bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growing the Next Generation of Trauma Surgeon Scientists – Reflections on 20 Years of Research Investment
Authors: Callcut Rachael A. , Dixon Rachel , Smith Jason W. , Zarzaur Ben ,   the EAST Research-Scholarship Committee
Published: June 2022

Introduction
The EAST mission includes fostering research and providing career development opportunities. EAST has awarded for 20 years a Research Scholarship to a promising young investigator. The Research mentorship efforts were expanded 5 yrs ago with the INVEST-C Hack-a-thon. INVEST-C provides an intensive, short-term engagement to propel junior faculty toward establishing research independence. This study investigates the impact of these programs on academic productivity.

Methods
Pubmed records, NIH Reporter data, and SCOPUS h-index was acquired for all scholarship [SCH] awardees from 2002-2021 (n = 20) and all INVEST-C [INV] participants (2017-2020, n = 19). Current type of practice, total number of funding awards, and timing of first award were ascertained. INVEST-C participants were also surveyed on an annual basis to track their progress. Medians (IQR) are reported and compared (ANOVA).

Results
Median publications (PUB) of SCH awardees was 56 [IQR 33-88], h-index 16 (12-21), and 25% with > = 1 NIH grant since their SCH. Amongst the last 10 awardees with a minimum of 2 yrs from SCH, 40% have received a NIH award compared with a mean NIH funding rate of 18.5% over the same time period. For those remaining in academics (90% SCH), PUB were higher for those >5 yrs (66, 51-115) vs. <5 yrs from their SCH (33, 22-59, p = 0.05), but there was no difference in h-index (16, IQR 14-25, vs 15, 9-19, p = NS). Comparing the most recent 5 yrs of SCH to INV group, there was no difference in academic productivity as measured by total PUB (SCH 33, IQR 22-59 vs INV 34, IQR 18-44, p = 0.7) or h-index (INV 9, 5-14, p = 0.1). However, no attendee held research funding prior to INV, but 31.6% (6/19) have subsequently acquired > = 1 funding award (11 non-NIH, 1 NIH) in the short interval since participation.

Conclusion
Investments in research activities have translated to significant extramural funding. Those in the last 5 yrs have been particularly fruitful with INV participants already achieving equal median academic productivity to SCH recipients.

Level of Evidence
Level III, Epidemiologic, Cohort
Lipidome- and genome-wide study to understand sex differences in circulatory lipids
Authors: Tabassum Rubina , Ruotsalainen Sanni , Ottensmann Linda , Gerl Mathias J. , Klose Christian , Tukiainen Taru , Pirinen Matti , Simons Kai , Widén Elisabeth , Ripatti Samuli 
Published: June 2022

AbstractDespite well-recognized difference in the atherosclerotic cardiovascular disease (ASCVD) risk between men and women, sex differences in risk factors and sex specific mechanisms in the pathophysiology of ASCVD remain poorly understood. Lipid metabolism plays a central role in the development of ASCVD. Understanding sex differences in lipids and their genetic determinants could provide mechanistic insights into sex differences in ASCVD and aid in precise risk assessment. Thus, we examined sex differences in plasma levels of 179 lipid species from 7,266 participants and performed sex-stratified genome-wide association studies (GWAS) to evaluate contribution of genetic factors in sex differences. We sought for replication using independent data from 2,045 participants. Significant sex differences in levels of 141 lipid species were observed (P<7.0×10−4). Interestingly, 121 lipid species showed significant age-sex interactions with opposite age-related changes in 39 lipid species. In general, most of the cholesteryl esters, ceramides, lysophospholipids and glycerides were higher in 45-50-year-old men compared with women of same age, but the sex-differences narrowed down or reversed with age. We did not observe any major differences in genetic effect in the sex stratified GWAS which suggests that common genetic variants do not have a major role in sex differences in lipidome. In conclusion, our study provides a comprehensive view of sex differences in circulatory lipids pointing to potential sex differences in lipid metabolism, highlighting need for sex- and age-specific prevention strategies.
The cost of the COVID-19 pandemic vs the cost-effectiveness of mitigation strategies in the EU/UK/EEA and OECD countries: a systematic review
Authors: Vardavas Constantine , Zisis Konstantinos , Nikitara Katerina , Lagou Ioanna , Aslanoglou Katerina , Athanasakis Kostas , Phalkey Revati , Leonardi-Bee Jo , Fernandez Esteve , Condell Orla , Lamb Favelle , Sandmann Frank , Pharris Anastasia , Deogan Charlotte , Suk Jonathan E. 
Published: June 2022

ABSTRACTObjectivesCOVID-19 poses a threat of loss of life, economic instability, and social disruption. We conducted a systematic review of published economic analyses to assess the direct and indirect costs of the SARS-CoV-2 pandemic, and to contrast these with the costs and the cost-benefit of public health surveillance, preparedness, and response measures in averting and/or responding to SARS-CoV-2 pandemic.SettingA systematic literature review was conducted to identify peer-reviewed articles estimating the cost of the COVID-19 pandemic and the cost-effectiveness of pharmaceutical or non-pharmaceutical interventions in EU/EEA/UK and OECD countries, published from the 1st of January 2020 through 22nd April 2021 in Ovid Medline and EMBASE. The cost-effectiveness of interventions was assessed through a dominance ranking matrix approach. All cost data were adjusted to the 2021 Euro, with interventions compared with the null.Primary and secondary outcome measuresDirect and indirect costs for SARS-CoV-2 and preparedness and/or response or cost-benefit and cost-effectiveness were measured.ResultsWe included data from 41 economic studies. Ten studies evaluated the cost of COVID-19 pandemic, while 31 assessed the cost-benefit of public health surveillance, preparedness, and response measures. Overall, the economic burden of SARS-CoV-2 was found to be substantial for both the general population and within specific population subgroups. Community screening, bed provision policies, investing in personal protective equipment and vaccination strategies were cost-effective, in most cases due to the representative economic value of below acceptable cost-effectiveness thresholds. Physical distancing measures were associated with health benefits; however, their cost-effectiveness was dependent on the duration, compliance and the phase of the epidemic in which it was implemented.ConclusionsSARS-CoV-2 is associated with substantial economic costs to healthcare systems, payers, and societies, both short term and long term, while interventions including testing and screening policies, vaccination and physical distancing policies were identified as those presenting cost-effective options to deal with the pandemic, dependent on population vaccination and the Re at the stage of the pandemic.
Impact of Adverse Drug Reactions in the outcomes of Tuberculosis Treatment
Authors: Sant’Anna Flávia M. , Araújo-Pereira Mariana , Schmaltz Carolina A. S. , Arriaga María B. , Andrade Bruno B. , Rolla Valeria C. 
Published: June 2022

ABSTRACTAdverse drug reactions (ADR) challenge successful anti-tuberculosis treatment (ATT). The aim of this study was to evaluate the impact of ATT-associated ADR and related factors on treatment outcomes. A prospective cohort study of persons with tuberculosis at a referral center in Rio de Janeiro, Brazil, from 2010 to 2016. ADRs, favorable (cure and treatment completion) and unfavorable (death, loss to follow up and failure) outcomes were prospectively captured. The Kaplan-Meier curve was used to estimate probability ADR-free time. A logistic regression model was performed to identify independent associations with unfavorable outcomes. 550 patients were enrolled and 35.1% were people living with HIV (PLHIV). ADR occurred in 78.6% of participants and was associated with favorable outcomes. Smokers (OR:2.32;95%CI:1.34-3.99) and illicit drug users (OR:2.02;95%CI:1.15-3.55) exhibited higher risk of unfavorable outcome. PLHIV more frequently experienced grade 3/4-ADR, specially “liver and biliary system disorders”. Lower CD4 counts were associated with hepatotoxicity (p=0.03). Male sex, low schooling, smoking and illicit-drug use are independent risk factors for unfavorable outcomes, as well alcohol abuse and previous ART in PLHIV. ADR increases the odds of favorable outcomes, although it is more severe in PLHIV and related to a higher risk of hepatotoxicity.
U.S. CDC support to international SARS-CoV-2 seroprevalence surveys, May 2020–February 2022
Authors: Hamida Amen Ben , Charles Myrna , Murrill Christopher , Henao Olga , Gallagher Kathleen 
Published: June 2022

ABSTRACTSARS-CoV-2 seroprevalence surveys provide critical information to assess the burden of COVID-19, describe population immunity, and guide public health strategies. Early in the pandemic, most of these surveys were conducted within high-income countries, leaving significant knowledge gaps in low-and middle-income (LMI) countries. To address this gap, the U.S. Centers for Disease Control and Prevention (CDC) is supporting serosurveys internationally.We conducted a descriptive analysis of international serosurveys supported by CDC during May 12, 2020–February 28, 2022, using an internal tracker including data on the type of assistance provided, study design, population surveyed, laboratory testing performed, and status of implementation. Since the beginning of the pandemic, CDC has supported 72 serosurveys (77 serosurvey rounds) in 35 LMI countries by providing technical assistance (TA) on epidemiologic, statistical, and laboratory methods, financial assistance (FA), or both. Among these serosurvey rounds, the majority (61%) received both TA and FA from CDC, 30% received TA only, 3% received only FA, and 5% were part of informal reviews. Fifty-four percent of these serosurveys target the general population, 13% sample pregnant women, 7% sample healthcare workers, 7% sample other special populations (internally displaced persons, patients, students, and people living with HIV), and 18% assess multiple or other populations. These studies are in different stages of implementation, ranging from protocol development to dissemination of results. They are conducted under the leadership of local governments, who have ownership over the data, in collaboration with international partners. Thirty-four surveys rounds have completed data collection.CDC TA and FA of SARS-CoV-2 seroprevalence surveys will enhance the knowledge of the COVID-19 pandemic in almost three dozen LMI countries. Support for these surveys should account for current limitations with interpreting results, focusing efforts on prospective cohorts, identifying, and forecasting disease patterns over time, and helping understand antibody kinetics and correlates of protection.
Vaccine effectiveness against SARS-CoV-2 reinfection during periods of Alpha (B.1.1.7), Delta (B.1.617.2) or Omicron (B.1.1.529) dominance: A Danish nationwide study
Authors: Nielsen Katrine Finderup , Moustsen-Helms Ida Rask , Schelde Astrid Blicher , Gram Mie Agermose , Emborg Hanne-Dorthe , Nielsen Jens , Hansen Christian Holm , Andersen Michael Asger , Meaidi Marianna , Wohlfahrt Jan , Valentiner-Branth Palle 
Published: June 2022

AbstractIntroductionIndividuals with a prior severe acute respiratory corona virus 2 (SARS-CoV-2) infection have a moderate to high degree of protection against reinfection, though seemingly less so when the Omicron variant of SARS-CoV-2 started to circulate. The aim of this study was to evaluate the vaccine effectiveness (VE) against SARS-CoV-2 reinfection, that is, in individuals with prior SARS-CoV-2 infection, during periods with different dominant SARS-CoV-2 variants.MethodsA nationwide cohort study design including all individuals with a confirmed SARS-CoV-2 infection, who were alive and residing in Denmark between 1 January 2020 and 31 January 2022 were used. Using Danish nationwide registries, we obtained information on SARS-CoV-2 infections, Coronavirus Disease 2019 (COVID-19) vaccination, age, sex, comorbidity, staying at hospital and region of affiliation. The study population included were individuals with prior SARS-CoV-2 infection. Crude and adjusted estimates of VE against SARS-CoV-2 reinfection with 95% confidence intervals (CIs) were calculated using Poisson and Cox regression models, respectively. The VE estimates were calculated separately for three periods with different dominant SARS-CoV-2 variants (Alpha (B.1.1.7), Delta (B.1.617.2), or Omicron (B.1.1.529)) and by time since vaccination using unvaccinated as the reference.FindingsThe study population comprised of 209,814 individuals infected before or during the Alpha period, 292,978 before or during the Delta period and 245,530 before or during the Omicron period. Of these, 40,281 individuals had completed their primary vaccination series during the Alpha period (19.2%), 190,026 during the Delta period (64.9%) and 158,563 during the Omicron period (64.6%). VE against reinfection following any COVID-19 vaccine type administered in Denmark, peaked at 85% (95% CI: 37% to 97%) at 104 days or more after vaccination during the Alpha period, 88% (95% CI: 81% to 92%) 14-43 days after vaccination during the Delta period and 60% (95% CI: 58% to 62%) 14-43 days after vaccination during the Omicron period. Waning immunity was observed, and was most pronounced during the Omicron period.InterpretationThis study shows that, in previously infected individuals, completing a primary vaccination series was associated with a significant protection against SARS-CoV-2 reinfection compared with no vaccination for all three variant periods. Even though vaccination seems to protect to a lesser degree against reinfection with the Omicron variant, these findings are of public health relevance as they show that previously infected individuals still benefit from COVID-19 vaccination in all three variant periods.
Obesity and longevity: The retrospective longitudinal analysis of international data
Authors: Liapin G. , Vlassov V. 
Published: June 2022

AbstractObjectivesDue to the economic growth at the end of the 20th century people in low-income countries live longer, but still spend on food most of their income, and suffer from the low food quality. These countries, as well as affluent countries demonstrate rising prevalence of obesity, which is a risk factor for bad health and increased mortality. The interplay of longevity and obesity at different levels of economic development is not clear.DesignWe used World Bank, International Monetary Fund, and Global Burden of Disease project data on population size, longevity, prevalence of obesity, and income as Gross domestic product per capita adjusted to purchasing power in international dollars.ResultsAfter we stratified countries by income, we found that there is a long-term increase in life expectancy with an increase in the prevalence of obesity in countries of all income levels. There is a higher prevalence of obesity in poor countries than in the affluent countries at the equal life expectancy.ConclusionsThe economic growth in all countries lead to increase in length of life and is associated with the increase of obesity prevalence. In poor countries the access to food and the food quality is limited as well as customs of consumption are different. It leads to the higher prevalence of overweight and obesity at similar level of length of life. It may be the cause of the slower progress in life expectancy.
Midkine expression by stem-like tumor cells drives persistence to mTOR inhibition and rewires the microenvironment toward an immune-suppressive state
Authors: Tang Yan , Kwiatkowski David J. , Henske Elizabeth P. 
Published: June 2022

AbstractmTORC1 regulates cell metabolism to enable cell proliferation, and is hyperactive in multiple cancer types1, 2. Here, we performed integrative analysis of single cell transcriptomic profiling, paired T cell receptor (TCR) sequencing, and spatial transcriptomic profiling on Tuberous Sclerosis Complex (TSC) associated tumors with mTORC1 hyperactivity, and identified a stem-like tumor cell state (SLS) linked to T cell dysfunction via tumor-modulated immunosuppressive macrophages. Rapamycin and its derivatives (rapalogs) are the primary treatments for TSC tumors, and the stem-like tumor cells showed rapamycin resistance in vitro, reminiscent of the cytostatic effects of these drugs in patients. The pro-angiogenic factor midkine (MDK) was highly expressed by the SLS population, and associated with enrichment of endothelial cells in SLS-dominant samples. Inhibition of MDK showed synergistic benefit with rapamycin in reducing the growth of TSC cell lines in vitro and in vivo. In aggregate, this study suggests an autocrine rapamycin resistance mechanism and a paracrine tumor survival mechanism via immune suppression adopted by the stem-like state tumor cells with mTORC1 hyperactivity. We also provide a comprehensive resource to advance the understanding of TSC and potentially other mTORC1-hyperactive tumors.
Mapping-by-sequencing reveals genomic regions associated with seed quality parameters in Brassica napus
Authors: Schilbert Hanna Marie , Pucker Boas , Ries David , Viehöver Prisca , Micic Zeljko , Dreyer Felix , Beckmann Katrin , Wittkop Benjamin , Weisshaar Bernd , Holtgräwe Daniela 
Published: June 2022

AbstractRapeseed (Brassica napus L.) is an important oil crop and harbours the potential to serve as a highly productive source of protein. This protein exhibits an excellent amino acid composition and has a high nutritional value for humans. Seed protein content (SPC) and seed oil content (SOC) are two complex quantitative and polygenic traits which are negatively correlated and assumed to be controlled by additive and epistatic effects. A reduction of seed glucosinolate (GSL) content is desired as GSLs cause a stringent and bitter taste. The goal here was the identification of genomic intervals relevant for seed GSL content and SPC/SOC. Mapping-by-sequencing (MBS) revealed 30 and 15 new and known genomic intervals associated with seed GSL content and SPC/SOC, respectively. Within these intervals we identified known but also so far unknown putatively causal genes and sequence variants. A 4 bp insertion in the MYB28 homolog on C09 shows a significant correlation with a reduction in seed GSL content. This study provides insights into the genetic architecture and potential mechanisms underlying seed quality traits, which will enhance future breeding approaches in B. napus.
Evolutionary unpredictability in cancer model system
Authors: Chattopadhyay Subhayan , Karlsson Jenny , Mañas Adriana , Kanzaki Ryu , Fredlund Elina , Murphy Andrew J. , Morton Christopher L. , Andersson Natalie , Woolard Mary A. , Hansson Karin , Radke Katarzyna , Davidhoff Andrew M. , Mohlin Sofie , Pietras Kristian , Bexell Daniel , Gisselsson David 
Published: June 2022

AbstractDespite the advent of personalized medicine, it is still difficult to predict how a cancer develops over time at the level of the individual patient or even in cancer model systems which begs the question whether certain aspects of cancer can ever be predicted or if there is an inherent unpredictability in cancer, similar to other complex biological systems, We demonstrate by a combination of agent-based mathematical modelling and analysis of data from patient-derived xenograft systems from multiple cancer types that certain conditions may invoke chaotic fluctuations in the clonal landscape of cancer cells. Our findings indicate that under those conditions, the cancer genome behaves as a complex dynamic system, making its long-term evolution inherently unpredictable.
Genome-wide analyses of vocabulary size in infancy and toddlerhood: associations with Attention-Deficit/Hyperactivity Disorder and cognition-related traits
Authors: Verhoef Ellen , Allegrini Andrea G. , Jansen Philip R. , Lange Katherine , Wang Carol A. , Morgan Angela T. , Ahluwalia Tarunveer S. , Symeonides Christos ,   EAGLE working group, Eising Else , Franken Marie-Christine , Hypponen Elina , Mansell Toby , Olislagers Mitchell , Omerovic Emina , Rimfeld Kaili , Schlag Fenja , Selzam Saskia , Shapland Chin Yang , Tiemeier Henning , Whitehouse Andrew J.O. , Saffery Richard , Bønnelykke Klaus , Reilly Sheena , Pennell Craig E. , Wake Melissa , Cecil Charlotte A.M. , Plomin Robert , Fisher Simon E. , St Pourcain Beate 
Published: June 2022

AbstractBackgroundThe number of words children produce (expressive vocabulary) and understand (receptive vocabulary) changes rapidly during early development, partially due to genetic factors, although mechanisms are not well understood. Here, we performed a meta-genome-wide association study within the EAGLE consortium and investigated polygenic overlap with later-life traits, including Attention-Deficit/Hyperactivity Disorder (ADHD) and cognition.MethodsWe studied 37,913 parent-reported vocabulary size measures (English, Dutch, Danish) for 17,298 children of European descent. Meta-analyses were performed for early-phase expressive (infancy, 15-18 months), late-phase expressive (toddlerhood, 24-38 months) and late-phase receptive (toddlerhood, 24-38 months) vocabulary. Subsequently, we estimated Single-Nucleotide Polymorphism heritability (SNP-h2), genetic correlations (rg) and modelled underlying genetic factor structures with multivariate models.ResultsContributions of common genetic variation to early-life vocabulary were modest (SNP-h2: 0.08(SE=0.01) to 0.24(SE=0.03)) and multi-factorial. Genetic overlap between infant expressive and toddler receptive vocabulary was near zero (rg=0.07(SE=0.10)), although both measures were genetically related to toddler expressive vocabulary (rg=0.69(SE=0.14) and rg=0.67(SE=0.16), respectively). Consistently, polygenic association patterns with later-life traits differed: Genetic links with cognition emerged only in toddlerhood (e.g. toddler receptive vocabulary and intelligence: rg=0.36(SE=0.12)), despite comparable study power for infant measures. Furthermore, increased polygenic ADHD risk was associated with larger infant expressive vocabulary (rg=0.23(SE=0.08)), as confirmed by ADHD-symptom-based follow-up analyses in the Avon Longitudinal Study of Parents and Children (ALSPAC-rg=0.54(SE=0.26)). Genetic relationships with toddler receptive vocabulary were, however, opposite (ALSPAC-rg=-0.74(SE=0.23)), highlighting developmental changes in genetic architectures.ConclusionsMultiple genetic components contribute to early-life vocabulary development, shaping polygenic association patterns with later-life ADHD symptoms and cognition.