bluuebunny/crossref_metadata_2025_split huggingface dataset:
Obesity and effects of dapagliflozin on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus in the DECLARE–TIMI 58 trial
Authors: Oyama Kazuma , Raz Itamar , Cahn Avivit , Kuder Julia , Murphy Sabina A , Bhatt Deepak L , Leiter Lawrence A , McGuire Darren K , Wilding John P H , Park Kyong Soo , Goudev Assen , Diaz Rafael , Špinar Jindřich , Gause-Nilsson Ingrid A M , Mosenzon Ofri , Sabatine Marc S , Wiviott Stephen D 
Published: August 2021

Abstract

Aims
We investigated the associations between obesity, cardiorenal events, and benefits of dapagliflozin in patients with type 2 diabetes mellitus (T2DM).

Methods and results
DECLARE–TIMI 58 randomized patients with T2DM and either atherosclerotic cardiovascular (CV) disease or multiple risk factors to dapagliflozin vs. placebo. Patients were stratified by body mass index (BMI, kg/m2): normal (18.5 to &lt;25), overweight (25 to &lt;30), moderately obese (30 to &lt;35), severely obese (35 to &lt;40), and very-severely obese (≥40). Outcomes analysed were CV death, hospitalization for heart failure (HHF), renal-specific composite outcome, and atrial fibrillation or flutter (AF/AFL). Of 17 134 patients, 9.0% had a normal BMI, 31.5% were overweight, 32.4% were moderately, 17.2% severely, and 9.8% were very-severely obese. Higher BMI was associated with a higher adjusted risk of HHF and AF/AFL (hazard ratio 1.30 and 1.28, respectively, per 5 kg/m2; P &lt; 0.001 for all). Dapagliflozin reduced body weight by similar relative amounts consistently across BMI categories (percent difference: −1.9 to −2.4%). Although relative risk reductions in CV and renal-specific composite outcomes with dapagliflozin did not significantly differ across the range of BMI (P for interaction ≥0.20 for all outcomes), obese patients (BMI ≥ 30 kg/m2) tended to derive greater absolute risk reduction in HHF and AF/AFL (P for interaction 0.02 and 0.09, respectively) than non-obese patients.

Conclusions
In DECLARE–TIMI 58, patients with T2DM and higher BMI were more likely to have HHF and AF/AFL. Whereas relative risk reductions in CV and renal outcomes with dapagliflozin were generally consistent across the range of BMI, absolute risk reduction in obesity-related outcomes including HHF and AF/AFL tended to be larger in obese patients with T2DM.

Clinical trial registration
URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01730534.
Larval excretion/secretion of dipters of Lucilia cuprina species induces death in promastigote and amastigote forms of Leishmania amazonensis
Authors: Rodrigues Ana Carolina Jacob , Bortoleti Bruna Taciane da Silva , Carloto Amanda Cristina Machado , Silva Taylon Felipe , Concato Virgínia Márcia , Gonçalves Manoela Daiele , Tomiotto-Pelissier Fernanda , Detoni Mariana Barbosa , Diaz-Roa Andrea , Júnior Pedro Ismael da Silva , Costa Idessania Nazareth , Conchon-Costa Ivete , Bidoia Danielle Lazarin , Miranda-Sapla Milena Menegazzo , Pavanelli Wander Rogério 
Published: August 2021

ABSTRACT
Leishmaniasis is a neglected tropical disease that affects millions of people around the world. Larval excretion/secretion (ES) of the larvae of flies of the Calliphoridae family has microbicidal activity against Gram-positive and Gram-negative bacteria, in addition to some species of Leishmania. Our study aimed at assessing the in vitro efficacy of Lucilia cuprina larval ES against the promastigote and amastigote forms of Leishmania amazonensis, elucidating possible microbicidal mechanisms and routes of death involved. Larval ES was able to inhibit the viability of L. amazonensis at all concentrations, induce morphological and ultrastructural changes in the parasite, retraction of the cell body, roughness of the cytoplasmic membrane, leakage of intracellular content, ROS production increase, induction of membrane depolarization and mitochondrial swelling, the formation of cytoplasmic lipid droplets and phosphatidylserine exposure, thus indicating the possibility of apoptosis-like death. To verify the efficacy of larval ES on amastigote forms, we performed a phagocytic assay, measurement of total ROS and NO. Treatment using larval ES reduced the percentage of infection and the number of amastigotes per macrophage of lineage J774A.1 at all concentrations, increasing the production of ROS and TNF-α, thus indicating possible pro-inflammatory immunomodulation and oxidative damage. Therefore, treatment using larval ES is effective at inducing the death of promastigotes and amastigotes of L. amazonensis even at low concentrations.
Ancestral Physical Stress and Later Immune Gene Family Expansions Shaped Bivalve Mollusc Evolution
Authors: Regan Tim , Stevens Lewis , Peñaloza Carolina , Houston Ross D , Robledo Diego , Bean Tim P 
Published: August 2021

Abstract
Bivalve molluscs comprise 20,000 species occupying a wide diversity of marine habitats. As filter feeders and detritivores they act as ecosystem engineers clarifying water, creating reefs, and protecting coastlines. The global decline of natural oyster reefs has led to increased restoration efforts in recent years. Bivalves also play an important role in global food security contributing to &gt;20% of worldwide aquaculture production. Despite this importance, relatively little is known about bivalve evolutionary adaptation strategies. Difficulties previously associated with highly heterozygous and repetitive regions of bivalve genomes have been overcome by long-read sequencing, enabling the generation of accurate bivalve assemblies. With these resources we have analyzed the genomes of 32 species representing each molluscan class, including 15 bivalve species, to identify gene families that have undergone expansion during bivalve evolution. Gene family expansions across bivalve genomes occur at the point of evolutionary pressures. We uncovered two key factors that shape bivalve evolutionary history: expansion of bivalvia into environmental niches with high stress followed by later exposure to specific pathogenic pressures. The conserved expansion of protein recycling gene families we found across bivalvia is mirrored by adaptations to a sedentary lifestyle seen in plants. These results reflect the ability of bivalves to tolerate high levels of environmental stress and constant exposure to pathogens as filter feeders. The increasing availability of accurate genome assemblies will provide greater resolution to these analyses allowing further points of evolutionary pressure to become clear in other understudied taxa and potentially different populations of a single species.
Validation of a Deficit-Accumulation Frailty Index in the ASPirin in Reducing Events in the Elderly Study and Its Predictive Capacity for Disability-Free Survival
Authors: Ryan Joanne , Espinoza Sara , Ernst Michael E , Ekram A R M Saifuddin , Wolfe Rory , Murray Anne M , Shah Raj C , Orchard Suzanne G , Fitzgerald Sharyn , Beilin Lawrence J , Ward Stephanie A , Williamson Jeff D , Newman Anne B , McNeil John J , Woods Robyn L 
Published: August 2021

Abstract
Frailty is a state of heightened vulnerability and susceptibility to physiologic stressors that increases with age. It has shown increasing utility in predicting a range of adverse health outcomes. Here, we characterize a 67-item deficit-accumulation frailty index (FI) in 19 110 community-dwelling individuals in the ASPirin in Reducing Events in the Elderly clinical trial. Participants aged 65–98 years were recruited from the United States and Australia and were without diagnosed dementia and cardiovascular disease, and major physical disability. The median FI score was .10 (interquartile range: .07–.14) at baseline, and the prevalence of frailty (FI &gt; .21) increased from 8.1% to 17.4% after 6 years. FI was positively associated with age, and women had significantly higher scores than men at all ages. The FI was negatively correlated with gait speed (r = −.31) and grip strength (r = −.46), and strongly associated with a modified Fried’s frailty phenotype (p &lt; .0001, for all comparisons). Frailty was associated with the primary composite outcome capturing independent life lived free of major disability and dementia, and increased the rate of persistent physical disability (hazard ratio: 21.3, 95% confidence interval: 15.6–28.9). It added significantly to the predictive capacity of these outcomes above age, sex, and ethnicity alone. The FI is thus a useful biomarker of aging even among relatively healthy older individuals and provides important information about an individual’s vulnerability to and risk of disease.
Remembrance and Erasure in the Post-Holocaust United States
Authors: Topp Michael 
Published: July 2021

Abstract
Lee Topp, the author’s father, abandoned his faith just after World War II and hid his Jewishness from his children. Lee’s mother’s first cousin Philip Friedman became one of the United States’s first Holocaust scholars after evading the Nazis during the war. This essay juxtaposes Friedman’s ardent efforts to document the Jewish catastrophe with Topp’s attempts to erase his Jewishness. The author explains how his own life and academic career were shaped by his father’s decisions, and thus as well by the long reach of the Holocaust.
CONSENSUS: a Shiny application of dementia evaluation and reporting for the KU ADC longitudinal Clinical Cohort database
Authors: Sharma Palash , Montgomery Robert N , Graves Rasinio S , Meyer Kayla , Hunt Suzanne L , Vidoni Eric D , Mahnken Jonathan D , Swerdlow Russell H , Burns Jeffrey M , Mudaranthakam Dinesh Pal 
Published: August 2021

Abstract

Background
The University of Kansas Alzheimer’s Disease Center (KU ADC) maintains several large databases to track participant recruitment, enrollment, and capture various research-related activities. It is challenging to manage and coordinate all the research-related activities. One of the crucial activities involves generating a consensus diagnosis and communicating with participants and their primary care providers.

Process
To effectively manage the cohort, the KU ADC utilizes a combination of open-source electronic data capture (EDC) (i.e. REDCap), along with other homegrown data management and analytic systems developed using R-studio and Shiny.

Process evaluation
In this article, we describe the method and utility of the user-friendly dashboard that was developed for the rapid reporting of dementia evaluations which allows clinical researchers to summarize recruitment metrics, automatically generate letters to both participants and healthcare providers, which ultimately help optimize workflows.

Conclusions
We believe this general framework would be beneficial to any institution that build reports and summarizing key metrics of their research from longitudinal databases.
Characterization of β-adrenergic receptors in bovine intramuscular and subcutaneous adipose tissue: comparison of lubabegron fumarate with β-adrenergic receptor agonists and antagonists
Authors: Hwang Jinhee H , Spurlock Michael E , Kube John C , Li Xiang Z , Smith Stephen B 
Published: August 2021

Abstract
Chinese hamster ovary cell constructs expressing either the β 1-, β 2- or β 3-adrenergic receptor (AR) were used to determine whether a novel β-AR modulator, lubabegron fumarate (LUB; Experior, Elanco Animal Health) might exert greater potency for a specific β-AR subtype. EC50 values calculated based on cAMP accumulation in dose response curves indicate that LUB is highly selective for the β 3-AR subtype, with an EC50 of 6 × 10–9 M, with no detectible agonistic activity at the β 2-AR. We hypothesized that the accumulation of lipolytic markers would reflect the agonist activity at each of the β-receptor subtypes of the specific ligand; additionally, there would be differences in receptor subtype expression in subcutaneous (s.c.) and intrmuscular (i.m.) adipose tissues. Total RNA was extracted from adipose tissue samples and relative mRNA levels for β 1-, β2-, and β 3-AR were measured using real-time quantitative polymerase chain reaction. Fresh s.c. and i.m. adipose tissue explants were incubated with isoproterenol hydrochloride (ISO; β-AR pan-agonist), dobutamine hydrochloride (DOB; specific β 1-AA), salbutamol sulfate (SAL; specific β 2-AA), ractopamine hydrochloride (RAC), zilpaterol hydrochloride (ZIL), BRL-37344 (specific β 3-agonist), or LUB for 30 min following preincubation with theophylline (inhibitor of phosphodiesterase). Relative mRNA amounts for β 1-, β 2-, and β 3-AR were greater (P &lt; 0.05) in s.c. than in i.m. adipose tissue. The most abundant β-AR mRNA in both adipose tissues was the β 2-AR (P &lt; 0.05), with the β 1- and β 3-AR subtypes being minimally expressed in i.m. adipose tissue. ISO, RH, and ZH stimulated the release of glycerol and nonesterified fatty acid (NEFA) from s.c. adipose tissue, but these β-AR ligands did not alter concentrations of these lipolytic markers in i.m. adipose tissue. LUB did not affect glycerol or NEFA concentrations in s.c. or i.m. adipose tissue, but attenuated (P &lt; 0.05) the accumulation of cAMP mediated by the β 1- and β 2-AR ligands DOB and SAL in s.c. adipose tissue. Collectively, these data indicate that bovine i.m. adipose tissue is less responsive than s.c. adipose tissue to β-adrenergic ligands, especially those that are agonists at the β 1- and β3-receptor subtypes. The minimal mRNA expression of the β 1- and β 3 subtypes in i.m. adipose tissue likely limits the response potential to agonists for these β-AR subtypes.
Detection of ADB-BUTINACA Metabolites in Human Urine, Blood, Kidney and Liver
Authors: Kavanagh Pierce , Pechnikov Alexandr , Nikolaev Ivan , Dowling Geraldine , Kolosova Mariia , Grigoryev Andrej 
Published: August 2021

Abstract
The N-butyl indazole derivative, N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-butyl-1H-indazole-3-carboxamide (ADB-BUTINACA or ADB-BINACA), currently a drug of abuse in Russia, is reported to have a cannabinoid receptor potency and efficacy almost three times higher than JWH-018. ADB-BUTINACA was detected in blood from patients with suspected drug intoxications, as well as in blood, kidney and liver samples collected during postmortem investigations. Using liquid chromatography–time-of-flight–mass spectrometry, a number of ADB-BUTINACA metabolites were tentatively identified in urine samples. These include products of mono- and dihydroxylation, hydroxylation of the N-butyl side chain and dehydrogenation, formation of a dihydrodiol, hydrolysis of the terminal amide group, N-dealkylation of the indazole and a combination of these reactions. The dihydrodiol was found to be the predominant metabolite, with its chromatographic peak area exceeding those of other metabolites by almost an order of magnitude. For the routine analysis of blood, liver and kidney samples, the dihydrodiol and monohydroxylated metabolites along with the parent compound are recommended as target analytes. The same metabolites in free and glucuronidated forms are also recommended for analytical confirmation in urine samples.
Global patterns of species richness of the holarctic alpine herbSaxifraga: the role of temperature and habitat heterogeneity
Authors: Liu Lian , Xu Xiaoting , Zhang Lei , Li Yaoqi , Shrestha Nawal , Neves Danilo M , Wang Qinggang , Chang Hong , Su Xiangyan , Liu Yunpeng , Wu Jianyong , Dimitrov Dimitar , Wang Zhiheng , Liu Jianquan 
Published: August 2021

AbstractThe effects of contemporary climate, habitat heterogeneity and long-term climate change on species richness are well studied for woody plants in forest ecosystems, but poorly understood for herbaceous plants, especially in alpine–arctic ecosystems. Here, we aim to test if the previously proposed hypothesis based on the richness–environment relationship could explain the variation in richness patterns of the typical alpine–arctic herbaceous genus Saxifraga.Using a newly compiled distribution database of 437 Saxifraga species, we estimated the species richness patterns for all species, narrow- and wide-ranged species. We used generalized linear models and simultaneous autoregressive models to evaluate the effects of contemporary climate, habitat heterogeneity and historical climate on species richness patterns. Partial regressions were used to determine the independent and shared effects of different variables. Four widely used models were tested to identify their predictive power in explaining patterns of species richness.We found that temperature was negatively correlated with the richness patterns of all and wide-ranged species, and that was the most important environmental factor, indicating a strong conservatism of its ancestral temperate niche. Habitat heterogeneity and long-term climate change were the best predictors of the spatial variation of narrow-ranged species richness. Overall, the combined model containing five predictors can explain ca. 40%–50% of the variation in species richness. We further argued that additional evolutionary and biogeographical processes might have also played an essential role in shaping the Saxifraga diversity patterns and should be considered in future studies.
A Risk Prediction Model to Identify Newborns at Risk for Missing Early Childhood Vaccinations
Authors: Oster Natalia V , Williams Emily C , Unger Joseph M , Newcomb Polly A , deHart M Patricia , Englund Janet A , Hofstetter Annika M 
Published: August 2021

Abstract

Background
Approximately 30% of US children aged 24 months have not received all recommended vaccines. This study aimed to develop a prediction model to identify newborns at high risk for missing early childhood vaccines.

Methods
A retrospective cohort included 9080 infants born weighing ≥2000 g at an academic medical center between 2008 and 2013. Electronic medical record data were linked to vaccine data from the Washington State Immunization Information System. Risk models were constructed using derivation and validation samples. K-fold cross-validation identified risk factors for model inclusion based on alpha = 0.01. For each patient in the derivation set, the total number of weighted adverse risk factors was calculated and used to establish groups at low, medium, or high risk for undervaccination. Logistic regression evaluated the likelihood of not completing the 7-vaccine series by age 19 months. The final model was tested using the validation sample.

Results
Overall, 53.6% failed to complete the 7-vaccine series by 19 months. Six risk factors were identified: race/ethnicity, maternal language, insurance status, birth hospitalization length of stay, medical service, and hepatitis B vaccine receipt. Likelihood of non-completion was greater in the high (77.1%; adjusted odds ratio [AOR] 5.6; 99% confidence interval [CI]: 4.2, 7.4) and medium (52.7%; AOR 1.9; 99% CI: 1.6, 2.2) vs low (38.7%) risk groups in the derivation sample. Similar results were observed in the validation sample.

Conclusions
Our prediction model using information readily available in birth hospitalization records consistently identified newborns at high risk for undervaccination. Early identification of high-risk families could be useful for initiating timely, tailored vaccine interventions.
Generalization of the Menegozzi and Lamb maser algorithm to the transient superradiance regime
Authors: Wyenberg C M , Lankhaar B , Rajabi F , Chamma M A , Houde M 
Published: August 2021

ABSTRACT
We investigate the application of the conventional quasi-steady state maser modelling algorithm of Menegozzi & Lamb (ML) to the high field transient regime of the one-dimensional Maxwell-Bloch (MB) equations for a velocity distribution of atoms or molecules. We quantify the performance of a first order perturbation approximation available within the ML framework when modelling regions of increasing electric field strength, and we show that the ML algorithm is unable to accurately describe the key transient features of R. H. Dicke’s superradiance (SR). We extend the existing approximation to one of variable fidelity, and we derive a generalization of the ML algorithm convergent in the transient SR regime by performing an integration on the MB equations prior to their Fourier representation. We obtain a manifestly unique integral Fourier representation of the MB equations which is $\mathcal {O}\left(N\right)$ complex in the number of velocity channels N and which is capable of simulating transient SR processes at varying degrees of fidelity. As a proof of operation, we demonstrate our algorithm’s accuracy against reference time domain simulations of the MB equations for transient SR responses to the sudden inversion of a sample possessing a velocity distribution of moderate width. We investigate the performance of our algorithm at varying degrees of approximation fidelity, and we prescribe fidelity requirements for future work simulating SR processes across wider velocity distributions.
Long-term dynamical survival of deep Earth co-orbitals
Authors: Christou Apostolos A , Georgakarakos Nikolaos 
Published: August 2021

ABSTRACTWe investigate the long-term dynamical survival of Earth co-orbital asteroids, focusing on near-circular, near-planar orbits that existing studies suggest are the most stable. Through numerical integration of test particles, we show that about a quarter of an initial population can survive for at least 50 per cent of the age of the Solar system with horseshoe particles being four to five times more likely to survive than L4/L5 Trojans. From the end state statistics, we constrain the existence of planetesimal-sized objects originally in co-orbital libration, finding that typically $5^{-2}_{+7}$ such planetesimals and no more than $27^{-9}_{+30}$ (95 per cent confidence) could have been present. Our simulations also suggest that episodic variations in the terrestrial orbital eccentricity may have caused bulk escape of co-orbitals, though variations large enough (&gt;0.01) to generate such episodes are statistically unlikely. We then consider the orbital evolution of co-orbital asteroids of sizes down to D = 50 m under the Yarkovsky effect and find that objects with D &lt; 1 km should escape over 4 Gyr with the smallest asteroids escaping after 200 Myr. Further, we test whether the Earth’s co-orbital region may be populated by asteroids arriving via outward Yarkovsky drift, as conjectured by Zhou et al. We find this is an inefficient process, as planetary close encounters rapidly scatter the orbits far from the Earth’s and towards the asteroid belt. Finally, we discuss how the destabilizing action of Yarkovsky may be mitigated through spin state evolution or late collisional comminution of large parent asteroids.
Possibility of primordial black holes collision with Earth and the consequences of this collision
Authors: Rahvar Sohrab 
Published: August 2021

ABSTRACT
In the context of the existence of primordial black holes (PBHs), they may compose a fraction of the dark matter of the Universe. Assuming that PBHs fill the dark content of the Milky Way Galaxy in the Galactic halo and the dark disc, we calculate the probability of collision of the PBHs with Earth. This collision has different consequences as heating the interior of the Earth through dynamical friction and accretion processes. In this work, we calculate the rate of collisions and a fraction of black holes that can be trapped inside the Earth. Finally, we compare the danger of PBH collision with the asteroid impacts on Earth.