bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 risk factors amongst 14,786 care home residents: An observational longitudinal analysis including daily community positive test rates of COVID-19, hospital stays, and vaccination status in Wales (UK) between 1st September 2020 and 1st May 2021
Authors: Hollinghurst Joe , Hollinghurst Robyn , North Laura , Mizen Amy , Akbari Ashley , Long Sara , Lyons Ronan A , Fry Rich 
Published: October 2021

ABSTRACTObjectivesDetermine individual level risk factors for care home residents testing positive for SARS-CoV-2.Study DesignLongitudinal observational cohort study using individual-level linked data.SettingCare home residents in Wales (United Kingdom) between 1st September 2020 and 1st May 2021.Participants14,786 older care home residents (aged 65+). Our dataset consisted of 2,613,341 individual-level daily observations within 697 care homes.MethodsWe estimated odds ratios (ORs [95% confidence interval]) using multilevel logistic regression models. Our outcome of interest was a positive SARS-CoV-2 polymerase chain reaction (PCR) test. We included time dependent covariates for the estimated community positive test rate of COVID-19, hospital admissions, and vaccination status. Additional covariates were included for age, positive PCR tests prior to the study, sex, frailty (using the hospital frailty risk score), and specialist care home services.ResultsThe multivariable logistic regression model indicated an increase in age (OR 1.01 [1.00,1.01] per year of age), community positive test rate (OR 1.13 [1.12,1.13] per percent increase in positive test rate), hospital inpatients (OR 7.40 [6.54,8.36]), and residents in care homes with non-specialist dementia care (OR 1.42 [1.01,1.99]) had an increased odds of a positive test. Having a positive test prior to the observation period (OR 0.58 [0.49,0.68]) and either one or two doses of a vaccine (0.21 [0.17,0.25] and 0.05 [0.02,0.09] respectively) were associated with a decreased odds of a positive test.ConclusionsOur findings suggest care providers need to stay vigilant despite the vaccination rollout, and extra precautions should be taken when caring for the most vulnerable. Furthermore, minimising potential COVID-19 infection for care home residents admitted to hospital should be prioritised.SUMMARY BOXESSection 1: What is already known on this topicCare home residents are at a high risk of COVID-19 infection, but existing literature has mainly focussed on excess mortality rather than infection risk.In our study we were able to investigate associations between COVID-19 infections and the community positive test rate of COVID-19, the vaccination status of care home residents, hospital admissions, and frailty.Section 2: What this study addsOur study suggests an increased community positive test rate and hospital inpatients had an increased likelihood of a positive SARS-CoV-2 polymerase chain reaction test, whilst one or two doses of vaccination indicated a decreased chance of a positive test.Our findings suggest care providers need to stay vigilant despite the vaccination rollout, and extra precautions should be taken when caring for the most vulnerable, especially in a hospital setting.
Plaque Contact Surface Area and Flow Lumen Volume Predict Stroke Risk in Extracranial Carotid Artery Stenosis
Authors: Gedney Ryan , Kung Ethan , Mehta Veena , Brown Adam , Bridges Matthew , Veeraswamy Ravi 
Published: October 2021

AbstractThe standard indication for intervention in asymptomatic disease is currently percent stenosis in the internal carotid artery as measured by the NASCET method, which remains limited in discriminating power. CT angiography (CTA) is widely used to calculate NASCET stenosis but also offers the opportunity to analyze carotid artery plaques from a morphological perspective that has not been widely utilized. We aim to improve stroke risk stratification of patients with carotid artery stenosis using plaque 3D modeling and image analysis. Patients with CTAs appropriate for 3D reconstruction were identified from an NIH designated stroke center database, and carotid arteries were segmented and analyzed using software algorithms to calculate contact surface area between the plaque and blood flow (CSA), and volume of the flow lumen within the region of the plaque (FLV). These novel parameters factor in the 3D morphometry inherent to each carotid plaque. A total of 134 carotid arteries were analyzed, 33 of which were associated with an ipsilateral stroke. Plaques associated with stroke demonstrated statistically significant increases in average CSA and FLV when compared to those not associated with stroke. When compared to NASCET percent stenosis, CSA and FLV both demonstrated a larger area under the receiver operating characteristics curve (AUC) in predicting stroke risk in patients with carotid stenosis. The data presented here demonstrate morphological features of carotid plaques that are independent of NASCET criteria stratification and may present an improved method in assessing stroke risk in patients with carotid artery stenosis.
Direct brain recordings reveal continuous encoding of structure in random stimuli
Authors: Fuhrer Julian , Glette Kyrre , Ivanovic Jugoslav , Larsson Pål Gunnar , Bekinschtein Tristan , Kochen Silvia , Knight Robert T. , Tørresen Jim , Solbakk Anne-Kristin , Endestad Tor , Blenkmann Alejandro 
Published: October 2021

AbstractThe brain excels at processing sensory input, even in rich or chaotic environments. Mounting evidence attributes this to the creation of sophisticated internal models of the environment that draw on statistical structures in the unfolding sensory input. Understanding how and where this modeling takes place is a core question in statistical learning and predictive processing. In this context, we address the role of transitional probabilities as an implicit structure supporting the encoding of a random auditory stream. Leveraging information-theoretical principles and the high spatiotemporal resolution of intracranial electroencephalography, we analyzed the trial-by-trial high-frequency activity representation of transitional probabilities. This unique approach enabled us to demonstrate how the brain continuously encodes structure in random stimuli and revealed the involvement of a network outside of the auditory system, including hippocampal, frontal, and temporal regions. Linking the frame-works of statistical learning and predictive processing, our work illuminates an implicit process that can be crucial for the swift detection of patterns and unexpected events in the environment.
Distinct signatures of loss of consciousness during Focal Impaired Awareness versus Focal to Bilateral Tonic Clonic seizures
Authors: Juan Elsa , Górska Urszula , Kozma Csaba , Papantonatos Cynthia , Bugnon Tom , Denis Colin , Kremen Vaclav , Worrell Greg , Struck Aaron F. , Bateman Lisa M. , Merricks Edward M. , Blumenfeld Hal , Tononi Giulio , Schevon Catherine , Boly Melanie 
Published: October 2021

AbstractLoss of consciousness (LOC) is a hallmark of many epileptic seizures and carries risks of serious injury and sudden death. While cortical sleep-like activities accompany LOC during focal impaired awareness (FIA) seizures, the mechanisms of LOC during focal to bilateral tonic-clonic (FBTC) seizures remain unclear. Quantifying differences in markers of cortical activation and ictal recruitment between FIA and FBTC seizures may also help to understand their different consequences for clinical outcomes and to optimize neuromodulation therapies.We quantified clinical signs of LOC and intracranial EEG (iEEG) activity during 129 FIA and 50 FBTC from 41 patients. We characterized iEEG changes both in the seizure onset zone (SOZ) and in areas remote from SOZ with a total of 3386 electrodes distributed across brain areas. First, we compared the dynamics of iEEG sleep-like activities: slow-wave activity (SWA; 1-4 Hz) and beta/delta ratio (B/D; a validated marker of cortical activation) during FIA vs. FBTC. Second, we quantified differences between FBTC and FIA for a marker validated to detect ictal cross-frequency coupling: phase-locked high-gamma (PLHG; high gamma phased locked to low frequencies) and a marker of ictal recruitment: the epileptogenicity index (i.e. the number of channels crossing an energy ratio threshold for high vs. low frequency power). Third, we assessed changes in iEEG activity preceding and accompanying behavioral generalization onset and their correlation with electromyogram (EMG) channels. In addition, we analyzed human cortical multi-unit activity recorded with Utah arrays during three FBTC.Compared to FIA, FBTC seizures were characterized by deeper LOC and by stronger increases in SWA in parieto-occipital cortex. FBTC also displayed more widespread increases in cortical activation (B/D), ictal cross-frequency coupling (PLHG) and ictal recruitment (epileptogenicity index). Even before generalization, FBTC displayed deeper LOC; this early LOC was accompanied by a paradoxical increase in B/D in fronto-parietal cortex. Behavioral generalization coincided with complete loss of responsiveness and a subsequent increase in high-gamma in the whole brain, which was especially synchronous in deep sources and could not be explained by EMG. Similarly, multi-unit activity analysis of FBTC revealed sustained increases in cortical firing rates during and after generalization onset in areas remote from the SOZ.Unlike during FIA, LOC during FBTC is characterized by a paradoxical increase in cortical activation and neuronal firing. These findings suggest differences in the mechanisms of ictal LOC between FIA and FBTC and may account for the more negative prognostic consequences of FBTC.
Generation of a molecular interactome of the glioblastoma perivascular niche reveals Integrin Binding Sialoprotein as a key mediator of tumor cell migration
Authors: Ghochani Yasmin , Sohrabi Alireza , Muthukrishnan Sree Deepthi , Kawaguchi Riki , Condro Michael C. , Bastola Soniya , Gao Fuying , Qin Yue , Mottahedeh Jack , Iruela Arispe M. Luisa , Rao Nagesh , Laks Dan R. , Liau Linda M. , Mathern Gary W. , Goldman Steven A. , Carmichael S. Thomas , Nakano Ichiro , Coppola Giovanni , Seidlits Stephanie , Kornblum Harley I. 
Published: October 2021

SummaryGlioblastoma (GBM) is characterized by extensive microvascular hyperproliferation. In addition to supplying blood to the tumor, GBM vessels also provide trophic support to glioma cells and serve as conduits for migration into the surrounding brain promoting recurrence. Here, we enriched CD31-expressing glioma vascular cells (GVC) and A2B5-expressing glioma tumor cells (GTC) from primary GBM and utilized RNA sequencing to create a comprehensive interaction map of the secreted and extracellular factors elaborated by GVC that can interact with receptors and membrane molecules on GTC. To validate our findings, we utilized functional assays, including a novel hydrogel-based migration assay and in vivo mouse models to demonstrate that one identified factor, the little-studied integrin binding sialoprotein (IBSP) enhances tumor growth and promotes the migration of GTC along the vasculature. This perivascular niche interactome will serve a resource to the research community in defining the potential functions of the GBM vasculature.
Long-term analysis of pertussis vaccine immunity uncovers a memory B cell response to whole cell pertussis immunization that is absent from acellular immunized mice
Authors: Weaver Kelly L. , Blackwood Catherine B. , Horspool Alexander M. , Pyles Gage M. , Sen-Kilic Emel , Grayson Emily M. , Huckaby Annalisa B. , Witt William T. , DeJong Megan A. , Wolf M. Allison , Damron F. Heath , Barbier Mariette 
Published: October 2021

ABSTRACTOver two decades ago acellular pertussis vaccines (aP) replaced whole cell pertussis vaccines (wP) in several countries. Since then, a resurgence in pertussis has been observed, which is hypothesized to be linked to waning immunity. To better understand why waning immunity occurs, we developed a long-term outbred CD1 mouse model to conduct the longest murine pertussis vaccine studies to date, spanning out to 532 days post primary immunization. Vaccine-induced memory results from follicular responses and germinal center formation; therefore, cell populations and cytokines involved with memory were measured alongside protection from challenge. Both aP and wP immunization elicit protection from intranasal challenge and generation of pertussis specific antibody responses in mice. Responses to wP vaccination were characterized by a significant increase in T follicular helper cells in the draining lymph nodes and CXCL13 levels in sera compared to aP mice. In addition, a population of B. pertussis+ memory B cells was found to be unique to wP vaccinated mice. This population peaked post-boost, and was measurable out to day 365 post-vaccination. Anti-B. pertussis and anti-pertussis toxoid antibody secreting cells increased one day after boost and remained high at day 532. The data suggest that follicular responses, and in particular CXCL13 levels in sera, should be monitored in pre-clinical and clinical studies for the development of the next-generation pertussis vaccines.
Single-cell transcription profiles in Bloom syndrome patients link BLM deficiency with altered condensin complex expression signatures
Authors: Gönenc Ipek Ilgin , Wolff Alexander , Schmidt Julia , Zibat Arne , Müller Christian , Cyganek Lukas , Argyriou Loukas , Räschle Markus , Yigit Gökhan , Wollnik Bernd 
Published: October 2021

AbstractBloom syndrome (BS) is an autosomal recessive disease clinically characterized by primary microcephaly, growth deficiency, immunodeficiency, and predisposition to cancer. It is mainly caused by biallelic loss-of-function mutations in the BLM gene, which encodes the BLM helicase, acting in DNA replication and repair processes. Here, we describe the gene expression profiles of three BS fibroblast cell lines harboring causative, biallelic truncating mutations obtained by single-cell (sc) transcriptome analysis. We compared the scRNA transcription profiles from three BS patient cell lines to two age-matched wild-type controls and observed specific deregulation of gene sets related to the molecular processes characteristically affected in BS, such as mitosis, chromosome segregation, cell cycle regulation, and genomic instability. We also found specific upregulation of genes of the Fanconi anemia pathway, in particular FANCM, FANCD2, and FANCI, which encode known interaction partners of BLM. The significant deregulation of genes associated with inherited forms of primary microcephaly observed in our study might explain in part the molecular pathogenesis of microcephaly in BS, one of the main clinical characteristics in patients. Finally, our data provide first evidence of a novel link between BLM dysfunction and transcriptional changes in condensin complex I and II genes. Overall, our study provides novel insights into gene expression profiles in BS on a single-cell level, linking specific genes and pathways to BLM dysfunction.
Partitioning of ribonucleoprotein complexes from the cellular actin cortex
Authors: Angert Isaac , Karuka Siddarth Reddy , Mansky Louis M. , Mueller Joachim D. 
Published: October 2021

AbstractThe cell cortex plays a crucial role in cell mechanics, signaling, and development. However, little is known about the influence of the cortical meshwork on the spatial distribution of cytoplasmic biomolecules. Here, we describe a new fluorescence microscopy method to infer the intracellular distribution of labeled biomolecules with sub-resolution accuracy. Unexpectedly, we find that RNA-binding proteins are partially excluded from the cytoplasmic volume adjacent to the plasma membrane that corresponds to the actin cortex. Complementary diffusion measurements of RNA-protein complexes suggest that a rudimentary model based on excluded volume interactions can explain this partitioning effect. Our results suggest the actin cortex meshwork may play a role in regulating the biomolecular content of the volume immediately adjacent to the plasma membrane.TeaserA novel microscopy method reveals exclusion of RNA-protein complexes from the actin cortex due to their large hydrodynamic size.
Local brain-state dependency of effective connectivity: evidence from TMS–EEG
Authors: Granö Ida , Mutanen Tuomas P. , Tervo Aino E. , Nieminen Jaakko O. , Souza Victor H. , Fecchio Matteo , Rosanova Mario , Lioumis Pantelis , Ilmoniemi Risto J. 
Published: October 2021

AbstractBackgroundSpontaneous cortical oscillations have been shown to modulate cortical responses to transcranial magnetic stimulation (TMS). If not controlled for, they might increase variability in responses and mask meaningful changes in the signals of interest when studying the brain with TMS combined with electroencephalography (TMS–EEG). To address this challenge in future closed-loop stimulation paradigms, we need to understand how spontaneous oscillations affect TMS-evoked responses.ObjectiveTo describe the effect of the pre-stimulus phase of cortical mu (8–13 Hz) and beta (13–30 Hz) oscillations on TMS-induced effective connectivity patterns.MethodsWe applied TMS to the left primary motor cortex and right pre-supplementary motor area of three subjects while recording EEG. We classified trials off-line into positive- and negative-phase classes according to the mu and beta rhythms. We calculated differences in the global mean-field amplitude (GMFA) and compared the cortical spreading of the TMS-evoked activity between the two classes.ResultsPhase had significant effects on the GMFA in 11 out of 12 datasets (3 subjects × 2 stimulation sites × 2 frequency bands). Seven of the datasets showed significant differences in the time range 15–50 ms, nine in 50–150 ms, and eight after 150 ms post-stimulus. Source estimates showed complex spatial differences between the classes in the cortical spreading of the TMS-evoked activity.ConclusionsTMS-evoked effective connectivity appears to depend on the phase of local cortical oscillations at the stimulated site. This may be crucial for efficient design of future brain-state-dependent and closed-loop stimulation paradigms.
Maintenance of community function through compensation breaks down over time in a desert rodent community
Authors: Diaz Renata M. , Ernest S. K. Morgan 
Published: October 2021

AbstractUnderstanding the ecological processes that maintain community function in systems experiencing species loss, and how these processes change over time, is key to understanding the relationship between community structure and function and predicting how communities may respond to perturbations in the Anthropocene. Using a 30-year experiment on desert rodents, we show that the impact of species loss on community-level energy use has changed repeatedly and dramatically over time, due to 1) the addition of new species to the community, and 2) a reduction in functional redundancy among the same set of species. Although strong compensation, initially driven by the dispersal of functionally redundant species to the local community, occurred in this system from 1997-2010, since 2010, compensation has broken down due to decreasing functional overlap within the same set of species. Simultaneously, long-term changes in sitewide community composition due to niche complementarity have decoupled the dynamics of compensation from the overall impact of species loss on community-level energy use. Shifting, context-dependent compensatory dynamics, such as those demonstrated here, highlight the importance of explicitly long-term, metacommunity, and eco-evolutionary perspectives on the link between species-level fluctuations and community function in a changing world.
Contrast Solution Properties and Scan Parameters Influence the Apparent Diffusivity of Computed Tomography Contrast Agents in Articular Cartilage
Authors: Hall Mary E. , Wang Adam S. , Gold Garry E. , Levenston Marc E. 
Published: October 2021

ABSTRACTThe inability to detect early degenerative changes to the articular cartilage surface that commonly precede bulk osteoarthritic degradation is an obstacle to early disease detection for research or clinical diagnosis. Leveraging a known artifact that blurs tissue boundaries in clinical arthrograms, contrast agent diffusivity can be derived from computed tomography arthrography (CTa) scans. We combined experimental and computational approaches to study protocol variations that may alter the CTa-derived apparent diffusivity. In experimental studies on bovine cartilage explants, we examined how contrast agent dilution and transport direction (absorption vs. desorption) influence the apparent diffusivity of untreated and enzymatically digested cartilage. Using multiphysics simulations, we examined mechanisms underlying experimental observations and the effects of image resolution, scan interval and early scan termination. The apparent diffusivity during absorption decreased with increasing contrast agent concentration by an amount similar to the increase induced by tissue digestion. Models indicated that osmotically induced fluid efflux strongly contributed to the concentration effect. Simulated changes to spatial resolution, scan spacing and total scan time all influenced the apparent diffusivity, indicating the importance of consistent protocols. With careful control of imaging protocols and interpretations guided by transport models, CTa-derived diffusivity offers promise as a biomarker for early degenerative changes.
Frailty and rate of fractures in patients initiating antihypertensive medications: a cohort study in primary care
Authors: Österdahl Marc F , Sinnott Sarah-Jo , Douglas Ian , Clegg Andrew , Tomlinson Laurie , Wong Angel 
Published: October 2021

AbstractBackgroundTreatment for hypertension improves cardiovascular outcomes. Frailty is common in people treated for hypertension, and associated with increases in adverse drug effects, potentially including falls resulting in fractures. We aimed to determine the association between baseline frailty and fractures in patients initiated on antihypertensive treatment.MethodsWe conducted a retrospective cohort study using United Kingdom primary care data, including new-users of first-line antihypertensives aged 65 years or over. We reported degree of frailty (fit, mild, moderate, severe) at antihypertensive initiation using the Electronic Frailty Index. We examined the association of frailty with fractures using multivariable Poisson regression, and assessed for interaction between antihypertensive class and frailty.Results49634 (43%) people initiated on first-line antihypertensives were mildly or more frail. Over 4.1 years mean follow-up, 6567 (5.8%) experienced a fracture, with 3832 (58%) of these fractures occurring in frail people. Among those with severe frailty doubling of fracture risk was observed after antihypertensive initiation, compared with fit people [adjusted rate ratio 2.26 (95% CI 1.93-2.65)]. This pattern was replicated for hip and arm fractures, and strongest for spine fractures. The association between different types of antihypertensives and fractures varied by frailty (P=0.004), with a lower rate in moderately frail users of renin-angiotensin blockers compared with calcium-channel blockers (RR 0.81 95% CI 0.71-0.94)ConclusionsFrailty is common among people initiating first-line antihypertensive treatment, and was associated with an increased fracture rate. Awareness of this is important to encourage clinicians to consider risk of falls and fractures when treating hypertension.