bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neopterin level can be measured by intraocular liquid biopsy
Authors: Kuvbachieva-Benarrosh Anelia , Nefzaoui Chaker , Quadrio Isabelle , Remignon Charles-Henry , Jullian Eric , Perret-Liaudet Armand 
Published: July 2022

AbstractRobust intraocular markers are needed in clinical practice for several inflammatory ophthalmological conditions in addition to advanced imaging, histology and immunohistochemistry tests in order to assure reliable diagnosis. Neopterin (NPt) is produced by activated lymphocyte T cells and is known to increase within the CNS in proinflammatory or early infectious states. This study aimed to measure intraocular NPt in aqueous liquid following intraocular liquid biopsy using standard methods. We enrolled 20 healthy patients without known inflammatory history or medication underdoing cataract surgery and analyzed samples for 19 out of 20. NPt level was measured below 1,9 nmol/l in 16 patients (84 %) and less than 3 nmol/l in 94,74%. Given the first time that NPt is measured in intraocular liquids we compared with the established reference limits within the CSF. These findings suggest that NPt could serve as a potential additional signature in ophthalmological conditions to differentiate between any or proinflammatory intraocular state, as well in follow-up.
The size of myocardial infarction and peri-infarction edema are not major determinants of diastolic impairment after acute myocardial infarction
Authors: Sundqvist Martin G , Verouhis Dinos , Sörensson Peder , Henareh Loghman , Persson Jonas , Saleh Nawzad , Settergren Magnus , Witt Nils , Böhm Felix , Pernow John , Tornvall Per , Ugander Martin 
Published: July 2022

AbstractAimsDiastolic dysfunction after myocardial infarction (MI) is a marker of poor prognosis. The relationship between myocardial infarction size (IS), myocardial edema, and diastolic dysfunction is poorly understood, both in the acute phase, and in the development of diastolic dysfunction in the follow-up setting. Using a mechanistic approach could potentially add insights.Methods and resultsPatients underwent cardiovascular magnetic resonance (CMR) imaging and echocardiography including mechanistic analysis using the parameterized diastolic filling method within 4-7 days (acute) and 6 months after a first acute anterior MI (n=74). Linear regression modeling of echocardiographic diastolic parameters using CMR IS with and without inclusion of the myocardium at risk (MAR) and model comparisons with likelihood ratio tests were performed. Diastolic parameters at 6 months follow-up were modelled using final IS. For most parameters there was no association with acute IS, except for deceleration time (R2=0.24, p<0.001), left atrial volume index (R2=0.13, p=0.01) and the mechanistic stiffness parameter (R2=0.21, p<0.001). Adding MAR improved only the e′ model (adjusted R2 increase: 0.08, p=0.02). At 6 months follow-up, final IS was only associated with viscoelastic energy loss (R2=0.22, p=0.001).ConclusionIn acute MI, both IS and MAR are related to diastolic function but only to a limited extent. At 6 months after infarction, increasing IS is related to less viscoelastic energy loss, albeit also to a limited extent. The relationship between IS and diastolic dysfunction seems to be mediated by mechanisms beyond simply the spatial extent of ischemia or infarction.
Debriefing to improve interprofessional teamwork in the operating room: a systematic review
Authors: Skegg Emma , McElroy Canice , Mudgway Mercedes , Hamill James 
Published: July 2022

AbstractPurposeDebriefing has been pivotal in medical simulation training but its application to the real-world operating room environment has been challenging. We reviewed the literature on routine surgical debriefing with special reference to its implementation, barriers, and effectiveness.DesignDescriptive systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.MethodsInclusion criteria were papers pertaining to debriefing in routine surgical practice. Excluded were papers reporting simulation training. We searched Google Scholar, CINAHL, Web of Science Core Collection, PsychINFO, Medline, Embase, and ProQuest Theses & Dissertations Global. The last search was performed on 14 March 2022. Quality was assessed on a 21-point checklist adapted from a standard reporting guideline. Synthesis was descriptive.FindingsThe search process resulted in 19 papers. Publication date ranged from 2007 – 2022. Study methods included surveys, interviews, and analysis of administrative data. Five papers involved a specific intervention. Quality scores ranged from 12 – 19 out of 21. On synthesis, we identified five topics: explanations of how debriefing had been implemented; the value of coaching and audit; the learning dimensions of debriefing, both team learning and quality improvement at the organizational level; the effect of debriefing on patient safety or the organization’s culture; and barriers to debriefing.ConclusionsDebriefing is valuable for team learning, efficiency, patient safety, and psychological safety. Successful implementation programs were characterized by strong commitment from management and support by frontline workers. Integration with administrative quality and safety processes, and information feedback to frontline workers are fundamental to successful debriefing programs.
Weight cycling induces innate immune memory in adipose tissue macrophages
Authors: Caslin Heather L. , Cottam Matthew A. , Piñon Jacqueline M. , Boney Likem Y. , Hasty Alyssa H. 
Published: July 2022

AbstractWeight loss improves obesity-associated diabetes risk. However, most individuals regain weight, which worsens the risk of developing diabetes and cardiovascular disease. We previously reported that male mice retain obesity-associated immunological changes even after weight loss, suggesting that immune cells may remember the state of obesity. Therefore, we hypothesized that cycles of weight gain and loss, otherwise known as weight cycling, can induce innate memory in adipose macrophages. We first treated bone marrow derived macrophages in a culture model of innate immune memory. Priming the cells with palmitic acid or adipose tissue conditioned media increased maximal glycolysis, oxidative phosphorylation, and increased LPS-induced TNFα and IL-6 production. While weight loss improved glucose tolerance, adipose macrophages retained elevated LPS-induced cytokine production. In a model of weight cycling, adipose macrophages had elevated metabolism and secreted higher levels of basal TNFα. Together, these data suggest that obesity and subsequent weight loss can prime adipose macrophages for enhanced inflammation upon weight regain. This innate immune memory response may contribute to worsened glucose tolerance following weight cycling.
Single-cell transcriptional landscape of peripheral immunity and biomarkers for human sporadic amyotrophic lateral sclerosis patients
Authors: Ma Albert Ziye , Kirk Brian D. , Yan Deyu , Zhang Mingchao , Yao Jing , Dai Xiaomin , Lu Lingdan , Wang Qinghua , Ying Weihai , Han Yan 
Published: July 2022

AbstractSporadic amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disease with unknown causes and few treatment options. Here we report the first multi-dimensional single-cell landscape of the peripheral blood mononuclear cell samples from seven ALS patients representing three distinct disease stages: Early, Mid and Late. Our multipronged analyses revealed the over-activation of immune cells especially in the Mid and Late ALS stages, which is characterized by the increased cytotoxic CD8+effector cells, expanded TCR clonotypes, upregulated oxidative phosphorylation and ribosomal genes across many cell types. More importantly, the current study discovered novel genes strongly correlated with ALS conditions, such asFOXO1andTGFBR2responsible for the aberrant T cell activation, andXBP1andSPIBaccountable for excessive oxidative stress. We further identified 60 genes that distinguished ALS patients from healthy donors with an unprecedented accuracy of 93% against an independent cohort of 792 specimens. Our findings provide new molecular and cellular insights into the mechanisms of ALS onset and progression, and offer novel strategies for accurate diagnosis and potential therapeutic development.
Design and Performance Characteristics of the Elecsys Anti-SARS-CoV-2 S assay
Authors: Taffertshofer Karin , Walter Mirko , Mackeben Peter , Kraemer Julia , Potapov Sergej , Jochum Simon 
Published: July 2022

AbstractBackgroundAutomated, high throughput assays are required to quantify the immune response after infection with or vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study on the Roche Elecsys® Anti-SARS-CoV-2 S (ACOV2S) assay provides insights on the assay design and performance.MethodsThe ACOV2S assay quantifies antibodies to the receptor-binding domain of the SARS-CoV-2 spike protein. The assigned units and the underlying standardization were compared to the international reference standard in BAU/mL. Assay specificity was assessed in samples (n=5981) collected prior to the COVID-19 pandemic and in samples from patients with non-COVID-19 respiratory infections (n=697) or other infectious diseases (n=771). Sensitivity was measured in 1313 samples from patients with mild COVID-19 and 297 samples from patients hospitalized with COVID-19. Comparison of results was performed to a comparator semi-quantitative anti-S1 assay of indirect detection format as well as a commercially available and an in-house version of a surrogate neutralization assay (ACE2-RBD).ResultsThe originally assigned units for the ACOV2S assay were shown to be congruent to the units of the First International WHO Standard for anti-SARS-CoV-2 immunoglobulins. Overall specificity was 99.98% with no geographical differences noted and no loss of specificity in samples containing potentially cross-reacting antibodies. High sensitivity was observed, with 98.8% of samples reported to be reactive >14 days after infection and sustained detection of antibodies over time. For all samples, ACOV2S titers and neutralization capacities developed with comparable dynamics. Robust standardization and assay setup enable excellent reproducibility of results, independent of lot or analyzer used.ConclusionThe results from this study confirmed that ACOV2S is a highly sensitive and specific assay and correlates well with surrogate neutralization assays. The units established for ACOV2S are also interchangeable with the units of the First International WHO Standard for anti-SARS-CoV-2 immunoglobulins. Worldwide availability of the assay and analyzers render ACOV2S a highly practical tool for population-wide assessment and monitoring of the humoral response to SARS-CoV-2 infection or vaccination.
Transcriptomic and connectomic correlates of differential spatial patterning among glioblastomas and low-grade gliomas
Authors: Romero-Garcia Rafael , Mandal Ayan S. , Bethlehem Richard AI , Crespo-Facorro Benedicto , Hart Michael G , Suckling John 
Published: July 2022

SUMMARYBackgroundUnravelling the complex events driving grade-specific spatial distribution of brain tumour occurrence requires rich datasets from both healthy individuals and patients. Here, we combined open-access data from The Cancer Genome Atlas, the UKBiobank and the Allen Brain Human Atlas to disentangle how the different spatial occurrences of Glioblastoma Multiforme (GBM) and Low-Grade Gliomas (LGG) are linked to brain network features and the normative transcriptional profiles of brain regions.MethodsFrom MRI of brain tumour patients we first constructed a grade-related frequency map of the regional occurrence of LGG and the more aggressive GBM. Using associated mRNA transcription data, we derived a set of differential gene expressions from GBM and LGG tissues of the same patients. By combining the resulting values with normative gene expressions frompostmortembrain tissue, we constructed a grade-related expression map indicating which brain regions express genes dysregulated in aggressive gliomas. Additionally, we derived an expression map of genes previously associated with tumour subtypes in a GWAS study (tumour-related genes).ResultsThere were significant associations between grade-related frequency, grade-related expression, and tumour-related expression maps, as well as functional brain network features (specifically, nodal strength and participation coefficient) that are implicated in neurological and psychiatric disorders.ConclusionsThese findings identify brain network dynamics and transcriptomic signatures as key factors in regional vulnerability for GBM and LGG occurrence, placing primary brain tumours within a well-established framework of neurological and psychiatric cortical alterations.
Strong neutralizing antibody responses to SARS-CoV-2 variants following a single vaccine dose in subjects with previous SARS-CoV-2 infection
Authors: Ekström Nina , Haveri Anu , Solastie Anna , Virta Camilla , Österlund Pamela , Nohynek Hanna , Nieminen Tuomo , Ivaska Lauri , Tähtinen Paula A. , Lempainen Johanna , Jalkanen Pinja , Julkunen Ilkka , Palmu Arto A. , Melin Merit 
Published: July 2022

AbstractBackgroundPrevious SARS-CoV-2 infection primes the immune system and thus individuals who recovered from infection have enhanced immune responses to subsequent vaccination (hybrid immunity). However, it remains unclear how well hybrid immunity induced by severe or mild infection can cross-neutralize emerging variants. We aimed to compare the strength and breadth of antibody responses in vaccinated recovered and uninfected subjects.MethodsWe measured spike-specific IgG and neutralizing antibodies (NAbs) from vaccinated subjects including 320 with hybrid immunity and 20 without previous infection. From 29 subjects with a previous severe or mild infection, we also measured NAb responses against Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2) and Omicron (B.1.1.529/BA.1) variants following vaccination.ResultsA single vaccine dose induced 2-fold higher anti-spike IgG concentrations and 3-fold higher neutralizing potency of antibodies in previously infected compared to uninfected fully vaccinated subjects. We found similar IgG concentrations in previously infected subjects after one or two vaccine doses. NAb titers were higher in subjects with severe compared to those with mild infection. This difference remained after vaccination with sequentially decreasing titers against Alpha, Beta, Delta, and Omicron variants.ConclusionsHybrid immunity induced strong IgG responses, particularly after severe infection. However, the NAb titers were low against heterologous variants, especially against Omicron.
SARS-CoV-2 seroprevalence among public school staff in Metro Vancouver after the first Omicron wave in British Columbia, Canada
Authors: Watts Allison W , Mâsse Louise C , Goldfarb David M , Irvine Michael A , Hutchison Sarah M , Muttucomaroe Lauren , Poon Bethany , Barakauskas Vilte E , O’Reilly Collette , Bosman Else S , Reicherz Frederic , Coombs Daniel , Pitblado Mark , O’Brien Sheila F , Lavoie Pascal M 
Published: July 2022

AbstractObjectiveTo determine the SARS-CoV-2 seroprevalence among school workers in the setting of full in-person schooling and the highly transmissible Omicron variants of concern.DesignCross-sectional study among school staff, comparing to period-, age-, sex- and postal code-weighted data from Canadian blood donors from the same community.SettingThree large school districts in the greater Vancouver metropolitan area, British Columbia, Canada, with serology sampling done between January 26, 2022 and April 8, 2022.ParticipantsSchool staff actively working in the Vancouver, Richmond and Delta School Districts.Main outcome measureSARS-CoV-2 seroprevalence based on nucleocapsid (N)-protein testing, adjusted for the sensitivity and specificity of the assay.ResultsA majority (65.8%) of the 1845 school staff enrolled reported close contact with a COVID-19 case outside the household. Of those, about half reported close contact with a COVID-19 case at school either in a student (51.5%) or co-worker (54.9%). In a representative sample of 1620 (87.8%) school staff, the adjusted seroprevalence was 26.5% [95%CrI: 23.9 – 29.3%]. This compared to an age, sex and residency area-weighted seroprevalence of 32.4% [95%CrI: 30.6 – 34.5%] among 7164 blood donors.ConclusionDespite frequent COVID-19 exposures, the prevalence of SARS-CoV-2 infections among the staff of three main school districts in the Vancouver metropolitan area was no greater than a reference group of blood donors, even after the emergence of the more transmissible Omicron variant.What is already known on this subject?Earlier studies indicate that COVID-19 infection rates are not increased among school staff at previous stages of the pandemic compared to the community, yet controversy remains whether this will remain true after the emergence of the highly transmissible Omicron variant.What this study adds?Despite frequent COVID-19 exposures, this study identified no detectable increase in SARS-CoV-2 seroprevalence among school staff working in three metro Vancouver public school districts after the first Omicron wave in British Columbia, compared to a reference group of blood donors from the same age, sex and community area.
Modelling the epidemiological implications for SARS-CoV-2 of Christmas household bubbles in England
Authors: Hill Edward M. 
Published: July 2022

AbstractThe emergence of SARS-CoV-2 saw severe detriments to public health being inflicted by COVID-19 disease throughout 2020. In the lead up to Christmas 2020, the UK Government sought an easement of social restrictions that would permit spending time with others over the Christmas period, whilst limiting the risk of spreading SARS-CoV-2. In November 2020, plans were published to allow individuals to socialise within ‘Christmas bubbles’ with friends and family. This policy involved a planned easing of restrictions in England between 23-27 December 2020, with Christmas bubbles allowing people from up to three households to meet throughout the holiday period. We estimated the epidemiological impact of both this and alternative bubble strategies that allowed extending contacts beyond the immediate household. We used a stochastic individual-based model for a synthetic population of 100,000 households, with demographic and SARS-CoV-2 epidemiological characteristics comparable to England as of November 2020. We evaluated five Christmas bubble scenarios for the period 23-27 December 2020, assuming our populations of households did not have symptomatic infection present and were not in isolation as the eased social restrictions began. Assessment comprised incidence and cumulative infection metrics. We tested the sensitivity of the results to a situation where it was possible for households to be in isolation at the beginning of the Christmas bubble period and also when there was lower adherence to testing, contact tracing and isolation interventions. We found that visiting family and friends over the holiday period for a shorter duration and in smaller groups was less risky than spending the entire five days together. The increases in infection from greater amounts of social mixing disproportionately impacted the eldest. We provide this account as an illustration of a real-time contribution of modelling insights to a scientific advisory group, the Scientific Pandemic Influenza Group on Modelling, Operational sub-group (SPI-M-O) for the Scientific Advisory Group for Emergencies (SAGE) in the UK, during the COVID-19 pandemic. This manuscript was submitted as part of a theme issue on “Modelling COVID-19 and Preparedness for Future Pandemics”.
Tandemly repeated genes promote RNAi-mediated heterochromatin formation via an anti-silencing factor Epe1 in fission yeast
Authors: Asanuma Takahiro , Inagaki Soichi , Kakutani Tetsuji , Aburatani Hiroyuki , Murakami Yota 
Published: July 2022

AbstractIn most eukaryotes, constitutive heterochromatin, defined by histone H3 lysine 9 methylation (H3K9me), is enriched on repetitive DNA, such as pericentromeric repeats and transposons. Furthermore, repetitive transgenes also induce heterochromatin formation in diverse model organisms. However, the mechanisms that promote heterochromatin formation at repetitive DNA elements are still not clear. Here, using fission yeast, we show that tandemly repeated mRNA genes promote RNA interference (RNAi)-mediated heterochromatin formation in co-operation with an anti-silencing factor, Epe1. Although the presence of tandemly repeated genes itself does not cause heterochromatin formation, once complementary small RNAs are artificially supplied in trans, the RNAi machinery assembled on the repeated genes starts producing cognate small RNAs in cis to autonomously maintain heterochromatin at these sites. The establishment of this “repeat-induced RNAi” depends on the copy number of repeated genes and also requires Epe1, which is known to remove H3K9me and derepress the transcription of genes underlying heterochromatin. Analogous to repeated genes, the DNA sequence underlying constitutive heterochromatin encodes widespread transcription start sites (TSSs), from which Epe1 activates ncRNA transcription to promote RNAi-mediated heterochromatin formation. Our results suggest that, when repetitive transcription units underlie heterochromatin, Epe1 generates sufficient transcripts for the activation of RNAi without disruption of heterochromatin.
Characteristics of circadian rhythm-related genes and establishment of a prognostic scoring system (CRscore) for lung adenocarcinoma with experimental verification
Authors: Zhang Fengbin , Zhang Qi , Jiang Taie , Fan Xiaoyu , Wang Wenmiao , Liu Lehan , Liu Kun 
Published: July 2022

AbstractBackgroundNon-small-cell lung cancer (NSCLC) is one of the most common malignant tumors worldwide. Lung adenocarcinoma (LUAD), which is the m ain subtype of NSCLC, has a poor prognosis. In recent years, circadian rhythm (CR)-related genes (CRRGs) have demonstrated associations with tumor occurrence and development, but the relationship between CRRGs and LUAD is not clear.MethodsBased on data from The Cancer Genome Atlas and Gene Expression Omnibus databases, we explored the biological function and immune cell infiltration of LUAD in different CR clusters and quantified CR genes using principal component analysis. Then, we built a CR scoring system (CRscore) to explore the relationship between CRRGs and LUAD prognosis.ResultsPatients were divided into three clusters (A, B, and C). Biological characteristics, such as survival, immune cell infiltration, and gene enrichment, were significantly different among the three clusters. We then established the usefulness of the CR score, which could effectively predict the prognosis of LUAD. Specifically, patients with a high CR score had a better prognosis and were more sensitive to chemotherapy than patients with a low CR score.ConclusionCRRGs can be used to assess the prognosis of patients with LUAD. Quantification of CR using the CRscore tool in patients with LUAD could help to guide personalized cancer immunotherapy strategies in the future. Thus, the CRscore may be a powerful prognostic tool for LUAD.