Noise Mitigation Analysis of a Pi-Filter for an Automotive Control Module

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The effect of Melatonin on histological changes of ovary in induced polycystic ovary syndrome model in mice

Antioxidants can be used as adjuvant treatment of polycystic ovary syndrome (PCOS). Melatonin (MT) is one of the antioxidant that is used nowadays. Objective: In this study, the effect of MT on the histological changes of ovary in the experimental model of polycystic ovary syndrome is investigated. Methods: In this study 30 immature female NMRI mice were divided into 5 groups including: (1) control group received distilled water, (2) received a dose of 10. mg/kg MT for 5. days, (3) received Dehydroepiandrostenedione (DHEA) at a dose of 6. mg/kg for 20. days to induce PCOS, (4) after induction of PCOS received MT at a dose of 10. mg/kg for 5. days, and (5) received 6. mg/kg DHEA and 10. mg/kg MT for 20. days simultaneously. Results: The evaluation of ovarian tissue characteristics such as the granulosa layer, theca, number and diameter of cysts and follicles was performed. PCOS caused a significant reduction in the number of antral follicles and corpus luteum and an increase in the number of primordial, primary, pre-antral and cystic follicles in comparison with the control group (P. <. 0.05). Moreover, MT resulted in a significant increase in the granulosa layer thickness in group 4 (P. <. 0.001), and group 5 (P = 0.001) and a significant reduction in the thickness of theca layer between groups 4 and 5 compared with group 3 (P. <. 0.001). Conclusion: These findings indicate that MT have a protective effects on polycystic ovary damages induced by DHEA, although the mechanism is unclear. It is likely that this is happening by reducing oxidative damage. © 2017

Ligand-based transport resonances of single-molecule magnet spin filters: Suppression of the Coulomb blockade and determination of the orientation of the magnetic easy axis

We investigate single molecule magnet transistors (SMMTs) with ligands that support transport resonances. We find the lowest unoccupied molecular orbitals of Mn12-benzoate SMMs (with and without thiol or methyl-sulfide termination) to be on ligands, the highest occupied molecular orbitals being on the Mn12 magnetic core. We predict gate controlled switching between Coulomb blockade and coherent resonant tunneling in SMMTs based on such SMMs, strong spin filtering by the SMM in both transport regimes, and that if such switching is observed then the magnetic easy axis of the SMM is parallel to the direction of the current through the SMM.Comment: 5 pages, 3 figure

Analysis of hand-forearm anthropometric components in assessing handgrip and pinch strengths of school-aged children and adolescents: a partial least squares (PLS) approach

Background: The purpose of this study was to examine the influence of hand-forearm anthropometric dimensions on handgrip and pinch strengths among 7�18 years children and adolescents and to investigate the extent to which these variables can be used to predict hand strength. Methods: Four types of hand strengths including handgrip, tip to tip, key, and three-jaw chuck pinches were measured in 2637 healthy children and adolescents (1391 boys and 1246 girls) aged 7�18 years using standard adjustable Jamar hydraulic hand dynamometer and pinch gauge. A set of 17 hand-forearm anthropometric dimensions were also measured with an accurate digital caliper and tape measure. Results: No significant differences were found between the hand strengths of boys and girls up to the age of 10 years. Gender related differences in handgrip and pinches were observed from the age of 11 years onwards, with boys always being stronger. The dominant hand was stronger than the non-dominant hand (8 for handgrip and by about 10 for all three types of pinches). The strongest correlations were found between the hand length and hand strengths (r > 0.83 for handgrip and three all pinches; p < 0.001, 2-tailed). Based on the partial least squares (PLS) analysis, 8 out of 17 anthropometric indices including hand length, hand circumference, thumb length, index finger length, middle finger length, and forearm length had considerable loadings in the PLS analysis, which together accounted for 46 of the total variance. Conclusions: These results may be used by health professionals in clinical settings as well as by designers to create ergonomic hand tools. © 2021, The Author(s)

The value of standards for health datasets in artificial intelligence-based applications

Artificial intelligence as a medical device is increasingly being applied to healthcare for diagnosis, risk stratification and resource allocation. However, a growing body of evidence has highlighted the risk of algorithmic bias, which may perpetuate existing health inequity. This problem arises in part because of systemic inequalities in dataset curation, unequal opportunity to participate in research and inequalities of access. This study aims to explore existing standards, frameworks and best practices for ensuring adequate data diversity in health datasets. Exploring the body of existing literature and expert views is an important step towards the development of consensus-based guidelines. The study comprises two parts: a systematic review of existing standards, frameworks and best practices for healthcare datasets; and a survey and thematic analysis of stakeholder views of bias, health equity and best practices for artificial intelligence as a medical device. We found that the need for dataset diversity was well described in literature, and experts generally favored the development of a robust set of guidelines, but there were mixed views about how these could be implemented practically. The outputs of this study will be used to inform the development of standards for transparency of data diversity in health datasets (the STANDING Together initiative)

Arterial hypertension and β-amyloid accumulation have spatially overlapping effects on posterior white matter hyperintensity volume: a cross-sectional study

Background: White matter hyperintensities (WMH) in subjects across the Alzheimer’s disease (AD) spectrum with minimal vascular pathology suggests that amyloid pathology—not just arterial hypertension—impacts WMH, which in turn adversely influences cognition. Here we seek to determine the effect of both hypertension and Aβ positivity on WMH, and their impact on cognition. Methods: We analysed data from subjects with a low vascular profile and normal cognition (NC), subjective cognitive decline (SCD), and amnestic mild cognitive impairment (MCI) enrolled in the ongoing observational multicentre DZNE Longitudinal Cognitive Impairment and Dementia Study (n = 375, median age 70.0 [IQR 66.0, 74.4] years; 178 female; NC/SCD/MCI 127/162/86). All subjects underwent a rich neuropsychological assessment. We focused on baseline memory and executive function—derived from multiple neuropsychological tests using confirmatory factor analysis—, baseline preclinical Alzheimer’s cognitive composite 5 (PACC5) scores, and changes in PACC5 scores over the course of three years (ΔPACC5). Results: Subjects with hypertension or Aβ positivity presented the largest WMH volumes (pFDR < 0.05), with spatial overlap in the frontal (hypertension: 0.42 ± 0.17; Aβ: 0.46 ± 0.18), occipital (hypertension: 0.50 ± 0.16; Aβ: 0.50 ± 0.16), parietal lobes (hypertension: 0.57 ± 0.18; Aβ: 0.56 ± 0.20), corona radiata (hypertension: 0.45 ± 0.17; Aβ: 0.40 ± 0.13), optic radiation (hypertension: 0.39 ± 0.18; Aβ: 0.74 ± 0.19), and splenium of the corpus callosum (hypertension: 0.36 ± 0.12; Aβ: 0.28 ± 0.12). Elevated global and regional WMH volumes coincided with worse cognitive performance at baseline and over 3 years (pFDR < 0.05). Aβ positivity was negatively associated with cognitive performance (direct effect—memory: − 0.33 ± 0.08, pFDR < 0.001; executive: − 0.21 ± 0.08, pFDR < 0.001; PACC5: − 0.29 ± 0.09, pFDR = 0.006; ΔPACC5: − 0.34 ± 0.04, pFDR < 0.05). Splenial WMH mediated the relationship between hypertension and cognitive performance (indirect-only effect—memory: − 0.05 ± 0.02, pFDR = 0.029; executive: − 0.04 ± 0.02, pFDR = 0.067; PACC5: − 0.05 ± 0.02, pFDR = 0.030; ΔPACC5: − 0.09 ± 0.03, pFDR = 0.043) and WMH in the optic radiation partially mediated that between Aβ positivity and memory (indirect effect—memory: − 0.05 ± 0.02, pFDR = 0.029). Conclusions: Posterior white matter is susceptible to hypertension and Aβ accumulation. Posterior WMH mediate the association between these pathologies and cognitive dysfunction, making them a promising target to tackle the downstream damage related to the potentially interacting and potentiating effects of the two pathologies. Trial registration: German Clinical Trials Register (DRKS00007966, 04/05/2015)

Machine learning‐based classification of Alzheimer's disease and its at‐risk states using personality traits, anxiety, and depression

Background Alzheimer's disease (AD) is often preceded by stages of cognitive impairment, namely subjective cognitive decline (SCD) and mild cognitive impairment (MCI). While cerebrospinal fluid (CSF) biomarkers are established predictors of AD, other non-invasive candidate predictors include personality traits, anxiety, and depression, among others. These predictors offer non-invasive assessment and exhibit changes during AD development and preclinical stages. Methods In a cross-sectional design, we comparatively evaluated the predictive value of personality traits (Big Five), geriatric anxiety and depression scores, resting-state functional magnetic resonance imaging activity of the default mode network, apoliprotein E (ApoE) genotype, and CSF biomarkers (tTau, pTau181, Aβ42/40 ratio) in a multi-class support vector machine classification. Participants included 189 healthy controls (HC), 338 individuals with SCD, 132 with amnestic MCI, and 74 with mild AD from the multicenter DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). Results Mean predictive accuracy across all participant groups was highest when utilizing a combination of personality, depression, and anxiety scores. HC were best predicted by a feature set comprised of depression and anxiety scores and participants with AD were best predicted by a feature set containing CSF biomarkers. Classification of participants with SCD or aMCI was near chance level for all assessed feature sets. Conclusion Our results demonstrate predictive value of personality trait and state scores for AD. Importantly, CSF biomarkers, personality, depression, anxiety, and ApoE genotype show complementary value for classification of AD and its at-risk stages

Aβ oligomers peak in early stages of Alzheimer's disease preceding tau pathology

INTRODUCTION Soluble amyloid beta (Aβ) oligomers have been suggested as initiating Aβ related neuropathologic change in Alzheimer's disease (AD) but their quantitative distribution and chronological sequence within the AD continuum remain unclear. METHODS A total of 526 participants in early clinical stages of AD and controls from a longitudinal cohort were neurobiologically classified for amyloid and tau pathology applying the AT(N) system. Aβ and tau oligomers in the quantified cerebrospinal fluid (CSF) were measured using surface-based fluorescence intensity distribution analysis (sFIDA) technology. RESULTS Across groups, highest Aβ oligomer levels were found in A+ with subjective cognitive decline and mild cognitive impairment. Aβ oligomers were significantly higher in A+T− compared to A−T− and A+T+. APOE ε4 allele carriers showed significantly higher Aβ oligomer levels. No differences in tau oligomers were detected. DISCUSSION The accumulation of Aβ oligomers in the CSF peaks early within the AD continuum, preceding tau pathology. Disease-modifying treatments targeting Aβ oligomers might have the highest therapeutic effect in these disease stages. Highlights Using surface-based fluorescence intensity distribution analysis (sFIDA) technology, we quantified Aβ oligomers in cerebrospinal fluid (CSF) samples of the DZNE-Longitudinal Cognitive Impairment and Dementia (DELCODE) cohort Aβ oligomers were significantly elevated in mild cognitive impairment (MCI) Amyloid-positive subjects in the subjective cognitive decline (SCD) group increased compared to the amyloid-negative control group Interestingly, levels of Aβ oligomers decrease at advanced stages of the disease (A+T+), which might be explained by altered clearing mechanism

Plasma amyloid beta X‐42/X‐40 ratio and cognitive decline in suspected early and preclinical Alzheimer's disease

INTRODUCTION Blood-based biomarkers are a cost-effective and minimally invasive method for diagnosing the early and preclinical stages of amyloid positivity (AP). Our study aims to investigate our novel immunoprecipitation-immunoassay (IP-IA) as a test for predicting cognitive decline. METHODS We measured levels of amyloid beta (Aβ)X-40 and AβX-42 in immunoprecipitated eluates from the DELCODE cohort. Receiver-operating characteristic (ROC) curves, regression analyses, and Cox proportional hazard regression models were constructed to predict AP by Aβ42/40 classification in cerebrospinal fluid (CSF) and conversion to mild cognitive impairment (MCI) or dementia. RESULTS We detected a significant correlation between AßX-42/X-40 in plasma and CSF (r = 0.473). Mixed-modeling analysis revealed a substantial prediction of AßX-42/X-40 with an area under the curve (AUC) of 0.81 for AP (sensitivity: 0.79, specificity: 0.74, positive predictive value [PPV]: 0.71, negative predictive value [NPV]: 0.81). In addition, lower AβX-42/X-40 ratios were associated with negative PACC5 slopes, suggesting cognitive decline. DISCUSSION Our results suggest that assessing the plasma AβX-42/X-40 ratio via our semiautomated IP-IA is a promising biomarker when examining patients with early or preclinical AD. Highlights New plasma Aβ42/Aβ40 measurement using immunoprecipitation–immunoassay Plasma Aβ42/Aβ40 associated with longitudinal cognitive decline Promising biomarker to detect subjective cognitive decline at-risk for brain amyloid positivit