Temporal Trends in the Impact Factor of European versus USA Biomedical Journals

BACKGROUND: The impact factors of biomedical journals tend to rise over time. We sought to assess the trend in the impact factor, during the past decade, of journals published on behalf of United States (US) and European scientific societies, in four select biomedical subject categories (Biology, Cell Biology, Critical Care Medicine, and Infectious Diseases). METHODS: We identified all journals included in the above-mentioned subject categories of Thomson Reuters Journal Citation Reports® for the years 1999, 2002, 2005, and 2008. We selected those that were published on behalf of US or European scientific societies, as documented in journal websites. RESULTS: We included 167 journals (35 in the subject category of Biology, 79 in Cell Biology, 27 in Critical Care Medicine, and 26 in Infectious Diseases). Between 1999 and 2008, the percentage increase in the impact factor of the European journals was higher than for the US journals (73.7±110.0% compared with 39.7±70.0%, p = 0.049). Regarding specific subject categories, the percentage change in the factor of the European journals tended to be higher than the respective US journals for Cell Biology (61.7% versus 16.3%), Critical Care Medicine (212.4% versus 65.4%), Infectious Diseases (88.3% versus 48.7%), whereas the opposite was observed for journals in Biology (41.0% versus 62.5%). CONCLUSION: Journals published on behalf of European scientific societies, in select biomedical fields, may tend to close the "gap" in impact factor compared with those of US societies. WHAT'S ALREADY KNOWN ABOUT THIS TOPIC?: The impact factors of biomedical journals tend to rise through years. The leading positions in productivity in biomedical research are held by developed countries, including those from North America and Western Europe. WHAT DOES THIS ARTICLE ADD?: The journals from European biomedical scientific societies tended, over the past decade, to increase their impact factor more than the respective US journals

Microglial activation, tau and amyloid deposition in TREM2 p.R47H carriers and mild cognitive impairment patients: a multi-modal/multi-tracer PET/MRI imaging study with influenza vaccine immune challenge

Availability of data and materials: The datasets used and analysed during the current study are available from the corresponding author on reasonable request.Supplementary information is available online at: https://link.springer.com/article/10.1186/s12974-023-02945-0#Sec20 .Copyright © The Author(s) 2023. Background: Microglia are increasingly understood to play an important role in the pathogenesis of Alzheimer’s disease. The rs75932628 (p.R47H) TREM2 variant is a well-established risk factor for Alzheimer’s disease. TREM2 is a microglial cell surface receptor. In this multi-modal/multi-tracer PET/MRI study we investigated the effect of TREM2 p.R47H carrier status on microglial activation, tau and amyloid deposition, brain structure and cognitive profile. Methods: We compared TREM2 p.R47H carriers (n = 8; median age = 62.3) and participants with mild cognitive impairment (n = 8; median age = 70.7). Participants underwent two [18F]DPA-714 PET/MRI scans to assess TSPO signal, indicative of microglial activation, before and after receiving the seasonal influenza vaccination, which was used as an immune stimulant. Participants also underwent [18F]florbetapir and [18F]AV1451 PET scans to assess amyloid and tau burden, respectively. Regional tau and TSPO signal were calculated for regions of interest linked to Braak stage. An additional comparison imaging healthy control group (n = 8; median age = 45.5) had a single [18F]DPA-714 PET/MRI. An expanded group of participants underwent neuropsychological testing, to determine if TREM2 status influenced clinical phenotype. Results: Compared to participants with mild cognitive impairment, TREM2 carriers had lower TSPO signal in Braak II (P = 0.04) and Braak III (P = 0.046) regions, despite having a similar burden of tau and amyloid. There were trends to suggest reduced microglial activation following influenza vaccine in TREM2 carriers. Tau deposition in the Braak VI region was higher in TREM2 carriers (P = 0.04). Furthermore, compared to healthy controls TREM2 carriers had smaller caudate (P = 0.02), total brain (P = 0.049) and white matter volumes (P = 0.02); and neuropsychological assessment revealed worse ADAS-Cog13 (P = 0.03) and Delayed Matching to Sample (P = 0.007) scores. Conclusions: TREM2 p.R47H carriers had reduced levels of microglial activation in brain regions affected early in the Alzheimer’s disease course and differences in brain structure and cognition. Changes in microglial response may underlie the increased Alzheimer’s disease risk in TREM2 p.R47H carriers. Future therapeutic agents in Alzheimer’s disease should aim to enhance protective microglial actions.This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115976. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. This project received funding and access to the [18F]florbetapir and [18F]AV1451 PET tracers from Avid and Lilly UK. Avid and Lilly UK were not involved in data analysis and interpretation. This project has received funding from the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. This research was supported by the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. This research was supported by researchers at the National Institute for Health Research University College London Hospitals Biomedical Research Centre. A partnership between UCL and University College London Hospitals NHS Foundation Trust. This work was funded in part through the MRC Proximity to Discovery: Industry Engagement Fund (External Collaboration, Innovation and Entrepreneurism: Translational Medicine in Exeter 2 (EXCITEME2) ref. MC_PC_17189) awarded to Dr Creese and MRC grant MR/N015746/1

Differential Effect of Demographics, Processing Speed, and Depression on Cognitive Function in 755 Non-demented Community-dwelling Elderly Individuals

Background:Several factors may account for inter-and intra-individual variability in cognitive functions, including age, gender, education level, information processing speed, and mood.Objective:To evaluate the combined contribution of demographic factors, information processing speed, and depressive symptoms to scores on several diagnostic cognitive measures that are commonly used in geriatric neuropsychological practice in Greece.Methods:Using a cross-sectional study, we established a multivariate general linear model and analyzed the predictive role of age, gender, education, information processing speed (Trail Making Test-Part A), and depressive symptoms (Geriatric Depression Scale-15 Items) on measures of general cognitive status (Mini-Mental State Examination), verbal memory (Rey Auditory Verbal Learning Test), language (Confrontation Naming), and executive functions (Category and Phonemic Fluency, Trail Making Test-Part B) for a sample of 755 healthy, community-dwelling Greek individuals aged 50 to 90 years.Results:Participant factors significantly but differentially contributed to cognitive measures. Demographic factors and information processing speed emerged as the significant predictors for the majority of the cognitive measures (Mini-Mental State Examination; Rey Auditory Verbal Learning Test; Confrontation Naming; Category and Phonemic Fluency; Trail Making Test-Part B), whereas depressive symptoms significantly predicted verbal memory and semantic fluency measures (Rey Auditory Verbal Learning Test and Category Fluency).Conclusions:Clinicians should consider participant demographics, underlying slowing of processing speed, and depressive symptoms as potential confounding factors in cognitive measures. Our findings may explain the observed inter-and intra-individual variability in cognitive functions in the elderly population. © 2019 Wolters Kluwer Health, Inc. All rights reserved

Activation of FADD-Dependent neuronal death pathways as a predictor of pathogenicity for LRRK2 mutations

Background Despite the plethora of sequence variants in LRRK2, only a few clearly segregate with PD. Even within this group of pathogenic mutations, the phenotypic profile can differ widely. Objective We examined multiple properties of LRRK2 behavior in cellular models over-expressing three sequence variants described in Greek PD patients in comparison to several known pathogenic and non-pathogenic LRRK2 mutations, to determine if specific phenotypes associated with pathogenic LRRK2 can be observed in other less-common sequence variants for which pathogenicity is unclear based on clinical and/or genetic data alone. Methods The oligomerization, activity, phosphorylation, and interaction with FADD was assessed in HEK293T cells over-expressing LRRK2; while the induction of neuronal death was determined by quantifying apoptotic nuclei in primary neurons transiently expressing LRRK2. Results One LRRK2 variant, A211V, exhibited a modest increase in kinase activity, whereas only the pathogenic mutants G2019S and I2020T displayed significantly altered auto-phosphorylation. We observed an induction of detergent-insoluble high molecular weight structures upon expression of pathogenic LRRK2 mutants, but not the other LRRK2 variants. In contrast, each of the variants tested induced apoptotic death of cultured neurons similar to pathogenic LRRK2 in a FADD-dependent manner. © 2016 Melachroinou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Distinct profiles of LRRK2 activation and Rab GTPase phosphorylation in clinical samples from different PD cohorts

Despite several advances in the field, pharmacodynamic outcome measures reflective of LRRK2 kinase activity in clinical biofluids remain urgently needed. A variety of targets and approaches have been utilized including assessments of LRRK2 itself (levels, phosphorylation), or its substrates (e.g. Rab10 or other Rab GTPases). We have previously shown that intrinsic kinase activity of LRRK2 isolated from PBMCs of G2019S carriers is elevated, irrespective of disease status. In the present study we find that phosphorylation of Rab10 is also elevated in G2019S carriers, but only those with PD. Additionally, phosphorylation of this substrate is also elevated in two separate idiopathic PD cohorts, but not in carriers of the A53T mutation in α-synuclein. In contrast, Rab29 phosphorylation was specifically reduced in urinary exosomes from A53T and idiopathic PD patients. Taken together, our findings highlight the need for the assessment of multiple complimentary targets for a more comprehensive picture of the disease. © 2022, The Author(s)