bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative profiles of SARS-CoV-2 Spike-specific human milk antibodies elicited by mRNA- and adenovirus-based COVID-19 vaccines
Authors: Yang Xiaoqi , Fox Alisa , DeCarlo Claire , Norris Caroline , Griffin Samantha , Wedekind Sophie , Flanagan James M. , Shenker Natalie , Powell Rebecca L. 
Published: July 2021

AbstractNumerous COVID-19 vaccines are authorized globally. To date, ∼71% of doses are comprised of the Pfizer/BioNTech vaccine, and ∼17% the Moderna/NIH vaccine, both of which are mRNA-based. The chimpanzee Ad-based Oxford/AstraZeneca (AZ) vaccine comprises ∼9%, while the Johnson & Johnson/Janssen (J&J) human adenovirus (Ad26) vaccine ranks 4th at ∼2% [1]. No COVID-19 vaccines are yet available for children 0-4. One method to protect this population may be passive immunization via antibodies (Abs) provided in the milk of a lactating vaccinated person. Our early work [2] and other reports [3-5] have demonstrated that unlike the post-SARS-CoV-2 infection milk Ab profile, which is rich in specific secretory (s)IgA, the vaccine response is highly IgG-dominant. In this report, we present a comparative assessment of the milk Ab response elicited by Pfizer, Moderna, J&J, and AZ vaccines. This analysis revealed 86% -100% of mRNA vaccine recipient milk exhibited Spike-specific IgG endpoint titers, which were 12 – 28-fold higher than those measured for Ad vaccine recipient milk. Ad-based vaccines elicited Spike-specific milk IgG in only 33%-38% of recipients. Specific IgA was measured in 52%-71% of mRNA vaccine recipient milk and 17%-23% of Ad vaccine recipient milk. J&J recipient milk exhibited significantly lower IgA than Moderna recipients, and AZ recipients exhibited significantly lower IgA titers than Moderna and Pfizer. <50% of milk of any group exhibited specific secretory Ab, with Moderna recipient IgA titers measuring significantly higher than AZ. Moderna appeared to most frequently elicit >2-fold increases in specific secretory Ab titer relative to pre-vaccine sample. These data indicate that current Ad-based COVID-19 vaccines poorly elicit Spike-specific Ab in milk compared to mRNA-based vaccines and that mRNA vaccines are preferred for immunizing the lactating population. This study highlights the need to design vaccines better aimed at eliciting an optimal milk Ab response.
Phase I single center trial of Ketogenic Diet for Adults with Traumatic Brain Injury
Authors: Arora Niraj , Litofsky N. Scott , Mojgan Golzy , Aneja Rachna , Staudenmyer Danielle , Qualls Kathyrn , Patil Sachin 
Published: July 2021

AbstractBackgroundTraumatic Brain injury (TBI) is a major cause of mortality and morbidity in the United States. Ketogenic diet (KD) has been shown to have neuroprotective effects in acute brain injury, but limited data about its use in adult TBI patients is available. The objective of this study is to investigate the feasibility and safety of ketogenic diet (KD) for adult TBI patients in the Neuroscience Intensive Care Unit (NSICU).MethodsTBI patients admitted to NSICU between June 2019 to March 2021 were enrolled in this single-center, open label, single-arm prospective intervention study. The primary feasibility outcome was achievement of ketosis (detection and maintenance of serum beta-hydroxybutyrate (BOB) levels above normal); secondary outcomes included laboratory and clinical adverse effects related to KD.Results10 adults with TBI with Abbreviated Injury Score (AIS)-Head of at least 3 and ventriculostomy tube inserted met inclusion/exclusion criteria and were considered for KD. Mean age was47 years, and all patients were male. Eight out of 10 patients achieved ketosis within mean 2.2 days. KD was initiated within 8-33 hours (average 23 hours) of hospital admission. No clinical adverse effects were noted, 2 patients developed hypertriglyceridemia and 1 patient developed hypoglycemia. Serum glucose showed a decreasing trend in most patients.ConclusionsThis pilot study shows that KD is feasible and safe in the management of TBI patients. A randomized controlled trial (RCT) is justified to further understand the optimal serum BOB levels, dose and duration of KD in TBI and its effect on the outcome.ClinicalTrials.gov Identifier: NCT03982602, Registered 06/11/2019, https://clinicaltrials.gov/ct2/show/NCT03982602?term=brain+injury&cond=ketogenic+diet&draw=2&rank=3.
Gene Therapy Restores the Transcriptional Program of Hematopoietic Stem Cells in Fanconi Anemia
Authors: Lasaga Miren , Río Paula , Vilas-Zornoza Amaia , Planell Nuria , Navarro Susana , Alignani Diego , Fernández-Varas Beatriz , Zubicaray Josune , Pujol Roser M. , Nicoletti Eileen , Schwartz Jonathan D. , Sevilla Julián , Ainciburi Marina , Ullate-Agote Asier , Surrallés Jordi , Perona Rosario , Sastre Leandro , Prosper Felipe , Gomez-Cabrero David , Bueren Juan A. 
Published: July 2021

ABSTRACTFanconi anemia (FA) is an inherited disease associated with marked hematopoietic stem and progenitor cell (HSPC) defects. Ongoing clinical trials have shown that lentiviral-mediated gene therapy can ameliorate bone marrow failure (BMF) in non-conditioned FA patients thanks to the proliferative advantage of corrected FA HSPCs. Here we investigated whether gene therapy can revert affected molecular pathways in diseased HSPCs, a question not previously addressed in any HSC gene therapy trial. Single-cell RNA sequencing was performed in chimeric populations of corrected and uncorrected HSPCs coexisting in BM of gene therapy treated FA patients. Our study demonstrates that gene therapy reverts the transcriptional signature of FA HSPCs, which then resembles the transcriptional program of healthy donor HSPCs. This includes a downregulated expression of TGF-β and p21, typically upregulated in FA HSPCs, and upregulation of DNA damage response and telomerase maintenance pathways. Our results show for the first time the potential of gene therapy to rescue defects in the HSPC transcriptional program from patients with inherited diseases, in this case in FA characterized by BMF and cancer predisposition.
Intentions to participate in cervical and colorectal cancer screening during the COVID-19 pandemic: a mixed-methods study
Authors: Wilson Rebecca , Quinn-Scoggins Harriet , Moriarty Yvonne , Hughes Jacqueline , Goddard Mark , Cannings-John Rebecca , Whitelock Victoria , Whitaker Katriina L , Grozeva Detelina , Townson Julia , Osborne Kirstie , Smits Stephanie , Robling Michael , Hepburn Julie , Moore Graham , Gjini Ardiana , Brain Kate , Waller Jo 
Published: July 2021

AbstractWorldwide, cancer screening faced significant disruption in 2020 due to the COVID-19 pandemic. If this has led to changes in public attitudes towards screening and reduced intention to participate, there is a risk of long-term adverse impact on cancer outcomes. In this study, we examined previous participation and future intentions to take part in cervical and colorectal cancer (CRC) screening following the first national lockdown in the UK.Overall, 7543 adults were recruited to a cross-sectional online survey in August-September 2020. Logistic regression analyses were used to identify correlates of strong screening intentions among 2,319 participants eligible for cervical screening and 2,502 eligible for home-based CRC screening. Qualitative interviews were conducted with a sub-sample of 30 participants. Verbatim transcripts were analysed thematically.Of those eligible, 74% of survey participants intended to attend cervical screening and 84% intended to complete home-based CRC screening when next invited. Thirty percent and 19% of the cervical and CRC samples respectively said they were less likely to attend a cancer screening appointment now than before the pandemic. Previous non-participation was the strongest predictor of low intentions for cervical (aOR 26.31, 95% CI: 17.61-39.30) and CRC (aOR 67.68, 95% CI: 33.91-135.06) screening. Interview participants expressed concerns about visiting healthcare settings but were keen to participate when screening programmes resumed.Intentions to participate in future screening were high and strongly associated with previous engagement in both programmes. As screening services recover, it will be important to monitor participation and to ensure people feel safe to attend.
Change in age distribution of COVID-19 deaths with the introduction of COVID-19 vaccination
Authors: Pastorino Roberta , Pezzullo Angelo Maria , Villani Leonardo , Causio Francesco Andrea , Axfors Cathrine , Contopoulos-Ioannidis Despina G. , Boccia Stefania , Ioannidis John P.A. 
Published: July 2021

ABSTRACTBackgroundMost countries initially deployed COVID-19 vaccines preferentially in elderly populations. Population-level vaccine effectiveness may be heralded by an increase in the proportion of deaths among non-elderly populations that were less covered by vaccination programs.MethodsWe collected data from 40 countries on age-stratified COVID-19 deaths during the vaccination period (1/14/2021-5/31/2021) and two control periods (entire pre-vaccination period and excluding the first wave). We meta-analyzed the proportion of deaths in different age groups in vaccination versus control periods in countries with low vaccination rates; (2) countries with age-independent vaccination policies; and (3) countries with standard age-dependent vaccination policies.FindingsCountries that prioritized vaccination among older people saw an increasing share of deaths among 0-69 year old people in the vaccination versus the two control periods (summary prevalence ratio 1·32 [95 CI% 1·24-1·41] and 1·35 [95 CI% 1·26-1·44)]. No such change was seen on average in countries with age-independent vaccination policies (1·05 [95 CI% 0·78-1·41 and 0·97 [95 CI% 0·95-1·00], respectively) and limited vaccination (0·93 [95 CI% 0·85-1·01] and 0·95 [95 CI% 0·87-1·03], respectively). Prevalence ratios were associated with the difference of vaccination rates in elderly versus non-elderly people. No significant changes occurred in the share of deaths in age 0-49 among all 0-69 deaths in the vaccination versus pre-vaccination periods.InterpretationThe substantial shift in the age distribution of COVID-19 deaths in countries that rapidly implemented vaccination predominantly among elderly may herald the population level-effectiveness of COVID-19 vaccination and a favorable evolution of the pandemic towards endemicity with fewer elderly deaths.FundingThis study received no specific funding.
Excess mortality in India from June 2020 to June 2021 during the COVID pandemic: death registration, health facility deaths, and survey data
Authors: Deshmukh Yashwant , Suraweera Wilson , Tumbe Chinmay , Bhowmick Aditi , Sharma Sankalp , Novosad Paul , Fu Sze Hang , Newcombe Leslie , Gelband Hellen , Brown Patrick , Jha Prabhat 
Published: July 2021

AbstractBackgroundIndia’s official death totals from the COVID pandemic are widely regarded as under-reports.MethodsWe quantified all-cause excess mortality in India, comparing deaths during the peak of the first and second COVID waves (Jul-Dec 2020 and April-June 2021) with month wise deaths in 2015-19 from three sources: Civil Registration System (CRS) mortality reports from 15 states or cities with 37% of India’s population; deaths in 0.2 million health facilities; and a representative survey of 0.14 million adults about COVID deaths.ResultsDuring the first viral wave, the median excess mortality compared to CRS baseline was 22% and 41%, respectively, in included states and cities, rising to 46% and 85% during the second wave. In settings with 10 or more months of data across the two waves, the median excess mortality was 32% and 37% for states and cities, respectively. Deaths in health facilities showed a 27% excess mortality from July 2020-May 2021, reaching 120% during April-May 2021. The national survey found 3.5% of adults reported a COVID death in their household in April-June 2021, approximately doubling the 3.2% expected overall deaths. The national survey showed 29-32% excess deaths from June 1, 2020 to June 27, 2021, most of which were likely to be COVID. This translates to 3.1-3.4 million COVID deaths (including 2.5-2.8 million during April-June 2021). National extrapolations from health facility and CRS data suggest 2.7-3.3 million deaths during the year.ConclusionsIndia’s COVID death rate may be about 7-8 times higher than the officially reported 290/million population.
Simple, accurate calculation of mechanical power in Pressure Controlled Ventilation (PCV)
Authors: Trinkle Christine A. , Broaddus Richard N. , Sturgill Jamie L. , Waters Christopher M. , Morris Peter E. 
Published: July 2021

AbstractPower is a promising new metric to assess energy transfer from a ventilator to a patient, as it combines the effects of multiple different parameters into a single comprehensive value. For volume-controlled ventilation (VCV), excellent equations exist for calculating power from basic ventilator parameters, but for pressure-controlled ventilation (PCV), an accurate, easy-to-use equation has been elusive. Here, we present a new power equation and evaluate its accuracy compared to the three published PCV power equations. When applied to a sample of 50 patients on PCV with a non-zero rise time, we found that our equation estimated power within an average of 8.4% ± 5.9% (mean ± standard deviation) of the reference value. This new equation is accurate and simple to use, making it an attractive option to estimate power in PCV cases at the bedside.
Optimal vaccine allocation for COVID-19 in the Netherlands: a data-driven prioritization
Authors: Miura Fuminari , Leung Ka Yin , Klinkenberg Don , Ainslie Kylie E. C. , Wallinga Jacco 
Published: July 2021

AbstractFor the control of COVID-19, vaccination programmes provide a long-term solution. The amount of available vaccines is often limited, and thus it is crucial to determine the allocation strategy. While mathematical modelling approaches have been used to find an optimal distribution of vaccines, there is an excessively large number of possible schemes to be simulated.Here, we propose an algorithm to find a near-optimal allocation scheme given an intervention objective such as minimization of new infections, hospitalizations, or deaths, where multiple vaccines are available. The proposed principle for allocating vaccines is to target subgroups with the largest reduction in the outcome of interest, such as new infections, due to vaccination that fully immunizes a single individual. We express the expected impact of vaccinating each subgroup in terms of the observed incidence of infection and force of infection. The proposed approach is firstly evaluated with a simulated epidemic and then applied to the epidemiological data on COVID-19 in the Netherlands.Our results reveal how the optimal allocation depends on the objective of infection control. In the case of COVID-19, if we wish to minimize deaths, the optimal allocation strategy is not efficient for minimizing other outcomes, such as infections. In simulated epidemics, an allocation strategy optimized for an outcome outperforms other strategies such as the allocation from young to old, from old to young, and at random. Our simulations clarify that the current policy in the Netherlands (i.e., allocation from old to young) was concordant with the allocation scheme that minimizes deaths.The proposed method provides an optimal allocation scheme, given routine surveillance data that reflect ongoing transmissions. The principle of allocation is useful for providing plausible simulation scenarios for complex models, which give a more robust basis to determine intervention strategies.Author summaryVaccination is the key to controlling the ongoing COVID-19 pandemic. In the early stages of an epidemic, there is shortage of vaccine stocks. Here, we propose an algorithm that computes an optimal vaccine distribution among groups for each intervention objective (e.g., minimizing new infections, hospitalizations, or deaths). Unlike existing approaches that use detailed information on at-risk contacts between and among groups, the proposed algorithm requires only routine surveillance data on the number of cases. This method is applicable even when multiple vaccines are available. Simulation results show that the allocation scheme optimized by our algorithm performed the best compared with other strategies such as allocating vaccines at random and in the order of age. Our results also reveal that an allocation scheme optimized for one specific objective is not necessarily efficient for another, indicating the importance of the decision-making at the early phase of distributions.
A newly identified group of P-like (PL) fimbriae from extra-intestinal pathogenic Escherichia coli (ExPEC) encode distinct adhesin subunits and mediate adherence to host cells
Authors: Habouria Hajer , Bessaiah Hicham , Buron Julie , Houle Sébastien , Dozois Charles M. 
Published: July 2021

AbstractFimbrial adhesins play a critical role for bacterial adherence and biofilm formation. Sequencing of avian pathogenic Escherichia coli (APEC) strain QT598 identified a fimbrial gene cluster belonging to the π group that we named PL (P-like) fimbriae, since genetic organization and sequence are similar to Pap and related fimbriae. Screening of genomic databases indicated that genes encoding PL fimbriae located on IncF plasmids are present in a diversity of E. coli isolates from poultry, human systemic infections, and other sources. As with P fimbriae, PL fimbriae exhibit sequence divergence in adhesin encoding genes, and strains could be divided into 5 classes based on differences in sequences of the PlfG adhesin protein. The plf genes from two predominant PlfG adhesin classes, PlfG-I and PlfG-II were cloned. PL fimbriae were visualized by electron microscopy, promoted biofilm formation, demonstrated distinct hemagglutination profiles and promoted adherence to human bladder and kidney epithelial cell lines. Hybrid fimbriae comprised of genes from plfQT598 wherein plfG was replaced by papG encoding adhesin genes were also shown to be functional and mediate adherence to epithelial cells, further indicating similarity and functional compatibility between these two types of fimbriae. Although deletion of plf genes did not significantly reduce colonization of the mouse urinary tract, plf gene expression was increased over 40-fold in the bladder compared to during in vitro culture. Overall, PL fimbriae represent a new group of fimbriae demonstrating both functional differences and similarities to P fimbriae and may contribute to adherence to cells and colonization of host tissues.ImportanceFimbriae are important colonization factors in many bacterial species. The identification of a new type of fimbriae encoded on some IncF plasmids in E. coli was investigated. Genomic sequences demonstrated these fimbrial gene clusters have genetic diversity, particularly in the adhesin encoding PlfG gene. Functional studies demonstrated differences in hemagglutination specificity, although both types of Plf adhesin under study mediated adherence to human urinary epithelial cells. Such fimbriae may represent previously unrecognized adhesins that could contribute to host specificity and tissue tropism of some E. coli strains.
Workplace risk management for SARS-CoV-2: a three-step early in-tervention strategy for effective containment of infection chains with special regards to virus variants with increased infectivity
Authors: Paaßen Andreas , Anderle Laura , John Karsten , Wilbrand Sebastian 
Published: July 2021

AbstractBackgroundPriority during the SARS-CoV2 pandemic is that employees need to be protected from infection risks and business activities need to be ensured. New virus variants with increased infection risks require an evolved risk strategy.Material and methodsSeveral standard measures such as testing, isolation and quarantine are combined to a novel risk strategy. Epidemiological model calculations and scientific knowledge about the course of SARS-CoV2 infectivity are used to optimize this strategy. The procedure is implemented in an easy-to-use calculator based on Excel.Layout in practice and resultsAlternative combinations of measures and practical aspects are discussed. Example calculations are used to demonstrate the effect of the discussed measures.ConclusionThat quarantine calculator derived from these principles enables even non-specialists to perform a differentiated risk analysis and to introduce optimized measures. Targeted testing routines and alternative measures ensure staff availability.
Increasing SARS-CoV-2 antibody prevalence in England at the start of the second wave: REACT-2 Round 4 cross-sectional study in 160,000 adults
Authors: Ward Helen , Atchison Christina , Whitaker Matt , Donnelly Christl A , Riley Steven , Ashby Deborah , Darzi Ara , Barclay Wendy S , Cooke Graham , Elliott Paul ,   for the REACT study team
Published: July 2021

AbstractBackgroundREACT-2 Study 5 is a population survey of the prevalence of SARS-CoV-2 antibodies in the community in England.MethodsWe contacted a random sample of the population by sending a letter to named individuals aged 18 or over from the NHS GP registrations list. We then sent respondents a lateral flow immunoassay (LFIA) kit for SARS-CoV-2 antibody self-testing and asked them to perform the test at home and complete a questionnaire, including reporting of their test result. Overall, 161,537 adults completed questionnaires and self-administered LFIA tests for IgG against SARS-CoV-2 between 27 October and 10 November 2020.ResultsThe overall adjusted and weighted prevalence was 5.6% (95% CI 5.4-5.7). This was an increase from 4.4% (4.3-4.5) in round 3 (September), a relative increase of 26.9% (24.0-29.9).The largest increase by age was in the 18 to 24 year old age group, which increased (adjusted and weighted) from 6.7% (6.3-7.2) to 9.9% (9.3-10.4), and in students, (adjusted, unweighted) from 5.9% (4.8-7.1) to 12.1% (10.8-13.5). Prevalence increased most in Yorkshire and The Humber, from 3.4% (3.0-3.8) to 6.3% (5.9-6.8) and the North West from 4.5% (4.2-4.9) to 7.7% (7.2-8.1). In contrast, the prevalence in London was stable, at 9.5% (9.0-9.9) and 9.5% (9.1-10.0) in rounds 3 and 4 respectively. We found the highest prevalence in people of Bangladeshi 15.1% (10.9-20.5), Pakistani 13.9% (11.2-17.2) and African 13.5% (10.7-16.8) ethnicity, and lowest in those of white British ethnicity at 4.2% (4.0-4.3).InterpretationThe second wave of infection in England is apparent in increasing antibody prevalence, particularly in younger people, students, and in the Northern Regions. By late October a large proportion of the population remained susceptible to SARS-CoV-2 infection in England based on naturally acquired immunity from the first and early second wave.