bluuebunny/crossref_metadata_2025_split huggingface dataset:
Premature white matter microstructure in female children with a history of concussion
Authors: Nishat Eman , Stojanovski Sonja , Scratch Shannon E , Ameis Stephanie H , Wheeler Anne L 
Published: December 2021

AbstractAs maturation of the brain continues throughout development, there is a risk of interference from concussions which are common in childhood. A concussion can cause widespread disruption to axons and inflammation in the brain and may influence emerging cognitive abilities. Females are more likely to experience persistent problems after a concussion, yet the sex-specific impact of concussions on brain microstructure in childhood is not well understood.In children from a large population sample, this study (1) investigated differences in white matter and cortical microstructure between children with and without a history of concussion, and (2) examined relationships between altered brain microstructure and cognitive performance.Neurite density measures from diffusion weighted magnetic resonance imaging were examined in 9-to 10-year-old children in the Adolescent Brain Cognitive Development Study with (n= 336) and without (n= 7368) a history of concussion. (1) Multivariate regression models were used to investigate the relationships between concussion history, sex, and age in the deep white matter, superficial white matter, subcortical structures, and cortex. (2) Principal component analysis was performed on neurite density, and components were examined in relation to performance on the Flanker Inhibitory Control and Attention Task and the Pattern Comparison Processing Speed Task to investigate the relationship between altered neurite density and cognitive performance.Neurite density in all tissue types demonstrated robust positive relationships with age reflecting maturation of brain microstructure. (1) Comparisons between children with and without a history of concussion revealed higher neurite density in deep and superficial white matter in females with concussion. No group differences were observed in subcortical or cortical neurite density. (2) Higher neurite density in superficial white matter beneath the frontal and temporal cortices was associated with lower scores on the processing speed test in females with concussion, and higher scores on the processing speed test in males with concussion.These findings suggest that concussion in childhood leads to premature white matter maturation in females and that this may be associated with slower processing speed. These sex-specific effects on the developing brain may contribute to the enhanced vulnerability to persistent symptoms after concussion in females.
New Phylogenetic Models Incorporating Interval-Specific Dispersal Dynamics Improve Inference of Disease Spread
Authors: Gao Jiansi , May Michael R. , Rannala Bruce , Moore Brian R. 
Published: December 2021

AbstractPhylodynamic methods reveal the spatial and temporal dynamics of viral geographic spread, and have featured prominently in studies of the COVID-19 pandemic. Virtually all such studies are based on phylodynamic models that assume—despite direct and compelling evidence to the contrary—that rates of viral geographic dispersal are constant through time. Here, we: (1) extend phylodynamic models to allow both the average and relative rates of viral dispersal to vary independently between pre-specified time intervals; (2) implement methods to infer the number and timing of viral dispersal events between areas; and (3) develop statistics to assess the absolute fit of discrete-geographic phylodynamic models to empirical datasets. We first validate our new methods using simulations, and then apply them to a SARS-CoV-2 dataset from the early phase of the COVID-19 pandemic. We show that: (1) under simulation, failure to accommodate interval-specific variation in the study data will severely bias parameter estimates; (2) in practice, our interval-specific discrete-geographic phylodynamic models can significantly improve the relative and absolute fit to empirical data; and (3) the increased realism of our interval-specific models provides qualitatively different inferences regarding key aspects of the COVID-19 pandemic—revealing significant temporal variation in global viral dispersal rates, viral dispersal routes, and the number of viral dispersal events between areas—and alters interpretations regarding the efficacy of intervention measures to mitigate the pandemic.
Brain Injury in COVID-19 is Associated with Autoinflammation and Autoimmunity
Authors: Needham EJ , Ren AL , Digby RJ , Outtrim JG , Chatfield DA , Manktelow AE , Newcombe VFJ , Doffinger R , Barcenas-Morales G , Fonseca C , Taussig MJ , Burnstein RM , Dunai C , Sithole N , Ashton NJ , Zetterberg H , Gisslen M , Edén A , Marklund E , Griffiths MJ , Cavanagh J , Breen G , Irani SR , Elmer A , Kingston N , Bradley JR , Taams LS , Michael BD , Bullmore ET , Smith KGC , Lyons PA , Coles AJC , Menon DK ,   the Cambridge NeuroCOVID Group,   the NIHR COVID-19 BioResource,   Cambridge NIHR Clinical Research Facility
Published: December 2021

AbstractCOVID-19 has been associated with many neurological complications including stroke, delirium and encephalitis. Furthermore, many individuals experience a protracted post-viral syndrome which is dominated by neuropsychiatric symptoms, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of severe COVID-19 more broadly.We sought to investigate the dynamics of, and relationship between, serum markers of brain injury (neurofilament light [NfL], Glial Fibrillary Acidic Protein [GFAP] and total Tau) and markers of dysregulated host response including measures of autoinflammation (proinflammatory cytokines) and autoimmunity. Brain injury biomarkers were measured using the Quanterix Simoa HDx platform, cytokine profiling by Luminex (R&D) and autoantibodies by a custom protein microarray.During hospitalisation, patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependant manner, and there was evidence of ongoing active brain injury at follow-up 4 months later. Raised NfL and GFAP were associated with both elevations of pro-inflammatory cytokines and the presence of autoantibodies; autoantibodies were commonly seen against lung surfactant proteins as well as brain proteins such as myelin associated glycoprotein, but reactivity was seen to a large number of different antigens.Furthermore, a distinct process characterised by elevation of serum total Tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses in the same manner as NfL and GFAP.
Guillain-Barré Syndrome after COVID-19 Vaccination in the Vaccine Safety Datalink
Authors: Hanson Kayla E. , Goddard Kristin , Lewis Ned , Fireman Bruce , Myers Tanya R. , Bakshi Nandini , Weintraub Eric , Donahue James G. , Nelson Jennifer C. , Xu Stan , Glanz Jason M. , Williams Joshua T.B. , Alpern Jonathan D. , Klein Nicola P. 
Published: December 2021

AbstractImportancePost-authorization monitoring of vaccines in a large population can detect rare adverse events not identified in clinical trials including Guillain-Barré syndrome (GBS). GBS has a background rate of 1-2 per 100,000 person-years.ObjectiveTo 1) describe cases and incidence of GBS following COVID-19 vaccination, and 2) assess the risk of GBS after vaccination for Ad.26.COV2.S (Janssen) and mRNA vaccines.DesignInterim analysis of surveillance data from the Vaccine Safety Datalink.SettingEight participating integrated healthcare systems in the United States.Participants10,158,003 individuals aged ≥12 years.ExposuresReceipt of Ad.26.COV2.S, BNT162b2 (Pfizer-BioNTech), or mRNA-1273 (Moderna) COVID-19 vaccine.Main Outcomes and MeasuresGBS with symptom onset in the 1-84 days after vaccination as confirmed by medical record review and adjudication. Descriptive characteristics of confirmed cases, GBS incidence rates during postvaccination risk intervals after each type of vaccine compared to the background rate, rate ratios (RRs) comparing GBS incidence in the 1-21 vs. 22-42 days postvaccination, and RRs directly comparing risk of GBS after Ad.26.COV2.S vs. mRNA vaccination, using Poisson regression adjusted for age, sex, race/ethnicity, site, and calendar day.ResultsFrom December 13, 2020 through November 13, 2021, 14,723,318 doses of COVID-19 vaccines were administered, including 467,126 Ad.26.COV2.S, 8,573,823 BNT162b2, and 5,682,369 mRNA-1273 doses. Eleven cases of GBS after Ad.26.COV2.S were confirmed. The unadjusted incidence rate of confirmed cases of GBS per 100,000 person-years in the 1-21 days after Ad.26.COV2.S was 34.6 (95% confidence interval [CI]: 15.8-65.7), significantly higher than the background rate, and the adjusted RR in the 1-21 vs. 22-42 days following Ad.26.COV2.S was 6.03 (95% CI: 0.79-147.79). Thirty-four cases of GBS after mRNA vaccines were confirmed. The unadjusted incidence rate of confirmed cases per 100,000 person-years in the 1-21 days after mRNA vaccines was 1.4 (95% CI: 0.7-2.5) and the adjusted RR in the 1-21 vs. 22-42 days following mRNA vaccines was 0.56 (95% CI: 0.21-1.48). In a head-to-head comparison of Ad.26.COV2.S vs. mRNA vaccines, the adjusted RR was 20.56 (95% CI: 6.94-64.66).Conclusions and RelevanceIn this interim analysis of surveillance data of COVID-19 vaccines, the incidence of GBS was elevated after Ad.26.COV2.S. Surveillance is ongoing.
Introduction and community transmission of SARS-CoV-2 lineage A.2.5 in Florida with novel spike INDELS
Authors: Schmedes Sarah E. , Azarian Taj , Cella Eleonora , Motes Jessy , Tekin Omer , Weiss James , Miller Nancimae , Blanton Jason 
Published: December 2021

AbstractSARS-CoV-2 (SC2) variants of concern (VOC) continue to emerge and spread globally, threatening the use of monoclonal antibody therapies and vaccine effectiveness. Several mutations in the SC2 spike glycoprotein have been associated with reduction in antibody neutralization. Genomic surveillance of SC2 variants has been imperative to inform the public health response regarding the use of clinical therapies in specific jurisdictions based on the proportion of particular variants (e.g., Gamma (P.1)) in a region. Florida Department of Health Bureau of Public Health Laboratories (BPHL) performs tiled-amplicon whole genome sequencing for baseline and targeted surveillance of SC2 isolates in Florida from clinical specimens collected from county health departments and hospitals throughout the state. Here, we describe the introduction of SC2 lineage A.2.5 in Florida, which contains S:L452R (a substitution of therapeutic concern) and two novel Spike INDELS, the deletion of 141-143 and ins215AGY, with unknown implications on immune response. The A.2.5 lineage was first detected in Florida among an outbreak at a healthcare facility in January 2021, and subsequent A.2.5 isolates were detected across all geographical regions throughout the state. A time-scaled maximum clade credibility phylogeny determined there were at least eight separate introductions of A.2.5 in the state. The time of introduction of a monophyletic Florida clade was established to be December 2020. The Spike INDELS were determined to reside in the N-terminal domain, a region associated with antibody neutralization. As community transmission of SARS-CoV-2 in Florida continues, genomic surveillance of circulating variants in Florida and the detection of emerging variants are critical for informing public health response to COVID-19.
Compartment-specific total RNA profile of Hippocampal and Cortical cells from Mesial Temporal Lobe Epilepsy tissue
Authors: Vangoor Vamshidhar R. , Giuliani Giuliano , de Wit Marina , Venø Morten T. , Puhakka Noora , Gomes-Duarte Andreia , van Rijen Peter C. , Gosselaar Peter H. , van Eijsden Pieter , Kjems Jørgen , de Graan Pierre N.E. , Pasterkamp R. Jeroen 
Published: December 2021

AbstractMesial temporal lobe epilepsy (mTLE) is a chronic neurological disease characterized by recurrent seizures. The pathogenic mechanisms underlying mTLE involve defects in post-transcriptional regulation of gene expression. So far, transcriptome profiles from epileptic tissue have been generated using whole cells, thereby lacking information on RNA localization and function at a subcellular level. In line with this, we have previously observed by in situ hybridization that a few microRNAs (miRNAs) display subcellular mis-localization with aberrant enrichment in the nucleus in human hippocampal mTLE tissue samples (Kan et al., 2012). To further investigate the possible mechanisms leading to the mis-localization of miRNAs, we set out to understand the compartment-specific total RNA (coding and non-coding) profile of human mTLE tissue samples. For this, we have successfully established a protocol to isolate cytoplasmic and nuclear compartments from human hippocampal tissue. After confirming the purity of the isolated cell compartments, we performed total RNA-sequencing (RNA-seq) on five resected hippocampal (HC) mTLE (no hippocampal sclerosis (non-HS)) samples and five HC postmortem control samples. Similarly, six neo-cortical (Cx) tissue samples from mTLE non-HS and HS International League Against Epilepsy (ILAE) Type 1, or mTLE+HS, samples were compared with six Cx postmortem controls. Our dataset provides a comprehensive overview of compartment-specific transcriptomic profiles of pharmacoresistant mTLE patient HC and Cx tissue, which in further studies can be used to investigate disease mechanisms.
A randomized clinical trial to stimulate the cholinergic anti-inflammatory pathway in patients with moderate COVID-19-pneumonia using a slow-paced breathing technique
Authors: Balint Elisabeth Maria , Grüner Beate , Haase Sophia , Kaw-Geppert Mandakini , Thayer Julian F. , Gündel Harald , Jarczok Marc N. 
Published: December 2021

AbstractImportanceVagus nerve stimulation via slow-paced breathing could serve as an adjuvant therapeutic approach to reduce excessive inflammation in coronavirus disease 2019 (COVID-19) pneumonia.ObjectiveDoes a slow-paced breathing technique increasing vagal activity reduce Interleukin-6 (IL-6) in patients hospitalized with moderate COVID-19 pneumonia compared to standard care?DesignSingle-center randomized controlled clinical trial with enrolment from February 23rd 2021 through June 17th 2021 and follow-up until July 22nd 2021.SettingWard for infectious diseases and temporary COVID-19 ward, Ulm University Hospital, GermanyParticipantsConsecutive sample of patients hospitalized with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (primary diagnosis). Of 131 patients screened, 48 patients were randomized and 46 patients analyzed (N=23 per group).InterventionsSlow-paced 20-minute breathing exercise three times a day with six breaths per minute (inhalation-to-exhalation ratio 4:6).Main outcomes and measuresDifferences between intervention and control group in IL-6 calculated using multilevel mixed-effect linear regression models with random slope including the covariates relevant comorbidities, COVID-19 medication, and age.ResultsMean age 57 years±13 years, N= 28 (60%) male, N=30 (65%) with relevant comorbidities.The model including group by time interaction revealed a significantly lower trajectory of IL-6 in the intervention group compared to the control group (effect size Cohens f2=0.11, LR-test p=.040) in the intention-to-treat sample, confirmed by treatment-per-protocol analysis (f2=0.15, LR-test p=.022). Exploratory analysis using the median split of practice time to predict IL-6 of the next morning indicated a dose-response relationship with beneficial effects of practice time above 45 minutes a day.Three patients in each group were admitted to ICU, one died. Oxygen saturation increased during slow-paced breathing (from 95.1%±2.1% to 95.4%±1.6%, p=0.006).Conclusion and relevancePatients practicing slow-paced breathing had significantly lower IL-6 values than controls with a small to medium effect size and without relevant side effects. Further trials should evaluate clinical outcomes as well as an earlier start of the intervention, i.e., at symptom onset. This would offer an access to a therapy option not only for high-income, but also for low- and middle-income countries.Trial registrationGerman register of clinical trials (ID: DRKS00023971) https://www.drks.de, Universal Trial Number (UTN) U1111-1263-8658;
Spike-specific T cells are enriched in breastmilk following SARS-CoV-2 mRNA vaccination
Authors: Armistead Blair , Jiang Yonghou , Carlson Marc , Ford Emily S , Jani Saumya , Houck John , Wu Xia , Jing Lichen , Pecor Tiffany , Kachikis Alisa , Yeung Winnie , Nguyen Tina , Minkah Nana , Larsen Sasha E , Coler Rhea N , Koelle David M , Harrington Whitney E 
Published: December 2021

AbstractHuman breastmilk is rich in T cells; however, their specificity and function are largely unknown. We compared the phenotype, diversity, and antigen specificity of T cells in the breastmilk and peripheral blood of lactating individuals who received SARS-CoV-2 mRNA vaccination. Relative to blood, breastmilk contained higher frequencies of T effector and central memory populations that expressed mucosal-homing markers. T cell receptor (TCR) sequence overlap was limited between blood and breastmilk. Overabundan t breastmilk clones were observed in all individuals, were diverse, and contained CDR3 sequences with known epitope specificity including to SARS-CoV-2 Spike. Spike-specific TCRs were more frequent in breastmilk compared to blood and expanded in breastmilk following a third mRNA vaccine dose. Our observations indicate that the lactating breast contains a distinct T cell population that can be modulated by maternal vaccination with potential implications for infant passive protection.One-Sentence SummaryThe breastmilk T cell repertoire is distinct and enriched for SARS-CoV-2 Spike-specificity after maternal mRNA vaccination.
RNA Sequencing-Based Single Sample Predictors of Molecular Subtype and Risk of Recurrence for Clinical Assessment of Early-Stage Breast Cancer
Authors: Staaf Johan , Häkkinen Jari , Hegardt Cecilia , Saal Lao H , Kimbung Siker , Hedenfalk Ingrid , Lien Tonje , Sørlie Therese , Naume Bjørn , Russnes Hege , Marcone Rachel , Ayyanan Ayyakkannu , Brisken Cathrin , Malterling Rebecka R. , Asking Bengt , Olofsson Helena , Lindman Henrik , Bendahl Pär-Ola , Ehinger Anna , Larsson Christer , Loman Niklas , Rydén Lisa , Malmberg Martin , Borg Åke , Vallon-Christersson Johan 
Published: December 2021

ABSTRACTBackgroundMultigene expression assays for molecular subtypes and biomarkers can aid clinical management of early invasive breast cancer (IBC). Based on RNA-sequencing we aimed to develop robust single-sample predictor (SSP) models for conventional clinical markers as well as molecular intrinsic subtype and risk of recurrence (ROR) that provide clinically relevant prognostic stratification.MethodsA uniformly accrued breast cancer cohort of 7743 patients with RNA-sequencing data from fresh tissue was divided into a training set (n=5250) and a reserved test set (n=2412). We trained SSPs for PAM50 molecular subtypes and ROR assigned by nearest-centroid (NC) methods and SSPs for conventional clinical markers from histopathology data. Additionally, SSP classifications were compared with Prosigna in two external cohorts (ABiM, n=100 and OSLO2-EMIT0, n=103). Prognostic value was assessed using distant recurrence-free interval (DRFi).ResultsIn the test set, agreement between SSP and NC classifications for PAM50 (five subtypes) and Subtype (four subtypes) was high (85%, Kappa=0.78) and very high (90%, Kappa=0.84) respectively. Accuracy for ROR risk category was high (84%, Kappa=0.75, weighted Kappa=0.90). The prognostic value for SSP and NC classification was assessed as equivalent and added clinically relevant prognostic information. Agreement for SSP and histopathology was very high or high for receptor status, while moderate and poor for Ki67 status and Nottingham histological grade, respectively. SSP concordance with Prosigna was high for subtype (OSLO 83% and ABiM 80%, Kappa=0.73 and 0.72, respectively) and moderate and high for ROR risk category (68% and 84%, Kappa=0.50 and 0.70, weighted Kappa=0.70 and 0.78). In pooled analysis, concordance between SSP and Prosigna for emulated treatment recommendation dichotomized for chemotherapy (yes vs. no) was high (85%, Kappa=0.66). In postmenopausal ER+/HER2-/N0 patients SSP application suggested changed treatment recommendations for up to 17% of patients, with nearly balanced escalation and de-escalation of chemotherapy.ConclusionsRobust SSP models, mimicking histopathological variables, PAM50, and ROR classifications can be derived from RNA-sequencing that closely matches clinical tests. Agreement and DRFi analyses suggest that NC and SSP models are interchangeable on a group-level and nearly so on a patient level. Retrospective evaluation in ER+/HER2-/N0 IBC suggested that molecular testing could lead to a changed therapy recommendation for almost one-fifth of patients.
Evaluating the policy of closing bars and restaurants in Cataluña and its effects on mobility and COVID19 incidence
Authors: Smith Matthew , Ponce-de-Leon Miguel , Valencia Alfonso 
Published: December 2021

ABSTRACTThe world has gone through unprecedented changes since the global pandemic hit. During the early phase of the pandemic, the absence of known drugs or pharmaceutical treatments forced governments to introduce different policies in order to help reduce contagion rates and manage the economic consequences of the pandemic. This paper analyses the causal impact on mobility and COVID19 incidence from policy makers in Cataluña, Spain. We use annonimized phone-based mobility data together with reported incidence and apply a series of causal impact models frequently used in econometrics and policy evaluation in order to measure the policies impact.. We analyse the case of Cataluña and the public policy decision of closing all bars and restaurants down for a 5 week period between the 2020-16-10 to 2020-23-11. We find that this decision led to a significant reduction in mobility. It not only led to reductions in mobility but from a behavioural economics standpoint we highlight how people responded to the policy decision. Moreover, the policy of closing bars and restaurants slowed the incidence rate of COVID19 after a time lag has been taken into account. These finding are significant since governments worldwide want to restrict movements of people in order to slow down COVID19 incidence without infringing on their rights directly.