Publications by authors named "Amanda G. Smith"

Background: Von Willebrand factor (VWF) is a critical glycoprotein in hemostasis and is an important factor in diagnosing bleeding disorders. Albeit the analysis of VWF is often compromised by inconsistent methodologies and challenges quantifying multimeric size. Current VWF multimer analysis methods are costly, time-consuming, and often inconsistent; thus, demanding skilled professionals.

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Heat shock protein 90 (Hsp90) is a family of chaperone proteins that consists of four isoforms: Hsp90α, Hsp90β, glucose-regulated protein 94 (Grp94), and tumor necrosis factor type 1 receptor-associated protein (TRAP1). They are involved in modulating the folding, maturation, and activation of their client proteins to regulate numerous intracellular signaling pathways. Previous studies demonstrated that pan-Hsp90 inhibitors reduce inflammatory signaling pathways resulting in a reduction of inflammation and pain but show toxicities in cancer-related clinical trials.

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  • - The study addresses the issue of limited ancestral diversity in genome-wide association studies (GWAS), which makes it hard to find genetic risk variants in non-European ancestry groups, focusing on Alzheimer's Disease (AD).
  • - Researchers analyzed a multi-ancestry GWAS dataset within the Alzheimer's Disease Genetics Consortium (ADGC) involving individuals from various ancestries, identifying 13 shared risk loci and 3 ancestry-specific loci, highlighting the benefits of diverse samples.
  • - The findings underscore the importance of including underrepresented populations in genetic research, suggesting that even smaller sample sizes can lead to the discovery of novel genetic variants related to AD and implicating specific biological pathways like amyloid regulation and neuronal development.
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Ex vivo hemocompatibility testing is a vital element of preclinical assessment for blood-contacting medical devices. Current approaches are resource intensive; thus, we investigated the feasibility of accelerating hemocompatibility testing by standardizing the number of pump exposures in loops of various sizes. Three identical blood loops were constructed, each with a custom-molded reservoir able to facilitate large-volume expansion.

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Arnica has traditionally been used in treating numerous medical conditions, including inflammation and pain. This review aims to summarize the results of studies testing Arnica products for pain management under different conditions, including post-operation, arthritis, low back pain, and other types of musculoskeletal pain. Based on data from clinical trials, Arnica extract or gel/cream containing Arnica extract shows promising effects for pain relief.

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Rodent models are important in mechanistic studies of the physiological and pathophysiological determinants of behaviour. The Open Field Test (OFT) is one of the most commonly utilised tests to assess rodent behaviour in a novel open environment. The key variables assessed in an OFT are general locomotor activity and exploratory behaviours and can be assessed manually or by automated systems.

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Heat shock protein 90 (Hsp90) is a molecular chaperone that plays an essential role in tumor growth. Numerous Hsp90 inhibitors have been discovered and tested in preclinical and clinical trials. Recently, several preclinical studies have demonstrated that Hsp90 inhibitors could modulate pain sensitization.

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  • An amendment to the original paper has been released.
  • You can find the amendment through a link provided at the top of the paper.
  • This update may contain important changes or additional information related to the original content.
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  • Late-onset Alzheimer's disease (LOAD) is the most common type of dementia and is influenced by genetics.
  • Researchers studied a lot of people (94,437) to find specific genes that may increase the risk of developing LOAD, confirming 20 known ones and discovering 5 new ones.
  • They also found that certain genetic traits related to the immune system and how the brain processes proteins are linked to a higher risk of LOAD, suggesting there are more rare genes yet to be identified that could also play a role.
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  • A study investigated the genetic overlap between 25 brain disorders using data from over 1.2 million individuals, finding that psychiatric disorders share more genetic risk compared to neurological disorders, which seem more distinct.
  • The research identified significant relationships between these disorders and various cognitive measures, suggesting shared underlying traits.
  • Simulations were conducted to understand how factors like sample size and diagnosis accuracy influence genetic correlations, emphasizing the role of common genetic variations in the risk of brain disorders.
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  • * Our research uncovered three significant variants: a protective variant in the PLCG2 gene and risk variants in ABI3 and TREM2, known for their roles in Alzheimer's susceptibility.
  • * The findings emphasize the importance of microglia, immune cells in the brain, suggesting that their genetic variations may contribute directly to the progression of Alzheimer's disease.
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Background: There is a need to investigate biomarkers that are indicative of the progression of dementia in ethnic patient populations. The disparity of information in these populations has been the focus of many clinical and academic centers, including ours, to contribute to a higher success rate in clinical trials. In this study, we have investigated plasma biomarkers in amnestic mild cognitively impaired (aMCI) female patient cohorts in the context of ethnicity and cognitive status.

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  • - The study investigates a rare variant in the APP gene (A673T) that may protect against late-onset Alzheimer's disease (AD), originally found in Iceland, by comparing its frequency in US and Swedish populations.
  • - Researchers conducted a case-control analysis involving over 17,000 participants (including AD cases and cognitively normal controls) from multiple medical centers to assess the prevalence of this variant using advanced genotyping techniques.
  • - Results showed only a few individuals with the A673T variant; specifically, 3 heterozygous cases were found among US participants, indicating that this variant is not common in the studied populations and may not significantly impact AD risk assessment.
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Background: Minocycline, a member of the tetracycline family, has a low risk of adverse effects and an ability to improve behavioral performance in humans with cognitive disruption. We performed a single-arm open-label trial in which 25 children diagnosed with Angelman syndrome (AS) were administered minocycline to assess the safety and tolerability of minocycline in this patient population and determine the drug's effect on the cognitive and behavioral manifestations of the disorder.

Methods: Participants, age 4-12 years old, were randomly selected from a pool of previously screened children for participation in this study.

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  • The study investigates how known genetic risk factors for late-onset Alzheimer disease (LOAD) influence the age at which symptoms appear in affected individuals, particularly focusing on the APOE locus and other established risk loci.
  • Researchers utilized data from the Alzheimer Disease Genetics Consortium, analyzing 9,162 patients over several years, to determine the cumulative effects of these genetic factors on age at onset (AAO) of LOAD.
  • Results indicated that variants at the APOE locus are strongly associated with earlier onset of Alzheimer’s symptoms, with other loci like CR1, BIN1, and PICALM showing statistically significant effects as well, together explaining a portion of the AAO variation.
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Angelman syndrome (AS) is characterized by severe cognitive disruption, seizures, difficulty speaking and ataxia. Nearly all cases are attributed to the disruption or absence of the imprinted maternal copy of UBE3A, transcribing an E3-type ubiquitin ligase. Much of what is known about the molecular and biochemical changes in the CNS associated with AS has been obtained through this murine model.

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Behavioral disturbances in Alzheimer's disease and related disorders are common throughout all stages of these dementing illnesses. They are a major source of caregiver distress and can lead to premature institutionalization of the patient if not properly addressed. Fortunately, such behaviors are often treatable.

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Topiramate is a medication introduced in the United States in 1997 for the treatment of epilepsy. Studies are currently underway to determine its effectiveness in the treatment of multiple conditions including bipolar disorder. It is generally well tolerated at doses commonly used in the clinical setting, however, there is little information regarding its safety in overdose.

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