bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of Aspirin and Non-Aspirin Non-Steroidal Anti-Inflammatory Drugs With Colorectal Cancer Mortality After Diagnosis
Authors: Figueiredo Jane C , Jacobs Eric J , Newton Christina C , Guinter Mark A , Cance William G , Campbell Peter T 
Published: January 2021

Abstract

Background
Aspirin use reduces colorectal cancer (CRC) incidence, but there is limited evidence regarding associations of aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) with CRC-specific survival.

Methods
This prospective analysis includes women and men from the Cancer Prevention Study-II Nutrition Cohort who were cancer free at baseline (1992 or 1993) and diagnosed with CRC during incidence follow-up through 2015. Detailed information on aspirin and non-aspirin NSAID use was self-reported on questionnaires at baseline, in 1997, and every 2 years thereafter. Pre- and postdiagnosis data were available for 2686 and 1931 participants without distant metastases, respectively, among whom 512 and 251 died from CRC during mortality follow-up through 2016. Secondary analyses examined associations between prediagnosis aspirin use and stage at diagnosis (distant metastatic vs localized or regional). All statistical tests were 2-sided.

Results
Long-term regular use of aspirin (&gt;15 times per month) before diagnosis was associated with lower CRC-specific mortality (multivariable-adjusted hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.52 to 0.92). Postdiagnosis regular aspirin use was not statistically significantly associated with risk of CRC-specific mortality overall (HR = 0.82, 95% CI = 0.62 to 1.09), although participants who began regular aspirin use only after their diagnosis were at lower risk than participants who did not use aspirin at both the pre- and postdiagnosis periods (HR = 0.60, 95% CI = 0.36 to 0.98). Long-term aspirin use before diagnosis was also associated with lower odds of diagnosis with distant metastases (multivariable-adjusted odds ratio = 0.73, 95% CI = 0.53 to 0.99).

Conclusions
Our results suggest that long-term aspirin use before a diagnosis of nonmetastatic colorectal cancer may be associated with lower CRC-specific mortality after diagnosis, consistent with possible inhibition of micrometastases before diagnosis.
New insights into the effects of vinpocetine against neurobehavioral comorbidities in a rat model of temporal lobe epilepsy via the downregulation of the hippocampal PI3K/mTOR signalling pathway
Authors: El-Sayed Sarah S , El-Yamany Mohammed F , Salem Hesham A , El-Sahar Ayman E 
Published: January 2021

Abstract

Objectives
As one of the most frequent worldwide neurological disorders, epilepsy is an alteration of the central nervous system (CNS) characterized by abnormal increases in neuronal electrical activity. The mammalian target of rapamycin (mTOR) signalling pathway has been investigated as an interesting objective in epilepsy research. Vinpocetine (VNP), a synthesized derivative of the apovincamine alkaloid, has been used in different cerebrovascular disorders. This study aimed to examine the modulatory effects of VNP on neurobehavioral comorbidities via the mTOR signalling pathway in a lithium-pilocarpine (Li-Pil) rat model of seizures.

Methods
In male Wistar rats, seizures were induced with a single administration of pilocarpine (60 mg/kg; i.p.) 20 hours after the delivery of a single dose of lithium (3 mEq/kg; i.p.). VNP (10 mg/kg; i.p.) was administered daily for 14 consecutive days before Li-Pil administration.

Key findings
VNP had a protective effect against Li-Pil-induced seizures. VNP improved both the locomotor and cognitive abilities, moreover, VNP exerted a neuroprotective action, as verified histologically and by its inhibitory effects on hippocampal glutamate excitotoxicity, mTOR pathway, and inflammatory and apoptotic parameters.

Conclusions
VNP is a valuable candidate for epilepsy therapy via its modulation of the mechanisms underlying epileptogenesis with emphasis on its modulatory effect on mTOR signalling pathway.
Penopubic testicular ectopia with bilateral cryptorchidism presenting as obstructed inguinal Amyand’s hernia
Authors: Otuu O , Nnadozie U U , Maduba C C , Eni U E 
Published: January 2021

Abstract
Testicular ectopia is an aberrant deviation of the migration of the testis from its usual path of descent into the scrotum. Of the forms of ectopic testis, the penopubic (also called pubopenile) type is one of the least common; in this case, presented as an obstructed hernia. We report a rare case of penopubic testicular ectopia with bilateral cryptorchidism in a 17-year-old boy who presented to the emergency room with right obstructed inguinal hernia. Intraoperative findings included bilateral cryptorchidism, hernia sac with right undescended testis and normal vermiform appendix, a left penopubic testis abutting the hernia sac. Both testes had separate epididymides and adequate length of vasa deferentia and were transposed into their respective hemiscrotum via an open inguinal approach. The patient had an uneventful recovery.
Penopubic testicular ectopia can present as obstructed Amyand’s hernia. Early open groin exploration with orchidopexy was satisfactory.
Rare Multidrug-resistant Pseudomonas aeruginosa Identified in a U.S. Deployed Service Member Following Host-nation Medical Treatment
Authors: Lawrence Matthew W , Sachdeva Mohit , Bennett Jason W , Menninger George U , Barrera Melissa A , Benitez John G , Kliewer Maurice L 
Published: January 2021

ABSTRACT
Decision-making related to the utilization of host-nation medical resources in austere forward-deployed environments is complex. Clinical circumstances, local medical intelligence availability, transportation assets, uncertainty regarding standard-of-care variations, military/host-nation funding complications, and regional security concerns all factor into consideration. A case of a U.S. active duty military service member who suffered a cardiac arrest on a military base in Southwest Asia is described in this report. After return of circulation following defibrillation, he was administered thrombolytic therapy for an electrocardiogram-identified ST-elevation myocardial infarction and transported to a local host-nation cardiac hospital for emergent percutaneous coronary intervention. During his subsequent transportation back to the USA, surveillance testing identified that he was colonized with a rare strain of Pseudomonas aeruginosa, demonstrating New Delhi metallo-beta-lactamase-1 and 16S RNA methyltransferase-2 enzymes, which confer significant resistance to carbapenem and aminoglycoside antibiotics, respectively.1–3 This combination of antibiotic resistance has been reported very rarely in the medical literature and has never been reported within the deployed military health system until now. The risk of exposure to multidrug-resistant organisms was not a factor initially considered in the decision to utilize host-nation medical resources in this case, which provided lesson learned and raised new questions, for future operational medical planning.
Setting the stage: structures from Gaussian random fields
Authors: Sawala Till , Jenkins Adrian , McAlpine Stuart , Jasche Jens , Lavaux Guilhem , Johansson Peter H , Frenk Carlos S 
Published: January 2021

ABSTRACT
We study structure formation in a set of cosmological simulations to uncover the scales in the initial density field that gave rise to the formation of present-day structures. Our simulations share a common primordial power spectrum (here Λ cold dark matter, ΛCDM), but the introduction of hierarchical variations of the phase information allows us to systematically study the scales that determine the formation of structure at later times. We consider the variance in z = 0 statistics such as the matter power spectrum and halo mass function. We also define a criterion for the existence of individual haloes across simulations, and determine what scales in the initial density field contain sufficient information for the non-linear formation of unique haloes. We study how the characteristics of individual haloes such as the mass and concentration, as well as the position and velocity, are affected by variations on different scales, and give scaling relations for haloes of different mass. Finally, we use the example of a cluster-mass halo to show how our hierarchical parametrization of the initial density field can be used to create variants of particular objects. With properties such as mass, concentration, kinematics, and substructure of haloes set on distinct and well-determined scales, and its unique ability to introduce variations localized in real space, our method is a powerful tool to study structure formation in cosmological simulations.
Stability time-scale prediction for main-belt asteroids using neural networks
Authors: Liu Chao , Gong Shengping , Li Junfeng 
Published: January 2021

ABSTRACT
Many asteroids move in the belt between the orbits of Mars and Jupiter under the gravitational attraction of the Sun and planets in the Solar system. If one of these asteroids does not leave the belt during a period, it is considered to be temporarily stable on that time-scale. This paper aims to study the time-scales on which asteroids could stay in the main belt. A simplified situation is studied in which the initial orbital inclinations and the longitudes of the ascending nodes of the asteroids are set to zero. Numerical integration is used to study the temporal stability of the main-belt asteroids. In the integration, the distribution of the instability time for randomly generated particles can be fitted with a function. Thus a reasonable method is presented to choose an integration time-scale based on the percentage of the already unstable particles in relation to all unstable particles. A total of 151 000 particles are generated and then integrated for 8.09 × 106 yr. The integration data are used to train the probabilistic neural networks to predict the stability of particles. A temporal stability map in the a-e plane is obtained from the prediction results of the neural networks.
Modelling intergalactic low ionization metal absorption line systems near the epoch of reionization
Authors: Suarez Teresita , Meiksin Avery 
Published: January 2021

ABSTRACT
We interpret observations of intergalactic low ionization metal absorption systems at redshifts z ≳ 5 in terms of pressure-confined clouds. We find clouds confined by the expected pressure of galactic haloes with masses $11\lt \log M_h/h^{-1}\, \mathrm{M}_\odot \lt 12$ provide a good description of the column density ratios between low ionization metal absorbers. Some of the ratios, however, require extending conventional radiative transfer models of irradiated slabs to spherical (or cylindrical) clouds to allow for lines of sight passing outside the cores of the clouds. Moderate depletion of silicon on to dust grains is also indicated in some systems. The chemical abundances inferred span the range between solar and massive-star-dominated stellar populations as may arise in starburst galaxies. The typical H i column densities matching the data correspond to damped Ly α absorbers (DLAs) or sub-DLAs, with sizes of 40 pc to 3 kpc, gas masses 3.5 &lt; log Mc/M⊙ &lt; 8 and metallicites $0.001\!-\!0.01\, \mathrm{Z}_\odot$. Such systems continue to pose a challenge for galaxy-scale numerical simulations to reproduce.
Higher order Hamiltonian Monte Carlo sampling for cosmological large-scale structure analysis
Authors: Hernández-Sánchez Mónica , Kitaura Francisco-Shu , Ata Metin , Dalla Vecchia Claudio 
Published: January 2021

ABSTRACT
We investigate higher order symplectic integration strategies within Bayesian cosmic density field reconstruction methods. In particular, we study the fourth-order discretization of Hamiltonian equations of motion (EoM). This is achieved by recursively applying the basic second-order leap-frog scheme (considering the single evaluation of the EoM) in a combination of even numbers of forward time integration steps with a single intermediate backward step. This largely reduces the number of evaluations and random gradient computations, as required in the usual second-order case for high-dimensional cases. We restrict this study to the lognormal-Poisson model, applied to a full volume halo catalogue in real space on a cubical mesh of 1250 h−1 Mpc side and 2563 cells. Hence, we neglect selection effects, redshift space distortions, and displacements. We note that those observational and cosmic evolution effects can be accounted for in subsequent Gibbs-sampling steps within the COSMIC BIRTH algorithm. We find that going from the usual second to fourth order in the leap-frog scheme shortens the burn-in phase by a factor of at least ∼30. This implies that 75–90 independent samples are obtained while the fastest second-order method converges. After convergence, the correlation lengths indicate an improvement factor of about 3.0 fewer gradient computations for meshes of 2563 cells. In the considered cosmological scenario, the traditional leap-frog scheme turns out to outperform higher order integration schemes only when considering lower dimensional problems, e.g. meshes with 643 cells. This gain in computational efficiency can help to go towards a full Bayesian analysis of the cosmological large-scale structure for upcoming galaxy surveys.
The formation history of the Milky Way disc with high-resolution cosmological simulations
Authors: Giammaria Marco , Spagna Alessandro , Lattanzi Mario G , Murante Giuseppe , Re Fiorentin Paola , Valentini Milena 
Published: January 2021

ABSTRACT
We analyse from an observational perspective the formation history and kinematics of a Milky Way-like galaxy from a high-resolution zoom-in cosmological simulation that we compare to those of our Galaxy as seen by Gaia DR2 to better understand the origin and evolution of the Galactic thin and thick discs. The cosmological simulation was carried out with the gadget-3 TreePM+SPH code using the MUlti-Phase Particle Integrator (muppi) model. We disentangle the complex overlapping of stellar generations that rises from the top-down and inside-out formation of the galactic disc. We investigate cosmological signatures in the phase-space of mono-age populations and highlight features stemming from past and recent dynamical perturbations. In the simulation, we identify a satellite with a stellar mass of $1.2 \times 10^9~\rm {M}_\odot$, i.e. stellar mass ratio Δ ∼ 5.5 per cent at the time, accreted at z ∼ 1.6, which resembles the major merger Gaia–Sausage–Enceladus that produced the Galactic thick disc, i.e. Δ ∼ 6 per cent. We found at z ∼ 0.5–0.4 two merging satellites with a stellar mass of $8.8 \times 10^8~\rm {M}_\odot$ and $5.1 \times 10^8~\rm {M}_\odot$ that are associated to a strong starburst in the star formation history, which appears fairly similar to that recently found in the solar neighbourhood. Our findings highlight that detailed studies of coeval stellar populations kinematics, which are made available by current and future Gaia data releases and in synergy with simulations, are fundamental to unravel the formation and evolution of the Milky Way discs.
Spatial segregation impact on star formation in nearby dwarf spheroidal galaxies
Authors: Makarova L N , Makarov D I 
Published: January 2021

ABSTRACT
Using our Hubble Space Telescope/Advanced Camera for Surveys (HST/ACS) observations of the recently found isolated dwarf spheroidal (dSph) galaxies, we homogeneously measured their star formation histories (SFHs). We determined SF rate as a function of time, as well as age and metallicity of the stellar populations. All objects demonstrate complex SFH, with a significant portion of stars formed 10–13 Gyr ago. Nevertheless, stars of middle ages (1–8 Gyr) are presented. In order to understand how the SF parameters influence the evolution of dSphs, we also studied a sample of nearest dSphs in different environment: isolated (d &lt; 2 Mpc); beyond the Local Group (LG) virial radius (but within the LG zero-velocity sphere); and the satellites of M 31 located within the virial zone (300 kpc). Using archival HST/ACS observations, we measured their SFHs. A comparative analysis of the parameters obtained allow us to distinguish a possible effect of the spatial segregation on the dSphs evolution scenario.
The Landscape of Recombination Events That Create Nonribosomal Peptide Diversity
Authors: Baunach Martin , Chowdhury Somak , Stallforth Pierre , Dittmann Elke 
Published: January 2021

Abstract
Nonribosomal peptides (NRP) are crucial molecular mediators in microbial ecology and provide indispensable drugs. Nevertheless, the evolution of the flexible biosynthetic machineries that correlates with the stunning structural diversity of NRPs is poorly understood. Here, we show that recombination is a key driver in the evolution of bacterial NRP synthetase (NRPS) genes across distant bacterial phyla, which has guided structural diversification in a plethora of NRP families by extensive mixing and matching of biosynthesis genes. The systematic dissection of a large number of individual recombination events did not only unveil a striking plurality in the nature and origin of the exchange units but allowed the deduction of overarching principles that enable the efficient exchange of adenylation (A) domain substrates while keeping the functionality of the dynamic multienzyme complexes. In the majority of cases, recombination events have targeted variable portions of the Acore domains, yet domain interfaces and the flexible Asub domain remained untapped. Our results strongly contradict the widespread assumption that adenylation and condensation (C) domains coevolve and significantly challenge the attributed role of C domains as stringent selectivity filter during NRP synthesis. Moreover, they teach valuable lessons on the choice of natural exchange units in the evolution of NRPS diversity, which may guide future engineering approaches.
Human Rev1 relies on insert-2 to promote selective binding and accurate replication of stabilized G-quadruplex motifs
Authors: Ketkar Amit , Smith Lane , Johnson Callie , Richey Alyssa , Berry Makayla , Hartman Jessica H , Maddukuri Leena , Reed Megan R , Gunderson Julie E C , Leung Justin W C , Eoff Robert L 
Published: January 2021

Abstract
We previously reported that human Rev1 (hRev1) bound to a parallel-stranded G-quadruplex (G4) from the c-MYC promoter with high affinity. We have extended those results to include other G4 motifs, finding that hRev1 exhibited stronger affinity for parallel-stranded G4 than either anti-parallel or hybrid folds. Amino acids in the αE helix of insert-2 were identified as being important for G4 binding. Mutating E466 and Y470 to alanine selectively perturbed G4 binding affinity. The E466K mutant restored wild-type G4 binding properties. Using a forward mutagenesis assay, we discovered that loss of hRev1 increased G4 mutation frequency &gt;200-fold compared to the control sequence. Base substitutions and deletions occurred around and within the G4 motif. Pyridostatin (PDS) exacerbated this effect, as the mutation frequency increased &gt;700-fold over control and deletions upstream of the G4 site more than doubled. Mutagenic replication of G4 DNA (±PDS) was partially rescued by wild-type and E466K hRev1. The E466A or Y470A mutants failed to suppress the PDS-induced increase in G4 mutation frequency. These findings have implications for the role of insert-2, a motif conserved in vertebrates but not yeast or plants, in Rev1-mediated suppression of mutagenesis during G4 replication.
Restriction of an intron sizeen routeto endothermy
Authors: Královičová Jana , Borovská Ivana , Pengelly Reuben , Lee Eunice , Abaffy Pavel , Šindelka Radek , Grutzner Frank , Vořechovský Igor 
Published: January 2021

AbstractCa2+-insensitive and -sensitive E1 subunits of the 2-oxoglutarate dehydrogenase complex (OGDHC) regulate tissue-specific NADH and ATP supply by mutually exclusive OGDH exons 4a and 4b. Here we show that their splicing is enforced by distant lariat branch points (dBPs) located near the 5′ splice site of the intervening intron. dBPs restrict the intron length and prevent transposon insertions, which can introduce or eliminate dBP competitors. The size restriction was imposed by a single dominant dBP in anamniotes that expanded into a conserved constellation of four dBP adenines in amniotes. The amniote clusters exhibit taxon-specific usage of individual dBPs, reflecting accessibility of their extended motifs within a stable RNA hairpin rather than U2 snRNA:dBP base-pairing. The dBP expansion took place in early terrestrial species and was followed by a uridine enrichment of large downstream polypyrimidine tracts in mammals. The dBP-protected megatracts permit reciprocal regulation of exon 4a and 4b by uridine-binding proteins, including TIA-1/TIAR and PUF60, which promote U1 and U2 snRNP recruitment to the 5′ splice site and BP, respectively, but do not significantly alter the relative dBP usage. We further show that codons for residues critically contributing to protein binding sites for Ca2+ and other divalent metals confer the exon inclusion order that mirrors the Irving-Williams affinity series, linking the evolution of auxiliary splicing motifs in exons to metallome constraints. Finally, we hypothesize that the dBP-driven selection for Ca2+-dependent ATP provision by E1 facilitated evolution of endothermy by optimizing the aerobic scope in target tissues.
At the Crossroads of Language, Race, and Sexuality
Authors: Chun Elaine , Walters Keith 
Published: January 2021

Abstract
This chapter explores how researchers have examined race and sexuality as mutually implicated dimensions of language use and interpretation. While past descriptions of language have inadvertently conflated these dimensions by foregrounding certain speakers and erasing others, recent research has decentered the privileged gaze of whiteness and heterosexuality by examining the language of racially and sexually marginalized communities and by exploring the semiotic mapping of hierarchies of race onto those of sexuality. The chapter analyzes interactions among Korean American girls who highlight the sexual value of locally racialized body parts, illustrating how their acts of intersectional highlighting allow them to contest the sexual devaluation of Korean bodies while reproducing the very ideologies they challenge. Researchers are encouraged to reflexively consider their own strategies of intersectional highlighting by asking what ends are served—and not served—when making intersectional facts visible in their analyses.
The Nubian Experience of Egyptian Domination During the New Kingdom
Authors: Smith Stuart Tyson 
Published: January 2021

AbstractThe Nubian experience of Egyptian domination during the New Kingdom (ca. 1500–1070 bce) was complex and variable. Outright rebellion to Egyptian rule is attested but was rare. Instead Nubians employed highly variable strategies of collaboration/assimilation, ethnic solidarity, and the creation of hybridity in order to cope with the Egyptian hegemony. The dynamic and variable entanglement and juxtaposition of Nubian and Egyptian ceramic traditions, foodways, and burial practice established the foundations for the survival of elements of Nubian culture despite five hundred years of Egyptian domination and widespread assimilation north of the Third Cataract. The formation of a new blended or hybrid Nubian identity forged through the colonial experience helped to break down the imperial ideology of Egyptian self and Nubian other. In the end, the accumulation of individual choices by Nubians and their Egyptian counterparts, constrained by larger political and economic dynamics, produced outcomes that transformed both indigenous and colonial society.