bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel eDNA approaches to monitor Western honey bee (Apis mellifera) microbial and arthropod communities
Authors: Boardman Leigh , Marcelino Jose A.P. , Valentin Rafael E. , Boncristiani Humberto , Standley Jennifer , Ellis James D. 
Published: September 2022

AbstractPests and pathogens are a continuous threat to the health of Western honey bees Apis mellifera L. Monitoring honey bee colonies for arthropod pests, disease-causing bacteria and fungi, and early detection of new invasions is essential to maintain the pollination services provided by honey bees. Here, we investigated the feasibility of using eDNA metabarcoding to detect honey bee pests and pathogens in their hives and across their foraging environment. We sampled 13 different surfaces within and outside hives from our test apiary to determine where the most informative eDNA could be obtained. Furthermore, we compared two main eDNA collection techniques – wiping surfaces with moistened forensic swabs and using a spray/wash technique that washed surface DNA into a bucket, before collecting the DNA on a filter. We used DNA metabarcoding with universal primer sets to target arthropod, bacterial and fungal communities. Our results showed that most surfaces yielded usable DNA, and that results of the swabs and spray/wash methods were similar when they could be applied to the same surface. We were able to detect DNA from the small hive beetle (Aethina tumida), Varroa destructor mites and European foulbrood (Melissococcus plutonius), all of which matched our visual observations of clinical signs of these pests and pathogens in the hives we tested. DNA from some species was location specific, which has implications for using eDNA as a monitoring tool. Collectively, our data show that eDNA metabarcoding can accurately detect DNA from arthropods and microbes honey bees contact and has the potential to provide information on disease and pest incidence, Apis species identity, and A. mellifera subspecies identity of the colony and/or apiary. In sum, eDNA metabarcoding can be used as a comprehensive molecular predictor tool for colony health surveys.
Microfluidic immuno-serology assay revealed a limited diversity of protection against COVID-19 in patients with altered immunity
Authors: Kim Dongjoo , Biancon Giulia , Bai Zhiliang , VanOudenhove Jennifer , Liu Yuxin , Kothari Shalin , Gowda Lohith , Kwan Jennifer M. , Buitrago-Pocasangre Nicholas Carlos , Lele Nikhil , Asashima Hiromitsu , Racke Michael K. , Wilson JoDell E. , Givens Tara S. , Tomayko Mary M. , Schulz Wade L. , Longbrake Erin E. , Hafler David A. , Halene Stephanie , Fan Rong 
Published: September 2022

AbstractThe immune response to SARS-CoV-2 for patients with altered immunity such as hematologic malignancies and autoimmune disease may differ substantially from that in general population. These patients remain at high risk despite wide-spread adoption of vaccination. It is critical to examine the differences at the systems level between the general population and the patients with altered immunity in terms of immunologic and serological responses to COVID-19 infection and vaccination. Here, we developed a novel microfluidic chip for high-plex immuno-serological assay to simultaneously measure up to 50 plasma or serum samples for up to 50 soluble markers including 35 plasma proteins, 11 anti-spike/RBD IgG antibodies spanning all major variants, and controls. Our assay demonstrated the quintuplicate test in a single run with high throughput, low sample volume input, high reproducibility and high accuracy. It was applied to the measurement of 1,012 blood samples including in-depth analysis of sera from 127 patients and 21 healthy donors over multiple time points, either with acute COVID infection or vaccination. The protein association matrix analysis revealed distinct immune mediator protein modules that exhibited a reduced degree of diversity in protein-protein cooperation in patients with hematologic malignancies and patients with autoimmune disorders receiving B cell depletion therapy. Serological analysis identified that COVID infected patients with hematologic malignancies display impaired anti-RBD antibody response despite high level of anti-spike IgG, which could be associated with limited clonotype diversity and functional deficiency in B cells and was further confirmed by single-cell BCR and transcriptome sequencing. These findings underscore the importance to individualize immunization strategy for these high-risk patients and provide an informative tool to monitor their responses at the systems level.
Altered correlation of concurrently recorded EEG-fMRI connectomes in temporal lobe epilepsy
Authors: Wirsich Jonathan , Iannotti Giannina Rita , Ridley Ben , Shamshiri Elhum A , Sheybani Laurent , Grouiller Frédéric , Bartolomei Fabrice , Seeck Margitta , Lazeyras François , Ranjeva Jean-Philippe , Guye Maxime , Vulliemoz Serge 
Published: September 2022

AbstractWhole brain, large-scale functional connectivity networks or connectomes have been characterized on different temporal and spatial scales in humans using EEG and fMRI. Whole brain epileptic networks have been investigated with both EEG and fMRI, but due to the different acquisition approaches it is unclear to what extent those results can be related. In consequence clinical research in epilepsy would profit from a unified multimodal functional connectome description as a linking framework to better map underlying brain function and pathological functional networks. In this study we aim to characterize the spatial correlation between EEG and fMRI connectivity in temporal lobe epilepsy.From two independent centers, we acquired resting-state concurrent EEG-fMRI from a total of 35 healthy controls and 34 TLE patients (18 right TLE and 16 left TLE). Data was projected into the Desikan brain atlas (mean BOLD activity for fMRI and source reconstruction for EEG). Whole brain functional connectivity from fMRI (Pearson correlation) and EEG (corrected imaginary part of the coherency) were correlated for all subjects.In healthy controls, average EEG and fMRI whole-brain connectivity was moderately correlated (r∼0.3). For both imaging centers, correlation between EEG and fMRI whole brain connectivity was increased in rTLE when compared to controls for lower frequency bands (EEG-delta, theta and alpha). Conversely correlation between EEG and fMRI connectivity of lTLE patients was decreased in respect to healthy subjects (EEG-beta vs. fMRI connectivity only). While the alteration of the EEG-fMRI correlation in rTLE patients could not be related to a local effect, in lTLE patients it was locally linked to the Default Mode Network.We demonstrated, using two independent datasets, that EEG and fMRI connectivity is correlated for both healthy subjects and patients. The increased correlation of EEG and fMRI connectivity in rTLE patients vs. controls and decreased correlation in lTLE patients vs. controls suggests a differential organization of mono-lateral focal epilepsy of the same type, which needs to be considered when comparing fMRI to EEG connectivity. It also demonstrates that each modality provides distinct information, highlighting the benefit of multimodal assessment in epilepsy. The observed property of distinct topological patterns depending on the lateralization of the epilepsy could be taken into account when clinically defining the epileptic focus of patients.
Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK)
Authors: Tydeman Florence , Pfeffer Paul E , Vivaldi Giulia , Holt Hayley , Talaei Mohammad , Jolliffe David A , Davies Gwyneth A , Lyons Ronan A , Griffiths Christopher J , Kee Frank , Sheikh Aziz , Shaheen Seif O , Martineau Adrian R 
Published: September 2022

ABSTRACTBackgroundThe imposition of restrictions on social mixing early in the COVID-19 pandemic was followed by a reduction in asthma exacerbations in multiple settings internationally. Temporal trends in social mixing, incident acute respiratory infections (ARI) and asthma exacerbations following relaxation of COVID-19 restrictions have not yet been described.MethodsWe conducted a population-based longitudinal study in 2,312 UK adults with asthma between November 2020 and April 2022. Details of face covering use, social mixing, incident ARI and moderate/severe asthma exacerbations were collected via monthly on-line questionnaires. Temporal changes in these parameters were visualised using Poisson generalised additive models. Multilevel logistic regression was used to test for associations between incident ARI and risk of asthma exacerbations, adjusting for potential confounders.ResultsRelaxation of COVID-19 restrictions from April 2021 coincided with reduced face covering use (p<0.001), increased frequency of indoor visits to public places and other households (p<0.001) and rising incidence of COVID-19 (p<0.001), non-COVID-19 ARI (p<0.001) and moderate/severe asthma exacerbations (p=0.007). Incident non-COVID-19 ARI associated independently with increased risk of asthma exacerbation (adjusted odds ratio 5.75, 95% CI 4.75 to 6.97) as did incident COVID-19, both prior to emergence of the omicron variant of SARS-CoV-2 (5.89, 3.45 to 10.04) and subsequently (5.69, 3.89 to 8.31).ConclusionsRelaxation of COVID-19 restrictions coincided with decreased face covering use, increased social mixing and a rebound in ARI and asthma exacerbations. Associations between incident ARI and risk of moderate/severe asthma exacerbation were similar for non-COVID-19 ARI and COVID-19, both before and after emergence of the SARS-CoV-2 omicron variant.FundingBarts Charity, UKRI
An automated EEG algorithm detect polymorphic delta activity in acute encephalopathy presenting as postoperative delirium
Authors: Ditzel Fienke L , Hut Suzanne CA , Dijkstra-Kersten Sandra MA , Numan Tianne , Leijten Frans SS , van den Boogaard Mark , Slooter Arjen JC 
Published: September 2022

AbstractAimDelirium, a clinical manifestation of acute encephalopathy, is often unrecognised. An important electroencephalography (EEG) characteristic of acute encephalopathy is polymorphic delta activity (PDA), which can be detected automatically. We aimed to study whether automated assessment of PDA in unselected EEG could detect acute encephalopathy that presents clinically as delirium.MethodsWe assessed PDA in 145 elderly patients using the first 96 seconds of unselected single-channel EEG (Fp2-Pz). We compared fully automated PDA detection with visual inspection by EEG experts. Additionally, we tested its performance as a delirium monitor by comparing PDA detection with a standardized delirium assessment by a clinical expert panel.ResultsPDA detection showed an area under the receiver operating characteristic (AUC) of 0.86 (95%CI 0.81–0.90) compared to EEG experts. When compared with the delirium classification of clinical experts, PDA detection achieved an AUC of 0.78 (95%CI 0.71–0.85). PDA detection correlated with the likelihood of delirium, its severity and the levels of attention and consciousness (all p<0.001).ConclusionAutomated PDA detection in unselected, single-channel EEG can classify acute encephalopathy clinically presenting as delirium.SignificanceA fully automated EEG algorithm can assist in the recognition of delirium.
High-pass filter settings and possible mechanism of discrete electrograms in left bundle branch pacing
Authors: Shen Jiabo , Jiang Longfu , Wu Hao , Li Hengdong , Zhang Lu , Zhong Jinyan , Zhuo Shanshan , Pan Lifang 
Published: September 2022

AbstractObjectiveThe characteristics of discrete intracardiac electrograms in selective left bundle branch (SLBB) pacing (SLBBP) have not been described in detail previously. This study aimed to examine the effect of different high-pass filter (HPF) settings on discrete ventricular components in an intracardiac electrogram (EGM) and to analyze its possible mechanisms.MethodsThis study included 95 patients with indications of permanent cardiac pacing. EGMs were collected at four different HPF settings (30, 60, 100, and 200 Hz) with a low-pass filter at 500 Hz, and their possible mechanisms were analyzed.ResultsLBBP was successfully achieved in 92.6% (88/95) of patients. SLBBP was achieved in 80 patients. The occurrence rates of discrete EGM were 18.9%, 40.0%, 74.7%, and 84.2% for HPF settings of 30 Hz, 60 Hz, 100 Hz, and 200 Hz, respectively. The analysis of discrete ECG detection showed significant differences between the different HPF settings. By using the discrete EGM as the SLBB capture golden standard, the results of EGMs revealed that the 30 Hz HPF has a sensitivity of 23% and specificity of 100%. The 60 Hz HPF had a sensitivity of 48% and a specificity of 100%. The 100 Hz HPF had a sensitivity of 89% and a specificity of 100%. The 200 Hz HPF had a sensitivity of 100% and specificity of 100%.ConclusionsAn optimal HPF setting of 200 Hz is recommended for discrete electrogram detection. A discrete EGM should exhibit an isoelectric interval. A steep deflection and spinous ventricular EGM morphology nearly identify an intrinsic EGM morphology.
The impact and progression of the COVID-19 pandemic in Bulgaria in its first two years
Authors: Rangachev Antoni , Marinov Georgi K. , Mladenov Mladen 
Published: September 2022

AbstractAfter initially having low levels of SARS-CoV-2 infections for much of the year, at the end of 2020 Bulgaria experienced a major epidemic surge, which caused the highest recorded excess mortality in Europe and among the highest in the word (Excess Mortality Rate, or EMR ∼ 0.25%). Two more major waves followed in 2021, followed by another one in early 2022. In this study we analyze the temporal and spatial patterns of excess mortality at the national and local levels and across different demographic groups in Bulgaria, and compare those at the European level. The country has continued to exhibit the previous pattern of extremely high excess mortality as measured both by crude mortality metrics (EMR ∼ 1.05% up to the end of March 2022) and by standardized ones – Potential Years of Life Lost (PYLL) and Aged-Standardized Years of life lost Rate (ASYR). Unlike Western Europe, the bulk of excess mortality in Bulgaria, as well as in several other countries in Eastern Europe, occurred in the second year of the pandemic, likely related to the differences in the levels of vaccination coverage between these regions. We also observe even more extreme levels of excess mortality at the regional level and in some subpopulations (e.g. total EMR values for males ≥ 2% and EMR values for males aged 40-64 ≥ 1% in certain areas). We discuss these observations in light of the estimates of infection fatality rate (IFR) and eventual population fatality rate (PFR) made early in the course of the pandemic.
Mitochondrial dysfunction underlies cortical atrophy in prodromal synucleinopathies
Authors: Rahayel Shady , Tremblay Christina , Vo Andrew , Mišić Bratislav , Lehéricy Stéphane , Arnulf Isabelle , Vidailhet Marie , Corvol Jean-Christophe ,   the ICEBERG Study Group, Gagnon Jean-François , Postuma Ronald B. , Montplaisir Jacques , Lewis Simon , Matar Elie , Martens Kaylena Ehgoetz , Borghammer Per , Knudsen Karoline , Hansen Allan K. , Monchi Oury , Gan-Or Ziv , Dagher Alain 
Published: September 2022

ABSTRACTIsolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal synucleinopathy characterized by several changes including brain atrophy. The mechanisms underlying atrophy in iRBD are poorly understood. Here, we performed imaging transcriptomics and comprehensive spatial mapping in a multicentric cohort of 171 polysomnography-confirmed iRBD patients and 238 controls with T1-weighted MRI to investigate the gene expression patterns and the specific neurotransmitter, functional, cytoarchitectonic, and cognitive brain systems associated with cortical thinning in iRBD. We found that genes involved in mitochondrial function and macroautophagy were the strongest contributors to the thinning occurring in iRBD. Moreover, we demonstrated that thinning was constrained by the brain’s connectome and that it mapped onto specific networks involved in motor and planning functions. In contrast with thickness, changes in cortical surface area related to distinct gene and spatial mapping patterns. This study demonstrates that the development of atrophy in synucleinopathies is constrained by specific genes and networks.
Revisiting deficits in threat and safety appraisal in obsessive-compulsive disorder
Authors: Hearne Luke J. , Breakspear Michael , Harrison Ben J. , Hall Caitlin V. , Savage Hannah S. , Robinson Conor , Sonkusare Saurabh , Savage Emma , Nott Zoie , Marcus Leo , Naze Sebastien , Burgher Bjorn , Zalesky Andrew , Cocchi Luca 
Published: September 2022

AbstractCurrent behavioural treatment of obsessive-compulsive disorder (OCD) is informed by fear conditioning and involves iteratively re-evaluating previously threatening stimuli as safe. However, there is limited research investigating the neurobiological response to conditioning and reversal of threatening stimuli in individuals with OCD. A clinical sample of individuals with OCD (N=45) and matched healthy controls (N=45) underwent functional Magnetic Resonance Imaging (fMRI). While in the scanner, participants completed a well-validated fear reversal task and a resting-state scan. We found no evidence for group differences in task-evoked brain activation or functional connectivity in OCD. Multivariate analyses encompassing all participants in the clinical and control groups suggested that subjective appraisal of threatening and safe stimuli were associated with a larger difference in brain activity than the contribution of OCD symptoms. In particular, we observed a brain-behaviour continuum whereby heightened affective appraisal was related to increased bilateral insula activation during the task (r= 0.39,pFWE= 0.001). These findings suggest that changes in conditioned threat-related processes may not be a core neurobiological feature of OCD and encourage further research on the role of subjective experience in fear conditioning.
Zinc supplementation induced transcriptional changes in primary human retinal pigment epithelium: a single-cell RNA sequencing study to understand age-related macular degeneration
Authors: Emri Eszter , Cappa Oisin , Kelly Caoimhe , Kortvely Elod , SanGiovanni John Paul , McKay Brian , Bergen Arthur A , Simpson David A , Lengyel Imre 
Published: September 2022

AbstractZinc supplementation had been shown to be beneficial to slow the progression of age-related macular degeneration (AMD). However, the molecular mechanism underpinning this benefit is not well understood. In this study, we used single-cell RNA sequencing to identify transcriptomic changes induced by zinc supplementation in human primary retinal pigment epithelial (RPE) cells in culture. The RPE cells were allowed to mature for up to 19 weeks. After one or 18 weeks in culture, we supplemented the culture medium with 125 μM added zinc for one week. During maturation RPE cells developed high transepithelial electrical resistance, extensive, but variable, pigmentation and deposited sub-RPE material similar to the hallmark lesions of AMD. Unsupervised cluster analysis of the combined transcriptome of the cells isolated after two-, nine- and 19 weeks in culture, showed a significant degree of heterogeneity. Clustering based on 234 pre-selected RPE specific genes, identified from the literature, divided the cells into two distinct clusters we defined as more- and less-differentiated cells. The proportion of more differentiated cells increased with time in culture, but appreciable numbers of cells remained less differentiated even at 19 weeks. Pseudotemporal ordering identified 537 genes that could be implicated in the dynamics of RPE cell differentiation (FDR< 0.05). Zinc treatment resulted in the differential expression of 281 of these genes (FDR< 0.05). These genes were associated with several biological pathways including extracellular remodelling, retinoid metabolism and modulation ofID1/ID3transcriptional regulation, to name a few. Overall, zinc had a multitude of effects on the RPE transcriptome including a number of genes that are involved in pigmentation, complement regulation, mineralisation and cholesterol metabolism processes associated with AMD.
MMD scaffolds ACSL4 and MBOAT7 to promote polyunsaturated phospholipid synthesis and susceptibility to ferroptosis
Authors: Phadnis Vaishnavi V. , Snider Jamie , Wong Victoria , Vaccaro Kyle D. , Kunchok Tenzin , Allen Juliet , Yao Zhong , Geng Betty , Weiskopf Kipp , Stagljar Igor , Henry Whitney S. , Weinberg Robert A. 
Published: September 2022

SummaryFerroptosis is a form of regulated cell death with roles in degenerative diseases and cancer. Ferroptosis is driven by excessive iron-dependent peroxidation of membrane phospholipids, especially those containing the polyunsaturated fatty acid arachidonic acid. Here, we reveal that an understudied Golgi membrane scaffold protein, MMD, promotes susceptibility to ferroptosis in ovarian and renal carcinoma cells. Upregulation of MMD correlates with sensitization to ferroptosis upon monocyte-to-macrophage differentiation. Mechanistically, MMD interacts with ACSL4 and MBOAT7, two enzymes that catalyze consecutive reactions in the biosynthesis of phosphatidylinositol (PI) containing arachidonic acid. MMD increases cellular levels of arachidonoyl-phospholipids and heightens susceptibility to ferroptosis in an ACSL4- and MBOAT7-dependent manner. We propose that MMD potentiates the synthesis of arachidonoyl-PI by bridging ACSL4 with MBOAT7. This molecular mechanism not only clarifies the biochemical underpinnings of ferroptosis susceptibility, with potential therapeutic implications, but also contributes to our understanding of the regulation of cellular lipid metabolism.Graphical Abstract
The Arthropoda-specific Tramtrack group BTB protein domains use previously unknown interface to form hexamers
Authors: Bonchuk Artem N. , Balagurov Konstantin I. , Baradaran Rozbeh , Boyko Konstantin M. , Sluchanko Nikolai N. , Khrustaleva Anastasia M. , Burtseva Anna D. , Arkova Olga V. , Khalisova Karina K. , Popov Vladimir O. , Naschberger Andreas , Georgiev Pavel G. 
Published: September 2022

AbstractBTB (Bric-a-brack, Tramtrack and Broad Complex) is a diverse group of protein-protein interaction domains found within metazoan proteins. Transcription factors contain a dimerizing BTB subtype with a characteristic N-terminal extension. The Tramtrack group (TTK) is a distinct type of BTB domain, which can multimerize. Single-particle cryo-EM microscopy revealed that the TTK-type BTB domains assemble into a hexameric structure consisting of three canonical BTB dimers connected through a previously uncharacterized interface. We demonstrated that the TTK-type BTB domains are found only in Arthropods and have undergone lineage-specific expansion in modern insects. TheDrosophilagenome encodes 24 transcription factors with TTK-type BTB domains, whereas only four have non-TTK-type BTB domains. Yeast two-hybrid analysis revealed that the TTK-type BTB domains have an unusually broad potential for heteromeric associations presumably through dimer-dimer interaction interface. Thus, the TTK-type BTB domains are a structurally and functionally distinct group of protein domains specific to Arthropodan transcription factors.