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Four to ten milliseconds per year: age-related slowing of visual word identification.

This experiment examined the age-related slowing of visual word identification. Each of 108 subjects between 20 and 78 years of age performed a word/nonword discrimination (lexical decision) task in which the target was preceded by a single-word prime. Several aspects of the data were consistent with a generalized slowing model: There was a positive correlation between age and mean reaction time, the absolute magnitude of age differences increased as a function of task complexity, and the statistical control of a relatively task-independent index of processing speed attenuated the age-related variance in mean reaction time. The degree of age-related slowing was more pronounced for visually degraded targets (10 msec per year) than for intact targets (4 msec per year). Other aspects of lexical decision performance, however, suggested that some components of word identification, especially those involved in semantic activation, are relatively exempt from age-related slowing.

Adult

Effects of monocular occlusion on neural and motor response times for two-dimensional stimuli.

Previous studies have shown that there are advantages associated with the simultaneous use of both eyes to view two-dimensional stimuli. To investigate further this binocular advantage, three experiments were conducted using male and female names presented on a video display as stimuli. In the first experiment, simple reaction times (RT's) were found to increase by about 6% as a result of monocular occlusion. In the second experiment, visual evoked response (VER) and P300 implicit times were also found to increase as a result of occlusion. The third experiment confirmed these results and investigated the sensitivity of evoked potential techniques to changes in stimulus complexity. The three experiments demonstrate that monocular occlusion does have a significant effect on processing speed for two-dimensional visual stimuli. The major portion of this effect (62%) is manifest at the level of the visual cortex, and is not perceived by subjects as significantly increasing the mental workload associated with generating responses to these stimuli.

Adult

The mental status of patients with Friedreich's ataxia.

In the clinical literature, the majority of patients with Friedreich's ataxia are described as having signs of intellectual decline and serious psychiatric symptomatology. Recent studies contradict this clinical picture, but indicate some discrete mental status changes, such as slowing of information processing speed not related to motor abnormality, in a more strictly defined Friedreich's population. This study describes the mental status changes in a sample of 38 patients seen at the University of California at Los Angeles Neuropsychiatric Hospital, Ataxia Clinic. The sample was defined using strict clinical and biochemical criteria. Only one of the 38 patients showed evidence of intellectual deterioration. Ninety-two percent of the patients experienced some affective difficulty, however, ranging from major depression to normal grief. Three patients have reached their mid-forties (one is 64 years of age) without any serious mental status changes. These findings point out the importance of nurses' expecting these patients to function normally in the cognitive domain. Implications related to specific nursing interventions are discussed.

Adolescent

The Role of Artificial Intelligence Combined With Digital Cholangioscopy for Indeterminant and Malignant Biliary Strictures: A Systematic Review and Meta-analysis.

BACKGROUND: Current endoscopic retrograde cholangiopancreatography (ERCP) and cholangioscopic-based diagnostic sampling for indeterminant biliary strictures remain suboptimal. Artificial intelligence (AI)-based algorithms by means of computer vision in machine learning have been applied to cholangioscopy in an effort to improve diagnostic yield. The aim of this study was to perform a systematic review and meta-analysis to evaluate the diagnostic performance of AI-based diagnostic performance of AI-associated cholangioscopic diagnosis of indeterminant or malignant biliary strictures. METHODS: Individualized searches were developed in accordance with PRISMA and MOOSE guidelines, and meta-analysis according to Cochrane Diagnostic Test Accuracy working group methodology. A bivariate model was used to compute pooled sensitivity and specificity, likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristics curve (SROC). RESULTS: Five studies (n=675 lesions; a total of 2,685,674 cholangioscopic images) were included. All but one study analyzed a deep learning AI-based system using a convoluted neural network (CNN) with an average image processing speed of 30 to 60 frames per second. The pooled sensitivity and specificity were 95% (95% CI: 85-98) and 88% (95% CI: 76-94), with a diagnostic accuracy (SROC) of 97% (95% CI: 95-98). Sensitivity analysis of CNN studies (4 studies, 538 patients) demonstrated a pooled sensitivity, specificity, and accuracy (SROC) of 95% (95% CI: 82-99), 88% (95% CI: 72-95), and 97% (95% CI: 95-98), respectively. CONCLUSIONS: Artificial intelligence-based machine learning of cholangioscopy images appears to be a promising modality for the diagnosis of indeterminant and malignant biliary strictures.

Humans

OpenSpliceAI: An efficient, modular implementation of SpliceAI enabling easy retraining on non-human species.

The SpliceAI deep learning system is currently one of the most accurate methods for identifying splicing signals directly from DNA sequences. However, its utility is limited by its reliance on older software frameworks and human-centric training data. Here we introduce OpenSpliceAI, a trainable, open-source version of SpliceAI implemented in PyTorch to address these challenges. OpenSpliceAI supports both training from scratch and transfer learning, enabling seamless retraining on species-specific datasets and mitigating human-centric biases. Our experiments show that it achieves faster processing speeds and lower memory usage than the original SpliceAI code, allowing large-scale analyses of extensive genomic regions on a single GPU. Additionally, OpenSpliceAI's flexible architecture makes for easier integration with established machine learning ecosystems, simplifying the development of custom splicing models for different species and applications. We demonstrate that OpenSpliceAI's output is highly concordant with SpliceAI. In silico mutagenesis (ISM) analyses confirm that both models rely on similar sequence features, and calibration experiments demonstrate similar score probability estimates.

Journal Article

Upscaling Genotyping by Amplicon Sequencing With GBAS-GUI.

Genotyping by amplicon sequencing (GBAS) is a relatively low-cost approach for generating genotypic data compared with established genomic methods, making it highly scalable and particularly suitable for large-scale genetic monitoring projects. However, most existing analytical pipelines are either marker-specific, insufficiently scalable, or lacking efficient data management systems for the long-term integration of genotypic information, limiting the full potential of GBAS. Here, we address this gap by introducing GBAS-GUI (https://github.com/sonnenbe-dot/GBAS-GUI), a pipeline capable of generating GBAS-based genotypic data for a wide variety of loci at scale. GBAS-GUI integrates a graphical user interface with multiple checkpoints to improve accessibility and robustness. It implements multiprocessing architecture and a relational database that links genotypic data with associated sample metadata to enhance scalability and data management. The pipeline further enables marker screening through automated calculation of polymorphism information content (PIC) and implements a strategy to recover homologous genotypic information from paralogous loci with non-overlapping amplicon length ranges. Using multiple empirical datasets, we demonstrate substantial improvements in processing speed, database management and handling artefacts related to co-amplification of unspecific regions and duplicates of the same genomic region. We further show that incorporating the full sequence information captured by an amplicon increases marker information content beyond what is achievable with length-based genotyping alone and expands the analytical versatility of GBAS. Overall, GBAS-GUI provides a robust, scalable and versatile framework that unlocks the potential of GBAS for large-scale population genetic and phylogeographic studies.

Genotyping Techniques

Cognitive resemblance in reading-disabled twins.

This study examined the cognitive abilities of 60 pairs of reading-disabled twins aged between eight and 18 years (at least one member of each twin pair had been diagnosed as having a reading disability). Principal component analysis of nine cognitive tests yielded three readily interpretable composites of cognitive abilities--reading, symbol-processing speed and sequential memory. Scores on these three cognitive composites were significantly lower for the disabled readers than for normal readers. Individual differences in these cognitive composites within the reading-disabled twin sample were found to be due to genetic differences. Furthermore, deficits in the reading composite for the reading-disabled sample appear to be heritable.

Adolescent

Auditive and cognitive factors in speech perception by elderly listeners. I: Development of test battery.

This study compares performance of 24 young normal-hearing (aged 18-28 years) and 24 elderly (aged 61-85 years) listeners on auditive (sensitivity, frequency selectivity, and temporal resolution), cognitive (memory performance, processing speed, and divided attention ability), and speech perception tests (at the phoneme, spondee, and sentence level). Its principal aim is to assess whether the tests selected yield meaningful results. The results obtained will be used to reduce the test battery in order to be manageable in a second study on a much larger number of elderly listeners. The relationships between the tests are explored by multivariate statistical methods. The results show that: (a) in young listeners, individual differences in speech perception performance are remarkably small resulting in low correlations between the tests, while in the elderly tests of phoneme, spondee, and sentence perception overlap considerably; (b) speech perception in the elderly seems to be largely determined by hearing loss at the higher frequencies, whereas the effects of other auditive and cognitive factors seem to be relatively small or absent; and (c) performance in the elderly is only partly correlated with age.

Acoustic Stimulation

Auditive and cognitive factors in speech perception by elderly listeners. II: Multivariate analyses.

In part I of this study [van Rooij et al., J. Acoust. Soc. Am. 86, 1294-1309 (1989)], the validity and manageability of a test battery comprising auditive (sensitivity, frequency resolution, and temporal resolution), cognitive (memory performance, processing speed, and intellectual abilities), and speech perception tests (at the phoneme, spondee, and sentence level) were investigated. In the present article, the results of a selection of these tests for 72 elderly subjects (aged 60-93 years) are analyzed by multivariate statistical techniques. The results show that the deterioration of speech perception in the elderly consists of two statistically independent components: (a) a large component mainly representing the progressive high-frequency hearing loss with age that accounts for approximately two-thirds of the systematic variance of the tests of speech perception and (b) a smaller component (accounting for one-third of the systematic variance of the speech perception tests) mainly representing a general performance decrement due to reduced mental efficiency, which is indicated by a general slowing of performance and a reduced memory capacity. Although both components are correlated with age, it was found that the balance between auditive and cognitive contributions to speech perception performance did not change with age.

Adolescent

Psychomotor slowing and subcortical-type dysfunction in depression.

Elderly patients with major depression and normal controls completed the Sternberg short-term memory scanning procedure and WAIS Digit Symbol. Depressed patients demonstrated psychomotor slowing on both tasks, but normal response latency as a function of memory set size on the Sternberg procedure. While cognitive-behavioural slowing may be observed in both depressive illness and subcortical neurological disorders, a normal rate of processing information centrally appears to distinguish depression from certain of these disorders. Psychomotor slowing in the presence of normal information processing speed might be explained by a deficit in motivational state associated with depression.

Aged

Increased radiation dose at mammography due to prolonged exposure, delayed processing, and increased film darkening.

Four single-emulsion films introduced over the past 2 years--Du Pont Microvision, Fuji MiMa, Konica CM, and Eastman Kodak OM--were compared with Eastman Kodak OM SO-177 (Min-RE) film to evaluate their varying effects on mean glandular dose of reciprocity law failure due to prolonged exposure, delayed processing, and increased film darkening as a result of increased radiation exposure to improve penetration of glandular tissue. Exposures over 1.3 seconds led to increased radiation doses of 20%-30%. Delays in processing of 6 hours decreased processing speed by 11%-32% for all films except Du Pont Microvision. Optical density increases of 0.40 required 20%-30% more skin exposure for all five films. Optimal viewing densities were also evaluated and found to be different for each of the five films. Mammographers need to be aware of these differences in mammographic films to achieve maximum contrast at mammography.

Breast

Plasma von Willebrand Factor and ADAMTS13 Interact With APOE-ε4 in Predicting Longitudinal Brain Atrophy and Cognitive Decline Over a 9-Year Follow-Up.

BACKGROUND: Von Willebrand factor (VWF) and ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, 13) are linked to dementia risk, and limited evidence suggests apolipoprotein E (APOE)-&#x3b5;4 alters VWF release. This study assessed whether baseline VWF and ADAMTS13 levels predict neurodegeneration and cognitive decline and evaluated effect modification by APOE-&#x3b5;4 carriership. METHODS: Vanderbilt Memory and Aging Project cohort participants (n=332, 73&#xb1;7&#x2009;years, 59% male) completed serial blood draw, neuropsychological assessment, and brain magnetic resonance imaging over 6.4&#x2009;years (range 1.4-9.7&#x2009;years). Baseline plasma VWF and ADAMTS13 levels were quantified using mass spectrometry and Olink. Fully adjusted linear mixed-effects models related protein&#xd7;time and protein&#xd7;APOE-&#x3b5;4&#xd7;time interaction terms to longitudinal brain magnetic resonance imaging and neuropsychological outcomes. RESULTS: Lower baseline ADAMTS13 predicted faster declines in language (&#x3b2;=0.11, P=0.01), information processing speed (&#x3b2;=0.27, P=0.001), executive function (&#x3b2;=0.01, P=0.03), episodic memory (&#x3b2;=0.01, P=0.03), and visuospatial ability (&#x3b2;=0.11, P=0.001) and faster increases in global (&#x3b2;=-0.29, P=0.01) and frontal (&#x3b2;=-0.17, P=0.01) white matter hyperintensity volumes. Associations between ADAMTS13 and faster rates of cognitive decline and white matter injury were driven by APOE-&#x3b5;4 carriers. Models relating VWF to longitudinal outcomes were null. APOE-&#x3b5;4 interacted with VWF on longitudinal gray matter volumetric outcomes, such that faster rates of global gray matter atrophy were observed with higher baseline VWF levels among APOE-&#x3b5;4 noncarriers only (&#x3b2;=-1530.5, P<0.001). CONCLUSIONS: ADAMTS13 shows promise as a potential plasma biomarker for brain aging outcomes, but additional research is warranted to understand the performance of VWF in the presence versus absence of an APOE-&#x3b5;4 allele.

Humans

Free-water: A promising structural biomarker for cognitive decline in aging and mild cognitive impairment.

Diffusion MRI derived free-water (FW) metrics show promise in predicting cognitive impairment and decline in aging and Alzheimer's disease (AD). FW is sensitive to subtle changes in brain microstructure, so it is possible these measures may be more sensitive than traditional structural neuroimaging biomarkers. In this study, we examined the associations among FW metrics (measured in the hippocampus and two AD signature meta-ROIs) with cognitive performance, and compared FW findings to those from more traditional neuroimaging biomarkers of AD. We leveraged data from a longitudinal cohort (nparticipants = 296, nobservations = 870, age at baseline: 73 &#xb1; 7 years, 40% mild cognitive impairment [MCI]) of older adults who underwent serial neuropsychological assessment (episodic memory, information processing speed, executive function, language, and visuospatial skills) and brain MRI over a maximum of four time points, including baseline (n = 284), 18-month (n = 246), 3-year (n = 215), and 5-year (n = 125) visits. The mean follow-up period was 2.8 &#xb1; 1.3 years. Structural MRI was used to quantify hippocampal volume, in addition to Schwarz and McEvoy AD Signatures. FW and FW-corrected fractional anisotropy (FAFWcorr) were quantified in the hippocampus (hippocampal FW) and the AD signature areas (SchwarzFW, McEvoyFW) from diffusion-weighted (dMRI) images using bi-tensor modeling (FW elimination and mapping method). Linear regression assessed the association of each biomarker with baseline cognitive performance. Additionally, linear mixed-effects regression assessed the association between baseline biomarker values and longitudinal cognitive performance. A subsequent competitive model analysis was conducted on both baseline and longitudinal data to determine how much additional variance in cognitive performance was explained by each biomarker compared to the covariate only model, which included age, sex, race/ethnicity, apolipoprotein-&#x3b5;4 status, cognitive status, and modified Framingham Stroke Risk Profile scores. All analyses were corrected for multiple comparisons using an FDR procedure. Cross-sectional results indicate that hippocampal volume, hippocampal FW, Schwarz and McEvoy AD Signatures, and the SchwarzFW and McEvoyFW metrics are all significantly associated with memory performance. Baseline competitive model analyses showed that the McEvoy AD Signature and SchwarzFW explain the most unique variance beyond covariates for memory (&#x394;Radj 2 = 3.47 &#xb1; 1.65%) and executive function (&#x394;Radj 2 = 2.43 &#xb1; 1.63%), respectively. Longitudinal models revealed that hippocampal FW explained substantial unique variance for memory performance (&#x394;Radj 2 = 8.13 &#xb1; 1.25%), and outperformed all other biomarkers examined in predicting memory decline (pFDR = 1.95 x 10-11). This study shows that hippocampal FW is a sensitive biomarker for cognitive impairment and decline, and provides strong evidence for further exploration of this measure in aging and AD.

Alzheimer&#x2019;s disease (AD)

Self-reported visual problems of older drivers.

We conducted a survey in order to gain insights into the reasons older persons decide to give up driving. Our survey focused on vision. We probed the relationship between visual deficiencies and driving status by asking older people about the problems they encountered while performing routine visual tasks. The results showed that older persons who had recently given up driving reported more visual problems than did their driving counterparts. These problems related to difficulties in dynamic vision, visual processing speed, visual search, light sensitivity, and near vision. The results suggested that older persons are sensitive to their own visual deficits and that this awareness influences decisions about driving.

Activities of Daily Living

Neuropsychologic test performance in amateur boxers.

Cognitive functions of 23 amateur boxers were assessed immediately before and after an amateur boxing event. A range of cognitive measures were employed including tasks of verbal, figural, and incidental memory, motor functions, attention and concentration, and information processing speed. Compared to their prefight performance, boxers demonstrated impairments in verbal and incidental memory, but enhanced executive and motor functions postfight. There were no observed differences between winners and losers on any of the measures. The results are compared to other studies that have shown only minor changes in cognitive functions in amateur boxers compared to controls.

Adolescent

Cluster analysis applied to symptom ratings of psychiatric patients: an evaluation of its predictive ability.

Rating on 39 symptoms were examined for patients admitted to the Neuropsychiatric Institute of the University of Michigan Medical Center. A detailed evaluation was made of the clusters derived by a hierarchical clustering algorithm, using complete linkage and a simple matching coefficient on the binary variables of presence or absence of symptoms. The four groups of patients suggested by the cluster analysis can be characterized as follows: (1) generalized multiplicity of symptoms; (2) capacity to cope except for orientation apart from generally held norms; (3) activity level and thought processes speeded up, intensified, and unselected; (4) inwardly punitive, slowed down and distressed. It is shown that these groups received significantly different treatment and that the effect of treatment was significantly different, while no such differences were noted for groups defined in terms of diagnoses. By means of linear discriminant functions, rules are suggested for assigning other psychiatric patients to one of these four groups.

Antipsychotic Agents

The effect of neuroleptics on cognitive and psychomotor function. A preliminary study in healthy volunteers.

The effects of haloperidol (1 mg), benzhexol (5 mg), diazepam (10 mg) and caffeine (400 mg) on subjective and objective measures of cognitive and psychomotor function were compared with placebo in 20 healthy volunteers. While both diazepam and benzhexol were associated with highly significant impairments in subjective altertness, critical flicker fusion threshold and choice reaction time (CRT), haloperidol could not be distinguished from placebo in most tests but was actually associated with an apparent improvement in CRT (in males) and simple visual reaction time. The perceptual maze test detected impairment by benzhexol on processing speed but was not sensitive to any other drug effects. Multiple-dose studies are required to establish if there is a true activating effect of haloperidol using a test of sustained attention. No effect of Eysenck personality subtype or life events on baseline or drug response data was detected.

Adult

The Edinburgh cohort of HIV-positive drug users: pattern of cognitive impairment in relation to progression of disease.

To examine the neuropsychiatric effects of infection with HIV, 220 drug users (27 HIV negative, 193 HIV positive) completed tests evaluating premorbid intelligence, memory, non-verbal performance, information processing speed, and mood. When these measures were compared cross-sectionally by the severity of HIV illness, symptomatic patients (in CDC stage IV) were impaired on Trails B, two-choice decision time, delayed recall of the Wechsler Logical Memory Test and most components of the Auditory Verbal Learning Test. These findings imply reduced capacity for concentration, speed of thought and memory. When 101 patients were retested a mean of 16 months after their initial assessment, performance on Trails A and B, Block Design and delayed recall of the Wechsler Logical Memory Test deteriorated more for patients at, or progressing within, CDC stage IV, than performance of patients at stage III. The results broadly correspond to the cross-sectional findings. However, there was a decline in all tests of memory function for the sample independent of clinical staging. This may be evidence of brain involvement before the appearance of other symptoms. Self-rated measures of mood did not change cross-sectionally, progressively, or interactively with time and stage of HIV illness, and cannot account for the changes in cognitive function observed. Change in drug use, similarly, does not account for the cognitive findings. Four (5%) of the retested subjects developed AIDS dementia complex, but most of the performance and memory impairments seen were subclinical despite the destructive neuropathology presumed to underlie intellectual decline in patients with HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Dementia Complex