bluuebunny/crossref_metadata_2025_split huggingface dataset:
IDENTIFICATION OF GENOTYPE III OF HEPATITIS DELTA VIRUS IN ANDEAN AND AMAZONIAN COMMUNITIES OF PERU
Authors: Balbuena-Torres Johanna N. , Santos-Solis Lorena , Navarro-Oviedo Ronald D. , Cabezas Cesar 
Published: May 2022

ABSTRACTObjectivesto identify the genotypes of Hepatitis Delta Virus (HDV) circulating in populations of the inter-Andean valley of Huanta and three indigenous peoples of the Peruvian Amazon.Materials and MethodsObservational and cross-sectional study, from 582 reactive samples for anti-HBc-HBV antibodies in inhabitants of the andean province of Huanta (Ayacucho) and the Amazonian towns of Matsés, Kandozi and Chapra (Loreto). Analysis was performed for HDV infection markers: anti-HDV IgM and anti-HDV IgG by ELISA using Wantai brand kits. Anti-HDV positive samples by ELISA were processed with the nRT-PCR method for the detection of HDV RNA. HDV genotype was determined by direct Sanger-type sequencing and phylogenetic analysis of the R0 fragment. 111 reference sequences from GenBank were used. The 42 sequences of the study were edited, assembled and cut with the programs Chromas 2.6.5, Bioedit v7.2, ClustalW v.1.6 of Mega v.7.0 and the Gblocks server. Phylogenetic and evolutionary analysis was performed with the following software: Beast V2.5.2, Jmodeltest v2.1.10, Tracer v1.7.1, Tree Annotator and Figtree v1.4.4. The Bayesian Yule and Birth Death skyline serial models were used, the MCMC at 30 and 80 million respectively, with the relaxed uncorrelated Exponential molecular clock. Summary and central tendency measures were calculated using the program in STATA 14.0.ResultsThe mean age was 38 years (0 to 86 years), 52.75% (N=307) were women. 582 blood samples positive for anti-HBc were analyzed for anti-HVD antibodies using the ELISA method, with 101 positive samples being found. HDV RNA was detected in 49.50% of the anti-HDV ELISA reactive samples. Phylogenetic analysis determined the presence of genotype 3.ConclusionsThe presence of HDV genotype 3 in Andean and Amazonian communities of Peru is evidenced.
Durability of the immune response to a third BNT162b2 dose; five months follow-up
Authors: Gilboa Mayan , Regev-Yochay Gili , Mandelboim Michal , Indenbaum Victoria , Asraf Keren , Fluss Ronen , Amit Sharon , Mendelson Ella , Doolman Ram , Afek Arnon , Freedman Laurence S. , Kreiss Yitshak , Lustig Yaniv 
Published: May 2022

AbstractBackgroundTwo doses of the BNT162b2 vaccine yielded high effectiveness that wanes within several months. The third dose was effective in mounting a significant humoral and cellular immune response..MethodsWe followed BNT162b2-vaccinated health-care workers monthly for IgG and neutralizing antibody (NeutAb) titers. Avidity, T-cell activation and microneutralization of sera against different variants of concern (VOC) were assessed for a sub-cohort. Linear mixed models were used to compare the durability of the second and third doses, and to assess if Omicron breakthrough infections were associated with waning dynamics.ResultsOverall 3972 participants with a third dose were followed, the rate of waning of IgG and NeutAb was slower after the third (1.32%/day and 1.32%/day, respectively) compared to the second (2.26%/per day and 3.34%/day) dose. Live-neutralization of Omicron VOC was lower compared to previous strains and demonstrated similar waning from 111 (95%CI:75-166) to 26 (95%CI:16-42) within 4 months. Mean T cell activity decreased from 98±5.4 T cells/106 PBMC to 59±9.3, within 3-5 months. Omicron breakthrough infections were associated with lower IgG peak (ratio of means 0.86 95%CI 0.80-0.91), and among participants over 65y with faster waning of both IgG and NeutAb (ratio of mean rates 1.40 95% CI 1.13-1.68 and 3.58 95% CI 1.92-6.67). No waining in IgG avidity was obsereved during 112 days after the 3rd dose.ConclusionThe third dose is more durable than the second dose, yet Omicron is relatively resistant to direct neutralization. The level of humoral response may predict breakthrough infections.
Childhood Stunting and Its Associated Factors in Ethiopia
Authors: Gobena Woldemariam Erkalo 
Published: May 2022

AbstractChild malnutrition is the root cause of nearly half (45%) of all child deaths, especially in low-income nations. Ethiopia has the highest frequency of stunting among Sub-Saharan African countries, at 38 percent. The study’s major goal was to use cluster specific models to identify risk factors for stunting in Ethiopian children under the age of five. The data was gathered from the EDHS 2016, a nationally representative survey of children aged 0 to 59 months. The research was carried out using generalized linear mixed models from the cluster specific model family. The variables child’s age, mother’s education level, mother’s BMI, place of residence, wealth index, and prior birth interval were determined to be important drivers of child malnutrition in Ethiopia as a result of the analysis. According to the findings, children with a shorter previous birth interval (less than 24 months) were more likely to be stunted than those with a longer previous birth interval. Rural Ethiopian children were more likely than urban Ethiopian children to be stunted. It is advised that in order to reduce childhood malnutrition, parents’ awareness and implementation of proper young child feeding practices, as well as frequent growth monitoring and appropriate and timely interventions, should be prioritized.
A comparison of mtDNA deletion mutant proliferation mechanisms
Authors: Holt Alan G , Davies Adrian M 
Published: May 2022

AbstractIn this paper we use simulation methods to investigate the proliferation of deletion mutations of mitochondrial DNA in neurons. We simulate three mtDNA proliferation mechanisms, namely, random drift, replicative advantage and vicious cycle. For each mechanism, we investigated the effect mutation rates have on neuron loss within a human host. We also compare heteroplasmy of each mechanism at mutation rates that yield the levels neuron loss that would be associated with dementia. Both random drift and vicious cycle predicted high levels of heteroplasmy, while replicative advantage showed a small number of dominant clones with a low background of heteroplasmy.
Trogocytic-molting of T-cell microvilli controls T-cell clonal expansion
Authors: Park Jeong-Su , Kim Jun-Hyeong , Soh Won-Chang , Lee Kyung-Sik , Kim Chang-Hyun , Chung Ik-Joo , Lee Sunjae , Kim Hye-Ran , Jun Chang-Duk 
Published: May 2022

ABSTRACTInternalization of the T-cell antigen receptor (TCR) is intimately linked to T-cell activation: a phenomenon thought to be related to the “exhaustion” of T-cell responses. To date, however, no report has considered that during physical interaction with cognate antigen-presenting cells, T cells release many TCRs via T-cell microvilli particles, which are derived from finger-like membrane structures (microvilli) in a combined process of trogocytosis and enzymatic vesiculation and correspond with the loss of membrane TCRs and many external membrane components. Surprisingly, in contrast to TCR internalization, this event leads to rapid upregulation of surface TCRs and remarkable metabolic reprogramming of cholesterol and fatty acids synthesis to meet the demands of clonal expansion, which drives multiple rounds of division and cell survival. We called this event “trogocytic-molting,” which represents an intrinsic molecular basis of T-cell clonal expansion by which T cells gain increased sensitivity to low antigen concentrations.TEASER“Trogocytic-molting,” led to the rapid upregulation of surface TCRs and tremendous metabolic reprogramming to meet the demands of clonal expansion.
Connecting single-cell ATP dynamics to overflow metabolism, cell growth and the cell cycle in Escherichia coli
Authors: Lin Wei-Hsiang , Jacobs-Wagner Christine 
Published: May 2022

SummaryAdenosine triphosphate (ATP) is a universal energy-carrying molecule that cells consume and regenerate in vast amounts to support growth. Despite this high turnover, bacterial cultures maintain a similar average concentration of ATP even when the carbon source conditions lead to large differences in population growth rate. What happens in individual bacterial cells is, however, less clear. Here, we use the QUEEN-2m biosensor to quantify ATP dynamics in single Escherichia coli cells in relation to their growth rate, metabolism, cell cycle, and cell lineage. We find that ATP dynamics are more complex than expected from population studies and are associated with growth rate variability. Under a nutrient-rich condition, cells can display large fluctuations in ATP level that are partially coordinated with the cell cycle. Abrogation of aerobic acetate fermentation (overflow metabolism) through genetic deletion considerably reduces both the amplitude of ATP level fluctuations and the cell cycle trend. Similarly, growth in media in which acetate fermentation is lower or absent results in reduction of ATP level fluctuation and cell cycle trend. This suggests that overflow metabolism exhibits temporal dynamics, which contributes to fluctuating ATP levels during growth. Remarkably, at the single-cell level, growth rate negatively correlates with the amplitude of ATP fluctuation for each tested condition, linking ATP dynamics to growth rate heterogeneity in clonal populations. Our work highlights the importance of single-cell analysis in studying cellular energetics and its implication to phenotypic diversity and cell growth.
Thermal cycling hyperthermia sensitizes non-small cell lung cancer A549 cells to EGFR-tyrosine kinase inhibitor Erlotinib
Authors: Lin Guan-Bo , Chen Wei-Ting , Kuo Yu-Yi , Liu Hsu-Hsiang , Chen You-Ming , Leu Shr-Jeng , Chao Chih-Yu 
Published: May 2022

ABSTRACTMolecular targeted therapy has emerged as a mainstream treatment for non-small cell lung cancer (NSCLC), the most common lung cancer, which has been the leading cause of cancer death in both genders. Erlotinib (Erl), a targeted therapy inhibiting epidermal growth factor receptor (EGFR) pathways, has been proved to have noticeable response rate for NSCLC cells. However, limited efficacy arises due to intrinsic and acquired resistance among most NSCLC patients. Therefore, sensitizers are required to potentiate the efficacy of Erl in NSCLC treatment. The study proposed a novel thermal therapy, thermal cycling hyperthermia (TC-HT), as a supplement to amplify the effects of Erl. We found that TC-HT remarkably reduced the half-maximal inhibitory concentration (IC50) of Erl to as little as 0.5 μM and demonstrated that TC-HT could sensitize A549 NSCLC cells to Erl via the downstream of EGFR signaling cascades. Furthermore, combination treatment induced G2/M cell cycle arrest, and inhibition of cell proliferation and migration. Besides, via raising the high temperature of TC-HT slightly, TC-HT treatment alone can produce excellent antineoplastic effect without hurting the normal cells. The method is expected to be applicable to other combination therapies and may be a starter for more sophisticated, side-effect-free anticancer treatments.
Effect of Digoxin on Interstage Outcomes following Stage I Palliation for Functionally Univentricular Hearts: A Systematic Review and Meta-Analysis
Authors: Loomba Rohit S. , Rausa Jacqueline , Villarreal Enrique , Farias Juan S. , Flores Saul 
Published: May 2022

ABSTRACTObjectivesThe goal of this systematic review and meta-analysis is to investigate the effects of digoxin on outcomes following stage I palliation for functionally univentricular hearts.Data SourcesWe conducted electronic searches of PubMed, Ovid and Cochrane.Study SelectionInclusion criteria included publication dates 1970–2018, children with functionally univentricular hearts between stage I and stage II palliation who received digoxin were compared to those who did not.Data ExtractionWe identified 148 unique citations; 5 full-text articles were included in the final review. Data from 4 studies was pooled for meta-analysis.Data SynthesisA total of 4 studies with 1,498 patients were included in the final analyses. Patient enrollment occurred between 2003 and 2013. A majority of patients were born full-term and approximately 25% were diagnosed with a syndrome. The most common cardiac diagnosis was hypoplastic left heart syndrome (70%). The most common initial surgical palliation was the Norwood procedure with a right ventricle to pulmonary artery conduit. The total amount of deaths was 121 (12 digoxin group versus 109 no digoxin group). The interstage mortality was reduced in the digoxin group [OR 0.25(95% CI 0.14 to 0.47)]. There was no statistically significant difference in the presence of arrhythmias or other complications.ConclusionsThis systematic review and meta-analysis suggests that digoxin significantly decreases interstage period mortality with a concurrent significant decrease in weight for age. The odds of arrhythmia or other complications are not significantly different with digoxin based on current data.
Protection against omicron severe disease 0-7 months after BNT162b2 booster
Authors: Amir Ofra , Goldberg Yair , Mandel Micha , Bar-On Yinon M. , Bodenheimer Omri , Freedman Laurence , Alroy-Preis Sharon , Ash Nachman , Huppert Amit , Milo Ron 
Published: May 2022

AbstractFollowing a rise in cases due to the delta variant and evidence of waning immunity after 2 doses of the BNT162b2 vaccine, Israel began administering a third BNT162b2 dose (booster) in July 2021. Recent studies showed that the 3rd dose provides a much lower protection against infection with the omicron variant compared to the delta variant and that this protection wanes quickly. In this study, we used data from Israel to estimate the protection of the 3rd dose against severe disease up to 7 months from receiving the booster dose. The analysis shows that protection conferred by the 3rd dose against omicron did not wane over a 7-month period and that a 4th dose further increased protection, with a severe disease rate approximately 3-fold lower than in the 3-dose cohorts.
Structure of the RAF1-HSP90-CDC37 complex reveals the basis of RAF1 regulation
Authors: García-Alonso Sara , Mesa Pablo , de la Puente Ovejero Laura , Aizpurua Gonzalo , Lechuga Carmen G , Zarzuela Eduardo , Santiveri Clara M , Sanclemente Manuel , Muñoz Javier , Musteanu Mónica , Campos-Olivas Ramón , Martínez-Torrecuadrada Jorge , Barbacid Mariano , Montoya Guillermo 
Published: May 2022

ABSTRACTRAF kinases are RAS-activated enzymes that initiate signalling through the MAPK cascade to control cellular proliferation, differentiation, and survival. Here, we describe the structure of the full-length RAF1 protein in complex with HSP90 and CDC37 obtained by cryo-electron microscopy. The reconstruction reveals a RAF1 kinase with an unfolded N-lobe separated from its C-lobe. The hydrophobic core of the N-lobe is trapped in the HSP90 dimer while CDC37 wraps around the chaperone and interacts with the N- and C-lobes of the kinase. The structure indicates how CDC37 can discriminate between the different members of the RAF family. Our structural analysis also reveals that the folded RAF1 assembles with 14-3-3 dimers, suggesting that after folding follows a similar activation as B-RAF. Finally, disruption of the interaction between CDC37 and the DFG segment of RAF1 unveils potential vulnerabilities to attempt the pharmacological degradation of RAF1 for therapeutic purposes.
Evaluation of Cognitive Function in the Dog Aging Project: Associations with Baseline Canine Characteristics
Authors: Yarborough Sarah , Fitzpatrick Annette , Schwartz Stephen M. ,   Dog Aging Project Consortium
Published: May 2022

ABSTRACTCanine Cognitive Dysfunction (CCD) is a neurodegenerative disease in aging dogs. It has been described previously in relatively small cohorts of dogs using multiple different rating scales. This study aimed to use a minimally modified CCD rating scale developed by previous researchers to describe the prevalence of CCD more thoroughly in a large, nationwide cohort of companion dogs participating in the Dog Aging Project (DAP). Associations between various canine characteristics, predicted lifespan quartiles, and CCD were examined using univariable and multivariable logistic regression models and Receiver Operating Curve (ROC) analysis.When controlling for all other characteristics, the odds of CCD increased 52% with each additional year of age. Among dogs of the same age, health status, breed type, and sterilization status, odds of CCD were 6.47 times higher in dogs who were not active compared to those who were very active. When controlling for age, breed type, activity level, and other comorbidities, dogs with a history of neurological, eye, or ear disorders had higher odds of CCD. Lifespan quartile analysis showed excellent discriminating ability between CCD positive and negative dogs. Weight-based lifespan quartile estimation could therefore serve as a tool to inform CCD screening by veterinarians.
Managerial ability and tax aggressiveness
Authors: Francis Bill B. , Sun Xian , Weng Chia-Hsiang , Wu Qiang 
Published: May 2022

PurposeThe aim of this paper is to examine how managerial ability affects corporate tax aggressiveness.Design/methodology/approachThe study follows the work of Demerjian, Lev, and McVay (2012) and quantifies managerial ability by calculating how efficiently managers generate revenues from given economic resources using the data envelopment analysis (DEA) approach. The study uses a wide range of measures of tax aggressiveness. Firm fixed-effects regressions and a difference-in-differences approach using information regarding CEO turnover to control for endogeneity are used.FindingsThe study finds a negative relationship between managerial ability and corporate tax aggressiveness. Further tests show that this negative relationship is more pronounced for firms with higher investment opportunities or firms with more reputational concerns.Originality/valueGiven the significant costs associated with tax aggressiveness and the negative effect it can have on managerial reputation if discovered, the results suggest that more able managers invest less effort in aggressive tax avoidance activities. This study furthers the understanding of how managerial personal traits affect corporate decision-making.
Bond market information disclosure and industry spillover effect
Authors: Zhang Xiaochen , Yin Huifang 
Published: May 2022

PurposeThe aim of this paper is to examine the effect of information disclosure by unlisted bond issuers on the stock price informativeness of listed firms in the same industry.Design/methodology/approachThis paper takes advantage of information disclosure during the bond issuance and examines the spillover effect of unlisted bond issuers' information disclosure on listed firms in the stock market. The sample is composed of A-share firms listed on the Shanghai and Shenzhen stock exchanges from 2007 to 2018. All the data are obtained from the China Stock Market and Accounting Research and WIND databases. The impact of bond market information disclosure on price informativeness of listed firms in the same industry is identified through multivariate regression analyses.FindingsEmpirical results show that price informativeness of listed firms has a significantly positive association with the information disclosure of same-industry unlisted bond issuers. Further analyses show that the above finding is more significant when information disclosure of bond issuers is a more important channel for acquiring industry information (i.e. when industry is more concentrated, when economic uncertainty is high, and when industry information is less transparent) and understanding the industry competitive landscape (i.e. when bond issuers are relatively large, when bond issuers and listed firms have more direct product competition, when bond issuance firms are large-scale state-owned business groups), and when there are more cross-market information intermediaries (i.e. more cross-market institutional investors and more sell-side analysts). This paper indicates that information disclosure of bond issuers has a positive spillover effect on the stock market.Originality/valueThe novelty of the research is that the authors examine industry information spillover from unlisted firms to listed firms leveraging on unlisted firms' information disclosure in bond markets.
The dual effect of idiosyncratic volatility on stock pricing and return
Authors: Cheng Zhuo (June) , Fang Jing (Bob) 
Published: May 2022

PurposeThis study aims to examine what underlies the estimated relation between idiosyncratic volatility and realized return.Design/methodology/approachIdiosyncratic volatility has a dual effect on stock pricing: it not only affects investors' expected return but also affects the efficiency of stock price in reflecting its value. Therefore, the estimated relation between idiosyncratic volatility and realized return captures its relations with both expected return and the mispricing-related component due to its dual effect on stock pricing. The sign of its relation with the mispricing-related component is indeterminate.FindingsThe estimated relation between idiosyncratic volatility and realized return decreases and switches from positive to negative as the estimation sample consists of proportionately more ex ante overvalued observations; it increases and switches from negative to positive as the estimation sample consists of proportionately more ex post overvalued observations. In sum, the relation of idiosyncratic volatility with the mispricing-related component dominates its relation with expected return in its estimated relation with realized return. Moreover, its estimated relation with realized return varies with research design choices and even switches sign due to their effects on its relation with the mispricing-related component.Originality/valueThe novelty of the study is evident in the implication of its findings that one cannot infer the sign of the relation of idiosyncratic volatility with expected return from its estimated relation with realized return.