Publications by authors named "David T Jones"

CATH (https://www.cathdb.info) is a structural classification database that assigns domains to the structures in the Protein Data Bank (PDB) and AlphaFold Protein Structure Database (AFDB) and adds layers of biological information, including homology and functional annotation.

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The AlphaFold Protein Structure Database (AFDB) contains more than 214 million predicted protein structures composed of domains, which are independently folding units found in multiple structural and functional contexts. Identifying domains can enable many functional and evolutionary analyses but has remained challenging because of the sheer scale of the data. Using deep learning methods, we have detected and classified every domain in the AFDB, producing The Encyclopedia of Domains.

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  • * Concerns are raised about purely biological definitions being used in clinical settings, especially since many biomarker-positive but cognitively normal individuals may never develop symptoms, complicating diagnosis and patient understanding.
  • * The authors advocate for a combined clinical-biological definition of AD that accommodates at-risk and presymptomatic stages, emphasizing the need for caution in diagnosing AD without fully understanding the implications for patients.
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Objective: Prion disease classically presents with rapidly progressive dementia, leading to death within months of diagnosis. Advances in diagnostic testing have improved recognition of patients with atypical presentations and protracted disease courses, raising key questions surrounding the relationship between patterns of neurodegeneration and survival. We assessed the contribution of fluorodeoxyglucose (FDG-PET) imaging for this purpose.

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Background: Microbial dysbiosis has been reported to contribute to development of neurodegenerative diseases, however, there is a need to identify causative/prognostic indicators.

Objectives: To comparatively analyze gut microbiome composition in symptomatic LBD (dementia/mild cognitive impairment), iRBD, and cohabiting controls without LBD or iRBD.

Methods: 16S rRNA amplicon sequencing was performed in 38 cases (27 LBD, 11 iRBD) and 39 cohabitant controls.

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  • The global population of adults aged 60 and older is projected to rise from 1 billion in 2019 to 2.1 billion by 2050, leading to increased health challenges like chronic diseases and cognitive disorders.
  • A study aims to explore how different indoor lighting conditions—specifically static vs. dynamic lighting—affect older adults’ sleep quality, cognitive function, and physical activity, with the potential to promote healthier aging.
  • Up to 70 participants from independent living residences will engage in a 16-week trial, experiencing three types of lighting while their health measures are monitored through wearable devices.
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  • - The study examines the relationship between amyloid beta (Aβ) PET scans and Aβ biomarkers in cerebrospinal fluid (CSF) to assess their effectiveness in treating Aβ-related conditions.
  • - A total of 505 participants aged 50 and older were analyzed, with a focus on their Aβ levels as measured by both PET and CSF, and a subgroup of 47 who underwent autopsy for further validation.
  • - Results indicated that Aβ PET scans detected earlier Aβ accumulation in the brain compared to CSF biomarkers, showing a higher sensitivity for identifying early stages of Aβ deposition.
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Electrophysiologic disturbances due to neurodegenerative disorders such as Alzheimer's disease and Lewy Body disease are detectable by scalp EEG and can serve as a functional measure of disease severity. Traditional quantitative methods of EEG analysis often require an a-priori selection of clinically meaningful EEG features and are susceptible to bias, limiting the clinical utility of routine EEGs in the diagnosis and management of neurodegenerative disorders. We present a data-driven tensor decomposition approach to extract the top 6 spectral and spatial features representing commonly known sources of EEG activity during eyes-closed wakefulness.

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Digital quantification of gait can be used to measure aging- and disease-related decline in mobility. Gait performance also predicts prognosis, disease progression, and response to therapies. Most gait analysis systems require large amounts of space, resources, and expertise to implement and are not widely accessible.

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Predominant limbic degeneration has been associated with various underlying aetiologies and an older age, predominant impairment of episodic memory and slow clinical progression. However, the neurological syndrome associated with predominant limbic degeneration is not defined. This endeavour is critical to distinguish such a syndrome from those originating from neocortical degeneration, which may differ in underlying aetiology, disease course and therapeutic needs.

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Objective: To evaluate the performance of Alzheimer disease (AD) cerebrospinal fluid (CSF) biomarkers in a tertiary neurology clinic setting with high frequency of non-AD cases, including normal pressure hydrocephalus (NPH).

Methods: There were 534 patients who underwent AD CSF biomarkers (Roche Elecsys Aβ42, p-Tau181, total-Tau) from April 1, 2020, through April 23, 2021. A behavioral neurologist blinded to CSF results assigned a clinical diagnosis retrospectively on the basis of consensus criteria, and a neuroradiologist blinded to the diagnosis and CSF studies graded brain magnetic resonance images for indicators of CSF dynamics disorders.

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Background: Large curated data sets are required to leverage speech-based tools in health care. These are costly to produce, resulting in increased interest in data sharing. As speech can potentially identify speakers (ie, voiceprints), sharing recordings raises privacy concerns.

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  • The study examines early deposition patterns of amyloid-β (Aβ) plaques in the neocortex of individuals, using Pittsburgh compound B (PiB) PET scans from 1,088 participants.
  • Researchers found that early Aβ loading primarily occurs in the temporal, cingulate, and occipital regions, with similar patterns observed in individuals with and without the apolipoprotein ε4 gene.
  • The analysis identified distinct clusters of early amyloid deposition, which could be important for improving diagnostic methods and understanding how Alzheimer’s disease develops.
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  • The study investigates whether maternal exercise can protect offspring from high-altitude pulmonary hypertension (PH) resulting from chronic hypoxic conditions, simulating high-altitude environments.
  • Female mice were assigned to exercise or non-exercise groups during pregnancy, and their offspring were either kept at low altitude or exposed to hypoxia, with various health metrics assessed after eight weeks.
  • Results showed that hypoxia led to smaller body sizes, reduced motor function, and PH signs in offspring, but maternal exercise did not significantly mitigate these effects, indicating the need for further research for conclusive findings.
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Large language models (LLMs) are advanced artificial intelligence (AI) systems that excel in recognizing and generating human-like language, possibly serving as valuable tools for neurology-related information tasks. Although LLMs have shown remarkable potential in various areas, their performance in the dynamic environment of daily clinical practice remains uncertain. This article outlines multiple limitations and challenges of using LLMs in clinical settings that need to be addressed, including limited clinical reasoning, variable reliability and accuracy, reproducibility bias, self-serving bias, sponsorship bias, and potential for exacerbating health care disparities.

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A research participant was monitored over nearly two decades at Mayo Clinic, undergoing annual neurologic assessments, neuropsychological tests, and multimodal imaging. Initially, he was cognitively normal but developed symptoms consistent with Posterior Cortical Atrophy (PCA) during the study. Early tests indicated mild, yet normal-range declines in language and visuospatial skills.

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The PSIRED Workbench is a long established and popular bioinformatics web service offering a wide range of machine learning based analyses for characterizing protein structure and function. In this paper we provide an update of the recent additions and developments to the webserver, with a focus on new Deep Learning based methods. We briefly discuss some trends in server usage since the publication of AlphaFold2 and we give an overview of some upcoming developments for the service.

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The genus Clostridium is a large and diverse group within the Bacillota (formerly Firmicutes), whose members can encode useful complex traits such as solvent production, gas-fermentation, and lignocellulose breakdown. We describe 270 genome sequences of solventogenic clostridia from a comprehensive industrial strain collection assembled by Professor David Jones that includes 194 C. beijerinckii, 57 C.

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Importance: Factors associated with clinical heterogeneity in Alzheimer disease (AD) lay along a continuum hypothesized to associate with tangle distribution and are relevant for understanding glial activation considerations in therapeutic advancement.

Objectives: To examine clinicopathologic and neuroimaging characteristics of disease heterogeneity in AD along a quantitative continuum using the corticolimbic index (CLix) to account for individuality of spatially distributed tangles found at autopsy.

Design, Setting, And Participants: This cross-sectional study was a retrospective medical record review performed on the Florida Autopsied Multiethnic (FLAME) cohort accessioned from 1991 to 2020.

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  • - The study investigated the safety of ventriculoperitoneal shunt placement in older patients with idiopathic normal pressure hydrocephalus (iNPH) who were either on anticoagulation therapy or not.
  • - Out of 234 patients reviewed, those on anticoagulants experienced a higher incidence of tract hemorrhage post-surgery (11.1% vs. 2.5%), but rates of other hemorrhagic complications were similar across both groups.
  • - The findings highlight the common use of anticoagulants in the iNPH patient population and suggest careful monitoring may be necessary for those undergoing shunt placement.
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Dementia with Lewy bodies (DLB) is a neurodegenerative condition often co-occurring with Alzheimer's disease (AD) pathology. Characterizing white matter tissue microstructure using Neurite Orientation Dispersion and Density Imaging (NODDI) may help elucidate the biological underpinnings of white matter injury in individuals with DLB. In this study, diffusion tensor imaging (DTI) and NODDI metrics were compared in 45 patients within the dementia with Lewy bodies spectrum (mild cognitive impairment with Lewy bodies (n = 13) and probable dementia with Lewy bodies (n = 32)) against 45 matched controls using conditional logistic models.

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  • Frontotemporal lobar degeneration (FTLD) is a rare condition characterized by behavioral and motor symptoms, making traditional neuropsychological assessments less effective for early detection; smartphone-based cognitive tests may provide a solution for remote evaluations.
  • A study conducted over four years involved 360 participants with varying stages of FTLD using smartphone apps to assess cognitive function, splitting them into discovery and validation groups, with a majority being asymptomatic or at preclinical stages.
  • Results indicate the smartphone-based tests showed moderate to excellent reliability in measuring cognitive function, suggesting they could serve as valid tools for remote assessments in FTLD patients.
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Background: Primary progressive aphasia (PPA) defines a group of neurodegenerative disorders characterised by language decline. Three PPA variants correlate with distinct underlying pathologies: semantic variant PPA (svPPA) with transactive response DNA-binding protein of 43 kD (TDP-43) proteinopathy, agrammatic variant PPA (agPPA) with tau deposition and logopenic variant PPA (lvPPA) with Alzheimer's disease (AD). Our objectives were to differentiate PPA variants using clinical and neuroimaging features, assess progression and evaluate structural MRI and a novel 18-F fluorodeoxyglucose positron emission tomography (FDG-PET) image decomposition machine learning algorithm for neuropathology prediction.

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Disruption of the default mode network is a hallmark of Alzheimer's disease, which has not been extensively examined in atypical phenotypes. We investigated cross-sectional and 1-year longitudinal changes in default mode network sub-systems in the visual and language variants of Alzheimer's disease, in relation to age and tau. Sixty-one amyloid-positive Alzheimer's disease participants diagnosed with posterior cortical atrophy ( = 33) or logopenic progressive aphasia ( = 28) underwent structural MRI, resting-state functional MRI and [F]flortaucipir PET.

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