bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD4+CD25HiFoxP3+ regulatory T cells in long‐term cardiac xenotransplantation
Authors: Singh Avneesh K. , Chan Joshua L. , Seavey Caleb N. , Corcoran Philip C. , Hoyt Robert F. , Lewis Billeta G.T. , Thomas Marvin L. , Ayares David L. , Horvath Keith A. , Mohiuddin Muhammad M. 
Published: December 2017

AbstractBackgroundCD4+CD25HiFoxP3+ T (Treg) cells are a small subset of CD4+ T cells that have been shown to exhibit immunoregulatory function. Although the absolute number of Treg cells in peripheral blood lymphocytes (PBL) is very small, they play an important role in suppressing immune reactivity. Several studies have demonstrated that the number of Treg cells, rather than their intrinsic suppressive capacity, may contribute to determining the long‐term fate of transplanted grafts. In this study, we analyzed Treg cells in PBL of long‐term baboon recipients who have received genetically modified cardiac xenografts from pig donors.MethodsHeterotopic cardiac xenotransplantation was performed on baboons using hearts obtained from GTKO.hCD46 (n = 8) and GTKO.hCD46.TBM (n = 5) genetically modified pigs. Modified immunosuppression regimen included antithymocyte globulin (ATG), anti‐CD20, mycophenolate mofetil (MMF), cobra venom factor (CVF), and costimulation blockade (anti‐CD154/anti‐CD40 monoclonal antibody). FACS analysis was performed on PBLs labeled with anti‐human CD4, CD25, and FoxP3 monoclonal antibodies (mAb) to analyze the percentage of Treg cells in six baboons that survived longer than 2 months (range: 42‐945 days) after receiving a pig cardiac xenograft.ResultsTotal WBC count was low due to immunosuppression in baboons who received cardiac xenograft from GTKO.hCD46 and GTKO.hCD46.hTBM donor pigs. However, absolute numbers of CD4+CD25HiFoxP3 Treg cells in PBLs of long‐term xenograft cardiac xenograft surviving baboon recipients were found to be increased (15.13 ± 1.50 vs 7.38 ± 2.92; P < .018) as compared to naïve or pre‐transplant baboons. Xenograft rejection in these animals was correlated with decreased numbers of regulatory T cells.ConclusionOur results suggest that regulatory T (Treg) cells may contribute to preventing or delaying xenograft rejection by controlling the activation and expansion of donor‐reactive T cells, thereby masking the antidonor immune response, leading to long‐term survival of cardiac xenografts.
Risk of exposure to Coxiella burnetii from ruminant livestock exhibited at Iowa agricultural fairs
Authors: Still Brooks K. M. , Stensland W. R. , Harmon K. M. , O'Connor A. M. , Plummer P. J. 
Published: December 2017

SummaryCoxiella burnetii is a zoonotic pathogen typically associated with clinical and asymptomatic infection in ruminant livestock. A re‐emerging pathogen of significant public health importance, C. burnetii has caused recent epidemics in the United States and Europe, and public livestock exhibitions are increasingly scrutinized as a potential source of C. burnetii exposure. Although C. burnetii prevalence data among North American domestic ruminants are extremely limited, contemporary studies suggest that this pathogen is both geographically widespread and highly prevalent on a herd basis, especially in dairy cattle and goat populations. We utilized a real‐time PCR assay to detect C. burnetii faecal shedding by clinically normal, non‐periparturient beef cattle, meat goats and sheep exhibited at Iowa agricultural fairs. Individual faecal samples were collected from beef cattle, meat goats and sheep exhibited at twelve Iowa county fairs during the summer of 2009. The sample pool was blocked by species and fair, and ten samples from each block were randomly selected for the diagnostic assay; this test pool is considered sufficient to identify with 95% confidence a shedding animal in a population prevalence of 2.85% (cattle and sheep) and 6.25% (goats). Detection of C. burnetii DNA was determined through use of a real‐time PCR assay validated for use in bovine, ovine and caprine faeces; threshold of detection is one DNA copy per PCR (sensitivity 95.8%, specificity 100%). All tested samples were negative for C. burnetii DNA. We conclude that non‐dairy, non‐periparturient ruminants exhibited at Iowa fairs are unlikely to shed C. burnetii in their faeces and that this population should not be considered to be a significant exposure risk to other livestock or fair attendees.
A Carbohydrate Ingestion Intervention in an Elite Athlete Who Follows a Low-Carbohydrate High-Fat Diet
Authors: Webster Christopher C. , Swart Jeroen , Noakes Timothy D. , Smith James A. 
Published: December 2017

This case study documents the performance of an elite-level, exceptionally well-fat-adapted endurance athlete as he reintroduced carbohydrate (CHO) ingestion during high-intensity training. He had followed a strict low-CHO high-fat (LCHF) diet for 2 y, during which he ate approximately 80 g of CHO per day and trained and raced while ingesting only water. While following this diet, he earned numerous podium finishes in triathlons of various distances. However, he approached the authors to test whether CHO supplementation during exercise would further increase his high-intensity performance without affecting his fat adaptation. This 7-wk n = 1 investigation included a 4-wk habitual LCHF diet phase during which he drank only water during training and performance trials and a 3-wk habitual diet plus CHO ingestion phase (LCHF + CHO) during which he followed his usual LCHF diet but ingested 60 g/h CHO during 8 high-intensity training sessions and performance trials. After each phase, rates of fat oxidation and 30-s sprint, 4-min sprint, 20-km time trial (TT), and 100-km TT performances were measured. Compared with LCHF, 20-km TT time improved by 2.8% after LCHF + CHO, which would be a large difference in competition. There was no change in 30-s sprint power, a small improvement in 4-min sprint power (1.6%), and a small reduction in 100-km TT time (1.1%). The authors conclude that CHO ingestion during exercise was likely beneficial for this fat-adapted athlete during high-intensity endurance-type exercise (4–30 min) but likely did not benefit his short-sprint or prolonged endurance performance.
Effects of Hip Abduction Fatigue on Trunk and Shoulder Kinematics During Throwing and Passive Hip Rotational Range of Motion
Authors: Oliver Gretchen D. , Washington Jessica K. , Gascon Sarah S. , Plummer Hillary A. , Escamilla Rafael F. , Andrews James R. 
Published: December 2017

Context: Hip abductor musculature contributes to the stability of the pelvis, which is needed for efficient energy transfer from the lower-extremity to the upper-extremity during overhead throwing. Objective: The purpose of this study was to examine the effects of a bilateral hip abduction fatigue protocol on overhead-throwing kinematics and passive hip range of motion. Design: Prospective cohort study. Setting: Controlled laboratory setting. Participants: A convenience sample of 19 collegiate female softball players (20.6 [1.9] y; 169.3 [9.7] cm; 73.2 [11.2] kg). Main Outcome Measures: Repeated hip abduction to fatigue was performed on an isokinetic dynamometer for 3 consecutive days. Trunk and shoulder kinematics during throwing and hip internal and external rotation range of motion were analyzed prior to fatigue on day 1 (prefatigue) and following fatigue on day 3 (postfatigue). Results: Repeated-measures analysis of variances revealed no statistically significant differences in trunk and shoulder kinematics prefatigue and postfatigue. A statistically significant time × side × direction interaction (F2,36 = 5.462, P = .02, ) was observed in hip passive range of motion. A decrease in throwing-side hip internal rotation prefatigue to postfatigue (mean difference = −2.284; 95% confidence interval, −4.302 to −0.266; P = .03) was observed. Conclusions: The hip abductor fatigue protocol used in this study did not significantly alter trunk and upper-extremity throwing kinematics. The lack of changes may indicate that fatigue of the hip abductors does not contribute to trunk and shoulder kinematics during throwing or the protocol may not have been sport-specific enough to alter kinematics.
Prostaglandin E
2
Receptor Antagonist with Antimicrobial Activity against Methicillin-Resistant Staphylococcus aureus
Authors: Ikeh Mélanie A. C. , Fidel Paul L. , Noverr Mairi C. 
Published: December 2017

ABSTRACT

Polymicrobial intra-abdominal infections (IAI) involving
Candida albicans
and
Staphylococcus aureus
are associated with severe morbidity and mortality (∼80%). Our laboratory discovered that the immunomodulatory eicosanoid prostaglandin E
2
(PGE
2
) plays a key role in the lethal inflammatory response during polymicrobial IAI using a mouse model of infection. In studies designed to uncover key PGE
2
biosynthesis/signaling components involved in the response, selective eicosanoid enzyme inhibitors and receptor antagonists were selected and prescreened for antimicrobial activity against
C. albicans
or
S. aureus
. Unexpectedly, we found that the EP
4
receptor antagonist L-161,982 had direct growth-inhibitory effects on
S. aureus
in vitro
at the physiological concentration required to block the PGE
2
interaction with EP
4
. This antimicrobial activity was observed with methicillin-sensitive
S. aureus
and methicillin-resistant
S. aureus
(MRSA) strains, with the MIC and minimum bactericidal concentration values for planktonic cells being 50 μg/ml and 100 μg/ml, respectively. In addition, L-161,982 inhibited
S. aureus
biofilm formation and had activity against preformed mature biofilms. More importantly, treatment of mice with L-161,982 following intraperitoneal inoculation with a lethal dose of MRSA significantly reduced the bioburden and enhanced survival. Furthermore, L-161,982 protected mice against the synergistic lethality induced by coinfection with
C. albicans
and
S. aureus
. The antimicrobial activity of L-161,982 is independent of EP
4
receptor inhibitory activity; an alternative EP
4
receptor antagonist exerted no antimicrobial or protective effects. Taken together, these findings demonstrate that L-161,982 has potent antimicrobial activity against MRSA and may represent a significant therapeutic alternative in improving the prognosis of mono- or polymicrobial infections involving MRSA.
Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling of Aerosolized Colistin in a Mouse Lung Infection Model
Authors: Lin Yu-Wei , Zhou Qi Tony , Han Mei-Ling , Onufrak Nikolas J. , Chen Ke , Wang Jiping , Forrest Alan , Chan Hak-Kim , Li Jian 
Published: December 2017

ABSTRACT

Optimized dosage regimens of aerosolized colistin (as colistin methanesulfonate [CMS]) are urgently required to maximize bacterial killing against multidrug-resistant Gram-negative bacteria while minimizing toxicity. This study aimed to develop a mechanism-based pharmacokinetic (PK)/pharmacodynamic (PD) model (MBM) for aerosolized colistin based upon PK/PD data in neutropenic infected mice and to perform a deterministic simulation with the PK of aerosolized colistin (as CMS) in critically ill patients.
In vivo
time-kill experiments were carried out with three different strains of
Pseudomonas aeruginosa
. An MBM was developed in S-ADAPT and evaluated by assessing its ability to predict the PK/PD index associated with efficacy in mice. A deterministic simulation with human PK data was undertaken to predict the efficacy of current dosage regimens of aerosolized colistin in critically ill patients. In the final MBM, the total bacterial population for each isolate consisted of colistin-susceptible and -resistant subpopulations. The antimicrobial efficacy of aerosolized colistin was best described by a sigmoidal
E
max
model whereby colistin enhanced the rate of bacterial death. Deterministic simulation with human PK data predicted that an inhalational dosage regimen of 60 mg colistin base activity (CBA) every 12 h is needed to achieve a ≥2-log
10
bacterial reduction (as the number of CFU per lung) in critically ill patients at 24 h after commencement of inhaled therapy. In conclusion, the developed MBM is a useful tool for optimizing inhalational dosage regimens of colistin. Clinical studies are warranted to validate and refine our MBM for aerosolized colistin.
Acyclic 4-choosability of planar graphs without intersecting short cycles
Authors: Sun Yingcai , Chen Min , Chen Dong 
Published: December 2017

A proper vertex coloring of [Formula: see text] is acyclic if [Formula: see text] contains no bicolored cycle. Namely, every cycle of [Formula: see text] must be colored with at least three colors. [Formula: see text] is acyclically [Formula: see text]-colorable if for a given list assignment [Formula: see text], there exists an acyclic coloring [Formula: see text] of [Formula: see text] such that [Formula: see text] for all [Formula: see text]. If [Formula: see text] is acyclically [Formula: see text]-colorable for any list assignment with [Formula: see text] for all [Formula: see text], then [Formula: see text] is acyclically [Formula: see text]-choosable. In this paper, we prove that planar graphs without intersecting [Formula: see text]-cycles are acyclically [Formula: see text]-choosable. This provides a sufficient condition for planar graphs to be acyclically 4-choosable and also strengthens a result in [M. Montassier, A. Raspaud and W. Wang, Acyclic 4-choosability of planar graphs without cycles of specific lengths, in Topics in Discrete Mathematics, Algorithms and Combinatorics, Vol. 26 (Springer, Berlin, 2006), pp. 473–491] which says that planar graphs without [Formula: see text]-, [Formula: see text]-cycles and intersecting 3-cycles are acyclically 4-choosable.
Pleiotropic Roles for ZEB1 in Cancer
Authors: Caramel Julie , Ligier Maud , Puisieux Alain 
Published: December 2017

Abstract
ZEB1 is a prime element of a network of transcription factors that controls epithelial-to-mesenchymal transition (EMT), a reversible embryonic transdifferentiation program that allows partial or complete transition from an epithelial to a mesenchymal state. Aberrant expression of ZEB1 has been reported in a variety of human cancers, where it is generally believed to foster migration, invasion, and metastasis. Over the past few years, in vitro and in vivo observations have highlighted unsuspected intrinsic oncogenic functions of ZEB1 that impact tumorigenesis from its earliest stages. Located downstream of regulatory processes that integrate microenvironmental signals and directly implicated in feedback loops controlled by miRNAs, ZEB1 appears to be a central switch that determines cell fate. Its expression fosters malignant transformation through the mitigation of critical oncosuppressive pathways and through the conferment of stemness properties. ZEB1 is also a key determinant of cell plasticity, endowing cells with the capacity to withstand an aberrant mitogenic activity, with a profound impact on the genetic history of tumorigenesis, and to adapt to the multiple constraints encountered over the course of tumor development. Cancer Res; 78(1); 30–35. ©2017 AACR.
Research Strategies for Nutritional and Physical Activity Epidemiology and Cancer Prevention
Authors: Mahabir Somdat , Willett Walter C. , Friedenreich Christine M. , Lai Gabriel Y. , Boushey Carol J. , Matthews Charles E. , Sinha Rashmi , Colditz Graham A. , Rothwell Joseph A. , Reedy Jill , Patel Alpa V. , Leitzmann Michael F. , Fraser Gary E. , Ross Sharon , Hursting Stephen D. , Abnet Christian C. , Kushi Lawrence H. , Taylor Philip R. , Prentice Ross L. 
Published: December 2017

Abstract
Very large international and ethnic differences in cancer rates exist, are minimally explained by genetic factors, and show the huge potential for cancer prevention. A substantial portion of the differences in cancer rates can be explained by modifiable factors, and many important relationships have been documented between diet, physical activity, and obesity, and incidence of important cancers. Other related factors, such as the microbiome and the metabolome, are emerging as important intermediary components in cancer prevention. It is possible with the incorporation of newer technologies and studies including long follow-up and evaluation of effects across the life cycle, additional convincing results will be produced. However, several challenges exist for cancer researchers; for example, measurement of diet and physical activity, and lack of standardization of samples for microbiome collection, and validation of metabolomic studies. The United States National Cancer Institute convened the Research Strategies for Nutritional and Physical Activity Epidemiology and Cancer Prevention Workshop on June 28–29, 2016, in Rockville, Maryland, during which the experts addressed the state of the science and areas of emphasis. This current paper reflects the state of the science and priorities for future research. Cancer Epidemiol Biomarkers Prev; 27(3); 233–44. ©2017 AACR.
Escitalopram Impairs Thrombin-Induced Platelet Response, Cytoskeletal Assembly and Activation of Associated Signalling Pathways
Authors: Lopez-Vilchez Irene , Jerez-Dolz Didac , Diaz-Ricart Maribel , Navarro Victor , Zafar M. Urooj , Zamorano-Leon Javier , Lopez-Farre Antonio , Badimon Juan , Gasto Cristobal , Escolar Gines 
Published: December 2017

Background Serotonin reuptake inhibitors (SSRIs) may impair platelet function. Thrombin is a strong platelet agonist causing irreversible aggregation, release of granules' contents, cytoskeletal rearrangement and activation of signalling pathways. We investigated the effects of the SSRI escitalopram (SCIT) on thrombin-induced platelet response.
Methods Isolated platelets were exposed to SCIT and activated with thrombin. We evaluated (1) platelet response by aggregometry and flow cytometry; (2) modifications in cytoskeleton proteins and signalling pathways by electrophoresis and Western blot; and (3) ultrastructural changes in platelets by electron microscopy.
Results SCIT inhibited platelet response to thrombin, measured as platelet aggregation and expression of activation markers CD62-P and CD63 from platelet granules. Platelet aggregation decreased in a dose-dependent manner, reaching statistical significance with SCIT ≥32 µg/mL (65.4 ± 6.8% vs. 77.7 ± 2.5% for controls; p < 0.05). Expression of activation markers was statistically reduced with SCIT ≥20 µg/mL (p < 0.05). SCIT impaired the polymerization of the actin cytoskeleton and association of contractile proteins during activation with thrombin (p < 0.05 with SCIT ≥50 µg/mL). Resting platelets incubated with SCIT became most spherical, with increased platelet roundness (p < 0.01, SCIT 50 µg/mL vs. control). SCIT interfered with signalling pathways modulated by thrombin (RhoA, PKC, Erk1/2 and PI3K/AKT).
Conclusions Our data indicate that SCIT inhibits thrombin-induced platelet response and interferes with cytoskeletal assembly and related signalling pathways, thus resulting in compromised release of granules' contents, reduced platelet activation and aggregation. These mechanisms may explain the antithrombotic benefits observed in patients treated with this SSRI, and could become new therapeutic targets for future antithrombotic strategies.
Use of Bypassing Agents and Risk of Thromboembolic Events in Patients with Haemophilia and Inhibitors
Authors: Bykov Katsiaryna , Bohn Rhonda , Ewenstein Bruce , Seeger John , Avorn Jerry , Bateman Brian 
Published: December 2017

AbstractPatients with haemophilia and inhibitors to factors VIII or IX require bypassing therapy. The primary safety concern of bypassing agents is thromboembolism; however, the incidence of thromboembolic adverse events (TAEs) in haemophilia patients with inhibitors remains poorly characterized. The aim of this study was to assess the incidence of TAEs following exposure to bypassing agents in patients with haemophilia. Using U.S. Medicaid database (2000–2010), we identified a cohort of 719 males (mean age: 10 years at cohort entry) with haemophilia A or B and use of either recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrate (aPCC). Patients were followed up until loss of insurance eligibility, end of study period, or the first occurrence of TAE. Exposure was assessed on as-treated basis, and outcomes were adjudicated through review of healthcare claims. During the observation of a total of 2,823 person-years (py; mean follow-up: 3.9 years), 22 TAEs were identified, leading to incidence rates of 4.2 events (95% confidence interval [CI]: 1.8–8.3) per 1,000 unexposed py; 15.4 events (95% CI: 6.7–30.3) per 1,000 aPCC-exposed py; 18.2 events (95% CI: 8.3–34.6) per 1,000 rFVIIa-exposed py; and 29.7 events (95% CI: 6.1–86.7) per 1,000 py of concomitant exposure to both agents. The results were consistent across sensitivity analyses. In conclusion, we found no difference in the rate of TAEs across agents, but the data are compatible with a possibly increased rate associated with a combination therapy, highlighting the need for continuing safety monitoring through prospective registries or observational data.
Compounding Compound Creatures
Authors: Kelly Peter 
Published: December 2017

Abstract
In Tristia 4.7, Ovid describes a series of mythological hybrid creatures. This paper will argue that this catalogue of hybrids alludes to scientific accounts of the primitive creatures that existed in the early stages in the evolution of living beings, as well as literary depictions of monstrous creatures. In particular it will argue that Ovid alludes to his own Metamorphoses, Vergil’s catalogue of insubstantial monsters at A. 6.285-289, Lucretius’ account of primitive creatures at DRN 5.890-894 (a model for both the Metamorphoses and the Vergilian catalogue), and most significantly Empedocles (fr. 60 DK). It will demonstrate that Ovid ‘remythologises’ this passage from Empedocles through the use of multiple allusions to both scientific and mythological discourse, in such a way as to question a series of distinctions, such as that between science and mythology. It will also discuss whether Ovid’s catalogue of hybrids could aid a reinterpretation of the compound creatures described by Empedocles.
How Does the Evaluation of the GPM IMERG Rainfall Product Depend on Gauge Density and Rainfall Intensity?
Authors: Tian Fuqiang , Hou Shiyu , Yang Long , Hu Hongchang , Hou Aizhong 
Published: December 2017

Abstract
This study investigates the dependency of the evaluation of the Integrated Multisatellite Retrievals for Global Precipitation Measurement (IMERG) rainfall product on the gauge density of a ground-based rain gauge network as well as rainfall intensity over five subregions in mainland China. High-density rain gauges (1.5 gauges per 100 km2) provide exceptional resources for ground validation of satellite rainfall estimates over this region. Eight different gauge networks were derived with contrasting gauge densities ranging from 0.04 to 4 gauges per 100 km2. The evaluation focuses on two warm seasons (April–October) during 2014 and 2015. The results show a strong dependency of the evaluation metrics for the IMERG rainfall product on gauge density and rainfall intensity. A dense rain gauge network tends to provide better evaluation metrics, which implies that previous evaluations of the IMERG rainfall product based on a relatively low-density gauge network might have underestimated its performance. The decreasing trends of probability of detection with gauge density indicate a limited ability to capture light rainfall events in the IMERG rainfall product. However, IMERG tends to overestimate (underestimate) light (heavy) rainfall events, which is a consistent feature that does not show strong dependency on gauge densities. The results provide valuable insights for the improvement of a rainfall retrieval algorithm adopted in the IMERG rainfall product.