bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monitoring emergence of SARS-CoV-2 B.1.1.7 Variant through the Spanish National SARS-CoV-2 Wastewater Surveillance System (VATar COVID-19) from December 2020 to March 2021
Authors: Carcereny Albert , Martínez-Velázquez Adán , Bosch Albert , Allende Ana , Truchado Pilar , Cascales Jenifer , Romalde Jesús L , Lois Marta , Polo David , Sánchez Gloria , Pérez-Cataluña Alba , Díaz-Reolid Azahara , Antón Andrés , Gregori Josep , Garcia-Cehic Damir , Quer Josep , Palau Margarita , González Ruano Cristina , Pintó Rosa M , Guix Susana 
Published: May 2021

ABSTRACTBackgroundSince its first identification in the United Kingdom in late 2020, the highly transmissible B.1.1.7 variant of SARS-CoV-2, become dominant in several European countries raising great concern.AimThe aim of this study was to develop a duplex real-time RT-qPCR assay to detect, discriminate and quantitate SARS-CoV-2 variants containing one of its mutation signatures, the ΔHV69/70 deletion, to trace the community circulation of the B.1.1.7 variant in Spain through the Spanish National SARS-CoV-2 Wastewater Surveillance System (VATar COVID-19).ResultsB.1.1.7 variant was first detected in sewage from the Southern city of Málaga (Andalucía) in week 20_52, and multiple introductions during Christmas holidays were inferred in different parts of the country, earlier than clinical epidemiological reporting by the local authorities. Wastewater-based B.1.1.7 tracking showed a good correlation with clinical data and provided information at the local level. Data from WWTPs which reached B.1.1.7 prevalences higher than 90% for ≥ 2 consecutive weeks showed that 8.1±1.8 weeks were required for B.1.1.7 to become dominant.ConclusionThe study highlights the applicability of RT-qPCR-based strategies to track specific mutations of variants of concern (VOCs) as soon as they are identified by clinical sequencing, and its integration into existing wastewater surveillance programs, as a cost-effective approach to complement clinical testing during the COVID-19 pandemic.
PUM1 represses CDKN1B translation and contributes to prostate cancer progression
Authors: Li Xin , Yang Jian , Chen Xia , Cao Dandan , Xu Eugene Yujun 
Published: May 2021

AbstractPosttranscriptional regulation of cancer gene expression programs plays a vital role in carcinogenesis; identifying the critical regulators of tumorigenesis and their molecular targets may provide novel strategies for cancer diagnosis and therapeutics. Highly conserved RNA binding protein PUM1 regulates mouse growth and cell proliferation, propelling us to examine its role in cancer. We found human PUM1 is highly expressed in a diverse group of cancer, including prostate cancer; enhanced PUM1 expression is also correlated with reduced survival among prostate cancer patients. Detailed expression analysis in twenty prostate cancer tissues showed enhanced expression of PUM1 at mRNA and protein levels. Knockdown of PUM1 reduced prostate cancer cell proliferation and colony formation, and subcutaneous injection of PUM1 knockdown cells led to reduced tumor size. Downregulation of PUM1 in prostate cancer cells consistently elevated CDKN1B protein expression through increased translation but did not impact its mRNA level, while overexpression of PUM1 reduced CDKN1B protein level. Our finding established a critical role of PUM1 mediated translational control, particularly the PUM1-CDKN1B axis, in prostate cancer cell growth and tumorigenesis. We proposed that PUM1-CDKN1B regulatory axis may represent a novel mechanism for the loss of CDKN1B protein expression in diverse cancers and could be potential targets for therapeutics development.
A rapid and simple protocol for concentration of SARS-CoV-2 from sewage
Authors: Wehrendt Diana P. , Massó Mariana G. , Gonzales Machuca Adrián , Vargas Claudia V. , Barrios Melina E. , Campos Josefina , Costamagna Damián , Bruzzone Luis , Cisterna Daniel M. , Iglesias Néstor Gabriel , Mbayed Viviana A. , Baumeister Elsa , Centrón Daniela , Quiroga María Paula , Erijman Leonardo 
Published: May 2021

AbstractThe aim of this study was to set up a simple protocol to concentrate SARS-CoV-2 from sewage, which can be implemented in laboratories with minimal equipment resources. The method avoids the need for extensive purification steps and reduces the concentration of potential inhibitors of RT-qPCR contained in sewage. The concentration method consists of a single step, in which a small volume of sewage sample is incubated with polyaluminum chloride (PAC). Virus particles adsorbed to the precipitate are collected by low-speed centrifugation, after which the recovered pellet is resuspended with a saline buffer. The PAC concentration method produced an average shift of 4.4-units in Cq values compared to non-concentrated samples, indicating a 25-fold increase in detection sensitivity. The lower detection limit corresponded approximately to 100 copies per ml. Kappa index indicated substantial agreement between PAC and PEG precipitation protocols (k=0.688, CI 0.457-0.919). PAC concentrated samples can be processed immediately for RNA purification and qPCR or sent refrigerated to a diagnosis center, where SARS-CoV-2 detection should be performed in the same way as for clinical samples. This low cost protocol could be useful to aid in the monitoring of community circulation of SARS-CoV-2, especially in low- and middle-income countries, which do not have massive access to support from specialized labs for sewage surveillance.
Inference of SARS-CoV-2 generation times using UK household data
Authors: Hart W.S. , Abbott S. , Endo A. , Hellewell J. , Miller E. , Andrews N. , Maini P.K. , Funk S. , Thompson R.N. 
Published: May 2021

AbstractThe distribution of the generation time (the interval between individuals becoming infected and passing on the virus) characterises changes in the transmission risk during SARS-CoV-2 infections. Inferring the generation time distribution is essential to plan and assess public health measures. We previously developed a mechanistic approach for estimating the generation time, which provided an improved fit to SARS-CoV-2 data from January-March 2020 compared to existing models. However, few estimates of the generation time exist based on data from later in the pandemic. Here, using data from a household study conducted from March-November 2020 in the UK, we provide updated estimates of the generation time. We consider both a commonly used approach in which the transmission risk is assumed to be independent of when symptoms develop, and our mechanistic model in which transmission and symptoms are linked explicitly. Assuming independent transmission and symptoms, we estimated a mean generation time (4.2 days, 95% CrI 3.3-5.3 days) similar to previous estimates from other countries, but with a higher standard deviation (4.9 days, 3.0-8.3 days). Using our mechanistic approach, we estimated a longer mean generation time (6.0 days, 5.2-7.0 days) and a similar standard deviation (4.9 days, 4.0-6.3 days). Both models suggest a shorter mean generation time in September-November 2020 compared to earlier months. Since the SARS-CoV-2 generation time appears to be changing, continued data collection and analysis is necessary to inform future public health policy decisions.
The rapid reemergence of seasonal respiratory viruses in Houston, Texas, after relaxing COVID-19 restrictions
Authors: Hodjat Parsa , Christensen Paul A. , Subedi Sishir , Bernard David W. , Olsen Randall J. , Long S. Wesley 
Published: May 2021

Brief abstractImplementation of measures to limit the spread of the SARS-CoV-2 virus at the start of the COVID-19 pandemic resulted in a rapid decrease in all other respiratory pathogens. As COVID-19 containment measures were relaxed, the first non-COVID respiratory viruses to return to prepandemic levels were members of the rhinovirus/enterovirus, followed by the rapid return of seasonal coronaviruses, parainfluenza, and respiratory syncytial virus after the complete removal of COVID-19 precautions at the state level, including an end to mask mandates. Inasmuch as COVID-19 has dominated the landscape of respiratory infections since early 2020, it is important for clinicians to recognize the return of non-COVID respiratory pathogens may be rapid and significant when COVID-19 containment measures are removed.
Small Airways Disease is a Post-Acute Sequelae of SARS-CoV-2 Infection
Authors: Cho Josalyn L. , Villacreses Raul , Nagpal Prashant , Guo Junfeng , Pezzulo Alejandro A. , Thurman Andrew L. , Hamzeh Nabeel Y. , Blount Robert J. , Fortis Spyridon , Hoffman Eric A. , Zabner Joseph , Comellas Alejandro P. 
Published: May 2021

AbstractBackgroundThe sequelae of SARS-CoV-2 infection on pulmonary structure and function remain incompletely characterized.MethodsAdults with confirmed COVID-19 who remained symptomatic more than thirty days following diagnosis were enrolled and classified as ambulatory, hospitalized or requiring the intensive care unit (ICU) based on the highest level of care received during acute infection. Symptoms, pulmonary function tests and chest computed tomography (CT) findings were compared across groups and to healthy controls. CT images were quantitatively analyzed using supervised machine-learning to measure regional ground glass opacities (GGO) and image-matching to measure regional air trapping. Comparisons were performed using univariate analyses and multivariate linear regression.ResultsOf the 100 patients enrolled, 67 were in the ambulatory group. All groups commonly reported cough and dyspnea. Pulmonary function testing revealed restrictive physiology in the hospitalized and ICU groups but was normal in the ambulatory group. Among hospitalized and ICU patients, the mean percent of total lung classified as GGO was 13.2% and 28.7%, respectively, and was higher than in ambulatory patients (3.7%, P<0.001). The mean percentage of total lung affected by air trapping was 25.4%, 34.5% and 27.2% in the ambulatory, hospitalized and ICU groups and 7.3% in healthy controls (P<0.001). Air trapping measured by quantitative CT correlated with the residual volume to total lung capacity ratio (RV/TLC; ρ=0.6, P<0.001).ConclusionsAir trapping is present in patients with post-acute sequelae of COVID-19 and is independent of initial infection severity, suggesting obstruction at the level of the small airways. The long-term consequences are not known.
SARS-CoV-2 spike glycoprotein-reactive T cells can be readily expanded from COVID-19 vaccinated donors
Authors: Taborska Pavla , Lastovicka Jan , Stakheev Dmitry , Strizova Zuzana , Bartunkova Jirina , Smrz Daniel 
Published: May 2021

AbstractIntroductionThe COVID-19 vaccine was designed to provide protection against infection by the severe respiratory coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19). However, the vaccine’s efficacy can be compromised in patients with immunodeficiencies or the vaccine-induced immunoprotection suppressed by other comorbidity treatments, such as chemotherapy or immunotherapy. To enhance the protective role of the COVID-19 vaccine, we have investigated a combination of the COVID-19 vaccination withex vivoenrichment and large-scale expansion of SARS-CoV-2 spike glycoprotein-reactive CD4+and CD8+T cells.MethodsSARS-CoV-2-unexposed donors were vaccinated with two doses of the BNT162b2 SARS-CoV-2 vaccine. The peripheral blood mononuclear cells of the vaccinated donors were cell culture-enriched with T cells reactive to peptides derived from SARS-CoV-2 spike glycoprotein. The enriched cell cultures were large-scale expanded using the rapid expansion protocol (REP) and the peptide-reactive T cells evaluated.ResultsWe show that vaccination with the SARS-CoV-2 spike glycoprotein-based mRNA COVID-19 vaccine induced humoral response against SARS-CoV-2 spike glycoprotein in all tested healthy SARS-CoV-2-unexposed donors. This humoral response was found to correlate with the ability of the donors’ PBMCs to become enriched with SARS-CoV-2 spike glycoprotein-reactive CD4+and CD8+T cells. Using an 11-day rapid expansion protocol, the enriched cell cultures were expanded nearly a thousand fold, and the proportions of the SARS-CoV-2 spike glycoprotein-reactive T cells increased.ConclusionsThese findings show for the first time that the combination of the COVID-19 vaccination andex vivoT cell large-scale expansion of SARS-CoV-2-reactive T cells could be a powerful tool for developing T cell-based adoptive cellular immunotherapy of COVID-19.
Assessment of the Effects of a Sage (Salvia officinalis) Extract on Cognitive Performance in Adolescents and Young Adults
Authors: Edwards Kieron D. , Dubberke Anne , Meyer Nadin , Kugel Simone , Hellhammer Juliane 
Published: May 2021

AbstractBackgroundCognitive health is a major concern for many people, and with potential benefits to academic and professional life, maximising cognitive performance is of interest far beyond the older demographics. Several natural products have been suggested as nootropics, including the herb sage. Previous assessments of various Salvia species have reported a range of effects on cognitive performance and mood in both older adult and younger adult populations. This study was conducted with Sibelius™: Sage, an aqueous-ethanol extract of S. officinalis, to assess for the beneficial effects on cognitive performance in adolescents (12-14 year olds) and young adults (18-25 year olds).Methods and FindingsAn acute, double-blind, placebo-controlled study was conducted with two single doses of Sibelius™: Sage (150 mg and 300 mg). Cognitive performance was evaluated using CogTrack™, which probes aspects of cognitive performance covering attention, working memory and episodic/declarative memory through a series of computer-based tasks. Consistent with previous study of Sibelius™: Sage a significant effect was seen on the Immediate Word Recall task in young adults; suggesting acute treatment benefits to verbal episodic/declarative memory performance. Physiological effects of the treatment on salivary cortisol and oxytocin levels, as well as blood pressure and heart rate were also assessed, with limited evidence of an effect on these factors. No adverse events or side-effects linked to the study product intake was observed. The study was registered at the German Clinical Trials Register (DRKS-ID: DRKS00015716).ConclusionsA significant improvement due to the Sage extract was shown for a task assessing short-term episodic memory (Immediate Word Recall), supporting beneficial effects on cognitive performance in young adults that are consistent with previous reports in healthy older adults. These findings suggest that further investigation of the effects observed in this study in larger, long-term human volunteer studies could be beneficial to pursue.
Effect of evidence updates on key determinants of measles vaccination impact: a DynaMICE modelling study in ten high-burden countries
Authors: Fu Han , Abbas Kaja , Klepac Petra , van Zandvoort Kevin , Tanvir Hira , Portnoy Allison , Jit Mark 
Published: May 2021

AbstractBackgroundModel-based estimates of measles burden and the impact of measles-containing vaccine (MCV) are crucial for global health priority setting. Recently, evidence from systematic reviews and database analyses have improved our understanding of key determinants of measles vaccine impact. We explore how updated representations of these determinants affect model-based estimation of MCV impact in ten countries with highest measles burden.MethodsUsing Dynamic Measles Immunisation Calculation Engine (DynaMICE), an age-structured compartmental model of measles transmission and vaccination, we evaluated the effect of evidence updates for five determinants of MCV impact: case fatality risk, contact patterns, age-dependent vaccine efficacy, the potential of supplementary immunisation activities (SIAs) to reach zero-dose children, and the basic reproduction number. We also evaluated the incremental impact of the first dose (MCV1), second dose (MCV2), and SIA dose of measles vaccines, based on country-specific coverage estimates from the World Health Organization. The MCV impact was assessed by cumulative vaccine-averted cases, deaths, and disability-adjusted life years over 2000–2050.ResultsIncorporated with the updated data sources, DynaMICE projected 252 million measles cases, 3.7 million deaths and 230 million disability-adjusted life years incurred over 2000–2050 in the ten high-burden countries when MCV1, MCV2, and SIA doses were implemented. Compared to no vaccination, the administration of MCV1 contributed to 66% reduction in cumulative measles burden, while MCV2 and SIAs reduced this further to 89%. With routine and supplementary vaccination, India and countries with high vaccination coverage could maintain measles incidence below 1 per million. Among the updated determinants, shifting from fixed to linearly-varying vaccine efficacy by age and from static to time-varying case fatality risks had the biggest effect on the model projections of MCV impact. While varying the basic reproduction number showed a limited effect on vaccine-averted burden, updates on the other four determinants together led to an overall reduction of MCV impact by 0.87–26.7%.ConclusionsHigh coverage of measles vaccine through both routine and SIA delivery platforms are essential for achieving and maintaining low incidence in high-measles burden settings. Incorporating updated evidence particularly on vaccine efficacy and case fatality risk reduces estimates of the impact of vaccination slightly, but its overall impact remains considerable.
CoMix: Changes in social contacts as measured by the contact survey during the COVID-19 pandemic in England between March 2020 and March 2021
Authors: Gimma Amy , Munday James D , Wong Kerry LM , Coletti Pietro , van Zandvoort Kevin , Prem Kiesha ,   CMMID COVID-19 working group, Klepac Petra , Rubin G. James , Funk Sebastian , Edmunds W John , Jarvis Christopher I 
Published: May 2021

AbstractBackgroundDuring the COVID-19 pandemic, the UK government imposed public health policies in England to reduce social contacts in hopes of curbing virus transmission. We measured contact patterns weekly from March 2020 to March 2021 to estimate the impact of these policies, covering three national lockdowns interspersed by periods of lower restrictions.MethodsData were collected using online surveys of representative samples of the UK population by age and gender. We calculated the mean daily contacts reported using a (clustered) bootstrap and fitted a censored negative binomial model to estimate age-stratified contact matrices and estimate proportional changes to the basic reproduction number under controlled conditions using the change in contacts as a scaling factor.ResultsThe survey recorded 101,350 observations from 19,914 participants who reported 466,710 contacts over 53 weeks. Contact patterns changed over time and by participants’ age, personal risk factors, and perception of risk. The mean of reported contacts among adults have reduced compared to previous surveys with adults aged 18 to 59 reporting a mean of 2.39 (95% CI 2.20 - 2.60) contacts to 4.93 (95% CI 4.65 - 5.19) contacts, and the mean contacts for school-age children was 3.07 (95% CI 2.89 - 3.27) to 15.11 (95% CI 13.87 - 16.41). The use of face coverings outside the home has remained high since the government mandated use in some settings in July 2020.ConclusionsThe CoMix survey provides a unique longitudinal data set for a full year since the first lockdown for use in statistical analyses and mathematical modelling of COVID-19 and other diseases. Recorded contacts reduced dramatically compared to pre-pandemic levels, with changes correlated to government interventions throughout the pandemic. Despite easing of restrictions in the summer of 2020, mean reported contacts only returned to about half of that observed pre-pandemic.
A potent myeloid response is rapidly activated in the lungs of premature Rhesus macaques exposed to intra-uterine inflammation
Authors: Jackson Courtney M. , Demmert Martin , Mukherjee Shibabrata , Isaacs Travis , Gray Jerilyn , Senthamaraikannan Paranthaman , Presicce Pietro , Chetal Kashish , Salomonis Nathan , Miller Lisa A. , Jobe Alan H. , Kallapur Suhas G. , Zacharias William J. , Lewkowich Ian P. , Deshmukh Hitesh , Chougnet Claire A. 
Published: May 2021

AbstractIntrauterine inflammation/infection (IUI), which is present in up to 40% of premature births, leads to elevated levels of pro-inflammatory mediators and microbial products within the amniotic fluid, which come in close contact to fetal mucosae. Yet, knowledge on the fetal mucosal responses to IUI exposure remains limited. To address these questions, we used a non-human primate model of IUI, in which pregnant Rhesus macaques received intra-amniotic (IA) LPS, compared with IA saline.We found that IA LPS exposure induced a robust and rapid inflammation of the fetal lung, but not the intestine. This inflammatory response was characterized by high levels of pro-inflammatory cytokines in the lung and the alveolar wash, and a potent myeloid cell response, dominated by neutrophils and monocytes/macrophages. scRNAseq analyses of fetal lungs showed that the infiltrating (neutrophils and inflammatory monocytes) and the resident (alveolar and interstitial macrophages) myeloid cells exhibited transcriptional profiles consistent with exposure to TLR ligands, as well as to cytokines, notably IL-1 and TNFα. However, blocking IL-1 signaling or TNFα, alone or simultaneously by administering inhibitors intra-amniotically and subcutaneously to the dam only partially blunted fetal lung inflammation.Together, our novel data indicate that the fetal innate immune system can mount a rapid multi-factorial mucosal innate response to IUI, responding both to direct signaling by bacterial products and to indirect cytokine-mediated pathways of activation. These data thus provide more mechanistic insights into the association between IUI exposure and the post-natal lung morbidities of the premature infant.
Mating Strategies of Invasive Versus Indigenous Crayfish: Multiple Paternity as Driver for Invasion Success?
Authors: Francesconi Caterina , Pîrvu Mălina , Schrimpf Anne , Schulz Ralf , Pârvulescu Lucian , Theissinger Kathrin 
Published: May 2021

ABSTRACTThe invasive spiny-cheek crayfish (Faxonius limosus) has been able to colonize many European waterbodies since its first introduction into Europe, threatening the indigenous crayfish fauna.Faxonius limosus’ remarkable reproductive plasticity has been suggested as an important factor contributing to this species’ alarming invasiveness. This is the first study comparing the reproductive strategies of an invasive (F. limosus) and a sympatric indigenous crayfish (Pontastacus leptodactylus). We investigated if and how parthenogenesis and multiple paternity contribute to the invasion process in the River Danube. Using microsatellites, we genotyped the offspring and their mothers of 11 clutches ofF. limosusand 18 clutches ofP. leptodactylus. While no parthenogenesis has been found inF. limosus’ populations, multiple paternity has been detected for the first time in both species, with comparable incidence. The results of the study indicate that multiple paternity does not play a dominant role inF. limosus’ successful colonization of the Danube. However, the presented results have to be regarded as pilot study, with a limited number of samples and loci investigated. Given the relevance of mating system knowledge for management measures, future studies with larger sample number could provide precious contributions to the conservation actions.