bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highly valued despite burdens: qualitative implementation research on rapid tests for hospital-based SARS-CoV-2 screening
Authors: Wachinger Jonas , McMahon Shannon A. , Lohmann Julia , De Allegri Manuela , Denkinger Claudia M. 
Published: August 2021

ABSTRACTAntigen-based rapid diagnostic tests (RDTs) for SARS-CoV-2 have good reliability and have been repeatedly implemented as part of pandemic response policies, especially for screening in high-risk settings (e.g., hospitals and care homes) where fast recognition of an infection is essential, but evidence from actual implementation efforts is lacking.We conducted a prospective qualitative study at a large tertiary care hospital in Germany where RDTs are used to screen incoming patients. We relied on semi-structured observations of the screening situation, as well as on 30 in-depth interviews with hospital staff (members of the regulatory body, department heads, staff working on the wards, staff training providers on how to perform RDTs, and providers performing RDTs as part of the screening) and patients being screened with RDTs.Despite some initial reservations, RDTs were rapidly accepted and adopted as the best available tool for accessible and reliable screening. Decentralized implementation efforts resulted in different procedures being operationalized across departments. Procedures were continuously refined based on initial experiences (e.g., infrastructural or scheduling constraints), pandemic dynamics (growing infection rates), and changing regulations (e.g., screening of all external personnel). To reduce interdepartmental tension, stakeholders recommended high-level, consistently communicated and enforced regulations.Despite challenges, RDT-based screening for all incoming patients was observed to be feasible and acceptable among implementers and patients, and merits continued consideration in the context of rising infections and stagnating vaccination rates.
Early immune responses have long-term associations with clinical, virologic, and immunologic outcomes in patients with COVID-19
Authors: Hu Zicheng , van der Ploeg Kattria , Chakraborty Saborni , Arunachalam Prabhu , Mori Diego Martinez , Jacobson Karen B. , Bonilla Hector , Parsonnet Julie , Andrews Jason , Hedlin Haley , de la Parte Lauren , Dantzler Kathleen , Ty Maureen , Tan Gene S , Blish Catherine A. , Takahashi Saki , Rodriguez-Barraquer Isabel , Greenhouse Bryan , Butte Atul J. , Singh Upinder , Pulendran Bali , Wang Taia T. , Jagannathan Prasanna 
Published: August 2021

AbstractThe great majority of SARS-CoV-2 infections are mild and uncomplicated, but some individuals with initially mild COVID-19 progressively develop more severe symptoms. Furthermore, mild to moderate infections are an important contributor to ongoing transmission. There remains a critical need to identify host immune biomarkers predictive of clinical and virologic outcomes in SARS-CoV-2-infected patients. Leveraging longitudinal samples and data from a clinical trial of Peginterferon Lambda for treatment of SARS-CoV-2 infected outpatients, we used host proteomics and transcriptomics to characterize the trajectory of the immune response in COVID-19 patients within the first 2 weeks of symptom onset. We define early immune signatures, including plasma levels of RIG-I and the CCR2 ligands (MCP1, MCP2 and MCP3), associated with control of oropharyngeal viral load, the degree of symptom severity, and immune memory (including SARS-CoV-2-specific T cell responses and spike (S) protein-binding IgG levels). We found that individuals receiving BNT162b2 (Pfizer–BioNTech) vaccine had similar early immune trajectories to those observed in this natural infection cohort, including the induction of both inflammatory cytokines (e.g. MCP1) and negative immune regulators (e.g. TWEAK). Finally, we demonstrate that machine learning models using 8-10 plasma protein markers measured early within the course of infection are able to accurately predict symptom severity, T cell memory, and the antibody response post-infection.
mRNA vaccines effectiveness against COVID-19 hospitalizations and deaths in older adults: a cohort study based on data-linkage of national health registries in Portugal
Authors: Nunes Baltazar , Rodrigues Ana Paula , Kislaya Irina , Cruz Camila , Peralta-Santos André , Lima João , Leite Pedro Pinto , Sequeira Duarte , Dias Carlos Matias , Machado Ausenda 
Published: August 2021

AbstractBackgroundWe used electronic health registries to estimate the mRNA vaccine effectiveness (VE) against COVID-19 hospitalizations and deaths in older adults.MethodsWe established a cohort of individuals aged 65 and more years, resident in Portugal mainland through data linkage of eight national health registries. For each outcome, VE was computed as one minus the confounder-adjusted hazard ratio, estimated by time-dependent Cox regression.ResultsVE against COVID-19 hospitalization ≥14 days after the second dose was 94% (95%CI 88 to 97) for age-group 65-79 years old (yo) and 82% (95%CI 72 to 89) for ≥80 yo. VE against COVID-19 related deaths ≥ 14 days after second dose was 96% (95%CI 92 to 98) for age-group 65-79 yo and 81% (95%CI 74 to 87), for ≥80 yo individuals. No evidence of VE waning was observed after 98 days of second dose uptake.ConclusionsmRNA vaccine effectiveness was high for the prevention of hospitalizations and deaths in age-group 65-79 yo and ≥80 yo with a complete vaccination scheme, even after 98 days of second dose uptake.
Predictors of eviction and quality of tenant-landlord relationships during the 2020-2021 eviction moratorium in the U.S.
Authors: Tsai Jack , Huang Minda , Blosnich John R. , Elbogen Eric B. 
Published: August 2021

AbstractIn 2020, the Centers for Disease Control and Prevention (CDC) issued several agency orders that put into effect a national moratorium on evictions for over one year to limit transmission of Coronavirus Disease 2019 (COVID-19). Little is known about landlord and tenant behaviors during the eviction moratorium. The current study used three waves of data from May 2020-April 2021 from a nationally representative sample of U.S. middle- and low-income tenants (n= 3,393 in Wave 1, n= 1,311 in Wave 2, and 814 in Wave 3) to examine tenants who were evicted during the eviction moratorium and the reported effects of the moratorium on tenant rental payments and tenant-landlord relationships. Across three Waves, 4.3% of tenants reported experiencing an eviction during the moratorium and 6-23% of tenants reported delaying paying rent because of the moratorium. Multivariable analyses found that tenants who delayed paying their rent, were female, or had a history of mental illness or substance use disorder were significantly more likely to report the eviction moratorium had a negative effect on the relationship with their landlord. Analyses also revealed that testing positive for COVID-19 was not a significant predictor of eviction but tenants with a history a homelessness were more than 9 times as likely to report an eviction than those without such a history. Together, these findings suggest the eviction moratorium has had some unintended consequences on rent payments and tenant-landlord relationships that need to be considered in the aftermath of the COVID-19 pandemic.
Analysis of daily reproduction rates of COVID-19 using Current Health Expenditure as Gross Domestic Product percentage (CHE/GDP) across countries
Authors: Oshinubi Kayode , Rachdi Mustapha , Demongeot Jacques 
Published: August 2021

Abstract(1)BackgroundImpact and severity of coronavirus pandemic on health infrastructure vary across countries. We examine the role percentage health expenditure plays in various countries in terms of their preparedness and see how countries improved their public health policy in the first and second wave of the coronavirus pandemic;(2)MethodsWe considered the infectious period during the first and second wave of 195 countries with their Current Health Expenditure as Gross Domestic Product percentage (CHE/GDP). Exponential model was used to calculate the slope of the regression line while the ARIMA model was used to calculate the initial autocorrelation slope and also to forecast new cases for both waves. The relationship between epidemiologic and CHE/GDP data was used for processing ordinary least square multivariate modeling and classifying countries into different groups using PC analysis, K-means and Hierarchical clustering;(3)ResultsResults show that some countries with high CHE/GDP improved their public health strategy against virus during the second wave of the pandemic;(4)ConclusionsResults revealed that countries who spend more on health infrastructure improved in the tackling of the pandemic in the second wave as they were worst hit in the first wave. This research will help countries to decide on how to increase their CHE/GDP in order to tackle properly other pandemic waves of the present Covid-19 outbreak and future diseases that may occur. We are also opening up a debate on the crucial role socio-economic determinants play during the exponential phase of the pandemic modelling.
A Systematic Review of the Protective Effect of Prior SARS-CoV-2 Infection on Repeat Infection
Authors: Kojima N , Shrestha NK , Klausner JD 
Published: August 2021

AbstractIntroductionWe systematically reviewed studies to estimate the risk of SARS-CoV-2 reinfection among those previously infected with SARS-CoV-2.MethodsFor this systematic review, we searched scientific publications on PubMed and, the pre-print server, MedRxiv through August 18, 2021. Eligible studies were retrieved on August 18, 2021. We used the following search term on PubMed: (((“Cohort Studies”[Majr]) AND (“COVID-19”[Mesh] OR “SARS-CoV-2”[Mesh])) OR “Reinfection”[Majr]) OR “Reinfection”[Mesh]. We used the following search term on MedRxiv: “Cohort Studies” AND “COVID-19” OR “SARS-CoV-2” AND “Reinfection”. The search terms were broad to encompass all possibilities for applicable studies. There were no restrictions on the date of publication. Studies that did not describe cohorts with estimates of the risk of SARS-CoV-2 reinfection among those with previous infection were excluded. Studies that included vaccinated participants were either excluded or limited to sub-groups of non-vaccinated individuals. To identify relevant studies with appropriate control groups, we developed the following criteria for studies to be included in the systematic analysis: (1) baseline polymerase chain reaction (PCR) testing, (2) a negative comparison group, (3) longitudinal follow-up, (4) a cohort of human participants, i.e., not a case report or case series, and (5) outcome determined by PCR. The review was conducted following PRISMA guidelines. We assessed for selection, information, and analysis bias, per PRISMA guidelines.ResultsWe identified 1,392 reports. Of those, 10 studies were eligible for our systematic review. The weighted average risk reduction against reinfection was 90.4% with a standard deviation of 7.7%. Protection against SARS-CoV-2 reinfection was observed for up to 10 months. Studies had potential information, selection, and analysis biases.ConclusionsThe protective effect of prior SARS-CoV-2 infection on re-infection is high and similar to the protective effect of vaccination. More research is needed to characterize the duration of protection and the impact of different SARS-CoV-2 variants.
Previous Infection Combined with Vaccination Produces Neutralizing Antibodies With Potency Against SARS-CoV-2 Variants
Authors: Ibarrondo F. Javier , Hofmann Christian , Ali Ayub , Ayoub Paul , Kohn Donald B. , Yang Otto O. 
Published: August 2021

ABSTRACTSARS-CoV-2 continues to evolve in humans. Spike protein mutations increase transmission and potentially evade antibodies raised against the original sequence used in current vaccines. Our evaluation of serum neutralizing activity in both persons soon after SARS-CoV-2 infection (in April 2020 or earlier) or vaccination without prior infection confirmed that common spike mutations can reduce antibody antiviral activity. However, when the persons with prior infection were subsequently vaccinated, their antibodies attained an apparent biologic ceiling of neutralizing potency against all tested variants, equivalent to the original spike sequence. These findings indicate that additional antigenic exposure further improves antibody efficacy against variants.LAY SUMMARYAs SARS-CoV-2 evolves to become better suited for circulating in humans, mutations have occurred in the spike protein it uses for attaching to cells it infects. Protective antibodies from prior infection or vaccination target the spike protein to interfere with its function. These mutations can reduce the efficacy of antibodies generated against the original spike sequence, raising concerns for re-infections and vaccine failures, because current vaccines contain the original sequence. In this study we tested antibodies from people infected early in the pandemic (before spike variants started circulating) or people who were vaccinated without prior infection. We confirmed that some mutations reduce the ability of antibodies to neutralize the spike protein, whether the antibodies were from past infection or vaccination. Upon retesting the previously infected persons after vaccination, their antibodies gained the same ability to neutralize mutated spike as the original spike, suggesting that the combination of infection and vaccination drove the production of enhanced antibodies to reach a maximal level of potency. Whether this can be accomplished by vaccination alone remains to be determined, but the results suggest that booster vaccinations may help improve efficacy against spike variants.
Quantification of circadian interactions and protein abundance defines a mechanism for operational stability of the circadian clock
Authors: Bagnall James S. , Koch Alex A. , Smyllie Nicola J. , Begley Nicola , Adamson Antony , Fribourgh Jennifer L. , Spiller David G. , Meng Qing-Jun , Partch Carrie L. , Strimmer Korbinian , House Thomas A. , Hastings Michael H. , Loudon Andrew S. I. 
Published: August 2021

AbstractThe mammalian circadian clock exerts substantial control of daily gene expression through cycles of DNA binding. Understanding of mechanisms driving the circadian clock is hampered by lack of quantitative data, without which predictive mathematical models cannot be developed. Here we develop a quantitative understanding of how a finite pool of BMAL1 protein can regulate thousands of target sites over daily time scales. We have used fluorescent correlation spectroscopy (FCS) to track dynamic changes in CRISPR-modified fluorophore-tagged proteins in time and space in single cells across SCN and peripheral tissues. We determine the contribution of multiple rhythmic processes in coordinating BMAL1 DNA binding, including the roles of cycling molecular abundance, binding affinities and two repressive modes of action. We find that nuclear BMAL1 protein numbers determine corresponding nuclear CLOCK concentrations through heterodimerization and define a DNA residence time of 2.6 seconds for this complex. Repression of CLOCK:BMAL1 is in part achieved through rhythmic changes to BMAL1:CRY1 affinity as well as a high affinity interaction between PER2:CRY1 which mediates CLOCK:BMAL1 displacement from DNA. Finally, stochastic modelling of these data reveals a dual role for PER:CRY complexes in which increasing concentrations of PER2:CRY1 promotes removal of BMAL1:CLOCK from genes consequently enhancing ability to move to new target sites.
Cerebrospinal fluid outflow through skull channels instructs cranial hematopoiesis
Authors: Pulous Fadi E. , Cruz-Hernández Jean C. , Yang Chongbo , Kaya Zeynep , Wojtkiewicz Gregory , Capen Diane , Brown Dennis , Wu Juwell W. , Vinegoni Claudio , Yamazoe Masahiro , Grune Jana , Schloss Maximillian J. , Rohde David , Richter Dmitry , McAlpine Cameron S. , Panizzi Peter , Weissleder Ralph , Kim Dong-Eog , Swirski Filip K. , Lin Charles P. , Moskowitz Michael A. , Nahrendorf Matthias 
Published: August 2021

AbstractInteractions between the immune and central nervous systems strongly influence brain health. Although the blood-brain barrier restricts this crosstalk, we now know that meningeal gateways through brain border tissues, particularly dural lymphatic vessels that allow cerebrospinal fluid outflow, facilitate intersystem communication. Here we observe that cerebrospinal fluid exits into the skull bone marrow. Fluorescent tracers injected into the cisterna magna of mice travel through hundreds of sub-millimeter skull channels into the calvarial marrow. During meningitis, bacteria usurp this perivascular route to infect the skull’s hematopoietic niches and initiate cranial hematopoiesis ahead of remote tibial sites. Because skull channels also directly provide leukocytes to meninges, the privileged sampling of brain-derived danger signals in cerebrospinal fluid by regional marrow has broad implications for neurological disorders.One-Sentence SummarySkull channels transport cerebrospinal fluid from the subarachnoid space to the cranial bone marrow via a perivascular route, which bacteria use during meningitis.
Experimental and mathematical models of intracellular calcium dynamics for evaluating combined anticancer effects of Afatinib and RP4010 in esophageal cancer
Authors: Chang Yan , Funk Marah , Roy Souvik , Stephenson Elizabeth , Choi Sangyong , Kojouharov Hristo , Chen Benito , Pan Zui 
Published: August 2021

AbstractTargeting dysregulated Ca2+ signaling in cancer cells is an emerging chemotherapy approach. We previously reported that store-operated Ca2+ entry (SOCE) blockers, such as RP4010, are promising antitumor drugs for esophageal cancer. As a tyrosine kinase inhibitor (TKI), afatinib received FDA approval to be used in targeted therapy for patients with EGFR mutation-positive cancers. While preclinical studies and clinical trials have shown that afatinib has benefits for esophageal cancer patients, it is not known whether combination of afatinib and RP4010 could achieve better anticancer effects. Since TKI can alter intracellular Ca2+ dynamics through EGFR/phospholipase C-γ pathway, in this study, we evaluated the inhibitory effect of afatinib and RP4010 on intracellular Ca2+ oscillations in esophageal cancer cells using both experimental and mathematical simulations. Our mathematical simulation of Ca2+ oscillations could fit well with experimental data responding to aftinib or RP4010, separately or in combination. The results showed that combination of afatinib and RP4010 presented synergistic anticancer effect. This intracellular Ca2+ dynamic-based mathematical simulation approach could be useful for a rapid and cost-effective evaluation of combined targeting therapy drugs.
Aβ oligomers trigger necroptosis-mediated neurodegeneration via microglia activation in Alzheimer’s disease
Authors: Salvadores Natalia , Moreno-Gonzalez Inés , Ruiz Nazaret Gamez , Quiroz Gabriel , Vegas Laura , Escandón Marcela , Jimenez Sebastian , Vitorica Javier , Gutierrez Antonia , Soto Claudio , Court Felipe A. 
Published: August 2021

AbstractAlzheimer’s disease (AD) is a major adult-onset neurodegenerative condition with no available treatment. Compelling reports point amyloid-β (Aβ) as the main etiologic agent that triggers AD. Although there is extensive evidence of detrimental crosstalk between Aβ and microglia that contributes to neuroinflammation in AD, the exact mechanism leading to neuron death remains unknown. Using postmortem human AD brain tissue, we show that Aβ pathology is associated with the necroptosis effector pMLKL. Moreover, we found that the burden of Aβo correlates with the expression of key markers of necroptosis activation. Additionally, inhibition of necroptosis by pharmacological or genetic means, reduce neurodegeneration and memory impairment triggered by Aβo in mice. Since microglial activation is emerging as a central driver for AD pathogenesis, we then tested the contribution of microglia to the mechanism of Aβo-mediated necroptosis activation in neurons. Using an in vitro model, we show that conditioned medium from Aβo-stimulated microglia elicited necroptosis in neurons through activation of TNF-α signaling, triggering extensive neurodegeneration. Notably, necroptosis inhibition provided significant neuronal protection. Together, these findings suggest that Aβo-mediated microglia stimulation in AD contributes to necroptosis activation in neurons and neurodegeneration. As necroptosis is a druggable degenerative mechanism, our findings might have important therapeutic implications to prevent the progression of AD.
Analyses of the 5’ Ends of Escherichia coli ORFs
Authors: Ward Michael , Curran James F. 
Published: August 2021

AbstractSequence biases at 5’ ends of coding sequences differ from those of the remainder of ORFs, reflecting differences in function. Internal sequence biases promote translational efficiency by several mechanisms including correlating codon usage and tRNA concentration. However, the early region may also facilitate translational initiation, establishment of the reading frame, and polypeptide processing. Here we examine the beginnings of the ORFs of an Escherichia coli K12 reference genome. The results extend previous observations of A-richness to include an overabundance of the AAA triplet in all reading frames, consistent with the hypothesis that the beginnings of ORFs contribute to initiation site accessibility. Results are also consistent with the idea that the first two amino acids are under selection because they facilitate solvation of the amino-terminus at the end of the ribosomal exit channel. Moreover, serine is highly overrepresented as the second amino acid, possibly because it can facilitate removal of the terminal formylmethionine. Non-AUG initiation codons are known to be less efficient than AUG at directing initiation, presumably because of relatively weak base pairing to the initiator-tRNA. But non-UAG initiation codons are not followed by unusual 3’ nearest neighbor codons. Moreover, the four NUG initiation codons do not differ in their propensity to frameshift in an assay known to be sensitive to base pair strength. Altogether, these data suggest that the 5’ ends of ORFs are under selection for several functions, and that initiation codon identity may not be critical beyond its role in initiation.
The contribution of cohesin to chromatid organisation is critical during chromosome segregation
Authors: Garcia-Luis Jonay , Bordelet Hélène , Thierry Agnès , Koszul Romain , Aragon Luis 
Published: August 2021

AbstractChromosome segregation requires both the separation of sister chromatids and the sustained condensation of chromatids during anaphase. In yeast cells, cohesin is not only required for sister chromatid cohesion but also plays a major role in determining the structure of individual chromatids in metaphase. Separase cleavage is thought to remove all cohesin complexes from chromosomes to initiate anaphase. It is thus not clear how the length and organisation of segregating chromatids are maintained during anaphase in the absence of cohesin. Here we show that degradation of cohesin at the anaphase onset causes aberrant chromatid segregation. Hi-C analysis on segregating chromatids demonstrates that cohesin depletion causes loss of intrachromatid organisation. Surprisingly, TEV-mediated cleavage of cohesin does not dramatically disrupt chromatid organisation in anaphase, explaining why bulk segregation is achieved. In addition, we identified a small pool of cohesin complexes bound to telophase chromosomes in wildtype cells and show that they play a role in the organisation of centromeric regions. Our data demonstrate that in yeast cells, cohesin function is not over in metaphase, but extends to the anaphase period when chromatids are segregating.One sentence summaryCohesin complexes on yeast chromosomes provide organisation to segregating chromatids.