Publications by authors named "Willingham A"

Ticks are important vectors and reservoirs of pathogens causing zoonotic diseases in camels and other livestock, rodents and other small mammals, birds and humans. is the most abundant tick species in Saudi Arabia and United Arab Emirates (UAE) affecting primarily camels, and to a lesser extent, other livestock. Species presence data, land use/landcover, elevation, slope and 19 bioclimatic variables were used to model current and future distribution of ticks using maximum entropy species distribution modelling (MaxEnt.

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Toll-like receptor (TLR) activation converts immunologically inactive tumors into immunologically active tumors by activating tumor residing antigen-presenting cells and recruitment of cytotoxic T lymphocytes. Targeted immune agonists (TIAs) are antibody drug conjugates with small-molecule TLR agonist payloads. The mechanism of action of TIAs involves tumor antigen recognition, Fcγ-receptor-dependent phagocytosis, and TLR-mediated activation to drive tumor killing by myeloid cells.

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Small ruminants and camels are important livestock species in the United Arab Emirates (UAE), although infection can limit their productivity. This study aimed to investigate the seroprevalence of infection and its associated risk factors in small ruminants and camels in the Emirate of Abu Dhabi. Additionally, seropositive animals were tested for the DNA of .

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Toll-like receptors 7 and 8 are involved in modulating the adaptive and innate immune responses, and their activation has shown promise as a therapeutic strategy in the field of immuno-oncology. While systemic exposure to TLR7/8 agonists can result in poor tolerance, combination therapies and targeted delivery through antibody-drug conjugates (ADCs) can help mitigate adverse effects. Described herein is the identification of a novel and potent series of pyrazolopyrimidine-based TLR7/8 agonists with tunable receptor selectivity.

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Despite extensive studies published on the canine brain, inconsistencies and disagreements in the nomenclature and representation of various cerebral structures continue to exist. This study aimed to create a comprehensive mapping of the external architecture of the mesocephalic canine brain with a focus on the major gyri and sulci. Standardized dissection techniques were used on 20 ethically sourced brains obtained from 6 to 10-year-old dogs that were free of neurological disorders.

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Background And Aim: Ostrich () farming in the United Arab Emirates (UAE) is a relatively new field of farming. Farmed ostriches are susceptible to ectoparasite infestation, which affects their production. This study was conducted to estimate the prevalence of ectoparasites on ostriches raised on a farm in Abu Dhabi Emirate.

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The morphological perspective of the camel brain remains largely unexplored. Therefore, studying the topography of the camel brain is of crucial importance. This study aimed to provide a detailed color-coded topographic representation of the camel brain's gross anatomy and nomenclature, showing its various gyri and sulci and their borders.

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Targeted immune agonist (TIA) comprising a TLR7 agonist conjugated to tumor-targeting antibodies have been shown to induce potent anti-tumor responses in various preclinical models. However, the clinical proof-of-concept of a TIA has been hampered by systemic dose-limiting immune-related toxicities, including rapid induction of anti-drug antibodies in patients. We have developed ELISPOT-based assay to measure activation of antibody-secreting cells (ASCs), intended to simulate the interaction between TIA and peripheral B cells as a tool to pre-clinically de-risk tumor target-independent peripheral B-cell activation by TIA.

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Antibody-drug conjugates (ADCs) have garnered worldwide attention for disease treatment, as they possess high target specificity, a long half-life, and outstanding potency to kill or modulate the functions of targets. FDA approval of multiple ADCs for cancer therapy has generated a strong desire for novel conjugation strategies with high biocompatibility and controllable bioproperties. Herein, we present a bisecting glycan-bridged conjugation strategy that enables site-specific conjugation without the need for the oligosaccharide synthesis and genetic engineering of antibodies.

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To provide information to guide considerations of declaring interruption of transmission of human schistosomiasis due to Schistosoma mansoni on St. Lucia, we undertook an island-wide survey in June-July 2022 to determine the presence of Biomphalaria snails, the intermediate hosts of S. mansoni, and their infection status.

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Background: Neurocysticercosis (NCC) is the most common infestation of the central nervous system, caused by the larval stage of the pig tapeworm . It is prevalent in regions with poor sanitation and underdevelopment, such as Latin America.

Case Description: We present four cases in which they harbored an intraventricular/intraparenchymal, frontal convexity, cerebellomedullary, and intraparenchymal NCC cyst of medium size, respectively.

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Article Synopsis
  • Coxsackievirus A21 (CVA21) has shown potential as a treatment for various cancers in research settings, and this study explores its ability to carry therapeutic genes despite its size and mutation rate.
  • Using reverse genetics, researchers successfully inserted a green fluorescent protein (GFP) gene into CVA21, demonstrating its capability to express foreign proteins.
  • To enhance the delivery of CVA21, a new method was developed by creating stable producer cells that integrate CVA21 cDNA, which may lead to improved virotherapy strategies using oncolytic viruses.
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LAG3 and PD1 are both immunomodulatory receptor that act by inhibiting activation of T cells, producing a more immunosuppressive environment. Even with the recent clinical success of PD1 and LAG3 co-blockade, signal transduction downstream of LAG3 remains largely unknown. We have leveraged an engineered Jurkat (T cell) and Raji (APC) co-culture system to assess simultaneous blockade of PD1 and LAG3 pathways using antibodies.

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Human strongyloidiasis is an important neglected tropical disease primarily caused by the nematode , and to a lesser extent which mainly infects non-human primates. Zoonotic sources of infection have important implications for control and prevention of morbidity and mortality caused by strongyloidiasis. Recent molecular evidence suggests that for primate host specificity is variable among genotypes across the Old World, and consequently that these types likely vary in their capacity for human spillover infections.

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Article Synopsis
  • Haematophagous arthropods, like mosquitoes and ticks, can carry various pathogens, including viruses, which pose risks to human and animal health.
  • Insects, equipped with an innate immune system that includes haemocytes, defend against infections through processes such as phagocytosis and encapsulation, though viruses often find ways to survive and spread.
  • The review emphasizes the need for multidisciplinary approaches to study the immune responses of these vectors and develop new strategies to prevent viral transmission to hosts.
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Immunomodulatory therapeutics such as monoclonal antibodies (mAb) carry an inherent risk of undesired immune reactions. One such risk is cytokine release syndrome (CRS), a rapid systemic inflammatory response characterized by the secretion of pro-inflammatory cytokines from immune cells. It is crucial for patient safety to correctly identify potential risk of CRS prior to first-in-human dose administration.

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Transmission of was interrupted on St. Kitts, a Caribbean island, in the 1950s. With no reported cases since that time and most spp.

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The programmed cell death 1 (PD-1) pathway represents a major immune checkpoint, which may be engaged by cells in the tumor microenvironment to overcome active T-cell immune surveillance. Pembrolizumab (Keytruda®, MK-3475) is a potent and highly selective humanized mAb of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This blockade enhances the functional activity of T cells to facilitate tumor regression and ultimately immune rejection.

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From the time it was conceptualized in 1998 to the present, RNAS has largely concentrated on research that will generate results to facilitate control, prevention and elimination of its target diseases. Diagnostics has remained an active field of research in order to develop tools that are appropriate for each stage from the first efforts until attempts to block transmission. For example, with regard to schistosomiasis, chemotherapy has excellent impact on morbidity, while better diagnostics and vaccine research have been promoted to complement the other components of the control programme.

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For the Regional Network on Asian Schistosomiasis and Other Helminth Zoonosis (RNAS), capacity building with emphasis on modern technology with correspondence to traditional techniques was found to be a priority. This article summarized the actual needs of capacity building among RNAS member countries and the working mechanism of capacity building during the last 20 years. The needs with respect to the RNAS target diseases are highly correlated with the research priorities, since most problems with regard to the performance of the national disease control programme in the member countries are connected with inadequate capacity in relation to implementation of innovative research, epidemiological investigations, laboratory performance; and sociological investigations.

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This paper introduces the three stages of development of the Regional Network on Asian Schistosomiasis and other Helminthic Zoonoses (RNAS), namely the preparatory stage, the strengthening stage and the expanding stage. Significant achievements have been made through the help of RNAS, particularly on research on helminthiases. As scientists, researchers, academics work closer with control authorities, elimination of these diseases is slowly getting nearer and within reach.

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Infections with Taenia solium cause significant public health and economic losses worldwide. Despite effective control tools, long-term sustained control/elimination of the parasite has not been demonstrated to date. Success of intervention programs is dependent on their acceptability to local communities.

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Background: Taenia solium is a neglected zoonotic parasite endemic throughout many low-income countries worldwide, including Zambia, where it causes human and pig diseases with high health and socioeconomic burdens. Lack of knowledge is a recognized risk factor, and consequently targeted health educational programs can decrease parasite transmission and disease occurrence in endemic areas. Preliminary assessment of the computer-based education program 'The Vicious Worm' in rural areas of eastern Zambia indicated that it was effective at increasing knowledge of T.

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Cytokine release syndrome (CRS) is a serious and potentially life-threatening complication typically associated with biological drug products. Pre-clinical testing in vitro and in vivo studies using non-human primates had failed to reliably predict CRS. To determine if bone marrow-thymus-liver (BLT) humanized mice with a fully engrafted human immune system or a CD34-humanized mouse model could predict CRS, we tested an anti-CD28 monoclonal antibody (mAb) similar to TGN1412.

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