bluuebunny/crossref_metadata_2025_split huggingface dataset:
Burden and predictors of statin use in primary and secondary prevention of atherosclerotic vascular disease in the US: from the National Health and Nutrition Examination Survey 2017–2020
Authors: Chobufo Muchi Ditah , Regner Sean R , Zeb Irfan , Lacoste Jordan L , Virani Salim S , Balla Sudarshan 
Published: June 2022

Abstract

Aims
To assess the current state of statin use, factors associated with non-use, and estimate the burden of potentially preventable atherosclerotic cardiovascular diseases (ASCVD) events.

Methods and results
Using nationally representative data from the 2017 to 2020 National Health and Nutrition Examination Survey, statin use was assessed in primary prevention groups: high ASCVD risk ≥ 20%, LDL-cholesterol (LDL-C) ≥ 190 mg/dL, diabetes aged 40–75 years, intermediate ASCVD risk (7.5 to &lt;20%) with ≥1 ASCVD risk enhancer and secondary prevention group: established ASCVD. Atherosclerotic cardiovascular disease risk was estimated using pooled cohort equations. We estimated 70 million eligible individuals (2.3 million with LDL-C ≥ 190 mg/dL; 9.4 million with ASCVD ≥ 20%; 15 million with diabetes and age 40–75years; 20 million with intermediate ASCVD risk and ≥1 risk enhancers; and 24.6 million with established ASCVD), about 30 million were on statin therapy. The proportion of individuals not on statin therapy was highest in the isolated LDL-C ≥ 190 mg/dL group (92.8%) and those with intermediate ASCVD risk plus enhancers (74.6%) followed by 59.4% with high ASCVD risk, 54.8% with diabetes, and 41.5% of those with established ASCVD groups. Increasing age and those with health insurance were more likely to be on statin therapy in both the primary and secondary prevention categories. Individuals without a routine place of care were less likely to be on statin therapy. A total of 385 000 (high-intensity statin) and 647 000 (moderate-intensity statin) ASCVD events could be prevented if all statin-eligible individuals were treated (and adherent) for primary prevention over a 10-year period.

Conclusion
Statin use for primary and secondary prevention of ASCVD remains suboptimal. Bridging the therapeutic gap can prevent ∼1 million ASCVD events over the subsequent 10 years for the primary prevention group. Social determinants of health such as access to care and healthcare coverage were associated with less statin treatment. Novel interventions to improve statin prescription and adherence are needed.
Association between REDUCE-IT criteria, coronary artery disease severity, and cardiovascular events: the Western Denmark Heart Registry
Authors: Mortensen Martin Bødtker , Dzaye Omar , Razavi Alexander C , Jensen Jesper Møller , Steffensen Flemming Hald , Bøtker Hans Erik , Cainzos-Achirica Miguel , Sørensen Henrik Toft , Maeng Michael , Blaha Michael J , Nasir Khurram , Nørgaard Bjarne Linde 
Published: June 2022

Abstract

Aims
The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) trial demonstrated that icosapent ethyl lowered the risk of atherosclerotic cardiovascular disease (ASCVD) among patients with elevated triglycerides. However, how to appropriately implement its use in clinical practice is not well-defined. We aimed to determine whether plaque burden as assessed by coronary artery calcium (CAC) could stratify ASCVD risk among patients eligible for icosapent ethyl.

Methods and results
Among 23 759 patients who underwent computed tomography angiography (CTA) in the Western Denmark Heart Registry, we identified eligibility for the REDUCE-IT trial. A total of 2146 participants (9%) met enrolment criteria for REDUCE-IT. During a median of 4.3 years of follow-up, 146 ASCVD events occurred. Overall, there was a stepwise increase in ASCVD event rates per 1000 person-years with increasing CAC (CAC = 0: 10.5, CAC 1-299: 18.7, CAC ≥300: 49.8). REDUCE-IT-eligible patients with CAC ≥300 had a multivariable-adjusted hazard ratio of 3.1 compared with CAC = 0 (95% confidence interval: 1.9–4.9). Coronary artery calcium differentiated risk similarly in patients with and without obstructive coronary artery disease (CAD). Overall, the 5-year estimated number needed to treat to prevent one event with icosapent ethyl was 45 and ranged from 87 in those with CAC = 0 to 17 in those with CAC ≥300. Some patients with non-obstructive CAD had lower estimated number needed to treat than patients with obstructive CAD when their plaque burden was higher.

Conclusion
Atherosclerotic plaque burden as assessed by CAC can identify REDUCE-IT-eligible patients who are expected to derive most, and least, absolute benefit from treatment with icosapent ethyl regardless of obstructive versus non-obstructive CAD status.
Genetic regulation of central synapse formation and organization in Drosophila melanogaster
Authors: Duhart Juan Carlos , Mosca Timothy J 
Published: June 2022

Abstract
A goal of modern neuroscience involves understanding how connections in the brain form and function. Such a knowledge is essential to inform how defects in the exquisite complexity of nervous system growth influence neurological disease. Studies of the nervous system in the fruit fly Drosophila melanogaster enabled the discovery of a wealth of molecular and genetic mechanisms underlying development of synapses—the specialized cell-to-cell connections that comprise the essential substrate for information flow and processing in the nervous system. For years, the major driver of knowledge was the neuromuscular junction due to its ease of examination. Analogous studies in the central nervous system lagged due to a lack of genetic accessibility of specific neuron classes, synaptic labels compatible with cell-type-specific access, and high resolution, quantitative imaging strategies. However, understanding how central synapses form remains a prerequisite to understanding brain development. In the last decade, a host of new tools and techniques extended genetic studies of synapse organization into central circuits to enhance our understanding of synapse formation, organization, and maturation. In this review, we consider the current state-of-the-field. We first discuss the tools, technologies, and strategies developed to visualize and quantify synapses in vivo in genetically identifiable neurons of the Drosophila central nervous system. Second, we explore how these tools enabled a clearer understanding of synaptic development and organization in the fly brain and the underlying molecular mechanisms of synapse formation. These studies establish the fly as a powerful in vivo genetic model that offers novel insights into neural development.
Coordinated transcriptional regulation of the carotenoid biosynthesis contributes to fruit lycopene content in high-lycopene tomato genotypes
Authors: Duduit James R , Kosentka Pawel Z , Miller Morgan A , Blanco-Ulate Barbara , Lenucci Marcello S , Panthee Dilip R , Perkins-Veazie Penelope , Liu Wusheng 
Published: June 2022

Abstract
Lycopene content in tomato fruit is largely under genetic control and varies greatly among genotypes. Continued improvement of lycopene content in elite varieties with conventional breeding has become challenging, in part because little is known about the underlying molecular mechanisms in high-lycopene tomatoes (HLYs). We collected 42 HLYs with different genetic backgrounds worldwide. High-performance liquid chromatography (HPLC) analysis revealed lycopene contents differed among the positive control wild tomato Solanum pimpinellifolium, HLYs, the normal lycopene cultivar “Moneymaker”, and the non-lycopene cultivar NC 1Y at the pink and red ripe stages. Real-time RT-PCR analysis of expression of the 25 carotenoid biosynthesis pathway genes of each genotype showed a significantly higher expression in nine upstream genes (GGPPS1, GGPPS2, GGPPS3, TPT1, SSU II, PSY2, ZDS, CrtISO and CrtISO-L1 but not the well-studied PSY1, PDS and Z-ISO) at the breaker and/or red ripe stages in HLYs compared to Moneymaker, indicating a higher metabolic flux flow into carotenoid biosynthesis pathway in HLYs. Further conversion of lycopene to carotenes may be prevented via the two downstream genes (β-LCY2 and ε-LCY), which had low-abundance transcripts at either or both stages. Additionally, the significantly higher expression of four downstream genes (BCH1, ZEP, VDE, and CYP97C11) at either or both ripeness stages leads to significantly lower fruit lycopene content in HLYs than in the wild tomato. This is the first systematic investigation of the role of the complete pathway genes in regulating fruit lycopene biosynthesis across many HLYs, and enables tomato breeding and gene editing for increased fruit lycopene content.
Macrophage circadian rhythms are differentially affected based on stimuli
Authors: Lellupitiyage Don Sujeewa S , Mas-Rosario Javier A , Lin Hui-Hsien , Nguyen Evelyn M , Taylor Stephanie R , Farkas Michelle E 
Published: June 2022

Abstract
Macrophages are white blood cells that play disparate roles in homeostasis and immune responses. They can reprogram their phenotypes to pro-inflammatory (M1) or anti-inflammatory (M2) states in response to their environment. About 8–15% of the macrophage transcriptome has circadian oscillations, including genes closely related to their functioning. As circadian rhythms are associated with cellular phenotypes, we hypothesized that polarization of macrophages to opposing subtypes might differently affect their circadian rhythms. We tracked circadian rhythms in RAW 264.7 macrophages using luminescent reporters. Cells were stably transfected with Bmal1:luc and Per2:luc reporters, representing positive and negative components of the molecular clock. Strength of rhythmicity, periods and amplitudes of time series were assessed using multiple approaches. M1 polarization decreased amplitudes and rhythmicities of Bmal1:luc and Per2:luc, but did not significantly affect periods, while M2 polarization increased periods but caused no substantial alterations to amplitudes or rhythmicity. As macrophage phenotypes are also altered in the presence of cancer cells, we tested circadian effects of conditioned media from mouse breast cancer cells. Media from highly aggressive 4T1 cells caused loss of rhythmicity, while media from less aggressive EMT6 cells yielded no changes. As macrophages play roles in tumors, and oncogenic features are associated with circadian rhythms, we tested whether conditioned media from macrophages could alter circadian rhythms of cancer cells. Conditioned media from RAW 264.7 cells resulted in lower rhythmicities and periods, but higher amplitudes in human osteosarcoma, U2OS-Per2:luc cells. We show that phenotypic changes in macrophages result in altered circadian characteristics and suggest that there is an association between circadian rhythms and macrophage polarization state. Additionally, our data demonstrate that macrophages treated with breast cancer-conditioned media have circadian phenotypes similar to those of the M1 subtype, and cancer cells treated with macrophage-conditioned media have circadian alterations, providing insight to another level of cross-talk between macrophages and cancer.
Climate Change in the UN Security Council: An Analysis of Discourses and Organizational Trends
Authors: Scartozzi Cesare M 
Published: June 2022

AbstractThe UN Security Council has published about eighty-three thousand documents between 2001 and 2021. This study analyzes this large corpus of text to identify, map, and trace the evolution of discourses on climate change and their impact on the organization. The article analyzes diplomatic speeches and other primary sources to identify instances of climatization of security and securitization, riskification, and mainstreaming of climate change. To fulfill its aim, the article introduces a mixed method that combines an automated content analysis with a discourse analytic approach. The findings suggest that, despite the stall in high-level discussions on climate security, the Security Council is de facto moving toward a climatization of security and riskification of climate change in daily practices, procedures, and operations.
Who Securitizes? Climate Change Discourse in the United Nations
Authors: Arias Sabrina B 
Published: June 2022

AbstractWhen and why do states reframe issues as security problems? Which states advocate for these shifts? While securitization theory predicts that states that are existentially threatened by a problem are most likely to attempt to securitize it, I argue that accounting for the dynamics of institutional agendas can better explain this phenomenon. States that stand to gain agenda control as a result of securitization are likely to rhetorically attempt to securitize, while those that are materially interested in the issue are less likely to do so. I test this theory in the case of the climate change in the United Nations, leveraging data on speeches in the General Assembly. I provide the first quantitative test of the securitization of climate politics, finding that P5 states securitize to expand their agenda control, while Small Island Developing States do not securitize, contra previous expectations. I further find that the overall climate discourse cannot be characterized as securitized. These findings imply that the Security Council is unlikely to be significantly involved in climate change policy and also demonstrate the importance of rhetoric for political outcomes and for the distribution of state power within international organizations.
Automated citation recommendation tools encourage questionable citations
Authors: Horbach Serge P J M , Oude Maatman Freek J W , Halffman Willem , Hepkema Wytske M 
Published: June 2022

Abstract
Citing practices have long been at the heart of scientific reporting, playing both socially and epistemically important functions in science. While such practices have been relatively stable over time, recent attempts to develop automated citation recommendation tools have the potential to drastically impact citing practices. We claim that, even though such tools may come with tempting advantages, their development and implementation should be conducted with caution. Describing the role of citations in science’s current publishing and social reward structures, we argue that automated citation tools encourage questionable citing practices. More specifically, we describe how such tools may lead to an increase in: perfunctory citation and sloppy argumentation; affirmation biases; and Matthew effects. In addition, a lack of transparency of the tools’ underlying algorithmic structure renders their usage problematic. Hence, we urge that the consequences of citation recommendation tools should at least be understood and assessed before any attempts to implementation or broad distribution are undertaken.
Menopausal Hormone Therapy Formulation and Breast Cancer Risk
Authors: Abenhaim Haim A. , Suissa Samy , Azoulay Laurent , Spence Andrea R. , Czuzoj-Shulman Nicholas , Tulandi Togas 
Published: June 2022

OBJECTIVE:
To evaluate whether the increased risk of breast cancer is dependent on the formulation of menopausal hormone therapy (HT) used.

METHODS:
We performed a population-based case–control study of women aged 50 years or older using data from the U.K. Clinical Practice Research Datalink. Women with incident cases of breast cancer were age-matched (1:10) with a control group of women with comparable follow-up time with no history of breast cancer. Exposures were classified as ever or never for the following menopausal HT formulations: bioidentical estrogens, animal-derived estrogens, micronized progesterone, and synthetic progestin. Logistic regression analyses were performed to estimate the adjusted effect of menopausal HT formulation on breast cancer risk.

RESULTS:
Between 1995 and 2014, 43,183 cases of breast cancer were identified and matched to 431,830 women in a control group. In adjusted analyses, compared with women who never used menopausal HT, its use was associated with an increased risk of breast cancer (odds ratio [OR] 1.12, 95% CI 1.09–1.15). Compared with never users, estrogens were not associated with breast cancer (bioidentical estrogens: OR 1.04, 95% CI 1.00–1.09; animal-derived estrogens: OR 1.01, 95% CI 0.96–1.06; both: OR 0.96, 95% CI 0.89–1.03). Progestogens appeared to be differentially associated with breast cancer (micronized progesterone: OR 0.99, 95% CI 0.55–1.79; synthetic progestin: OR 1.28, 95% CI 1.22–1.35; both OR 1.31, 0.30–5.73).

CONCLUSION:
Although menopausal HT use appears to be associated with an overall increased risk of breast cancer, this risk appears predominantly mediated through formulations containing synthetic progestins. When prescribing menopausal HT, micronized progesterone may be the safer progestogen to be used.
Association Between Social Vulnerability and Achieving Glycemic Control Among Pregnant Individuals With Pregestational Diabetes
Authors: Venkatesh Kartik K. , Germann Katherine , Joseph Joshua , Kiefer Miranda , Buschur Elizabeth , Thung Stephen , Costantine Maged M. , Gabbe Steven , Grobman William A. , Fareed Naleef 
Published: June 2022

OBJECTIVE:
To evaluate the association between community-level social vulnerability and achieving glycemic control (defined as hemoglobin A1c [Hb A1c] less than 6.0% or less than 6.5%) among individuals with pregestational diabetes.

METHODS:
We conducted a retrospective cohort of individuals with pregestational diabetes with singleton gestations from 2012 to 2016 at a tertiary care center. Addresses were geocoded using ArcGIS and then linked at the census tract to the Centers for Disease Control and Prevention's 2018 SVI (Social Vulnerability Index), which incorporates 15 Census variables to produce a composite score and four scores across thematic domains (socioeconomic status, household composition and disability, minority status and language, and housing type and transportation). Scores range from 0 to 1, with higher values indicating greater community-level social vulnerability. The primary outcome was Hb A1c less than 6.0%, and, secondarily, Hb A1c less than 6.5%, in the second or third trimesters. Multivariable Poisson regression with robust error variance was used to evaluate the association between SVI score as a continuous measure and target Hb A1c.

RESULTS:
Among 418 assessed pregnant individuals (33.0% type 1; 67.0% type 2 diabetes), 41.4% (173/418) achieved Hb A1c less than 6.0%, and 56.7% (237/418) Hb A1c less than 6.5% at a mean gestational age of 29.5 weeks (SD 5.78). Pregnant individuals with a higher SVI score were less likely to achieve Hb A1c less than 6.0% compared with those with a lower SVI score. For each 0.1-unit increase in SVI score, the risk of achieving Hb A1c less than 6.0% decreased by nearly 50% (adjusted risk ratio [aRR] 0.53; 95% CI 0.36–0.77), and by more than 30% for Hb A1c less than 6.5% (adjusted odds ratio 0.67; 95% CI 0.51–0.88). With regard to specific SVI domains, those who scored higher on socioeconomic status (aRR 0.50; 95% CI 0.35–0.71) as well as on household composition and disability (aRR 0.55; 95% CI 0.38–0.79) were less likely to achieve Hb A1c less than 6.0%.

CONCLUSION:
Pregnant individuals with pregestational diabetes living in an area with higher social vulnerability were less likely to achieve glycemic control, as measured by HgbA1c levels. Interventions are needed to assess whether addressing social determinants of health can improve glycemic control in pregnancy.
Timing of Delivery for Twins With Growth Discordance and Growth Restriction
Authors: Koch Ashlee K. , Burger Renée J. , Schuit Ewoud , Mateus Julio Fernando , Goya Maria , Carreras Elena , Biancolin Sckarlet E. , Barzilay Eran , Soliman Nancy , Cooper Stephanie , Metcalfe Amy , Lodha Abhay , Fichera Anna , Stagnati Valentina , Kawamura Hiroshi , Rustico Maria , Lanna Mariano , Munim Shama , Russo Francesca Maria , Nassar Anwar , Rode Line , Lim Arianne , Liem Sophie , Grantz Katherine L. , Hack Karien , Combs C. Andrew , Serra Vicente , Perales Alfredo , Khalil Asma , Liu Becky , Barrett Jon , Ganzevoort Wessel , Gordijn Sanne J. , Morris R. Katie , Mol Ben W. , Li Wentao 
Published: June 2022

OBJECTIVE:First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies.DATA SOURCES:A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded.METHODS OF STUDY SELECTION:Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs.TABULATION, INTEGRATION, AND RESULTS:We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7–6/7 and 37 0/7–6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7–6/7 weeks onward.CONCLUSION:Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone.SYSTEMATIC REVIEW REGISTRATION:PROSPERO, CRD42018090866.