometries that replicate the behavior of metal nanostructures at much lower frequencies via texturing surfaces so they will support a surface wave have been a central pillar of metamaterials research. However, previous work has focused largely on geometries that can be reduced to symmetries in one or two dimensions, such as strips, flat planes, and cylinders. Shapes with isotropic responses in three dimensions are important for applications, such as radar scattering and the replication of certain nanoscale behaviors.

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Background: X-linked agammaglobulinemia (XLA) is an inborn error of immunity that renders boys susceptible to life-threatening infections due to loss of mature B cells and circulating immunoglobulins. It is caused by defects in the gene encoding the Bruton tyrosine kinase (BTK) that mediates the maturation of B cells in the bone marrow and their activation in the periphery. This paper reports on a gene editing protocol to achieve "knock-in" of a therapeutic BTK cassette in hematopoietic stem and progenitor cells (HSPCs) as a treatment for XLA.

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Extracellular vesicles (EVs), including exosomes and microvesicles, mediate intercellular communication in cancer, from development to metastasis. EV-based liquid biopsy is a promising strategy for cancer diagnosis as EVs can be found in cancer patients' body fluids. In this study, the lipid composition of breast cancer-derived EVs was studied as well as the potential of blood plasma EVs for the identification of lipid biomarkers for breast cancer detection.

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Temperature sensors are one of the most fundamental sensors and are found in industrial, environmental, and biomedical applications. The traditional approach of reading the resistive response of Positive Temperature Coefficient thermistors at DC hindered their adoption as wide-range temperature sensors. Here, we present a large-area thermistor, based on a flexible and stretchable short carbon fibre incorporated Polydimethylsiloxane composite, enabled by a radio frequency sensing interface.

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Article Synopsis
  • - Recent advancements in gene editing, particularly using CRISPR/Cas9 and AAV, enable the replacement of faulty genes in hematopoietic stem cells, aiming to treat genetic blood disorders effectively.
  • - However, challenges like toxicity and loss of function in these stem cells make clinical applications difficult, necessitating a careful optimization of correction methods.
  • - A new Response Surface Methodology approach has been developed to efficiently balance gene correction with cell survival, leading to successful correction of p67-deficient chronic granulomatous disease in laboratory conditions.
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Introduction: The US is currently experiencing a maternal health crisis. Maternal morbidity and mortality in the US are higher than in other developed nations and continue to rise. Infant mortality, likewise, is higher in the US than in other developed nations.

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Article Synopsis
  • Over 1,000 unexplained pediatric hepatitis cases have been identified globally, with a study focusing on 38 cases and various control groups to understand potential viral causes.
  • High levels of adeno-associated virus 2 (AAV2) DNA were found in most cases, while low levels of adenovirus and human herpesvirus 6B were also detected; however, AAV2 appeared infrequently in healthy controls even when they were immunocompromised.
  • The study suggests that abnormal replication of AAV2, potentially influenced by other viruses like HAdV and HHV-6B, may be responsible for immune-related liver disease in susceptible children.
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Chronic wounds are a major healthcare problem, but their healing may be improved by developing biomaterials which can stimulate angiogenesis, e.g. by activating the Hypoxia Inducible Factor (HIF) pathway.

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  • X-linked lymphoproliferative disease (XLP) is a rare genetic immune disorder linked to mutations in the SAP gene, leading to severe immune dysregulation and affecting T cells.
  • Patients face serious health challenges, including hemophagocytic lymphohistiocytosis (HLH) and limited treatment options, with allogeneic stem cell transplants being risky and often ineffective.
  • Recent research explored gene editing techniques (TALEN, CRISPR-Cas9, CRISPR-Cas12a) using an AAV6 vector to restore SAP function in T cells from XLP patients, showing promise for improved therapeutic outcomes.
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We describe the outcome of a large international interlaboratory study of the measurement of particle number concentration of colloidal nanoparticles, project 10 of the technical working area 34, "Nanoparticle Populations" of the Versailles Project on Advanced Materials and Standards (VAMAS). A total of 50 laboratories delivered results for the number concentration of 30 nm gold colloidal nanoparticles measured using particle tracking analysis (PTA), single particle inductively coupled plasma mass spectrometry (spICP-MS), ultraviolet-visible (UV-Vis) light spectroscopy, centrifugal liquid sedimentation (CLS) and small angle X-ray scattering (SAXS). The study provides quantitative data to evaluate the repeatability of these methods and their reproducibility in the measurement of number concentration of model nanoparticle systems following a common measurement protocol.

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Extracellular vesicles (EVs) are biological nanoparticles naturally secreted by cells, acting as delivery vehicles for molecular messages. During the last decade, EVs have been assigned multiple functions that have established their potential as therapeutic mediators for a variety of diseases and conditions. In this review paper, we report on the potential of EVs in tissue repair and regeneration.

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Aim: The Covid-19 pandemic has delayed elective colorectal cancer (CRC) surgery. The aim of this study was to see whether or not this may affect overall survival (OS) and disease-free survival (DFS).

Method: A systematic review was carried out according to PRISMA guidelines (PROSPERO ID: CRD42020189158).

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A common approach to tailoring synthetic hydrogels for regenerative medicine applications involves incorporating RGD cell adhesion peptides, yet assessing the cellular response to engineered microenvironments at the nanoscale remains challenging. To date, no study has demonstrated how RGD concentration in hydrogels affects the presentation of individual cell surface receptors. Here we studied the interaction between human mesenchymal stem cells (hMSCs) and RGD-functionalized poly(ethylene glycol) hydrogels, by correlating macro- and nanoscale single-cell interfacial quantification techniques.

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Extracellular vesicles (EVs) represent a promising cell-free alternative for treatment of cardiovascular diseases. Nevertheless, the lack of standardised and reproducible isolation methods capable of recovering pure, intact EVs presents a significant obstacle. Additionally, there is significant interest in investigating the interactions of EVs with different cardiac cell types.

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Article Synopsis
  • Some EV isolation techniques can contaminate samples with non-EV factors, affecting biomarker identification and the understanding of EV bioactivity.
  • Research shows that hMSC-EVs play a role in tissue repair, but the contributions of EVs versus non-EV factors have not been fully compared.
  • Using size-exclusion chromatography, this study found that non-EV factors alone are essential for promoting angiogenesis and wound healing, suggesting that contaminants may exaggerate the perceived effects of EVs.
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Extracellular vesicles (EVs) are biologically-derived nanovectors important for intercellular communication and trafficking. As such, EVs show great promise as disease biomarkers and therapeutic drug delivery vehicles. However, despite the rapidly growing interest in EVs, understanding of the biological mechanisms that govern their biogenesis, secretion, and uptake remains poor.

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Extracellular vesicles (EVs) are secreted by the vast majority of cells and are being intensively studied due to their emerging involvement in a variety of cellular communication processes. However, the study of their cellular uptake and fate has been hampered by difficulty in imaging EVs against the cellular background. Here, we show that EVs combined with hydrophobic gold nanoclusters (AuNCs) can self-assemble into supraparticles, offering an excellent labeling strategy for high-resolution electron microscopic imaging in vitro.

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Controlled, localized drug delivery is a long-standing goal of medical research, realization of which could reduce the harmful side-effects of drugs and allow more effective treatment of wounds, cancers, organ damage and other diseases. This is particularly the case for protein "drugs" and other therapeutic biological cargoes, which can be challenging to deliver effectively by conventional systemic administration. However, developing biocompatible materials that can sequester large quantities of protein and release them in a sustained and controlled manner has proven challenging.

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Background: Vision loss and other ocular toxicities are rare, but detrimental, side effects of immune checkpoint inhibitors. Herein, we report two patients who developed vision loss while on pembrolizumab treatment.

Cases Presentation: Case 1 - A 58-year-old man was started on pembrolizumab for advanced melanoma.

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Background: To report a case of orbital inflammation after bisphosphonate infusion in a patient who was already receiving immunosuppressive therapy.

Case Presentation: A 56-year-old woman presented to the ophthalmology clinic with acute onset of right eye pain 24 h after receiving her first Zolendronic acid infusion. She has a past medical history of chronic inflammatory demyelinating polyneuropathy, Sjogren's syndrome, and systemic lupus erythematosus that have been controlled with immunosuppressive therapy for three years.

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Purpose: Surgical management of ophthalmic Graves' disease traditionally involves, in order, orbital decompression, followed by strabismus surgery and eyelid surgery. Nunery et al. previously described two distinct sub-types of patients with ophthalmic Graves' disease; Type I patients exhibit no restrictive myopathy (no diplopia) as opposed to Type II patients who do exhibit restrictive myopathy (diplopia) and are far more likely to develop new-onset worsening diplopia following medial wall and floor decompression.

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