bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infection fatality rate of COVID-19 in community-dwelling populations with emphasis on the elderly: An overview
Authors: Axfors Cathrine , Ioannidis John P A 
Published: July 2021

ABSTRACTObjectiveThis mixed design synthesis aimed to estimate the infection fatality rate (IFR) of Coronavirus Disease 2019 (COVID-19) in community-dwelling elderly populations and other age groups from seroprevalence studies. Protocol:https://osf.io/47cgb.Methods and analysesEligible were seroprevalence studies done in 2020 and identified by any of four existing systematic reviews; with ≥1000 participants aged ≥70 years that presented seroprevalence in elderly people; that aimed to generate samples reflecting the general population; and whose location had available data on cumulative COVID-19 deaths in elderly (primary cutoff ≥70 years; ≥65 or ≥60 also eligible). We extracted the most fully adjusted (if unavailable, unadjusted) seroprevalence estimates. We also extracted age- and residence-stratified cumulative COVID-19 deaths (until 1 week after the seroprevalence sampling midpoint) from official reports, and population statistics, to calculate IFRs corrected for unmeasured antibody types. Sample size-weighted IFRs were estimated for countries with multiple estimates. Secondary analyses examined data on younger age strata from the same studies.ResultsTwenty-five seroprevalence surveys representing 14 countries were included. Across all countries, the median IFR in community-dwelling elderly and elderly overall was 2.9% (range 0.2%-6.9%) and 4.9% (range 0.2%-16.8%) without accounting for seroreversion (2.4% and 4.0%, respectively, accounting for 5% monthly seroreversion). Multiple sensitivity analyses yielded similar results. IFR was higher with larger proportions of people >85 years. Younger age strata had low IFR values (median 0.0013%, 0.0088%, 0.021%, 0.042%, 0.14%, and 0.65%, at 0-19, 20-29, 30-39, 40-49, 50-59, and 60-69 years even without accounting for seroreversion).ConclusionsThe IFR of COVID-19 in community-dwelling elderly people is lower than previously reported. Very low IFRs were confirmed in the youngest populations.
Utilization of health care services before and after media attention about fatal side effects of the AstraZeneca vaccine: a nation-wide register-based event study
Authors: Larsen Vilde Bergstad , Grøsland Mari , Telle Kjetil , Magnusson Karin 
Published: July 2021

AbstractBackgroundSurvey studies have found that vaccinated persons tend to report more side effects after being given information about side effects rather than benefits. However, the impact of high media attention about vaccine-related side effects on the utilization of health care is unknown. We aimed to assess whether utilization of health care services for newly vaccinated health care workers changed after media attention about fatal side effects of the AstraZeneca vaccine on March 11th, 2021, and whether changes differed by age, sex, or occupation.MethodsWe utilized individual-level data on health care use, vaccination, employment, and demographics available in the Norwegian emergency preparedness register Beredt C19. In all 99,899 health care workers in Norway who were vaccinated with AstraZeneca between February 11th and March 11th, we used an event-study design with a matched comparison group to compare the change in primary and inpatient specialist care use from 14 days before to 14 days after the information shock on March 11th, 2021.ResultsPrimary health care use increased with 8.2 daily consultations per 1,000 health care workers (95% CI 7.51 to 8.89) the week following March 11th for those vaccinated with AstraZeneca (n = 99,899), compared with no increase for the unvaccinated comparison group (n = 186,885). Utilization of inpatient care also increased with 0.8 daily hospitalizations per 1,000 health care workers (95% CI 0.37 to 1.23) in week two after March 11th. The sharpest increase in daily primary health care use in the first week after March 11th was found for women aged 18-44 (10.6 consultations per 1,000, 95% CI 9.52 to 11.68) and for cleaners working in the health care sector (9.8 consultations per 1,000, 95% CI 3.41 to 16.19).ConclusionsHealth care use was higher after the media reports of a few cases of fatal or severe side effects of the AstraZeneca vaccine. Our results suggest that the reports did not only lead vaccinated individuals to contact primary health care more, but also that physicians referred and treated more cases to specialist care after the new information.
The anti-SARS-CoV-2 immunoglobulin G levels and neutralising capacities against alpha and delta virus variants of concern achieved after initial immunisation with vector vaccine followed by mRNA vaccine boost are comparable to those after double immunisation with mRNA vaccines
Authors: Rose Ruben , Neumann Franziska , Grobe Olaf , Lorentz Thomas , Fickenscher Helmut , Krumbholz Andi 
Published: July 2021

AbstractBackgroundThe humoral immune response after primary immunisation with a SARS-CoV-2 vector vaccine (AstraZeneca AZD1222, ChAdOx1 nCoV-19, Vaxzevria) followed by an mRNA vaccine boost (Pfizer/BioNTech, BNT162b2; Moderna, m-1273) was examined and compared with the antibody response after homologous vaccination schemes (AZD1222/AZD1222 or BNT162b2/BNT162b2).MethodsSera from 59 vaccinees were tested for anti-SARS-CoV-2 immunoglobulin G (IgG) and virus-neutralising antibodies (VNA) with four IgG assays, a surrogate neutralisation test (sVNT), and a Vero cell-based neutralisation test (cVNT) using the B.1.1.7 variant of concern (VOC; alpha) as antigen. Investigation was done before and after heterologous (n=31 and 42) or homologous booster vaccination (AZD1222/AZD1222, n=8/9; BNT162b2/BNT162b2, n=8/8). After the second immunisation, 26 age and gender matched sera (AZD1222/mRNA, n=9; AZD1222/AZD1222, n=9; BNT162b2/BNT162b2, n=8) were also tested for VNA against VOC B.1.617.2 (delta) in the cVNT. The strength of IgG binding to separate SARS-CoV-2 antigens was measured by avidity.ResultsAfter the first vaccination, prevalence of IgG directed against (trimeric) SARS-CoV-2 spike (S)-protein and its receptor-binding domain (RBD) varied from 55-95 % (AZD1222) to 100% (BNT162b2), depending on the vaccine used and the SARS-CoV-2 antigen used. The booster vaccination resulted in 100 percent seroconversion and appearance of highly avid IgG as well as VNA against VOC B.1.1.7. The results of the anti-SARS-CoV-2 IgG tests showed an excellent correlation to the VNA titres against this VOC. The agreement of cVNT and sVNT results was good. However, the sVNT seems to overestimate non and weak B.1.1.7-neutralising titres. The mean anti-SARS-CoV-2 IgG and B.1.1.7-neutralising titres were significantly higher after heterologous vaccination compared to the homologous AZD1222 scheme. If VOC B.1.617.2 was used as antigen, significantly lower mean VNAs were measured in the cVNT, and three (33.3%) vector vaccine recipients had a VNA titre <1:10.ConclusionsThe heterologous SARS-CoV-2 vaccination leads to a strong antibody response with anti-SARS-CoV-2 IgG and VNA titres at a level comparable to that of a homologous BNT162b2 vaccination scheme. Irrespectively of the chosen immunisation regime, highly avid IgG antibodies can be detected just two weeks after the second vaccine dose indicating the development of a robust humoral immunity. The observed reduction in the VNA titre against VOC B.1.617.2 is remarkable and may be attributed to a partial immune escape of the delta variant.
COVID-19 vaccine uptake, predictors of vaccination, and self-reported barriers to vaccination among primary school teachers in Poland
Authors: Malesza Marta , Sobolewska Karolina 
Published: July 2021

AbstractIt has been proposed that teachers, like healthcare workers, constitute a strategic target for COVID-19 vaccine programs as immunization is a key element in protecting both them and their pupils. The present study examined vaccine uptake among primary-school teachers and sought to identify factors associated with it. A sample was recruited from 553 Polish primary schools, and data were collected at two time points: December 2020 and March 2021. Associations between vaccine uptake among teachers and their attitudes toward COVID-19 vaccination were assessed through multivariate logistic regression. 6152 participants completed both baseline and follow-up surveys. Of these, 4502 (73.2%) reported their intention at baseline to receive a COVID-19 vaccination, if available; at follow-up, 3894 (86.5%) of the same 4502 reported having received the vaccination. A significant association was revealed between vaccine uptake and perceived severity, self-efficacy, and social norms. The principal driver for vaccine acceptance was the wish to avoid contracting the disease. Conversely, the principal driver for vaccine refusal was concern about side effects and safety. A strong association exists between intention to receive the COVID-19 vaccine and actual uptake. Future COVID-19 immunization programs may benefit from a stronger understanding of the factors associated with vaccine uptake among this cohort.
Genomic and transcriptomic analyses of the subterranean termite Reticulitermes speratus: gene duplication facilitates social evolution
Authors: Shigenobu Shuji , Hayashi Yoshinobu , Watanabe Dai , Tokuda Gaku , Hojo Masaru Y , Toga Kouhei , Saiki Ryota , Yaguchi Hajime , Masuoka Yudai , Suzuki Ryutaro , Suzuki Shogo , Kimura Moe , Matsunami Masatoshi , Sugime Yasuhiro , Oguchi Kohei , Niimi Teruyuki , Gotoh Hiroki , Hojo Masaru K , Miyazaki Satoshi , Toyoda Atsushi , Miura Toru , Maekawa Kiyoto 
Published: July 2021

SummaryTermites are model social organisms characterized by a polyphenic caste system. Subterranean termites (Rhinotermitidae) are ecologically and economically important species, including acting as destructive pests. Rhinotermitidae occupies an important evolutionary position within the clade representing an intermediate taxon between the higher (Termitidae) and lower (other families) termites. Here, we report the genome, transcriptome and methylome of the Japanese subterranean termite Reticulitermes speratus. The analyses highlight the significance of gene duplication in social evolution in this termite. Gene duplication associated with caste-biased gene expression is prevalent in the R. speratus genome. Such duplicated genes encompass diverse categories related to social functions, including lipocalins (chemical communication), cellulases (wood digestion and social interaction), lysozymes (social immunity), geranylgeranyl diphosphate synthase (social defense) and a novel class of termite lineage-specific genes with unknown functions. Paralogous genes were often observed in tandem in the genome, but the expression patterns were highly variable, exhibiting caste biases. Some duplicated genes assayed were expressed in caste-specific organs, such as the accessory glands of the queen ovary and frontal glands in soldier heads. We propose that gene duplication facilitates social evolution through regulatory diversification leading to caste-biased expression and subfunctionalization and/or neofunctionalization that confers caste-specialized functions.Significance StatementTermites are model social organisms characterized by a sophisticated caste system, where distinct castes arise from the same genome. Our genomics data of Japanese subterranean termite provides insights into the evolution of the social system, highlighting the significance of gene duplication. Gene duplication associated with caste-biased gene expression is prevalent in the termite genome. Many of the duplicated genes were related to social functions, such as chemical communication, social immunity and defense, and they often expressed in caste-specific organs. We propose that gene duplication facilitates social evolution through regulatory diversification leading to caste-biased expression and functional specialization. In addition, since subterranean termites are ecologically and economically important species including destructive pests in the world, our genomics data serves as a foundation for these studies.
Conditional ERK3 overexpression cooperates with PTEN deletion to promote lung adenocarcinoma formation in mice
Authors: Vallabhaneni Sreeram , Liu Jian , Morel Marion , Demayo Francesco J. , Long Weiwen 
Published: July 2021

AbstractExtracellular signal-regulated kinase 3 (ERK3), also known as MAPK6, belongs to the atypical mitogen-activated protein kinases (MAPKs) subfamily. In comparison with the well-studied classical MAPKs ERK1 and ERK2, much less is known about the cellular and molecular actions of ERK3. Accumulating studies have revealed the upregulation of ERK3 expression and suggested an important role for ERK3 in promoting tumor cell growth and invasion in multiple cancers, in particular lung cancer. However, it is unknown whether or not ERK3 plays a role in spontaneous tumorigenesis. To determine the role of ERK3 in lung tumorigenesis, we created a conditional ERK3 transgenic mouse line in which ERK3 transgene expression is controlled by Cre recombinase. By crossing with a lung tissue-specific CCSP-iCre mouse line, we have found that conditional ERK3 overexpression cooperates with PTEN deletion to induce the formation of lung adenocarcinomas (LUADs). Mechanistically, ERK3 overexpression stimulates activating phosphorylations of ERBB3 and ERBB2 by upregulating SP1-mediated gene transcription of NRG1, a potent ligand for ERBB3/ERBB2. To our knowledge, our study is the first revealing a bona fide tumor-promoting role for ERK3 using genetically engineered mouse models. Together with previous findings showing important roles of ERK3 in cultured cells and in xenograft lung tumor model, our findings corroborate that ERK3 acts as an oncoprotein in promoting LUAD development and progression.
Proteomic Signatures of Microbial Adaptation to the Highest UV-Irradiation on Earth: Lessons from a Soil Actinobacterium
Authors: Zannier Federico , Portero Luciano Raúl , Douki Thierry , Gärtner Wolfgang , Farías María Eugenia , Albarracin Virginia Helena 
Published: July 2021

ABSTRACTIn the Puna region, the total solar irradiation and the UV incidence is the highest on Earth, thus, restraining the physiology of individual microorganisms and the composition of microbial communities. UV-resistance of microbial strains thriving in High-Altitude Andean Lakes was demonstrated and their mechanisms were partially characterized by genomic analysis, biochemical and physiological assays. In this work, we present the molecular events involved in the adaptive response of the model HAAL extremophilic actinobacterium Nesterenkonia sp. Act20 under artificial UV-B radiation, herein called as UV-resistome. Proteomic profiles of cultures exposed to different UV-experimental conditions showed that the leading systems for adaptation to the UV-challenge in-vitro are DNA repair and antioxidant mechanisms.
Native MOWChIP-seq: Genome-wide profiles of key protein bindings reveal functional differences among various brain regions
Authors: Liu Zhengzhi , Naler Lynette B. , Zhu Yan , Deng Chengyu , Zhang Qiang , Zhu Bohan , Zhou Zirui , Sarma Mimosa , Murray Alexander , Xie Hehuang , Lu Chang 
Published: July 2021

AbstractGenome-wide profiling of interactions between genome and various functional proteins is critical for understanding regulatory processes involved in development and diseases. Conventional assays require a large number of cells and high-quality data on tissue samples are scarce. Here we optimized a low-input chromatin immunoprecipitation followed by sequencing (ChIP-seq) technology for profiling RNA polymerase II (Pol II), transcription factor (TF), and enzyme binding at the genome scale. The new approach, termed native MOWChIP-seq, produces high-quality binding profiles using 1000-50,000 cells. We used the approach to examine the binding of Pol II and two TFs (EGR1 and MEF2C) in cerebellum and prefrontal cortex of mouse brain and found that their binding profiles are highly reflective of the functional differences between the two brain regions. Our analysis reveals the potential for linking genome-wide TF or Pol II profiles with neuroanatomical origins of brain cells.
ERK-mediated Curvature Feedback Regulates Branching Morphogenesis in Lung Epithelial Tissue
Authors: Hirashima Tsuyoshi , Matsuda Michiyuki 
Published: July 2021

AbstractIntricate branching patterns emerge in internal organs because of the repetitive presence of simple deformations in epithelial tissues. During murine lung development, epithelial cells in distal tips of a single tube require fibroblast growth factor (FGF) signals generated by their surrounding mesenchyme to form repetitive tip bifurcations. However, it remains unknown how the cells employ FGF signaling to convert their behaviors to achieve the recursive branching processes. Here we show a self-sustained epithelial regulatory system during the murine lung branching morphogenesis, mediated by extracellular signal-regulated kinase (ERK), which acts as a downstream driver of FGF signaling. We found that tissue-scale curvature regulated ERK activity in the lung epithelium using two-photon live cell imaging and mechanical perturbations. ERK was activated specifically in epithelial tissues with a positive curvature, regardless of whether the change in curvature was attributable to morphogenesis or artificial perturbations. Moreover, ERK activation accelerated actin polymerization specifically at the apical side of cells, and mechanically contributed to the extension of the apical membrane, leading to a decrease in epithelial tissue curvature. These results indicate the existence of negative feedback loop between tissue curvature and ERK activity beyond scale. We confirmed that this regulation was sufficient to generate the recursive branching processes by a mathematical model. Taken together, we propose that ERK mediates the curvature feedback loop underlying the process of branching morphogenesis in developing lungs.
Isonicotinamide extends yeast chronological lifespan through a mechanism that diminishes nucleotides
Authors: Kalita Agata , Hesles Elisa Enriquez , Power Lindsey N. , Wang Dezhen , Singh Pankaj K. , Smith Jeffrey S. 
Published: July 2021

ABSTRACTChronological lifespan (CLS) of budding yeast,Saccharomyces cerevisiae,is a commonly utilized model for cellular aging of non-dividing cells such as neurons. CLS is strongly extended by isonicotinamide (INAM), a non-metabolized isomer of the NAD+precursor nicotinamide (NAM), but the underlying mechanisms of lifespan extension remain uncharacterized. To identify potential biochemical INAM targets, we performed a chemical genetic screen with the yeast gene knockout (YKO) strain collection for INAM-hypersensitive mutants. Significantly enriched Gene Ontology terms that emerged included SWR1 and other transcription elongation factors, as well as metabolic pathways converging on one-carbon metabolism and contributing to nucleotide biosynthesis, together suggesting that INAM perturbs nucleotide pools. In line with this model, INAM effects on cell growth were synergistic with mycophenolic acid (MPA), which extends lifespan by reducing guanine nucleotide pools. Direct measurements of nucleotides and precursors by mass spectrometry indicated that INAM reduced nucleotides, including cAMP, at 24- and 96-hour time points post-inoculation. Taken together, we conclude that INAM extends CLS by perturbing nucleotide metabolism, which may be a common functional feature of multiple anti-aging interventions.
From telomere to telomere: the transcriptional and epigenetic state of human repeat elements
Authors: Hoyt Savannah J. , Storer Jessica M. , Hartley Gabrielle A. , Grady Patrick G. S. , Gershman Ariel , de Lima Leonardo G. , Limouse Charles , Halabian Reza , Wojenski Luke , Rodriguez Matias , Altemose Nicolas , Core Leighton J. , Gerton Jennifer L. , Makalowski Wojciech , Olson Daniel , Rosen Jeb , Smit Arian F. A. , Straight Aaron F. , Vollger Mitchell R. , Wheeler Travis J. , Schatz Michael C. , Eichler Evan E. , Phillippy Adam M. , Timp Winston , Miga Karen H. , O’Neill Rachel J. 
Published: July 2021

AbstractMobile elements and highly repetitive genomic regions are potent sources of lineage-specific genomic innovation and fingerprint individual genomes. Comprehensive analyses of large, composite or arrayed repeat elements and those found in more complex regions of the genome require a complete, linear genome assembly. Here we present the first de novo repeat discovery and annotation of a complete human reference genome, T2T-CHM13v1.0. We identified novel satellite arrays, expanded the catalog of variants and families for known repeats and mobile elements, characterized new classes of complex, composite repeats, and provided comprehensive annotations of retroelement transduction events. Utilizing PRO-seq to detect nascent transcription and nanopore sequencing to delineate CpG methylation profiles, we defined the structure of transcriptionally active retroelements in humans, including for the first time those found in centromeres. Together, these data provide expanded insight into the diversity, distribution and evolution of repetitive regions that have shaped the human genome.
Multiplex viral tropism assay in complex cell populations with single-cell resolution
Authors: Tat Keng Choong , Ke Guo , Shern Daryl Lim , Chew Wei Leong 
Published: July 2021

AbstractGene therapy constitutes one of the most promising modes of disease treatments. Two key properties for therapeutic delivery vectors are the transduction efficiency (how well the vector delivers therapeutic cargo to desired target cells) and specificity (how well it avoids off-target delivery into the other unintended cells within the body). Here we developed a novel technology that enables multiplex measurement of transduction efficiency and specificity, particularly by measuring how libraries of delivery vectors transduce libraries of diverse cell types. We demonstrated that pairing high-throughput measurement of AAV identity with high-resolution single-cell RNA transcriptomic sequencing maps how natural and engineered AAV variants transduce individual cells within human cerebral and ocular organoids. This library- on-library technology is important for determining the safety and efficacy of therapeutic delivery vectors.