bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD19+IgD+CD27- naïve B Cells as predictors of humoral response to COVID-19 mRNA vaccination in immunocompromised patients
Authors: Schulz Eduard , Hodl Isabel , Forstner Patrick , Hatzl Stefan , Sareban Nazanin , Moritz Martina , Fessler Johannes , Dreo Barbara , Uhl Barbara , Url Claudia , Grisold Andrea , Khalil Michael , Kleinhappl Barbara , Enzinger Christian , Stradner Martin H. , Greinix Hildegard , Schlenke Peter , Steinmetz Ivo 
Published: August 2021

ABSTRACTImmunocompromised patients are considered high-risk and prioritized for vaccination against COVID-19. We aimed to analyze B-cell subsets in these patients to identify potential predictors of humoral vaccination response. Patients (n=120) suffering from hematologic malignancies or other causes of immunodeficiency and healthy controls (n=79) received a full vaccination series with an mRNA vaccine. B-cell subsets were analyzed prior to vaccination. Two independent anti-SARS-CoV-2 immunoassays targeting the receptor-binding domain (RBD) or trimeric S protein (TSP) were performed three to four weeks after the second vaccination. Seroconversion occurred in 100% of healthy controls, in contrast to 67% (RBD) and 82% (TSP) of immunocompromised patients, while only 32% (RBD) and 22% (TSP) achieved antibody levels comparable to those of healthy controls. The number of circulating CD19+IgD+CD27- naïve B cells was strongly associated with antibody levels (ρ=0.761, P<0.001) and the only independent predictor for achieving antibody levels comparable to healthy controls (OR 1.07 per 10-µl increase, 95%CI 1.02–1.12, P=0.009). Receiver operating characteristic analysis identified a cut-off at ≥61 naïve B cells per µl to discriminate between patients with and without an optimal antibody response. Consequently, measuring naïve B cells in immunocompromised hematologic patients could be useful in predicting their humoral vaccination response.
The fomite contribution to the transmission of COVID-19 in the UK: an evolutionary population estimate
Authors: Meiksin A. 
Published: August 2021

AbstractA SEIR model with an added fomite term is used to constrain the contribution of fomites to the spread of COVID-19 under the Spring 2020 lockdown in the UK. Assuming uniform priors on the reproduction number in lockdown and the fomite transmission rate, an upper limit is found on the fomite transmission rate of less than 1 contaminated object in 7 per day per infectious person (95% CL). Basing the prior on the reproduction rate during lockdown instead on the CoMix study results for the reduction in social contacts under lockdown, and assuming the reproduction number scales with the number of social contacts, provides a much more restrictive upper limit on the transmission rate by contaminated objects of fewer than 1 in 30 per day per infectious person (95% CL). Applied to postal deliveries and groceries, the upper limit on the fomite transmission rate corresponds to a probability below 1 in 70 (95% CL) that a contaminated object transmits the infection. Fewer than about half (95% CL) of the total number of deaths during the lockdown are found to arise from fomites, and most likely fewer than a quarter. These findings apply only to fomites with a transmission rate that is unaffected by a lockdown.
Hepatitis B and D: a forecast on actions needed to reduce incidence and achieve elimination
Authors: Greenhalgh Scott , Klug Andrew 
Published: August 2021

AbstractBackgroundViral hepatitis negatively affects the health of millions, with the worst health outcomes associated with the hepatitis D virus (HDV). Fortunately, HDV is rare and requires prior infection with the hepatitis B virus (HBV) before it can establish infection and transmit. As such, public health officials have opted to indirectly control HDV by reducing HBV incidence, primarily through hepatitis B vaccination, which has dramatically reduced HBV incidence since its rollout in the 1980s. However, investigations into the consequences of hepatitis B vaccination on both the control and evolution of HDV remain limited.MethodsWe developed a mathematical model of HBV and HDV transmission to investigate the effects of hepatitis B vaccination on both HBV and HDV. We calibrated our model to the HBV and HDV transmission scenarios occurring in Sub-Saharan Africa, and estimate HBV vaccination thresholds that cause HBV and HDV elimination, inhibit the spread of virulent HDV strains, and achieve the targets set by public health authorities for reducing all viral hepatitis incidence by 90%.ResultsOur findings illustrate hepatitis B vaccination rates above 0.0096 year−1and 0.018 year−1will likely achieve HDV and HBV elimination, respectively. Furthermore, in the majority of transmission settings, scaling-up vaccination rates to at least 0.009 year−1or 0.02136 year−1will achieve the 90% reduction in hepatitis D and B, respectively, called for by health authorities.ConclusionOur results suggest a scale-up of hepatitis B vaccination is required to achieve the targets set by public health officials for reducing all viral hepatitis by 90%. Furthermore, the scale-up required to achieve such targets would bring HBV and HDV to the brink of the vaccination threshold required for their elimination. Thus, with sufficient investments to scale up global hepatitis vaccination, prevention, testing, and treatment services, the eradication of both HBV and HDV are likely feasible endeavors, especially once the 90% reduction goal is reached.
Cardiovascular diseases associated with influenza infection: protocol for a systematic review and meta-analysis
Authors: del Carmen Caycho Torres María , Yamahuchi Johnny Clavo , Cornejo Ramos Cory Ximena , Diaz Gomez Katherine Ada , Gayoso Liviac Oscar Alonso , Zanoni Ramos Omar Fabricio , Zambrano Victor Vega , Ugarte-Gil Cesar 
Published: August 2021

ABSTRACTBackgroundCardiovascular diseases represent important diagnoses that can become fatal if an early and adequate management is not carried out. Since 1930, a possible relationship between these events and influenza virus infection has been proposed.ObjectivesTo determine the association between cardiovascular diseases and previous infection by influenza virus.Materials and methodsWe propose to do a systematic review and meta-analysis according to PRISMA. In order to do so, we will perform an electronic search in the databases of EMBASE, PubMed, Global Index Medicus, Google Scholar and Cochrane Library. Articles will first be selected according to their respective titles and abstracts; and subsequently, the full text of each article will be evaluated. Both phases will be executed by 4 authors. The extracted data will include study details, study methodology and results. The quality of the studies will be verified using standardized tools according to the study design and we will evaluate possible biases. In addition, a meta-analysis of the association measures will be performed using Cochrane’s Software Review Manager 5.4.1 and we will use the GRADE tool to assess the certainty of the results obtained from the analyzed studies.ResultsWe will publish the results of this systematic review and meta-analysis in a peer-reviewed journal.ConclusionsThis systematic review will provide more up-to-date evidence compared to previous work on the association between laboratory-confirmed influenza and cardiovascular diseases.
Agent-based modeling of DFNB1A prevalence with regard to intensity of selection pressure in isolated human population: will cochlear implantation increase the cases of hereditary deafness?
Authors: Romanov Georgii P. , Smirnova Anna A. , Zamyatin Vladimir I. , Mukhin Aleksey M. , Kazantsev Fedor V. , Pshennikova Vera G. , Teryutin Fedor M. , Solovyev Aisen V. , Fedorova Sardana A. , Posukh Olga L. , Lashin Sergey A. , Barashkov Nikolay A. 
Published: August 2021

ABSTRACTIt was evidenced, that the increase in the prevalence of autosomal recessive deafness 1A (DFNB1A) in populations of European descent was promoted by assortative marriages among deaf people. Assortative marriages become possible with a widespread introduction of sign language resulting in increased the genetic fitness of deaf individuals, thus relaxing selection against deafness. Currently, cochlear implantation is becoming a common method of rehabilitation for deaf patients, restoring their hearing ability and promoting the acquirement of spoken language. Whether the mass cochlear implantation could affect the spread of hereditary deafness is unknown. We have developed an agent-based computer model for analysis of the spread of DFNB1A. Using the model, we tested impact of different intensity of selection pressure on an isolated human population for 400 years. The modeling of the “purifying” selection pressure on deafness resulted in decrease of the proportion of deaf individuals and the pathogenic allele frequency. The modeling of relaxed selection resulted in increase of the proportion of deaf individuals and the decrease of the pathogenic allele frequency. The results of neutral selection pressure modeling showed no significant changes in both the proportion of deaf individuals and the pathogenic allele frequency after 400 years. Thus, initially low genetic fitness of deaf people can be significantly increased in the presence of assortative mating by deafness, resulting in a higher prevalence of DFNB1A. Contrary, frequency of pathogenic allele and the incidence of hereditary hearing loss will not increase in a population where all deaf individuals undergo cochlear implantation.
A Novel Convolutional Neural Network for COVID-19 detection and classification using Chest X-Ray images
Authors: Nafees Muhammad Talha , Irshadullah  , Rizwan Muhammad , Maazullah  , Khan Muhammad Irfanullah , Farhan Muhammad 
Published: August 2021

AbstractThe early and rapid diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), the main cause of fatal pandemic coronavirus disease 2019 (COVID-19), with the analysis of patients chest X-ray (CXR) images has life-saving importance for both patients and medical professionals. In this research a very simple novel and robust deep-learning convolutional neural network (CNN) model with less number of trainable-parameters is proposed to assist the radiologists and physicians in the early detection of COVID-19 patients. It also helps to classify patients into COVID-19, pneumonia and normal on the bases of analysis of augmented X-ray images. This augmented dataset contains 4803 COVID-19 from 686 publicly available chest X-ray images along with 5000 normal and 5000 pneumonia samples. These images are divided into 80% training and 20 % validation. The proposed CNN model is trained on training dataset and then tested on validation dataset. This model has a promising performance with a mean accuracy of 92.29%, precision of 99.96%, Specificity of 99.85% along with Sensitivity value of 85.92%. The result can further be improved if more data of expert radiologist is publically available.
Diversification by CofC and control by CofD govern biosynthesis and evolution of coenzyme F420 and its derivative 3PG-F420
Authors: Hasan Mahmudul , Schulze Sabrina , Berndt Leona , Palm Gottfried J. , Braga Daniel , Richter Ingrid , Last Daniel , Lammers Michael , Lackner Gerald 
Published: August 2021

AbstractCoenzyme F420 is a microbial redox cofactor that is increasingly used for biocatalytic applications. Recently, diversified biosynthetic routes to F420 and the discovery of a derivative, 3PG-F420, were reported. 3PG-F420 is formed via activation of 3-phospho-D-glycerate (3-PG) by CofC, but the structural basis of substrate binding, its evolution, as well as the role of CofD in substrate selection remained elusive.Here, we present a crystal structure of the 3-PG-activating CofC from Mycetohabitans sp. B3 and define amino acids governing substrate specificity. Site-directed mutagenesis enabled bidirectional switching of specificity and thereby revealed the short evolutionary trajectory to 3PG-F420 formation. Furthermore, CofC stabilized its product, thus confirming the structure of the unstable molecule, revealing its binding mode and suggesting a substrate channeling mechanism to CofD. The latter enzyme was shown to significantly contribute to the selection of related intermediates to control the specificity of the combined biosynthetic CofC/D step. Taken together, this work closes important knowledge gaps and opens up perspectives for the discovery, enhanced biotechnological production, and engineering of coenzyme F420 derivatives in the future.ImportanceThe microbial cofactor F420 is crucial for processes like methanogenesis, antibiotics biosynthesis, drug resistance, and biocatalysis. Recently, a novel derivative of F420 (3PG-F420) was discovered, enabling the production and use of F420 in heterologous hosts.By analyzing the crystal structure of a CofC homolog whose substrate choice leads to formation of 3PG-F420, we defined amino acid residues governing the special substrate selectivity. A diagnostic residue enabled reprogramming of the substrate specificity, thus mimicking the evolution of the novel cofactor derivative and successfully guiding the identification of further 3-PG-activating enzymes.Furthermore, a labile reaction product of CofC was revealed that has not been directly detected so far and CofD was shown to provide as another layer of specificity of the combined CofC/D reaction, thus controlling the initial substrate choice of CofC. The latter finding resolves a current debate in the literature about the starting point of F420 biosynthesis in various organisms.
Genetic study of late-onset neonatal sepsis reveals significant differences by sex
Authors: Ciesielski Timothy H. , Zhang Xueyi , Tacconelli Alessandra , Lutsar Irja , de Cabre Vincent Meiffredy , Roilides Emmanuel , Ciccacci Cinzia , Borgiani Paola , Scott William K. ,   NeoMero Consortium, Williams Scott M. , Sirugo Giorgio 
Published: August 2021

AbstractLate-Onset Neonatal Sepsis (LOS) is a rare, but life-threatening condition, involving widespread infection, immune disruption, organ dysfunction, and often death. Because exposure to pathogens is not 100% preventable, identifying susceptibility factors is critical to defining neonates at greater risk. Prior studies demonstrated that both genetics and infant sex influence susceptibility. We, therefore, performed a genome wide association study (GWAS) with 224 cases and 273 controls from six European countries to identify genetic risk factors. We tested for association with both autosomal and X-chromosome variants in the total sample and in the samples stratified by sex. In total 71 SNPs associated with neonatal sepsis at p<1×10−4in at least one analysis. Most importantly, the sex stratified analyses revealed associations with multiple SNPs (28 SNPs in males and 16 in females), but none of 44 SNPs from single-sex analyses associated with sepsis in the other sex at p<0.05, and the vast majority showed significant SNP X sex interactions (17 of 28 from the male-only analyses and all 16 from the female-only study). Pathway analyses showed that NOTCH signaling is over-represented among loci identified by the analyses. Our results indicate that susceptibility to LOS is genetically sexually dimorphic, and suggest that NOTCH signaling is likely to play a role in it.
Harmony COVID-19: a ready-to-use kit, low-cost detector, and smartphone app for point-of-care SARS-CoV-2 RNA detection
Authors: Panpradist Nuttada , Atkinson Robert G. , Roller Michael , Kline Enos , Wang Qin , Hull Ian T. , Kotnik Jack H. , Oreskovic Amy K. , Bennett Crissa , Leon Daniel , Lyon Victoria , Han Peter D. , Starita Lea M. , Thompson Matthew J. , Lutz Barry R. 
Published: August 2021

ABSTRACTRNA amplification tests allow sensitive detection of SARS-CoV-2 infection, but their complexity and cost are prohibitive for expanding COVID-19 testing. We developed “Harmony COVID-19”, a point-of-care test using inexpensive consumables, ready-to-use reagents, and a simple device that processes up to 4 samples simultaneously. Our lyophilized reverse-transcription, loop-mediated isothermal amplification (RT-LAMP) can detect as little as 15 SARS-CoV-2 RNA copies per reaction, and it can report as early as 17 min for samples with high viral load (2 x 105 RNA copies per reaction). Analysis of RNA extracted from clinical nasal specimens (n = 101) showed 95% concordance with RT-PCR, including 100% specificity in specimens positive for other viruses and bacteria. Analysis of contrived samples in the nasal matrix showed detection of 92% or 100% in samples with ≥20 or ≥100 particles per reaction, respectively. Usability testing showed 95% accuracy by healthcare workers operating the test for the first time.ONE SENTENCE SUMMARYHarmony COVID-19: point-of-care SARS-CoV-2 RNA detection
COVID-19 vaccine uptake among older people in relation to sociodemographic factors –cohort results from southern Sweden
Authors: Inghammar Malin , Moghaddassi Mahnaz , Rasmussen Magnus , Malmqvist Ulf , Kahn Fredrik , Björk Jonas 
Published: August 2021

AbstractThe aim of this cohort study was to investigate sociodemographic determinants of COVID-19 vaccine uptake in the 70+ age group in Skåne county, Sweden (n = 216 243 at baseline). Uptake of the first dose was high (91.9%) overall, but markedly lower (75.3%) among persons born outside the Nordic countries. Vaccine uptake was generally satisfactory among native Swedes also in areas with lower socioeconomic status, but dropped substantially among non-Nordic born in those areas. The identified clusters of unvaccinated older people, mainly representing ethnic minorities in disadvantaged areas, warrants intensified efforts regarding tailored communication, easier vaccine access and local engagement.Key pointsCOVID-19 vaccine uptake in the 70+ age group in Skåne county, Sweden, was high (91.9%) overall, but markedly lower (75.3%) within the group born outside the Nordic countriesInverse associations between indicators of neighbourhood deprivation and vaccine uptake were observed, which lowered the uptake among persons born outside the Nordic countries furtherThe identified clusters of unvaccinated older people, mainly representing ethnic minorities in disadvantaged areas, warrants intensified efforts regarding tailored communication, easier vaccine access and local engagement
Plasmodium falciparummalaria during pregnancy: the impact of parasitaemia and anaemia on birthweight
Authors: Abbas Dawood Ackom , Mutala Abdul-Hakim , Agordzo Samuel Kekeli , Owusu Christian Kwasi , Lawson Bernard Walter Lartekwei , Badu Kingsley 
Published: August 2021

AbstractMalaria in pregnancy remains a major problem of public health concern in Sub-Saharan Africa due to its endemicity and the diverse consequences on both the mother and the baby. Much attention, therefore, is needed to fully understand the epidemiology of the disease and to mitigate the devastating outcomes. The present study aimed at investigating malaria in pregnancy, its adverse effects on pregnant women and the impact on birthweight of babies. A total of 222 pregnant women gave their consent and were recruited into the study during their routine Antenatal care visits. This study employed a combination of cross-sectional and longitudinal cohort study designs. For 122 women in the cross-sectional arm, blood samples and data were obtained once, whilst 100 women in the longitudinal cohort arm were followed up from recruitment until delivery. Demographic information, obstetric history and risk factors were obtained by administering questionnaires. About 1.0 ml of venous blood was drawn to determine malaria parasitaemia and anaemia status of the participants. The birthweights of the babies were also taken at delivery. The prevalence of malaria and anaemia was 19.8% and 27.0% respectively at registration for all 222 participants. All infections wereP. falciparummalaria. One hundred and forty-six (65.8%) of participants had ITN but only 72 (32.4%) used it the previous night. Young age and rural settings were risk factors for malaria. Young age and malaria positive pregnant women had increased risk of anaemia. In the follow-up group which ended with 54 participants, the overall prevalence of malaria and anaemia were 18.7% and 32.4% respectively. Fifty-two (96.3%) of pregnant women attended ANC ≥ 4 times and 55.6% took ≥ 3 doses of SP. There were two cases of miscarriage. Low birthweight occurred in 5.6% of babies. Both malaria and anaemia during pregnancy had no significant impact on birthweight of the babies. Although few of the babies had low birthweight, this number can be further reduced when pregnant women attend ANC and take SP at the recommended number of times.
Characterising the persistence of RT-PCR positivity and incidence in a community survey of SARS-CoV-2
Authors: Eales Oliver , Walters Caroline E. , Wang Haowei , Haw David , Ainslie Kylie E. C. , Atchison Christina , Page Andrew J. , Prosolek Sophie J. , Trotter Alexander J. , Le Viet Thanh , Alikhan Nabil-Fareed , Jackson Leigh M , Ludden Catherine ,   The COVID-19 Genomics UK (COG-UK) Consortium, Ashby Deborah , Donnelly Christl A. , Cooke Graham , Barclay Wendy , Ward Helen , Darzi Ara , Elliott Paul , Riley Steven 
Published: August 2021

AbstractBackgroundCommunity surveys of SARS-CoV-2 RT-PCR swab-positivity provide prevalence estimates largely unaffected by biases from who presents for routine case testing. The REal-time Assessment of Community Transmission-1 (REACT-1) has estimated swab-positivity approximately monthly since May 2020 in England from RT-PCR testing of self-administered throat and nose swabs in random non-overlapping cross-sectional community samples. Estimating infection incidence from swab-positivity requires an understanding of the persistence of RT-PCR swab positivity in the community.MethodsDuring round 8 of REACT-1 from 6 January to 22 January 2021, of the 2,282 participants who tested RT-PCR positive, we recruited 896 (39%) from whom we collected up to two additional swabs for RT-PCR approximately 6 and 9 days after the initial swab. We estimated sensitivity and duration of positivity using an exponential model of positivity decay, for all participants and for subsets by initial N-gene cycle threshold (Ct) value, symptom status, lineage and age. Estimates of infection incidence were obtained for the entire duration of the REACT-1 study using P-splines.ResultsWe estimated the overall sensitivity of REACT-1 to detect virus on a single swab as 0.79 (0.77, 0.81) and median duration of positivity following a positive test as 9.7 (8.9, 10.6) days. We found greater median duration of positivity where there was a low N-gene Ct value, in those exhibiting symptoms, or for infection with the Alpha variant. The estimated proportion of positive individuals detected on first swab,P0, was found to be higher for those with an initially low N-gene Ct value and those who were pre-symptomatic. When compared to swab-positivity, estimates of infection incidence over the duration of REACT-1 included sharper features with evident transient increases around the time of key changes in social distancing measures.DiscussionHome self-swabbing for RT-PCR based on a single swab, as implemented in REACT-1, has high overall sensitivity. However, participants’ time-since-infection, symptom status and viral lineage affect the probability of detection and the duration of positivity. These results validate previous efforts to estimate incidence of SARS-CoV-2 from swab-positivity data, and provide a reliable means to obtain community infection estimates to inform policy response.