bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression of cannibalism in the intertidal copepod Tigriopus japonicus (Mori, 1932) and improvements in population density using artificial substrates
Authors: Koga Shinichi , Takayama Yoshiki , Toda Tatsuki 
Published: February 2022

AbstractThe present study investigated population growth, egg production and cannibalism in the intertidal harpacticoid copepod Tigriopus japonicus (Mori, 1932). Copepods were cultured on artificial substrates with different surface areas, from 13.5 × 103 to 10.6 × 104 mm2, to clarify the effect of surface area in a culture vessel on population density. The cannibalism rate at a surface area of 10.6 × 104 mm2 was significantly lower (by a sixth) than that at 13.5 × 103 mm2. These results suggest that artificial substrates play a role in preventing cannibalism by providing shelter and can increase the stocking population density of T. japonicus in a vessel.
Higher global efficiency in functional brain network could delay cognitive decline in amyloid‐positive individuals: The cognitive reserve theory
Authors: Seo Eun Hyun , Yoon Hyung‐Jun , Heo Mina ,   for the Alzheimer’s Disease Neuroimaing Initiative
Published: February 2022

AbstractBackgroundIt is known that cognitive reserve (CR) support resilience against the effects of brain pathology. However, it still remains to be elucidated what can be served as a proxy for the CR. In the current study we investigated whether particular functional brain features have protective effect for future cognitive decline. We also examined if the relationship is different according to amyloid‐beta (aß) positivity.MethodFunctional MRI data, clinical and neuropsychological data, and follow‐up information were downloaded from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. In the final analysis, 48 cognitively normal (CN) elderly and 46 elderly with mild cognitive impairment (MCI) were included. Cognitive decline was measured by mini mental status examination (MMSE) change score from baseline and the last follow‐up. Resting state function image data processing was carried out using FMRIB’s Software Library and Brain Connectivity Toolbox. Cox proportional hazards models were conducted to investigate the associations between several cognitive reserve proxies and future cognitive decline. In addition, the relationship was explored separately for aß positivityResultMean follow‐up month were 45.84 (50.33 for CN, 41.15 for MCI). Based on MMSE change score, 41 were identified as cognitively decliners. Among baseline functional brain network parameters (density, clustering coefficients, path length, and global efficiency) education, and American National Adult Reading Test (AMNART) error score, and 4 ADNI neuropsychological summary scores, global efficiency (HR=2.04, 95% CI 1.07‐3.91) and ADNI‐EF score (HR=0.41, 95% CI 0.26‐0.64) were significant in the Cox proportional hazard model (Figure1A). This association was observed only in aß positive group, whereas no significant association was found in aß negative group (Figure 1BC).ConclusionOur findings indicate that higher global efficiency in functional brain network and better executive function could delay cognitive decline, especially in aß positive group. Cognitive reserve is to preserve cognitive function better in the presence of brain pathology. Our study preliminary suggest that higher brain efficiency could play a key role in cognitive reserve in elders.
Serum oxylipins indicate subcortical ischemic vascular disease in patients with clinical stroke
Authors: Yu Di , Taha Ameer , Pedersen Theresa , Joel Ramirez , Goubran Maged , Ozzoude Miracle , Gao Fuqiang , Casaubon Leanne , Bartha Robert , Symons Sean , Kwan Donna , Dowlatshahi Dar , Hassan Ayman , Mandzia Jennifer , Sahlas Demetrios J. , Saposnik Gustavo , Arnott Stephen R. , Tan Brian , Lanctôt Krista L. , Masellis Mario , Black Sandra E. , Swartz Richard H. , Swardfager Walter ,   The ONDRI Study Group
Published: February 2022

AbstractBackgroundSubcortical ischemic vascular disease (SIVD) is the most common vascular pathology found in patients with late onset dementia. The soluble epoxide hydrolase (sEH) enzyme inactivates anti‐inflammatory and vasoactive cytochrome p450 derived polyunsaturated fatty acid epoxides by converting them into cytotoxic dihydroxy (diol) oxylipin species. Previously, we found that the ratios of linoleic acid (LA) diols to epoxides were associated with more white matter hyperintensity (WMH) in patients with transient ischemic attack; however, it remains univestigated if these oxylipins can identify SIVD in patients with ischemic stroke of heterogenous cerebrovascular pathologies such as large vessel occlusion and lacunar infarcts.MethodThe study cohort comprises patients from the Ontario Neurodegenerative Disease Research Initiative, who has clinical stroke of either large or small vessel etiology (according to TOAST criteria). 4 LA oxylipins (12,13‐dihydroxyoctadecamonoenoic acid (12,13‐DiHOME), 12,13‐epoxyoctadecenoic acid (12,13‐EpOME), 9,10‐DiHOME, 9,10‐EpOME) were extracted from blood and quantified with a targeted ultrahigh pressure liquid chromatography mass spectrometry (UPLC‐MS/MS) WMH and perivascular spaces (PVS) were quantified from structural MRI scans using a personalized semi‐automatic processing pipeline (Lesion Explorer). The associations between oxylipins and small vessel disease markers were examined using linear regression models.ResultIn 80 stroke patients (n=50 large vessel disease and n=30 lacunar infarcts), the ratio of 12,13‐DiHOME to its epoxide sEH substrate 12,13‐EpOME was higher among patients with small vessel etiology (F1,79 = 4.55, p = 0.036). In linear regression models controlling for age, sex, APOE, waist hip ratio, diabetes, and hyperlipidemia, the same ratio, and the ratio of 9,10‐DiHOME/9,10‐EpOME were positively associated with volume of deep (β = 0.338, p = 0.004; β = 0.288, p = 0.012, respectively) and periventricular (β = 0.316, p = 0.003; β = 0.400, p < 0.001, respectively) WMH. The same ratios were associated with higher volumes of perivascular spaces in the white matter (β = 0.293, p = 0.013; β = 0.276, p = 0.016, respectively) but not in the basal ganglia (β = 0.145, p = 0.212; β = 0.086, p = 0.450, respectively).ConclusionOxylipins derived from sEH activity may contribute to cerebral small vessel disease and to stroke of small vessel etiology.
Dynamic states of resting‐state connectivity in patients with mild cognitive impairment
Authors: Palmer William C. , Park Sung Min , Rane Swati ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: February 2022

AbstractBackgroundResting‐state functional connectivity (rsFC) has demonstrated promise as a biomarker for Alzheimer’s disease. Traditional rsFC assumes that brain connectivity is unvarying during the entire acquisition window. However, recent studies show that brain connection patterns or states are dynamic and change within a few seconds. We modified existing analyses of dynamic functional connectivity to identify differences between patients with Mild Cognitive Impairment (MCI) and controls.Method50 MCI patients (22 males, 74±8 years old) and 55 controls (35 males, age=75±8 y.o.) from ADNI3 with T1 and fast BOLD fMRI (TR=600ms) images were analyzed. Preprocessing consisted of motion correction, despiking, physiological noise correction, and registration to MNI space. Sliding windows had a stride length of 1 TR and contained 50 TRs. Correlation matrices were generated between brain regions of the default mode (DMN), salience (Sal), dorsal attention (DAN), and frontoparietal (FPN) networks. The data was then harmonized using ComBat to remove scanner‐related differences. Distinct brain connectivity patterns or states were extracted with Davies‐Bouldin optimized k‐means clustering. Dwell time (i.e., the number of TRs for which a state is sustained) and transition probability (i.e., the probability of changing state) were calculated. Significant differences were assessed using a t‐test without correcting for multiple comparisons.ResultWe identified eight states (Figure 1). No significant differences were discovered in dwell time (Figure 2). Six transition probabilities had p<0.05 (Figure 3). These included the transition from 2 to 5 (p=0.03), 2 to 6 (p=0.04), 2 to 7 (p=0.04), 4 to 3 (p=0.005), 6 to 3 (p=0.01), 8 to 4 (p=0.05), and 8 to 7 (p=0.05).ConclusionOur study showed MCI patients were less likely to transition from state 4 to 3 compared to controls. State 4 is characterized by positive rsFC within the DMN and FPN as well as between the networks. Compared to state 4, state 3 had decreased rsFC within the DMN and FPN and between the networks. State 3 also shows increased positive rsFC within and between Sal and DAN. Interaction between the 4 networks has been implicated in AD. The inability to perform this transition could explain cognitive deficits observed in MCI.
Urokinase plasminogen activator (uPA) as a novel biomarker for cerebral amyloid angiopathy
Authors: Vervuurt Marc , Zhu Xiaoyue , Schrader Joseph , de Kort Anna M. , Marques Tainá M. , Kersten Iris , Schreuder Floris H.B.M. , Klijn Catharina J.M. , Kuiperij H. Bea , Van Nostrand William E , Verbeek Marcel M. 
Published: February 2022

AbstractBackgroundDiagnosis of the highly prevalent disease cerebral amyloid angiopathy (CAA) is mainly based on radiological identification of cerebral micro‐ or macrobleeds (according to the diagnostically acclaimed Boston Criteria) in the end‐stage of disease. Body fluid biomarkers (e.g. in cerebrospinal fluid) could potentially act as alternatives and allow for earlier identification of disease in a minimally invasive manner. We have explored the involvement of potential CAA‐biomarker urokinase plasminogen activator (uPA) in CAA development and progression in human patients and rodent disease models (rTg‐DI). Additionally, we analyzed uPA cerebrospinal fluid (CSF) levels in rTg‐DI models and human CAA patients versus controls to assess diagnostic accuracy of uPA as a biomarker for CAA.MethodPLAU gene expression and uPA localization were studied in cerebrovascular tissue of a rTg‐DI models and wild‐type rats, alongside a human sporadic CAA patient and a control subject, using rt‐qPCR and immunohistochemistry respectively. Additionally, CSF Aβ40 and uPA levels were determined in rTg‐DI rats and in human patients with possible or probable CAA (according to the Boston Criteria; n=28), and control subjects (n=40), using ELISA.ResultImmunohistochemistry showed strong overexpression of uPA in brain tissue of rTg‐DI models and human CAA patients. Additionally, uPA showed a strong colocalization with Aβ peptides, restricted to the vasculature of rTg‐DI rats and human CAA patients. Expression and localization of both uPA and Aβ peptides were negligible in controls. Additionally, CAA rats displayed significant overexpression of the PLAU gene in brain vasculature as well as significant elevation of uPA in their CSF. In humans, CSF Aβ40 levels were reduced in CAA patients (7.66 ± 3.36 ng/mL) compared to controls (9.58 ± 3.88 ng/mL, p=0.04). CSF uPA levels were higher in CAA patients (median (IQR): 92.0 (76.1 ‐ 109.0) pg/mL compared to human controls (68.5 (56.6 ‐ 78.4) pg/mL; p<0.001). CSF Aβ40 and uPA combined yielded the highest AUC (0.87) to distinguish CAA from controls.ConclusionuPA was overexpressed in rTg‐DI rats and its levels were significantly elevated in both rodent and human CAA. CSF Aβ40 and uPA serve as excellent biomarkers to discriminate CAA from controls, especially when combined.
Spatial mapping of subcellular disease pathways and cytoarchitecture to anatomical brain regions for multi‐scale brain simulation with The Virtual Brain
Authors: Stefanovski Leon , Bülau Konstantin , Martin Leon , Courtiol Julie , Diaz‐Cortes Margarita‐Arimatea , Langford Chloê , Palmer Jessica , Ritter Petra ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: February 2022

AbstractBackgroundComprehensive knowledge bases as NeuroMMSig, a knowledge base of multimodal mechanistic signatures, catalog knowledge about Alzheimer's Disease (AD) and its underlying candidate mechanisms. Besides, digital atlases provide information about cytoarchitectonics and receptor densities, e.g. JuBrain at the EBRAINS platform of the Human Brain Project. However, a gap exists presently with respect to the integration of the various knowledge sources. The Virtual Brain (TVB) is a full brain simulation platform that integrates multimodal imaging data with mathematical brain networks. We present a methodology to map semantic information about AD to 3D brain atlases and to use it for simulations with TVB – increasing the biological plausibility of whole‐brain simulations and disease specificity.MethodOur framework allows topological assignment of brain‐related data from different sources to the Multimodal surface‐based cortical parcellation (MMP) of the Human Connectome Project. Our tool allows mapping of stochastic information from the literature database SCAIView to brain regions. The relevance score for a specific query is calculated for anatomy‐related words from the anatomic ontology Uberon, which we transfer by a unique matrix to MMP parcels. Re‐sampling by the fsaverage brain space of freesurfer allows interoperability with other atlases. In addition, atlas‐annotated data from EBRAINS and neuroimaging data are co‐registered with MMP, enabling knowledge integration into a standardized 3D brain space.ResultOur methodologic pipeline can be used as a software to map semantic information to the brain, which we demonstrate with NeuroMMSig pathways. We further demonstrate how the resulting maps constrain TVB simulations. Face validity is provided through reproducing group‐level (AD versus controls) results of simulations integrating subject‐specific positron emission tomography when semantic information about AD stages is integrated into TVB. We elucidate how brain maps derived from different semantic queries can change simulated brain dynamics fundamentally. Literature‐derived NMDA receptor densities show significant differences between AD and healthy controls. When used to constrain TVB models, this leads to an in silico disruption of functional subnetworks in AD.ConclusionWe developed a tool for mapping semantic knowledge to anatomical brain regions. This enables multi‐scale brain simulations with increases biological plausibility and disease‐specificity for translational research.
Understanding the knowledge and attitudes to dementia in Sub‐Saharan Africa: A systematic review
Authors: Larweh Maxwell 
Published: February 2022

AbstractBackgroundA direct result of an ageing population is an increase in the prevalence of chronic non‐communicable diseases such as dementia. Creating dementia awareness and promoting positive attitude is key in early symptom recognition, diagnosis, help seeking and clarifying misconceptions about dementia. This review sought to explore the knowledge and attitudes about dementia in SSA, where there has been a rapid increase in the number of people with dementia within the last decade, and a region where spirituality and superstitions affect health behaviours.MethodSix electronic databases were searched from inception to present using a predetermined search strategy and a defined eligibility criteria. Our search initially produced 1853 articles. Three independent reviewers screened the results in two phases and 14 articles were finally selected for this review. All included papers were assessed for quality with the Mixed Methods Appraisal Tool. Relevant information about the studies were extracted by three independent investigators and recorded on a standardised form. Data synthesis followed a thematic analysis and overall themes were discussed narratively.ResultThree themes were apparent; Dementia Conceptualization, Care Arrangements and Social Responses and Dementia Gaps. A consistent finding across majority of the studies was the poor to fair knowledge of dementia among the study populations. Majority of people believed dementia was part of normal ageing and a biomedical definition of dementia was vastly lacking. Treatment seeking was pluralistic with people often combining modern medicine, traditional medicine and their religious faith. Caregiving in dementia was considered a filial responsibility with positive and negative attributes described. Negative attitudes surrounding dementia originated from the superstitions and beliefs related to dementia causation such as the belief in witchcraft. The psychological sequalae from caregiving coupled with societal representations of dementia contribute to stigmatization and abuse of persons with dementia in SSA. Dementia training for health professionals, social support for caregivers and public education were identified as urgent needs.ConclusionDementia literacy is relatively poor in SSA. There is evidence of numerous challenges faced by persons with dementia, their caregivers and health professionals involved in dementia care. Culturally appropriate education campaigns are essential in advancing a dementia friendly SSA.
Magnetoencephalography insights to dementia and drug intervention
Authors: Hughes Laura E. , Adams Natalie E. , Phillips Holly , Murley Alexander G. , Shaw Alexander , Nesbitt David , Cope Thomas E. , Bevan‐Jones W. Richard , Passamonti Luca , Rowe James B. 
Published: February 2022

AbstractBackgroundMagnetoencephalography (MEG) is a promising tool for experimental medicine in dementia, and a core technology for the Dementias Platform UK. It quantifies in vivo human network and synaptic physiology, with high‐dimensional data at a millisecond time‐scale. Its proven sensitivity to neurodegenerative disease has applications in diagnostics and early detection, mechanistic studies of pathogenesis, and biomarkers to accelerate clinical trials and evidence target engagement. Here, we build on recent work with Serotonin and GABA‐ergic modulation, to illustrate MEG insights into the neurophysiological effects of the NMDA receptor antagonist Memantine. We use Frontotemporal dementia and Progressive supranuclear palsy (bvFTD, PSP) as demonstrator conditions in view of their focal glutamatergic deficits.Method24 Patients with bvFTD and PSP, and 20 healthy controls underwent magnetoencephalography, 7T MRI spectroscopy and a battery of cognitive tests in a double‐blind placebo‐controlled crossover design, using Memantine 10mg/Placebo. We test the relationship between cortical oscillations, baseline glutamate concentration and response to pharmacological intervention.ResultNeurophysiological activity was impaired in patients, with diminished low frequency oscillations and disrupted cortical connectivity. These abnormalities correlated with reduced baseline glutamate concentration. Memantine enhanced the neuronal response, particularly in prefrontal regions.ConclusionMEG provides insights into targetable pathophysiological effects of neurodegeneration and markers for treatment studies. It is sensitive to disease and individual differences in pathophysiology, reliable, safe, well‐tolerated and sufficiently scalable for early phase trials. MEG evidence of selective neuronal dysfunction and network reorganisation can couple with microcircuit models for synaptic assays, or be used directly as a readout for interventional studies. MEG is ideally suited to support both academic and pharma initiatives, with quantitative tools for early phase clinical trials, illustrated here with Memantine, but applicable to other compounds.
Factors influencing atrophy progression in primary progressive aphasia
Authors: Lombardi Jolina , Mayer Benjamin , Huppertz Hans‐Jürgen , Straub Sarah , Semler Elisa , Uttner Ingo , Kassubek Jan , Diehl‐Schmid Janine , Danek Adrian , Levin Johannes , Fassbender Klaus , Fliessbach Klaus , Schneider Anja , Jahn Holger , Kornhuber Johannes , Landwehrmeyer Bernhard , Lauer Martin , Prudlo Johannes , Wiltfang Jens , Schroeter Matthias L. , Ludolph Albert , Otto Markus ,   German FTLD Consortium
Published: February 2022

AbstractBackgroundPrimary progressive aphasia (PPA) is a rare primarily language‐related neurodegenerative disorder that subdivides into the non‐fluent (nfvPPA) and the semantic variant (svPPA). Atrophy progression shows variant‐specific patterns, however, its extent seems highly individual and thus difficult to predict.MethodWe investigated volumetric changes in patients with nfvPPA (n=18) and svPPA (n=15) with an MRI scan (3D T1 MPRAGE sequence, 3T) at baseline and 2‐years follow‐up that were recruited from the prospective German FTLD‐consortium study. According to the LONI Probabilistic Brain Atlas (Shattuck et al., 2009), 56 brain regions were assessed with automated atlas‐based volumetry (Huppertz et al., 2010). Longitudinal volumetric changes were analyzed by means of the R software (www.r‐project.org). A possible impact of group, adjusted for age and sex, had been investigated using a linear mixed effect model. Atrophy progression for each region over two years was correlated (Pearson or Kendall rank correlation; 95% BCa bootstrap CI with 1000 replicates) with age at symptom onset, years of education, and disease duration to review a possible relation.ResultVolume change within 2‐years revealed parts of the left frontal lobe (up to ‐10%) and subcortical regions in nfvPPA and parts of the left temporal lobe (up to ‐15%) and the hippocampus/amygdala complex in svPPA as most progressive.A correlation analysis with age at symptom onset rendered no relevant results. Higher educated patients showed more atrophy in the right parahippocampal gyrus in nfvPPA and less atrophy in white matter portions of the left superior frontal, the bilateral middle and inferior frontal, the right middle and bilateral lateral orbitofrontal and the bilateral cingulate gyrus in svPPA. Shorter disease duration correlated with higher atrophy in the caudate and putamen in nfvPPA, and in the left middle and inferior temporal gyrus, the right superior and bilateral middle occipital gyrus, the left cuneus, and left angular gyrus in svPPA.ConclusionAge at symptom onset showed no interrelation with atrophy progression in PPA. Higher education levels seem to slow white matter decrease of frontal areas in svPPA. Shorter disease duration is related to increased volume loss in some primarily affected regions in both nfvPPA and svPPA.