bluuebunny/crossref_metadata_2025_split huggingface dataset:
Markers Of Coagulation And Hemostatic Activation Identify COVID-19 Patients At High Risk For Thrombotic Events, ICU Admission and Intubation
Authors: Alabyad Darwish , Rangaraju Srikant , Liu Michael , Imran Rajeel , Kempton Christine L. , Sharifpour Milad , Auld Sara C. , Gaddh Manila , Sniecinski Roman , Maier Cheryl L. , Guarner Jeannette , Duncan Alexander , Nahab Fadi 
Published: October 2020

ABSTRACTBackgroundCoronavirus disease 2019 (COVID-19) has been associated with a coagulopathy giving rise to venous and arterial thrombotic events. The objective of our study was to determine whether markers of coagulation and hemostatic activation (MOCHA) on admission could identify COVID-19 patients at risk for thrombotic events and other complications.MethodsCOVID-19 patients admitted to a tertiary academic healthcare system from April 3, 2020 to July 31, 2020 underwent standardized admission testing of MOCHA profile parameters (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer) with abnormal MOCHA defined as ≥ 2 markers above the reference. Prespecified thrombotic endpoints included deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, and access line thrombosis; other complications included ICU admission, intubation and mortality. We excluded patients on anticoagulation therapy prior to admission and those who were pregnant.ResultsOf 276 patients (mean age 59 ± 6.4 years, 47% female, 62% African American race) who met study criteria, 45 (16%) had a thrombotic event. Each coagulation marker on admission was independently associated with a vascular endpoint (p<0.05). Admission MOCHA with ≥ 2 abnormalities (n=203, 74%) was associated with in-hospital vascular endpoints (OR 3.3, 95% CI 1.2-8.8), as were admission D-dimer ≥ 2000 ng/mL (OR 3.1, 95% CI 1.5-6.6), and admission D-dimer ≥ 3000 ng/mL (OR 3.6, 95% CI 1.6-7.9). However, only admission MOCHA with ≥ 2 abnormalities was associated with ICU admission (OR 3.0, 95% CI 1.7-5.2) and intubation (OR 3.2, 95% CI 1.6-6.4), while admission D-dimer ≥2000 ng/mL and admission D-dimer ≥ 3000 ng/mL were not associated. MOCHA and D-dimer cutoffs were not associated with mortality. Admission MOCHA with <2 abnormalities (26% of the cohort) had a sensitivity of 88% and negative predictive value of 93% for a vascular endpoint.ConclusionsAdmission MOCHA with ≥ 2 abnormalities identified COVID-19 patients at increased risk of ICU admission and intubation during hospitalization more effectively than isolated admission D-dimer measurement. Admission MOCHA with <2 abnormalities identified a subgroup of patients at low risk for vascular events. Our results suggest that an admission MOCHA profile can be useful to risk-stratify COVID-19 patients.
Repetitive and Brief Occlusion of the Majority of the Vena Cava Flow Attenuates Pulmonary Arterial Hypertension and ImprovesIK+of the Pulmonary Arterial Smooth Muscle Cells in Rat Models: a novel potential therapeutic strategy for PAH
Authors: Liu Nan , Xing Ying , Wang Lv , Wang Chen 
Published: October 2020

AbstractBy now, there are limited therapeutic approaches satisfactory for pulmonary arterial hypertension (PAH) treatment. In the present study, we established a novel rat model, repetitive and brief occlusion (RBO) of the majority of the right atrium venous blood flow in the conscious rats. Using this model, we found that the RBO treatment significantly improved the pulmonary hemodynamics with a lower pulmonary vascular resistance observed. The IK+and big-conductance Ca2+-activated K+(BK) channels were involved in the mechanism of the RBO treatment for PAH. Although the results are limited, the conclusion are solid and we believe this manuscript is valuable for all the researchers and clinical doctors who are interested in PAH.
Occurrence and distribution of fecal indicators and pathogenic bacteria in seawater andPerna pernamussel in the Gulf of Annaba (Southern Mediterranean)
Authors: Boufafa Mouna , Kadri Skander , Redder Peter , Bensouilah Mourad 
Published: October 2020

AbstractThe brown musselPerna pernais a marine bivalve that is widely distributed and consumed along the east coast of Algeria. Due to its filter-feeding capacity, this mollusk can accumulate large quantities of pathogenic microorganisms from the surrounding waters, thus acting as bio-indicator of coastal environments. The objective of this study is to investigate the occurrence and distribution of fecal indicators and pathogenic bacteria in seawaters and mussels collected from four different sites in the Gulf of Annaba through physicochemical, biochemical and molecular analysis. The obtained results revealed that the levels of fecal indicator bacteria (FIB) were alarmingly high at Sidi Salem and Rezgui Rachid when compared with the two other sites (p < 0.05) and largely exceeded the permissible limits. Besides,P. pernacollected from all sites were several fold more contaminated by these germs than seawater samples, notably, during the warm season of the study period. Biochemical and molecular analysis showed that isolated bacteria from both environmental compartments were mostly potentially pathogenic species such asE. coli, Salmonella, Staphylococcus, Klebsiella, Pseudomonas and Proteus. These principal findings demonstrate the strong involvement of anthropogenic activities on the microbiological quality of the Gulf and highlight the role ofP. pernaas an effective bio-indicator of the bacteriological quality of coastal waters.
Joint estimation of neural sources and their functional connections from MEG data
Authors: Subramaniyam Narayan Puthanmadam , Tronarp Filip , Särkkä Simo , Parkkonen Lauri 
Published: October 2020

AbstractCurrent techniques to estimate directed functional connectivity from magnetoencephalography (MEG) signals involve two sequential steps; 1) Estimation of the sources and their amplitude time series from the MEG data by solving the inverse problem, and 2) fitting a multivariate autoregressive (MVAR) model to these time series for the estimation of AR coefficients, which reflect the directed interactions between the sources. However, such a sequential approach is not optimal since i) source estimation algorithms typically assume that the sources are independent, ii) the information provided by the connectivity structure is not used to inform the estimation of source amplitudes, and iii) the limited spatial resolution of source estimates often leads to spurious connectivity due to spatial leakage.Here, we present an algorithm to jointly estimate the source and connectivity parameters using Bayesian filtering, which does not require anatomical constraints in form of structural connectivity or a-priori specified regions-of-interest. By formulating a state-space model for the locations and amplitudes of a given number of sources, we show that estimation of functional connectivity can be reduced to a system identification problem. We derive a solution to this problem using a variant of the expectation–maximization (EM) algorithm known as stochastic approximation EM (SAEM).Compared to the traditional two-step approach, the joint approach using the SAEM algorithm provides a more accurate reconstruction of connectivity parameters, which we show with a connectivity benchmark simulation as well as with an electrocorticography-based simulation of MEG data. Using real MEG responses to visually presented faces in 16 subjects, we also demonstrate that our method gives source and connectivity estimates that are both physiologically plausible and largely consistent across subjects. In conclusion, the proposed joint-estimation approach based on the SAEM algorithm outperforms the traditional two-step approach in determining functional connectivity structure in MEG data.
SdhA interferes with disruption of theLegionella-containing vacuole by hijacking the OCRL phosphatase
Authors: Choi Won Young , Creasey Elizabeth A. , Lowe Martin , Isberg Ralph R. 
Published: October 2020

SummaryLegionella pneumophilagrows intracellularly within a replication vacuole via action of Icm/Dot-secreted proteins. One such protein, SdhA, maintains the integrity of the vacuolar membrane, thereby preventing cytoplasmic degradation of bacteria. We show here that SdhA binds and blocks the action of OCRL (OculoCerebroRenal syndrome of Lowe), an inositol 5-phosphatase pivotal for controlling endosomal dynamics. OCRL depletion resulted in enhanced vacuole integrity and intracellular growth of asdhAmutant, consistent with OCRL participating in vacuole disruption. Overexpressed SdhA altered OCRL function, enlarging endosomes, driving endosomal accumulation of PI(4,5)P2, and interfering with endosomal trafficking. SdhA interrupted Rab GTPase-OCRL interactions by binding to the OCRL ASH domain, without directly altering OCRL 5-phosphatase activity. TheLegionellavacuole encompassing thesdhAmutant accumulated OCRL and endosomal antigen EEA1, consistent with SdhA blocking accumulation of OCRL-containing endosomal vesicles. Therefore, SdhA hijacking of OCRL is associated with blocking trafficking events that disrupt the pathogen vacuole.
Association between intrahospital transfers and hospital-acquired infection among elderly patients: A retrospective case-control study in one urban UK hospital trust
Authors: Boncea Estera , Expert Paul , Honeyford Kate , Kinderlerer Anne , Mitchell Colin , Cooke Graham S , Mercuri Luca , Costelloe Céire 
Published: October 2020

AbstractBackgroundIntrahospital transfers have become more common as hospital staff balance patient needs with bed availability. However, this may leave patients more vulnerable to potential pathogen transmission routes via increased exposure to contaminated surfaces and contacts with individuals.ObjectiveThis study aimed to quantify the association between the number of intrahospital transfers undergone during a hospital spell and the development of a hospital-acquired infection (HAI).MethodsA retrospective case-control study was conducted using data extracted from electronic health records and microbiology cultures of non-elective, medical admissions to a large urban hospital trust comprising 3 hospital sites between 2016 and 2018 (n=24,239). As elderly patients comprise a large proportion of hospital users and are a high-risk population for HAIs, the analysis focused on those over 65-years old. Logistic regression was conducted to obtain the odds ratio (OR) for developing a HAI as a function of intrahospital transfers until onset of HAI for cases, or hospital discharge for controls, while controlling for age, gender, time-at-risk, Elixhauser comorbidities, hospital site of admission, dominant treatment function code, intensive care admission, total number of procedures, and discharge destination.ResultsOf the 24,239 spells, 2879 cases were included in the analysis. 72.2% of spells contained at least one intrahospital transfer. On multivariable analysis, each additional intrahospital transfer increased the odds of acquiring a HAI by 9% (OR 1.09; 95%CI 1.05 to 1.13).ConclusionIntrahospital transfers are associated with increased odds of developing a HAI. Strategies for minimising intrahospital transfers should be considered, and further research is needed to identify unnecessary transfers. Their reduction may diminish spread of contagious pathogens in the hospital environment.
Chest pain presentations to hospital during the COVID-19 lockdown: lessons for public health media campaigns
Authors: Ferry Amy V , Keanie Collette , Denvir Martin A , Mills Nicholas L , Strachan Fiona E 
Published: October 2020

AbstractObjectiveEmergency Department (ED) attendances with chest pain reduced during the COVID-19 lockdown. To understand factors influencing patients’ decisions to attend hospital, we performed a local service evaluation project in NHS Lothian.MethodsWe collated data on online searches and local clinical services on the number of ED presentations and chest pain clinic (CPC) referrals with suspected acute coronary syndrome between January and May 2020 and compared findings with the same period in 2019. We also carried out 28 semi-structured telephone interviews with patients who presented with chest pain during lockdown and in patients with known coronary heart disease under the outpatient care of a cardiologist in April and May 2020. Interviews were audio recorded and salient themes and issues documented as verbatim extracts.ResultsOnline searches for the term “chest pain” doubled after 01/03/2020, peaking in week commencing 22/03/2020 and returning to 2019 levels during April 2020. In contrast, chest pain presentations to ED and CPC decreased, with the greatest reduction in the final week of March 2020 (128 v 287 (average weekly ED attendance 2019), and 6 v 23 (average weekly CPC referral 2019)). This aligned with key government messages to ‘Protect the NHS’ and the ‘NHS is open’ campaign. Patient interviews revealed three main themes; 1) pandemic help-seeking behaviour2) COVID-19 exposure concerns; 3) favourable Hospital experience if admitted.ConclusionsDynamic monitoring of public health and media messaging should evaluate public response to healthcare campaigns to ensure the net impact on health, pandemic and non-pandemic related, is optimised.What is already known about the subject?Reports from around the world revealed a decrease in the numbers of patients attending hospital for serious health complaints such as chest pain during the lockdown restrictions imposed by governments to decrease the spread of SARS-CoV-2.What does this study add?This service evaluation project has provided insight into how patients experiencing chest pain made the decision to attend hospital for assessment during this period. It has revealed how the pandemic shaped help-seeking practices, how patients interpreted their personal vulnerability to the virus, and describes patient experience of attending hospital for assessment during this time.How might this impact on clinical practice?Careful monitoring of the public response to health care messaging campaigns should be a key part of a pandemic strategy and careful adjustment of messaging, in a dynamically responsive way, should be considered in future.
A multiplex microsphere IgG assay for SARS-CoV-2 using ACE2-mediated inhibition as a surrogate for neutralization
Authors: Cameron Andrew , Porterfield Claire A. , Byron Larry D. , Wang Jiong , Pearson Zachary , Bohrhunter Jessica L. , Cardillo Anthony B. , Ryan-Muntz Lindsay , Sorensen Ryan A. , Caserta Mary T. , Angeloni Steven , Hardy Dwight J. , Zand Martin S. , Pecora Nicole D. 
Published: October 2020

ABSTRACTThe COVID-19 pandemic has highlighted the challenges inherent to the serological detection of a novel pathogen such as SARS-CoV-2. Serological tests can be used diagnostically and for surveillance, but their usefulness depends on their throughput, sensitivity and specificity. Here, we describe a multiplex fluorescent microsphere-based assay, 3Flex, that can detect antibodies to three major SARS-CoV-2 antigens—spike (S) protein, the spike ACE2 receptor-binding domain (RBD), and nucleocapsid (NP). Specificity was assessed using 213 pre-pandemic samples. Sensitivity was measured and compared to the Abbott™ ARCHITECT™ SARS-CoV-2 IgG assay using serum samples from 125 unique patients equally binned (n= 25) into 5 time intervals (≤5, 6 to 10, 11 to 15, 16 to 20, and ≥21 days from symptom onset). With samples obtained at ≤5 days from symptom onset, the 3Flex assay was more sensitive (48.0%vs. 32.0%), but the two assays performed comparably using serum obtained ≥21 days from symptom onset. A larger collection (n= 534) of discarded sera was profiled from patients (n= 140) whose COVID-19 course was characterized through chart review. This revealed the relative rise, peak (S, 23.8; RBD, 23.6; NP, 16.7; in days from symptom onset), and decline of the antibody response. Considerable interperson variation was observed with a subset of extensively sampled ICU patients. Using soluble ACE2, inhibition of antibody binding was demonstrated for S and RBD, and not for NP. Taken together, this study described the performance of an assay built on a flexible and high-throughput serological platform that proved adaptable to the emergence of a novel infectious agent.
Age disparities in lung cancer survival in New Zealand: the role of patient and clinical factors
Authors: Pilleron Sophie , Maringe Camille , Charvat Hadrien , Atkinson June , Morris Eva , Sarfati Diana 
Published: October 2020

AbstractBackgroundAge is an important prognostic factor for lung cancer. However, no studies have investigated the age difference in lung cancer survival per se. We, therefore, described the role of patient-related and clinical factors on the age pattern in lung cancer excess mortality hazard by stage at diagnosis in New Zealand.MethodsWe extracted 22 487 new lung cancer cases aged 50-99 (median age = 71, 47.1% females) diagnosed between 1 January 2006 and 31 July 2017 from the New Zealand population-based cancer registry and followed up to December 2019. We modelled the effect of age at diagnosis, sex, ethnicity, deprivation, comorbidity, and emergency presentation on the excess mortality hazard by stage at diagnosis, and we derived corresponding lung cancer net survival.ResultsThe age difference in net survival was particularly marked for localised and regional lung cancers, with a sharp decline in survival from the age of 70. No identified factors influenced age disparities in patients with localised cancer. However, for other stages, females had a greater age difference in survival between middle-aged and older patients with lung cancer than males. Comorbidity and emergency presentation played a minor role. Ethnicity and deprivation did not influence age disparities in lung cancer survival.ConclusionSex and stage at diagnosis were the most important factors of age disparities in lung cancer survival in New Zealand.Key messagesWhat is the key question?How do patient-related and clinical factors influence age pattern in lung cancer survival?What is the bottom line?Age disparities in lung cancer survival were strongest for females and non-advanced disease. Deprivation, ethnicity, comorbidity, and emergency presentation did not influence age disparities.Why read on?Our findings reinforce the call for a better representation of older adults in clinical trials and a wider use of geriatric assessment to identify patients who will benefit treatment.
Communicating personalised risks from COVID-19: guidelines from an empirical study
Authors: Freeman Alexandra L. J. , Kerr John , Recchia Gabriel , Schneider Claudia R. , Lawrence Alice C.E. , Finikarides Leila , Luoni Giulia , Dryhurst Sarah , Spiegelhalter David J 
Published: October 2020

AbstractAs increasing amounts of data accumulate on the effects of the novel coronavirus Sars-CoV-2 and the risk factors that lead to poor outcomes, it is possible to produce personalised estimates of the risks faced by groups of people with different characteristics. The challenge of how to communicate these then becomes apparent. Based on empirical work (total n=5,520, UK) supported by in-person interviews with the public and physicians, we make recommendations on the presentation of such information. These include: using predominantly percentages when communicating the absolute risk, but also providing, for balance, a format which conveys a contrasting (higher) perception of risk (expected frequency out of 10,000); using a visual linear scale cut at an appropriate point to illustrate the maximum risk, explained through an illustrative ‘persona’ who might face that highest level of risk; and providing context to the absolute risk through presenting a range of other ‘personas’ illustrating people who would face risks of a wide range of different levels. These ‘personas’ should have their major risk factors (age, existing health conditions) described. By contrast, giving people absolute likelihoods of other risks they face in an attempt to add context was considered less helpful.
Updating Herd Immunity Models for the U.S. in 2020: Implications for the COVID-19 Response
Authors: Sheils Natalie E. , Lyng Gregory D. , Berke Ethan M. 
Published: October 2020

AbstractObjectivesTo understand what levels of herd immunity are required in the COVID-19 pandemic, given spatial population heterogeneity, to best inform policy and action.MethodsUsing a network of counties in the United States connected by transit data we considered a set of coupled differential equations for susceptible-infectious-removed populations. We calculated the classical herd immunity level plus a version reflecting the heterogeneity of connections in the network by running the model forward in time until the epidemic completed.ResultsNecessary levels of herd immunity vary greatly from county to county. A population weighted average for the United States is 47.5% compared to a classically estimated level of 77.1%.ConclusionsCommon thinking argues that the nation needs to achieve at least 60% herd immunity to emerge from the COVID-19 pandemic. Heterogeneity in contact structure and individual variation in infectivity, susceptibility, and resistance are key factors that reduce the disease-induced herd immunity levels to 34.2–47.5% in our models. Looking forward toward vaccination strategies, these results suggest we should consider not just who is vaccinated but where those vaccinations will do the most good.
Obtaining deeper insights into microbiome diversity using a simple method to block host and non-targets in amplicon sequencing
Authors: Mayer Teresa , Mari Alfredo , Almario Juliana , Murillo-Roos Mariana , Abdullah Muhammad , Dombrowski Nina , Hacquard Stephane , Kemen Eric M. , Agler Matthew T. 
Published: October 2020

AbstractMicrobiome profiling is revolutionizing our understanding of biological mechanisms such as metaorganismal (host+microbiome) assembly, functions and adaptation. Amplicon sequencing of multiple conserved, phylogenetically informative loci is an instrumental tool for characterization of the highly diverse microbiomes of natural systems. Investigations in many study systems are hindered by loss of essential sequencing depth due to amplification of non-target DNA from hosts or overabundant microorganisms. This issue requires urgent attention to address ecologically relevant problems using high throughput, high resolution microbial profiling. Here, we introduce a simple, low cost and highly flexible method using standard oligonucleotides (“blocking oligos”) to block amplification of non-targets and an R package to aid in their design. They can be dropped into practically any two-step amplicon sequencing library preparation pipeline. We apply them in leaves, a system presenting exceptional challenges with host and non-target microbial amplification. Blocking oligos designed for use in eight target loci reduce undesirable amplification of host and non-target microbial DNA by up to 90%. In addition, 16S and 18S “universal” plant blocking oligos efficiently block most plant hosts, leading to increased microbial alpha diversity discovery without biasing beta diversity measurements. By blocking only chloroplast 16S amplification, we show that blocking oligos do not compromise quantitative microbial load information inherent to plant-associated amplicon sequencing data. Using these tools, we generated a near-complete survey of theArabidopsis thalianaleaf microbiome based on diversity data from eight loci and discuss complementarity of commonly used amplicon sequencing regions for describing leaf microbiota. The blocking oligo approach has potential to make new questions in a variety of study systems more tractable by making amplicon sequencing more targeted, leading to deeper, systems-based insights into microbial discovery.