bluuebunny/crossref_metadata_2025_split huggingface dataset:
A discrete chemo-dynamical model of M87’s globular clusters: Kinematics extending to ∼400 kpc
Authors: Li Chao , Zhu Ling , Long R J , Mao Shude , Peng Eric W , Sarzi Marc , van de Ven Glenn , Zhang Hongxin , Guo Rui , Xue Xiangxiang , Longobardi Alessia , Côté Patrick , Ferrarese Laura , Liu Chengze , Gwyn Stephen , Lim Sungsoon , Ko Youkyung 
Published: January 2020

ABSTRACT
We study the mass distribution and kinematics of the giant elliptical galaxy M87 (NGC 4486) using discrete chemo-dynamical, axisymmetric Jeans equation modelling. Our catalogue comprises 894 globular clusters (GCs) extending to a projected radius of ∼430 kpc with line-of-sight velocities and colours, and Multi Unit Spectroscopic Explorer integral field unit data within the central 2.4 kpc of the main galaxy. The gravitational potential for our models is a combination of a luminous matter potential with a varying mass-to-light ratio for the main galaxy, a supermassive black hole and a dark matter (DM) potential with a cusped or cored DM halo. The best-fitting models with either a cusped or a cored DM halo show no significant differences and both are acceptable. We obtain a total mass of $(2.16 \pm 0.38) \times 10^{13} \, \mathrm{M}_{\odot }$ within ∼400 kpc. By including the stellar mass-to-light ratio gradient, the DM fraction increases from ∼26 per cent (with no gradient) to ∼73 per cent within $1\, R_e^{\rm maj}$ (major axis of half-light isophote, 14.2 kpc), and from ∼84 per cent to ∼94 per cent within $5\, R_e^{\rm maj}$ (71.2 kpc). Red GCs have moderate rotation with Vmax/σ ∼ 0.4, and blue GCs have weak rotation with Vmax/σ ∼ 0.1. Red GCs have tangential velocity dispersion anisotropy, while blue GCs are consistent with being nearly isotropic. Our results suggest that red GCs are more likely to be born in situ, while blue GCs are more likely to be accreted.
Sexually dimorphic impact of the iron-regulating gene, HFE, on survival in glioblastoma
Authors: Nesterova Darya S , Midya Vishal , Zacharia Brad E , Proctor Elizabeth A , Lee Sang Y , Stetson Lindsay C , Lathia Justin D , Rubin Joshua B , Waite Kristin A , Berens Michael E , Barnholtz-Sloan Jill S , Connor James R 
Published: January 2020

Abstract

Background
The median survival for patients with glioblastoma (GBM), the most common primary malignant brain tumor in adults, has remained approximately 1 year for more than 2 decades. Recent advances in the field have identified GBM as a sexually dimorphic disease. It is less prevalent in females and they have better survival compared to males. The molecular mechanism of this difference has not yet been established. Iron is essential for many biological processes supporting tumor growth and its regulation is impacted by sex. Therefore, we interrogated the expression of a key component of cellular iron regulation, the HFE (homeostatic iron regulatory) gene, on sexually dimorphic survival in GBM.

Methods
We analyzed TCGA microarray gene expression and clinical data of all primary GBM patients (IDH-wild type) to compare tumor mRNA expression of HFE with overall survival, stratified by sex.

Results
In low HFE expressing tumors (below median expression, n = 220), survival is modulated by both sex and MGMT status, with the combination of female sex and MGMT methylation resulting in over a 10-month survival advantage (P &lt; .0001) over the other groups. Alternatively, expression of HFE above the median (high HFE, n = 240) is associated with significantly worse overall survival in GBM, regardless of MGMT methylation status or patient sex. Gene expression analysis uncovered a correlation between high HFE expression and expression of genes associated with immune function.

Conclusions
The level of HFE expression in GBM has a sexually dimorphic impact on survival. Whereas HFE expression below the median imparts a survival benefit to females, high HFE expression is associated with significantly worse overall survival regardless of established prognostic factors such as sex or MGMT methylation.
Comparison of Multiplex Gastrointestinal Pathogen Panel and Conventional Stool Testing for Evaluation of Patients With HIV Infection
Authors: Sobczyk Juliana , Jain Sonia , Sun Xiaoying , Karris Maile , Wooten Darcy , Stagnaro Janet , Reed Sharon 
Published: January 2020

Abstract

Background
Gastrointestinal pathogen panels (GPPs) are increasingly used to identify stool pathogens, but their impact in people with HIV (PWH) is unknown. We performed a retrospective cohort study comparing GPP and conventional stool evaluation in PWH.

Methods
We included all PWH who underwent GPP (Biofire Diagnostics; implemented September 15, 2015) or conventional testing, including stool culture, Clostridium difficile polymerase chain reaction testing, fluorescent smears for Cryptosporidium or Giardia, and ova and parasite exams (O&P) from 2013 to 2017. A total of 1941 specimens were tested, with 169 positive specimens detected in 144 patients. We compared result turnaround time, pathogen co-infection, antibiotic treatment, and treatment outcomes between positive specimens detected by conventional testing vs GPP.

Results
Overall, 124 patient samples tested positive by GPP, compared with 45 patient specimens by conventional testing. The GPP group demonstrated a higher co-infection rate (48.4% vs 13.3%; P &lt; .001) and quicker turnaround time (23.4 vs 71.4 hours; P &lt; .001). The GPP identified 29 potential viral infections that were undetectable by conventional stool tests. Unnecessary anti-infective therapy was avoided in 9 of 11 exclusively viral infections. Exclusively nonpathogenic parasites (n = 13) were detected by conventional stool tests, the majority of which were treated with metronidazole. There were no significant differences in clinical outcomes between groups.

Conclusions
In PWH, GPP implementation improved antibiotic stewardship through shorter turnaround times and detection of enteric viral pathogens.
Heparin sensitivity and postoperative blood loss in patients undergoing cardiac surgery with cardiopulmonary bypass
Authors: Ma Hai-Ping , Xu Wei-Fang , Yu Jin , Wang Jiang , Zheng Hong 
Published: January 2020

BACKGROUND
Heparin-associated coagulation disorder is an important factor related to postoperative bleeding in patients undergoing cardiac surgery with cardiopulmonary bypass. Currently, the relationship between heparin sensitivity and postoperative bleeding is unknown.

OBJECTIVE
To investigate the relationship between individual heparin sensitivity and postoperative blood loss in patients undergoing cardiac surgery.

DESIGN
Prospective controlled study.

SETTING
Tertiary teaching hospital, Urumqi, Xinjiang, PR China. The study was conducted from January 2016 to August 2018.

PATIENTS
A total of 195 adult patients undergoing cardiac valve replacement surgery were included.

INTERVENTION
After initial heparin dosing (2.5 mg kg−1), patients were divided into three groups according to the whole blood activated clotting time (ACT): group A, insensitive group (ACT < 480 s); group B, sensitive group (480 s < ACT < 750 s); group C, hypersensitive group (ACT > 750 s).

MAIN OUTCOME MEASURES
First, intra-operative and 24-h postoperative blood loss. Second, antithrombin (AT) and factor X mRNA levels. Third, the plasma levels of AT-III and factor X. Fourth, heparin sensitivity index.

RESULTS
Blood loss was approximately 20 to 25% lower in group B than in groups A and C, which was statistically significant (P < 0.01). The AT-III mRNA levels increased from groups A to C and was positively associated with heparin sensitivity; the factor X mRNA levels changed in the opposite direction; a significant difference was observed between groups A and C (P < 0.05). The factor X plasma level showed the same trend as its mRNA. The AT-III plasma level was significantly lower in group B than in groups A and C (P < 0.05).

CONCLUSION
Postoperative blood loss is related to heparin sensitivity in patients undergoing cardiac surgery, and the moderately sensitive patients have the least postoperative bleeding. Individual variation in heparin sensitivity is related to the mRNA and plasma levels of AT-III and factor X.

TRIAL REGISTRATION
Registration number ChiCTR-RPC-17012259.
Serpentinite and the search for life beyond Earth
Authors: Vance S. D. , Melwani Daswani M. 
Published: January 2020

Hydrogen from serpentinization is a source of chemical energy for some life forms on Earth. It is a potential fuel for life in the subsurface of Mars and in the icy ocean worlds in the outer solar system. Serpentinization is also implicated in life’s origin. Planetary exploration offers a way to investigate such theories by characterizing and ultimately searching for life in geochemical settings that no longer exist on Earth. At present, much of the current context of serpentinization on other worlds relies on inference from modelling and studies on Earth. While there is evidence from orbital spectral imaging and martian meteorites that serpentinization has occurred on Mars, the extent and duration of that activity has not been constrained. Similarly, ongoing serpentinization might explain hydrogen found in the ocean of Saturn’s tiny moon Enceladus, but this raises questions about how long such activity has persisted. Titan’s hydrocarbon-rich atmosphere may derive from ancient or present-day serpentinization at the bottom of its ocean. In Europa, volcanism or serpentinization may provide hydrogen as a redox couple to oxygen generated at the moon’s surface. We assess the potential extent of serpentinization in the solar system’s wet and rocky worlds, assuming that microfracturing from thermal expansion anisotropy sets an upper limit on the percolation depth of surface water into the rocky interiors. In this bulk geophysical model, planetary cooling from radiogenic decay implies the infiltration of water to greater depths through time, continuing to the present. The serpentinization of this newly exposed rock is assessed as a significant source of global hydrogen. Comparing the computed hydrogen and surface-generated oxygen delivered to Europa’s ocean reveals redox fluxes similar to Earth’s. Planned robotic exploration missions to other worlds can aid in understanding the planetary context of serpentinization, testing the predictions herein.This article is part of a discussion meeting issue ‘Serpentinite in the Earth System’.
Major element mobility during serpentinization, oxidation and weathering of mantle peridotite at low temperatures
Authors: de Obeso Juan Carlos , Kelemen Peter B. 
Published: January 2020

Mantle peridotite in Wadi Fins in eastern Oman exhibits three concentric alteration zones with oxide and sulfide mineralogy recording gradients in
f
O
2
and
f
S
2
(fugacity) of more than 20 orders of magnitude over 15–20 cm. The black cores of samples (approx. 5 cm in diameter) exhibit incomplete, nearly isochemical serpentinization, with relict primary mantle minerals (olivine, orthopyroxene and clinopyroxene) along with sulfide assemblages (pentlandite/heazlewoodite/bornite) recording low
f
O
2
and moderate
f
S
2
. In addition to the black cores, two alteration zones are evident from their colouration in outcrop and hand samples: green and red. These zones exhibit non-isochemical alteration characterized by intergrowths of stevensite/lizardite. All three reaction zones are cut by calcite ± serpentine veins, which are most abundant in the outer, red zones, sometimes are flanked by narrow red and/or green zones where they cut the black zones, and thus may be approximately coeval with all three alteration zones. The alteration zones record progressively higher
f
O
2
recorded by Ni-rich sulfides and iron oxides/hydroxides. These alteration zones lost 20–30% of their initial magnesium content, together with mobilization of iron over short distances from inner green zones into outer red zones, where iron is reprecipitated in goethite intermixed with silicates due to higher
f
O
2
. Thermodynamic modelling at 60°C and 50 MPa (estimated alteration conditions) reproduces sulfide assemblages,
f
O
2
changes and Mg and Fe mobility.

This article is part of a discussion meeting issue ‘Serpentinite in the Earth system’.
Performance of FRAX in predicting fracture in the US postmenopausal women with varied race and genetic profiles
Authors: Wu Qing , Xiao Xiangxue , Xu Yingke 
Published: January 2020

AbstractBackgroundWhether the Fracture Risk Assessment Tool (FRAX) performed differently in estimating the 10-year fracture probability in women of different genetic profiling and race remained unclear.MethodsThe genomic data in the Women’s Health Initiative study was analyzed (n=23,981). the genetic risk score (GRS) was calculated from 14 fracture-associated single nucleotide polymorphisms (SNPs) for each participant. FRAX without bone mineral density (BMD) was used to estimate fracture probability.ResultsFRAX significantly overestimated the risk of major osteoporotic fracture (MOF) in the WHI study. The most enormous overestimation was observed in women with low GRS (predicted/observed ratio [POR]: 1.61, 95% CI: 1.45-1.79), in Asian women (POR: 3.5, 95% CI 2.48-4.81), and in African American women (POR: 2.59, 95% CI: 2.33-2.87). Compared to the low GRS group, the 10-year probability of MOF adjusted for the FRAX score was 21% and 30% higher in median GRS group and high GRS group, respectively. Asian, African American, and Hispanic women respectively had a 78%, 76%, and 56% lower hazard than Caucasian women after the FRAX score was adjusted for. The results were similar when for hip fractures.ConclusionsOur study suggested the FRAX performance varies significantly by both genetic profiling and race in postmenopausal women.
Thrombospondin-4 mediates hyperglycemia- and TGF-beta-induced inflammation in breast cancer
Authors: Muppala Santoshi , Xiao Roy , Gajeton Jasmine , Krukovets Irene , Verbovetskiy Dmitriy , Stenina-Adognravi Olga 
Published: January 2020

AbstractInflammation drives the growth of tumors and is an important predictor of cancer aggressiveness. CD68, a marker of tumor-associated macrophages (TAM), is routinely used as a marker to aid in prognosis and treatment choices for breast cancer.We report that thrombospondin-4 (TSP-4) mediates breast cancer inflammation and growth in mouse models in response to hyperglycemia and TGF-beta by increasing TAM infiltration and production of inflammatory signals in tumors. Analysis of breast cancers and non-cancerous tissue specimens from hyperglycemic patients revealed that levels of TSP-4 and of macrophage marker CD68 are upregulated in diabetic tissues. TSP-4 was co-localized with macrophages in cancer tissues. Bone-marrow-derived macrophages (BMDM) responded to high glucose and TGF-beta by upregulating TSP-4 production and expression, as well as the expression of inflammatory markers.We report a novel function for TSP-4 in breast cancer: regulation of TAM infiltration and inflammation. The results of our study provide new insights into regulation of cancer growth by hyperglycemia and TGF-beta and suggest TSP-4 as a potential therapeutic target.Novelty and ImpactThrombospondin-4 (TSP-4) is a secreted extracellular protein that belongs to the family of matricellular proteins. TSP-4 is one of the top 1% of proteins upregulated in several cancers, including breast cancer. Inflammation and infiltration of macrophages drive cancer progression and metastasis and are clinically important markers of cancer aggressiveness and critical consideration in the process of selection of the appropriate therapeutic approaches. We report that TSP-4 promotes breast cancer inflammation and infiltration of macrophages and mediates the effects of hyperglycemia and TGF-beta on cancer growth and inflammation. Our work describes a role for TSP-4 in cancer inflammation and identifies the pathways, in which increased levels of TSP-4 mediate cancer growth.
Alzheimer’s Disease Neuropathological Comorbidities Are Common in the Younger-Old
Authors: Beach Thomas G. , Malek-Ahmadi Michael 
Published: January 2020

AbstractClinicopathological studies have demonstrated that Alzheimer’s disease dementia (ADD) is often accompanied by clinically undetectable comorbid neurodegenerative and cerebrovascular disease that alter the presence and rate of cognitive decline in aging and ADD. Aside from causing increased variability in clinical response, it is possible that the major ADD comorbidities may not respond to ADD-specific molecular therapeutics. As most reports have focused on comorbidity in the oldest-old, its extent in younger age groups that are more likely to be involved in clinical trials is largely unknown. We conducted a survey of neuropathological comorbidities in sporadic ADD using data from the US National Alzheimer’s Coordinating Center. Subject data was restricted to those with dementia and meeting National Institute on Aging-Alzheimer’s Association (NIA-AA) intermediate or high AD Neuropathological Change (ADNC) levels, excluding those with known autosomal dominant AD-related mutations. Subjects were divided into age-at-death categories for analysis: under 60, 60-69, 70-79, 80-89, 90-99 and 100 or over. Confirmatory of earlier reports, ADD histopathology is less severe with advancing age, effectively increasing the relative contribution of comorbidities, most of which rise in prevalence with age. Highly prevalent ADD comorbidities are not restricted to the oldest-old but are common even in early-onset ADD. The percentage of cases with ADD as the sole major neuropathological diagnosis is highest in the under-60 group, where “pure” ADD cases are still in the minority at 44%. After this AD as a sole major pathology in ADD declines to roughly 20% in the 70s and beyond. Comorbidity rates for some pathologies, especially LBD, are high even in subjects in their 60s and 70s, at nearly 60%, but for most others, their prevalence increases with age. TDP-43 pathology affects more than 35% of ADD subjects 80 and over while microscopic infarcts reach this rate a decade later. Gross infarcts rise more slowly and affect fewer subjects but still involve 15-20% of ADD after age 80. White matter rarefaction may be underestimated in the NACC database but is present in almost 70% of centenarians with ADD. Effective clinical trials depend on accurate estimates of required subject numbers, which are dependent on observed effect size and clinical response variability. Comorbidities are likely to affect both, leading to lower probability of clinical trial success. Stratifying ADD clinical trial analyses by presence and types of accompanying comorbidities might identify subgroups with higher effect sizes and greater clinical response rates, but accurate in-vivo diagnostic methods for most comorbidities are still lacking.
NMR Line Shapes in Molecular Mechanisms with Ligand Binding and Multiple Conformers
Authors: Kovrigin Evgenii L 
Published: January 2020

ABSTRACTInteractions of ligands with biological macromolecules are sensitively detected through changes of chemical shifts and line shapes of the NMR signals. This paper reports a mathematical analysis and simulations of NMR line shapes expected in titrations when ligand binding is coupled to multiple isomerization transitions. Such molecular mechanisms may correspond to ligand binding by intrinsically disordered proteins or by autoinhibited enzymes. Based on the simulation results, we anticipate several specific effects that may be observed in practice. First, the presence of non-binding conformers of the receptor molecule leads to a remarkable broadening in the binding transition even if the exchange between binding and non-binding conformers is very slow. Second, the ligand-binding mechanisms involving induced fit are expected to demonstrate deceptively decelerated exchange regimes even when the underlying kinetics are very fast. Conversely, the observation of fast-exchange shifting resonances with modest line-broadening (“marching peaks”) in practical NMR titrations may involve conformational selection transitions but less likely to be observed for the induced fit. Finally, in auto-inhibited molecules that open to form multiple binding-competent conformers, the fast dynamics of opening/closing transition are capable of masking the true kinetics of interconversion among transiently open forms of the receptor.
Repetitive DNA profiles Reveal Evidence of Rapid Genome Evolution and Reflect Species Boundaries in Ground Beetles
Authors: Sproul John S. , Barton Lindsey M. , Maddison David R. 
Published: January 2020

AbstractGenome architecture is a complex, multidimensional property of an organism defined by the content and spatial organization of the genome’s component parts. Comparative study of entire genome architecture in model organisms is shedding light on mechanisms underlying genome regulation, evolution, and diversification; but such studies require costly analytical approaches which make extensive comparative study impractical for most groups. However, lower-cost methods that measure a single architectural component (e.g., distribution of one class of repeats) have potential as a new data source for evolutionary studies insofar as that measure correlates with more complex biological phenomena, and for which it could serve as part of an explanatory framework. We investigated copy number variation (CNV) profiles in ribosomal DNA (rDNA) as a simple measure reflecting the distribution of rDNA subcomponents across the genome. We find that signatures present in rDNA CNV profiles strongly correlate with species boundaries in thebrevespecies group ofBembidion, and vary across broader taxonomic sampling inBembidionsubgenusPlataphus. Profiles of several species show evidence of re-patterning of rDNA-like sequences throughout the genome, revealing evidence of rapid genome evolution (including among sister pairs) not evident from analysis of traditional data sources such as multi-gene data sets. Major re-patterning of rDNA-like sequences has occurred frequently within the evolutionary history ofPlataphus. We confirm that CNV profiles represent an aspect of genomic architecture (i.e., the linear distribution of rDNA components across the genome) via fluorescencein-situhybridization. In at least one species, novel rDNA-like elements are spread throughout all chromosomes. We discuss the potential of copy number profiles of rDNA, or other repeats, as a low-cost tool for incorporating signal of genomic architecture variation in studies of species delimitation and genome evolution.