bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex
Authors: Malone Brandon , Chen James , Wang Qi , Llewellyn Eliza , Choi Young Joo , Olinares Paul Dominic B. , Cao Xinyun , Hernandez Carolina , Eng Edward T. , Chait Brian T. , Shaw David E. , Landick Robert , Darst Seth A. , Campbell Elizabeth A. 
Published: March 2021

AbstractBacktracking, the reverse motion of the transcriptase enzyme on the nucleic acid template, is a universal regulatory feature of transcription in cellular organisms but its role in viruses is not established. Here we present evidence that backtracking extends into the viral realm, where backtracking by the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) may aid viral transcription and replication. Structures of SARS-CoV-2 RdRp bound to the essential nsp13 helicase and RNA suggested the helicase facilitates backtracking. We use cryo-electron microscopy, RNA-protein crosslinking, and unbiased molecular dynamics simulations to characterize SARS-CoV-2 RdRp backtracking. The results establish that the single-stranded 3’-segment of the product-RNA generated by backtracking extrudes through the RdRp NTP-entry tunnel, that a mismatched nucleotide at the product-RNA 3’-end frays and enters the NTP-entry tunnel to initiate backtracking, and that nsp13 stimulates RdRp backtracking. Backtracking may aid proofreading, a crucial process for SARS-CoV-2 resistance against antivirals.Significance StatementThe COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 genome is replicated and transcribed by its RNA-dependent RNA polymerase (RdRp), which is the target for antivirals such as remdesivir. We use a combination of approaches to show that backtracking (backwards motion of the RdRp on the template RNA) is a feature of SARS-CoV-2 replication/transcription. Backtracking may play a critical role in proofreading, a crucial process for SARS-CoV-2 resistance against many antivirals.
Host phenology can drive the evolution of intermediate virulence strategies in some obligate-killer parasites
Authors: MacDonald Hannelore , Akçay Erol , Brisson Dustin 
Published: March 2021

AbstractThe traditional mechanistic trade-offs resulting in a negative correlation between transmission and virulence are the foundation of nearly all current theory on the evolution of parasite virulence. Several ecological factors have been shown to modulate the optimal virulence strategies predicted from mechanistic trade-off models, but these ecological factors have not yet been shown to be sufficient to explain the intermediate virulence strategies observed in any natural system. The timing of seasonal activity, or phenology, is a common factor that influences the types and impact of many ecological interactions but is difficult to incorporate into virulence evolution studies. We develop a mathematical model of a disease system with seasonal host activity to study the evolutionary consequences of host phenology on the virulence of obligate-killer parasite. Results from this model demonstrated that seasonal host activity is sufficient to drive the evolution of intermediate parasite virulence in some types of natural disease systems, even when a traditional mechanistic trade-off between transmission and virulence is not assumed in the modeling framework. The optimal virulence strategy in these systems can be determined by both the duration of the host activity period as well as the variation in the host emergence timing. Parasites with low virulence strategies are favored in environments with long host activity periods and in environments in which hosts emerge synchronously. The results demonstrate that host phenology can be sufficient to select for intermediate optimal virulence strategies, providing an alternative mechanism to account for virulence evolution in some natural systems.
Career decision-making difficulties among university students: does employment status matter?
Authors: Yaghi Abdulfattah , Alabed Nizar 
Published: March 2021

PurposeThe study adapted the Career Decision Making Difficulties Questionnaire for the Arab world. The purpose of the study was to test a popular but scientifically unverified belief that people who were employed could experience less CDD.Design/methodology/approachCareer Decision-Making Difficulties Questionnaire was administered to a sample of 500 university students to analyze CDD among full-time and part-time students and examine whether employment status determines to what extent they experience these difficulties. Univariate and bivariate analyses were used.FindingsEmployment status had no statistically significant effect on students' perceptions of CDD; 6 demographic variables were significantly correlated with CDD (gender, age, income, university grade-point average, satisfaction with the current major and social status); and students had dysfunctional beliefs about the career decision-making process, lack self-awareness, and had inconsistent information about internal and external difficulties.Research limitations/implicationsUniversities should design adequate career interventions before and after graduation and employers should implement human resource policies that reduce CDD and their negative impact on the workplace. Other methods of data collection and analysis could also be useful in the future, such as interviews. While scope of the study was acceptable, comparing countries and public versus private institutions could produce valuable findings.Practical implicationsThe study tested and validated ACDDQ which could be used as diagnostic instrument to design career interventions and training programs. Employers need to allocate resources in the recruitment process to help potential recruits to understand the nature of work, processes, and requirements. Educators need to provide better coaching and career education for students, especially those in senior years.Social implicationsUnderstanding career decision-making difficulties and factors that influence them will influence long-term human resource management, especially productivity, turn over and job satisfaction.Originality/valueThe study examined the important issue of difficulties in making career decisions among two groups of university students. With more employees go back to college for more education, it was not clear in the literature how career decisions might differ between the two groups. The issue was under-researched, especially within Arab countries.
Comparing the reproductive biological characteristics of the alien invasive Coreopsis lanceolata to those of the non‐invasive alien congener Coreopsis tinctoria
Authors: Zeng Jian‐Jun , Zhou Bing , Wang Ning 
Published: March 2021

AbstractIt is important to determine the characteristics associated with the success of alien species. However, there is no universal syndrome of invasion reproductive characteristics to explain the success of invasiveness has not been identified. Comparative studies on congeneric successful or non‐successful alien species are beneficial for revealing the drivers of invasion success and predicting future distributions. Reproductive biological characteristics, including the mating system, phenology of flowering, floral syndrome, pollination biology and seed germination have been investigated in the invasive Coreopsis lanceolata and non‐successful congener alien species Coreopsis tinctoria. The results revealed that C. lanceolata significantly attracted insect visitors by 11.67 times more than its congener, and the corolla density of C. lanceolata was positively correlated with the number of visiting insects. The high attraction of local insect bees Apis cerana guarantees the reproductive success and high seed production of C. lanceolata. Nevertheless, there was no versatile mating system, because its congener non‐successful alien species C. lanceolata still successfully invaded due to the combination strategies of self‐compatibility and presence of rhizomes. Furthermore, the ability of seed germination of C. lanceolata was lower than that of C. tinctoria, especially under drought and Al3+ stress, suggesting that germination performance can serve as a reference indicator. However, this was not an absolute trait for invasiveness. Hence, these germination traits might slow down the invasiveness of C. lanceolata in south China. These present findings highlight that the combination of self‐incompatibility and rhizomes should be given attention in the risk assessment protocols for plant invasiveness.
Development and implementation of a Pacific Island‐centred COVID‐19 Health Worker Safety Guide
Authors: Gittus Angela , Griffiths Bronwen , de Salis Dominic , Phillips Georgina 
Published: March 2021

AbstractObjectiveHealthcare workers in Pacific Island Countries face unique workload and infection control hazards because of limited resources, cultural practices and local disease burden. In the context of COVID‐19, concern around healthcare worker safety escalated in the region, triggering the need for a relevant resource.MethodsWe describe a collaborative, participatory action‐research approach with a diverse range of local clinicians in Pacific Island Countries to design, develop and implement a practical guideline assisting clinicians to work safely during the pandemic.ResultsThe resulting Health Worker Safety Guide for COVID‐19 is a relevant and usable protocol developed using local knowledge and now available in several Pacific languages.ConclusionWe recommend a creative approach to facilitate meaningful communication with this group of clinicians, including low resolution technology and use of social media platforms.
Retrospective analysis of a single institute's experience of transverse colectomy vs extended colectomy for the management of mid‐transverse colon cancer
Authors: Chow Tom Chi‐man , Wong Chi‐keung , Si Alvin Lok‐ping , Ng Andrew Sheung‐hey , Kong Chi‐kwan 
Published: March 2021

AbstractObjectiveMid‐transverse colon cancers are uncommon. The optimum operative strategy, whether extended colectomy or limited transverse colectomy, is not well established. Herein we share our local experience.MethodologyConsecutive patients with mid‐transverse colon cancer resection from January 2000 to January 2020 were identified from electronic records. Short‐ and long‐term outcomes were analyzed. Additional propensity‐score matching adjusted for potential treatment selection bias.ResultsA total of 107 patients were analyzed. 23 patients (21.5%) underwent transverse colectomy (TC) and 84 (78.5%) underwent extended colectomy (EC) of which 68 were extended right hemicolectomy. 53% of all operations were laparoscopic. Similar postoperative complication rate, postoperative length of stay and 30 day mortality rate were found. Although fewer lymph node (median 11 vs 19, P < .01) and shorter closest axial margin (3.8 vs 5.5 cm, P < .01) were achieved in the TC group, similar 5‐years overall survival, and 1‐year disease‐free survival were found. Subgroup analysis revealed a trend of poorer survival amongst stage III/IV patients with transverse colectomy.ConclusionsOur study verifies the feasibility and safety of transverse colectomy for mid‐transverse colon cancers. Attention should focus on achieving adequate margin length and nodal yield.
Internal Capital and Investment: Evidence from 2012 Pension Relief*
Authors: Kubick Thomas R. , Lockhart G. Brandon , Robinson John R. 
Published: March 2021

ABSTRACTWe use changes in mandatory pension funding to investigate the relation between internal financing constraints and incremental investment. Pension funding relief enacted in 2012 significantly reduced mandatory employer contributions to defined benefit pension plans. Prior to learning of the pension relief, firms disclosed their expected pension contributions under FAS 132R, which allows us to infer changes in investment plans in response to this unanticipated pension relief. Although our setting is pensions, our inferences contribute to the broader literature on how access to finance impacts the firm. We predict and find that pension relief resulted in increased nonpension investment in the year after enactment for financially constrained firms, and is stronger for constrained firms with greater pension underfunding. Our results are consistent with pension relief providing an important means of funding investment for financially constrained firms. Our identification strategy and results provide an important innovation to the literature examining the effect of financing constraints on investment.
Common Mutual Fund Ownership and Systemic Risk*
Authors: Iselin Michael , Liao Scott , Zhang Haiwen (Helen) 
Published: March 2021

ABSTRACTWe examine whether bank connections via common mutual fund ownership serve as a contagion channel affecting the systemic risk of the banking system. Examining this relation is important because common mutual fund ownership has increased dramatically over the past 20 years, and a buildup of systemic risk was at the heart of the 2008–2009 financial crisis. We predict and document that the extent of a bank's connection with other banks via common ownership increases its contribution to systemic risk. We further predict and find that this association is primarily driven by passive mutual funds. We provide evidence that common passive ownership results in higher systemic risk through two mechanisms: nondiscretionary sell‐offs of bank stocks and a common pattern of voting. Our results are also robust to two alternate instrumental variable analyses. This study contributes to the literature by documenting an unintended, macro‐level consequence of common mutual fund ownership. Our findings broaden the understanding of common ownership as one mechanism through which systemic risk materializes and should be particularly relevant for regulators who seek to prevent future systemic failures.
The influence of physical–chemical variables on phytoplankton and lesser flamingo (Phoeniconaiasminor) abundances in Lake Natron, Tanzania
Authors: Mgimwa Emmanuel F. , John Jasson R. , Lugomela Charles V. 
Published: March 2021

AbstractSoda lakes are alkaline ecosystems characterised by extreme conditions and are one of the most productive aquatic ecosystems. Lesser flamingo, an obligate phytoplankton filter feeder, is widely identified as the flagship species of these saline‐alkaline wetlands throughout the African continent. This study, carried out at three lagoons in Lake Natron for ten consecutive months from March 2019, investigated the relationship between Chlorophyll‐a and lesser flamingo abundances, and physical–chemical variables and Chlorophyll‐a abundance. Lake Natron is the only regular breeding site for the East African population of this specialised species and is known to host thousands of birds year‐round. There was a strong correlation between lesser flamingo and Chlorophyll‐a abundances. Chlorophyll‐a abundance was significantly influenced by dissolved oxygen, water turbidity, phosphate, nitrate and ammonium. Findings from this study suggest that annual fluctuation in the lesser flamingos numbers in Lake Natron is triggered by phytoplankton abundance whose primary productivity is influenced by physical–chemical variables in the lake waters. In turn, these changes are mainly due to both anthropogenic activities and weather changes within the lake basin and its surroundings. Thus, the conservation and management of this lake require concerted efforts from different stakeholders including those found in Kenya.
Beneficiaries of Forest Carbon: Precarious Inclusion in the Brazilian Amazon
Authors: Greenleaf Maron 
Published: March 2021

ABSTRACTSustainable development projects and progressive politics of all kinds emphasize inclusion. Sometimes inclusion is meant to occur through giving benefits to poorer people, who are then governed as “beneficiaries.” But what does it mean to be a beneficiary? I examine this question through analyzing climate‐motivated forest‐protection efforts in the Amazonian state of Acre, Brazil, that distribute benefits to poorer smallholders. This environmentally premised redistribution connects beneficiaries to the state, engendering a form of benefits‐based citizenship and everyday spaces for negotiating its meaning. Whereas the state positions the beneficiary as a temporary status, beneficiaries envision it as a long‐term relationship based on an exchange: state benefits given in exchange for them forgoing deforestation. Some beneficiaries use their new inclusion to assert this mutual dependence and claim more from the state. The increase in Amazonian deforestation threatens forest beneficiaries’ already precarious inclusion. [distribution, climate change, precarity, deforestation, Amazon]
Male seminal parameters are not associated with Leydig cell functional capacity in men
Authors: Anand‐Ivell Ravinder , Tremellen Kelton , Soyama Hiroaki , Enki Doyo , Ivell Richard 
Published: March 2021

AbstractBackgroundInsulin‐like peptide 3 (INSL3) is a constitutive, secreted peptide produced in the male uniquely by the Leydig cells of the testes. It is a biomarker for Leydig cell functional capacity, which is a measure of the numbers and differentiation status of these steroidogenic cells and lacks the biological and technical variance of the steroid testosterone. This retrospective study was carried out to examine the relationship between seminal parameters and the Leydig cell compartment, and secondarily to assess other factors responsible for determining Leydig cell functional capacity.MethodsINSL3 was assessed together with seminal, anthropometric, and hormonal parameters in a Swedish cohort of 18‐year‐old men, representing the average population, and in a smaller, more heterogeneous cohort of men visiting an Australian infertility clinic.Results and discussionAverage INSL3 concentration at 18 years is greater than that reported at younger or older ages and indicated a large 10‐fold variation. In neither cohort was there a relationship between INSL3 concentration and any semen parameter. For the larger, more uniform Swedish cohort of young men, there was a significant negative relationship between INSL3 and BMI, supporting the idea that adult Leydig cell functional capacity may be established during puberty. In both cohorts, there was a significant relationship between INSL3 and FSH, but not LH concentration. No relationship was found between INSL3 and androgen receptor trinucleotide repeat polymorphisms, reinforcing the notion that Leydig cell functional capacity is unlikely to be determined by androgen influence alone. Nor did INSL3 correlate with the T/LH ratio, an alternative measure of Leydig cell functional capacity, supporting the view that these are independent measures of Leydig cell function.
Management of major obstetric hemorrhage prior to peripartum hysterectomy and outcomes across nine European countries
Authors: Kallianidis Athanasios F. , Maraschini Alice , Danis Jakub , Colmorn Lotte B. , Deneux‐ Tharaux Catherine , Donati Serena , Gissler Mika , Jakobsson Maija , Knight Marian , Kristufkova Alexandra , Lindqvist Pelle G. , Vandenberghe Griet , van den Akker Thomas ,   INOSS (the International Network of Obstetric Survey Systems)
Published: March 2021

AbstractIntroductionPeripartum hysterectomy is applied as a surgical intervention of last resort for major obstetric hemorrhage. It is performed in an emergency setting except for women with a strong suspicion of placenta accreta spectrum (PAS), where it may be anticipated before cesarean section. The aim of this study was to compare management strategies in the case of obstetric hemorrhage leading to hysterectomy, between nine European countries participating in the International Network of Obstetric Survey Systems (INOSS), and to describe pooled maternal and neonatal outcomes following peripartum hysterectomy.Material and methodsWe merged data from nine nationwide or multi‐regional obstetric surveillance studies performed in Belgium, Denmark, Finland, France, Italy, the Netherlands, Slovakia, Sweden and the UK collected between 2004 and 2016. Hysterectomies performed from 22 gestational weeks up to 48 h postpartum due to obstetric hemorrhage were included. Stratifying women with and without PAS, procedures performed in the management of obstetric hemorrhage prior to hysterectomy between countries were counted and compared. Prevalence of maternal mortality, complications after hysterectomy and neonatal adverse events (stillbirth or neonatal mortality) were calculated.ResultsA total of 1302 women with peripartum hysterectomy were included. In women without PAS who had major obstetric hemorrhage leading to hysterectomy, uterotonics administration was lowest in Slovakia (48/73, 66%) and highest in Denmark (25/27, 93%), intrauterine balloon use was lowest in Slovakia (1/72, 1%) and highest in Denmark (11/27, 41%), and interventional radiology varied between 0/27 in Denmark and Slovakia to 11/59 (79%) in Belgium. In women with PAS, uterotonics administration was lowest in Finland (5/16, 31%) and highest in the UK (84/103, 82%), intrauterine balloon use varied between 0/14 in Belgium and Slovakia to 29/103 (28%) in the UK. Interventional radiology was lowest in Denmark (0/16) and highest in Finland (9/15, 60%). Maternal mortality occurred in 14/1226 (1%), the most common complications were hematologic (95/1202, 8%) and respiratory (81/1101, 7%). Adverse neonatal events were observed in 79/1259 (6%) births.ConclusionsManagement of obstetric hemorrhage in women who eventually underwent peripartum hysterectomy varied greatly between these nine European countries. This potentially life‐saving procedure is associated with substantial adverse maternal and neonatal outcome.
Variance reduction in the inverse probability weighted estimators for the average treatment effect using the propensity score
Authors: Liao Jiangang , Rohde Charles 
Published: March 2021

AbstractThe propensity methodology is widely used in medical research to compare different treatments in designs with a nonrandomized treatment allocation. The inverse probability weighted (IPW) estimators are a primary tool for estimating the average treatment effect but the large variance of these estimators is often a significant concern for their reliable use in practice. Inspired by Rao‐Blackwellization, this paper proposes a method to smooth an IPW estimator by replacing the weights in the original estimator by their mean over a distribution of the potential treatment assignment. In our simulation study, the smoothed IPW estimator achieves a substantial variance reduction over its original version with only a small increased bias, for example two‐to‐sevenfold variance reduction for the three IPW estimators in Lunceford and Davidian [Statistics in Medicine, 23(19), 2937–2960]. In addition, our proposed smoothing can also be applied to the locally efficient and doubly robust estimator for added protection against model misspecification. An implementation in R is provided.
Factor VIII levels and bleeding according to factor 8 (F8) mutation in pregnant carriers of haemophilia A: a multicentre retrospective cohort study
Authors: Collins Annie E. I. , Curry Nicola , Raza‐Burton Sayma , Bignell Patricia , Davies Claire , Joffe Michael , Shapiro Susan , Desborough Michael J. R. 
Published: March 2021

SummaryThis retrospective cohort study investigated the association between factor 8 (F8) genotype severity and factor VIII (FVIII) levels during pregnancy for 52 women (64 pregnancies) who were heterozygous carriers of mild, moderate or severe haemophilia A. There were no significant differences in FVIII levels for carriers of mild, moderate or severe haemophilia A at baseline [mean (SD) level: mild, 0·78 (0·22); moderate, 0·83 (0·33); severe, 0·70 (0·25) iu/ml; P = 0·81] or in the third trimester [mean (SD) level: mild, 1·42 (0·28); moderate, 1·47 (0·41); severe, 1·37 (0·49) iu/ml; P = 0·80). Post‐partum haemorrhage rates were higher for carriers of severe haemophilia A (13/24; 54·2%) compared to carriers of mild haemophilia A (four of 14; 28·6%).