bluuebunny/crossref_metadata_2025_split huggingface dataset:
The shear stess profile of the pivotal fenestrated endograft at the level of the renal branches: A computational study for complex aortic aneurysms
Authors: Georgakarakos Efstratios , Xenakis Antonios , Bisdas Theodosios , Georgiadis George S , Schoretsanitis Nikolaos , Antoniou George A , Lazarides Miltos 
Published: August 2015

Purpose This study investigated the impact of the variant angulations on the values and distribution of wall shear stress on the renal branches and the mating vessels of a pivotal fenestrated design. Methods An idealized endograft model of two renal branches was computationally reconstructed with variable angulations of the left renal branch. These ranged from the 1:30' to 3:30' o'clock position, corresponding from 45° to 105° with increments of 15°. A fluid-structure-interaction analysis was performed to estimate the wall shear stress. Results The proximal part of the renal branch preserved quite constant wall shear stress. The transition zone between its distal end and the renal artery showed the highest values compared to the proximal and middle segments, ranging from 8.9 to 12.4 Pa. The lowest stress values presented at 90° whereas the highest at 45°. The post-mating arterial segment showed constantly low stress values regardless of the pivotal branch angle (6.3 to 6.6 Pa). The 45° configuration showed a distribution of the highest stress posteriorly whereas the 105°-angulation anteriorly. Conclusions The variant horizontal branch orientation influences the wall shear stress distribution across its length and affects its values only at its transition with the mating vessel. These findings and their potential association with adverse effects deserve further clinical validation.
Mortality outcomes of ruptured abdominal aortic aneurysms and rural presentation
Authors: Munday Emily , Walker Stuart 
Published: August 2015

Objectives Centralisation of vascular surgery services has coincided with a move towards endovascular repair of ruptured abdominal aortic aneurysms with the goal to improve patient outcomes. The aim of this study was to assess the effect of rural presentation and transfer times on survival from ruptured abdominal aortic aneurysm. Design A retrospective review. Materials All patients presenting with ruptured abdominal aortic aneurysm to public hospitals in Tasmania between July 2006 and April 2013. Methods Demographic data, Glasgow aneurysm score, Hardman index, transfer times, operative technique and 30-day mortality were collected from medical records. Results Over the study period 127 patients presented to public hospitals in Tasmania with ruptured abdominal aortic aneurysm. A total of 27 presented to north west hospitals where no vascular surgery service is provided (NWRH), 23 to a northern hospital where an intermittent vascular surgery service is provided (LGH) and 77 to the state tertiary vascular surgery service (RHH). Of these, 4 (14.8%) died at NWRH, 6 (26.1%) died at LGH and 43 (55.8%) died at RHH without operation. Of the 35 patients transferred from NWRH and LGH to RHH, 5 died without operation. Median time from presentation to theatre at RHH if transferred from NWRH was 6.25 hours, from the LGH 4.75 hours, compared to 2.75 hours when presenting directly to RHH. Open repair was performed in 41 patients and endovascular repair in 23 patients. Overall 30-day mortality in those treated at RHH was 26.6% (39.0% for open repair, 4.3% for endovascular repair). Mortality for intended operative patients initially presenting to non-RHH hospitals was 33.3% vs. 32.3% for those initially presenting to RHH. p Value 0.93. Conclusion There was no clinical or statistical disadvantage to rural presentation and transfer for patients presenting with ruptured abdominal aortic aneurysm in Tasmania. Endovascular repair has a role despite long transfer times.
Parsimonious Description of Glucose Variability in Type 2 Diabetes by Sparse Principal Component Analysis
Authors: Fabris Chiara , Facchinetti Andrea , Fico Giuseppe , Sambo Francesco , Arredondo Maria Teresa , Cobelli Claudio ,   on behalf of the MOSAIC EU Project Consortium
Published: August 2015

Background: Abnormal glucose variability (GV) is a risk factor for diabetes complications, and tens of indices for its quantification from continuous glucose monitoring (CGM) time series have been proposed. However, the information carried by these indices is redundant, and a parsimonious description of GV can be obtained through sparse principal component analysis (SPCA). We have recently shown that a set of 10 metrics selected by SPCA is able to describe more than 60% of the variance of 25 GV indicators in type 1 diabetes (T1D). Here, we want to extend the application of SPCA to type 2 diabetes (T2D). Methods: A data set of CGM time series collected in 13 T2D subjects was considered. The 25 GV indices considered for T1D were evaluated. SPCA was used to select a subset of indices able to describe the majority of the original variance. Results: A subset of 10 indicators was selected and allowed to describe 83% of the variance of the original pool of 25 indices. Four metrics sufficient to describe 67% of the original variance turned out to be shared by the parsimonious sets of indices in T1D and T2D. Conclusions: Starting from a pool of 25 indices assessed from CGM time series in T2D subjects, reduced subsets of metrics virtually providing the same information content can be determined by SPCA. The fact that these indices also appear in the parsimonious description of GV in T1D may indicate that they could be particularly informative of GV in diabetes, regardless of the specific type of disease.
Decreased eGFR as a Risk Factor for Heart Failure in 13 781 Individuals With Type 1 Diabetes
Authors: Vestberg Daniel , Rosengren Annika , Olsson Marita , Gudbjörnsdottir Soffia , Haraldsson Börje , Svensson Ann-Marie , Lind Marcus 
Published: August 2015

Background: Impaired renal function is a well-known risk factor of cardiovascular disease, but its relation to heart failure in individuals with type 1 diabetes has been sparsely studied. The aim of our study was to quantify the risk increase for development of heart failure with decreasing kidney function in individuals with type 1 diabetes. Methods: Three equations were used to calculate eGFR (estimated glomerular filtration rate) for individuals with T1D and no known heart failure in the Swedish National Diabetes Registry. Proportional hazards regression models were constructed to evaluate the association between eGFR and hospitalization for heart failure (HF). Results: Among 13 781 individuals (mean age 41.1 [SD 13.3] years at baseline), 330 (2.4%) were hospitalized for HF over median follow-up of 7.0 years. Renal function was normal (eGFR > 90 mL/min/1.73 m2) in 67% of individuals according to the Cockcroft-Gault formula, compared to 51% and 41% according to the Chronic Kidney Disease Epidemiology (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) formulas. For eGFR 45-60 ml/min/1.73 m2, hazard ratios (HRs) for hospitalization (reference >90 mL/min/1.73 m2) were 3.18 (95% CI 2.17, 4.65), 2.12 (1.16, 3.08), and 2.44 (1.69, 3.55) using the Cockcroft-Gault, MDRD, and CKD-EPI formulas. With eGFR <30 ml/min/1.73 m2 there was a HR of 3.78 (2.15, 5.91), 3.44 (2.14, 5.51), and 3.51 (2.21, 5.51) compared to normal kidney function (>90 mL/min/1.73 m2). Conclusions: In individuals with T1D, risk of hospitalization for heart failure was over 2 times greater at eGFR 45-60 ml/min/1.73 m2 and more than 3 times greater at eGFR <30 ml/min/1.73 m2 when compared to normal eGFR.
Dimethyl fumarate-associated lymphopenia: Risk factors and clinical significance
Authors: Longbrake Erin E , Naismith Robert T , Parks Becky J , Wu Gregory F , Cross Anne H 
Published: August 2015

Background Dimethyl fumarate (DMF), a disease-modifying therapy for multiple sclerosis (MS), causes lymphopenia in a fraction of patients. The clinical significance of this is unknown. Several cases of progressive multifocal leukoencephalopathy in lymphopenic fumarate-treated patients have raised concerns about drug safety. Since lymphocytes contribute to MS pathology, lymphopenia may also be a biomarker for response to the drug. Objective The objective of this manuscript is to evaluate risk factors for DMF-induced lymphopenia and drug failure in a real-world population of MS patients. Methods We conducted a retrospective cohort study of 221 patients prescribed DMF at a single academic medical center between March 2013 and February 2015. Results Grade 2–3 lymphopenia developed in 17% of the total cohort and did not resolve during DMF treatment. Older age (>55), lower baseline absolute lymphocyte count and recent natalizumab exposure increased the risk of developing moderate to severe lymphopenia while on DMF. Lymphopenia was not predictive of good clinical response or of breakthrough MS activity on DMF. Conclusions Lymphopenia develops in a significant minority of DMF-treated patients, and if grade 2 or worse, is unlikely to resolve while on the drug. Increased vigilance in lymphocyte monitoring and infection awareness is particularly warranted in older patients and those switching from natalizumab.
Transcriptome analysis highlights the conserved difference between embryonic and postnatal-derived alveolar macrophages
Authors: Gibbings Sophie L. , Goyal Rajni , Desch A. Nicole , Leach Sonia M. , Prabagar Miglena , Atif Shaikh M. , Bratton Donna L. , Janssen William , Jakubzick Claudia V. 
Published: August 2015

Key Points
Of the 30 000 genes, there are ∼0.1% genes whose expression is linked to the origin of the cell rather than the environment. Marco was most conserved by embryonic origin and not altered by the environment, whereas C1qb and Plbd1 were most conserved by adult origin.
A multicenter randomized controlled trial of intravenous magnesium for sickle cell pain crisis in children
Authors: Brousseau David C. , Scott J. Paul , Badaki-Makun Oluwakemi , Darbari Deepika S. , Chumpitazi Corrie E. , Airewele Gladstone E. , Ellison Angela M. , Smith-Whitley Kim , Mahajan Prashant , Sarnaik Sharada A. , Casper T. Charles , Cook Lawrence J. , Dean J. Michael , Leonard Julie , Hulbert Monica L. , Powell Elizabeth C. , Liem Robert I. , Hickey Robert , Krishnamurti Lakshmanan , Hillery Cheryl A. , Nimmer Mark , Panepinto Julie A. 
Published: August 2015

Key PointsIntravenous magnesium did not shorten length of stay for pain crisis in children with sickle cell anemia. Collaboration between pediatric emergency medicine and hematology allowed for successful enrollment in a sickle cell acute management trial.
IFNAR signaling directly modulates T lymphocyte activity, resulting in milder experimental autoimmune encephalomyelitis development
Authors: Kavrochorianou Nadia , Evangelidou Maria , Markogiannaki Melina , Tovey Michael , Thyphronitis George , Haralambous Sylva 
Published: August 2015

Abstract
Although interferon-β is used as first-line therapy for multiple sclerosis, the cell type-specific activity of type I interferons in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis, remains obscure. In this study, we have elucidated the in vivo immunomodulatory role of type I interferon signaling in T cells during experimental autoimmune encephalomyelitis by use of a novel transgenic mouse, carrying a cd2–ifnar1 transgene on a interferon-α/β receptor 1 null genetic background, thus allowing expression of the interferon-α/β receptor 1 and hence, a functional type I interferon receptor exclusively on T cells. These transgenic mice exhibited milder experimental autoimmune encephalomyelitis with reduced T cell infiltration, demyelination, and axonal damage in the central nervous system. It is noteworthy that interferon-β administration in transgenic mice generated a more pronounced, protective effect against experimental autoimmune encephalomyelitis compared with untreated littermates. In vivo studies demonstrated that before experimental autoimmune encephalomyelitis onset, endogenous type I interferon receptor signaling in T cells led to impaired T-helper 17 responses, with a reduced fraction of CCR6+ CD4+ T cells in the periphery. At the acute phase, an increased proportion of interleukin-10- and interferon-γ-producing CD4+ T cells was detected in the periphery of the transgenic mice, accompanied by up-regulation of the interferon-γ-induced gene Irgm1 in peripheral T cells. Together, these results reveal a hitherto unknown T cell-associated protective role of type I interferon in experimental autoimmune encephalomyelitis that may provide valuable clues for designing novel therapeutic strategies for multiple sclerosis.
Interleukin-10 production by myeloid-derived suppressor cells contributes to bacterial persistence during Staphylococcus aureus orthopedic biofilm infection
Authors: Heim Cortney E , Vidlak Debbie , Kielian Tammy 
Published: August 2015

Abstract
Staphylococcus aureus is known to establish biofilms on medical devices. We recently demonstrated that Ly6GhighLy6C+ myeloid-derived suppressor cells are critical for allowing S. aureus biofilms to subvert immune-mediated clearance; however, the mechanisms whereby myeloid-derived suppressor cells promote biofilm persistence remain unknown. Interleukin-10 expression was significantly increased in a mouse model of S. aureus orthopedic implant biofilm infection with kinetics that mirrored myeloid-derived suppressor cell recruitment. Because myeloid-derived suppressor cells produce interleukin-10, we explored whether it was involved in orchestrating the nonproductive immune response that facilitates biofilm formation. Analysis of interleukin-10–green fluorescent protein reporter mice revealed that Ly6GhighLy6C+ myeloid-derived suppressor cells were the main source of interleukin-10 during the first 2 wk of biofilm infection, whereas monocytes had negligible interleukin-10 expression until day 14. Myeloid-derived suppressor cell influx into implant-associated tissues was significantly reduced in interleukin-10 knockout mice at day 14 postinfection, concomitant with increased monocyte and macrophage infiltrates that displayed enhanced proinflammatory gene expression. Reduced myeloid-derived suppressor cell recruitment facilitated bacterial clearance, as revealed by significant decreases in S. aureus burdens in the knee joint, surrounding soft tissue, and femur of interleukin-10 knockout mice. Adoptive transfer of interleukin-10 wild-type myeloid-derived suppressor cells into S. aureus–infected interleukin-10 knockout mice restored the local biofilm-permissive environment, as evidenced by increased bacterial burdens and inhibition of monocyte proinflammatory activity. These effects were both interleukin-10-dependent and interleukin-10-independent because myeloid-derived suppressor cell–derived interleukin-10 was required for promoting biofilm growth and anti-inflammatory gene expression in monocytes but was not involved in monocyte recruitment to biofilm-infected tissues. These results demonstrate that interleukin-10 production by myeloid-derived suppressor cells contributes to the persistence of S. aureus orthopedic biofilm infections.
Senescent profile of angiogenic T cells from systemic lupus erythematosus patients
Authors: López Patricia , Rodríguez-Carrio Javier , Martínez-Zapico Aleida , Caminal-Montero Luis , Suarez Ana 
Published: August 2015

Abstract
The chronic inflammatory environment associated with systemic lupus erythematosus can lead to an accelerated immunosenescence responsible for the endothelial damage and increased cardiovascular risk observed in these patients. The present study analyzed two populations with opposite effects on vascular endothelium, angiogenic T cells and the senescent CD4+CD28null subset, in 84 systemic lupus erythematosus patients and 46 healthy controls. Also, 48 rheumatoid arthritis patients and 72 individuals with traditional cardiovascular risk factors participated as disease controls. Phenotypic characterization of CD28+ and CD28null cells was performed by analyzing markers of senescence (CCR7, CD27, CD57) and cytotoxicity (CD56, perforin, granzyme B, IFN-γ). IL-1β, IL-6, IL-8, IL-10, IL-12, IL-17A, IFN-α, IFN-γ, TNF-α, B lymphocyte stimulator, and GM-CSF serum levels were analyzed in systemic lupus erythematosus patients and healthy controls. CD4+CD28null cells were notably increased in the systemic lupus erythematosus patients and disease controls compared with healthy controls. In contrast, angiogenic T cells were only reduced in the disease controls (those with rheumatoid arthritis or traditional cardiovascular risk factors). Nevertheless, an anomalous presence of CD28null-angiogenic T cells, with cytotoxic and senescent characteristics, was noted in systemic lupus erythematosus patients in association with anti-dsDNA titer, anti-SSA/Ro antibodies and circulating TNF-α, IL-8, IFN-α, and B lymphocyte stimulator amounts. This subset was also detected in those with traditional cardiovascular risk factors but not in the rheumatoid arthritis patients. In contrast, CD28+-angiogenic T cells were reduced in the systemic lupus erythematosus patients with cardiovascular disorders. In conclusion, CD28 expression must be used to redefine the angiogenic T cell population, because in pathologic conditions, a senescent CD28null-angiogenic T cell subset with inflammatory, rather than protective, effects could be present.
Immune deficiency vs. immune excess in inflammatory bowel diseases—STAT3 as a rheo-STAT of intestinal homeostasis
Authors: Leppkes Moritz , Neurath Markus F , Herrmann Martin , Becker Christoph 
Published: August 2015

Abstract
Genome-wide association studies have provided many genetic alterations, conferring susceptibility to multifactorial polygenic diseases, such as inflammatory bowel diseases. Yet, how specific genetic alterations functionally affect intestinal inflammation often remains elusive. It is noteworthy that a large overlap of genes involved in immune deficiencies with those conferring inflammatory bowel disease risk has been noted. This has provided new arguments for the debate on whether inflammatory bowel disease arises from either an excess or a deficiency in the immune system. In this review, we highlight the functional effect of an inflammatory bowel disease-risk allele, which cannot be deduced from genome-wide association studies data alone. As exemplified by the transcription factor signal transducer and activator of transcription 3 (STAT3), we show that a single gene can have a plethora of effects in various cell types of the gut. These effects may individually contribute to the restoration of intestinal homeostasis on the one hand or pave the way for excessive immunopathology on the other, as an inflammatory “rheo-STAT”.
Structure and signaling at hydroid polyp-stolon junctions, revisited
Authors: Harmata Katherine L. , Somova Emily L. , Parrin Austin P. , Bross Lori S. , Glockling Sally L. , Blackstone Neil W. 
Published: August 2015

ABSTRACTThe gastrovascular system of colonial hydroids is central to homeostasis, yet its functional biology remains poorly understood. A probe (2′,7′-dichlorodihydrofluorescein diacetate) for reactive oxygen species (ROS) identified fluorescent objects at polyp-stolon junctions that emit high levels of ROS. A nuclear probe (Hoechst 33342) does not co-localize with these objects, while a mitochondrial probe (rhodamine 123) does. We interpret these objects as mitochondrion-rich cells. Confocal microscopy showed that this fluorescence is situated in large columnar cells. Treatment with an uncoupler (2,4-dinitrophenol) diminished the ROS levels of these cells relative to background fluorescence, as did removing the stolons connecting to a polyp-stolon junction. These observations support the hypothesis that the ROS emanate from mitochondrion-rich cells, which function by pulling open a valve at the base of the polyp. The open valve allows gastrovascular fluid from the polyp to enter the stolons and vice versa. The uncoupler shifts the mitochondrial redox state in the direction of oxidation, lowering ROS levels. By removing the stolons, the valve is not pulled open, metabolic demand is lowered, and the mitochondrion-rich cells slowly regress. Transmission electron microscopy identified mitochondrion-rich cells adjacent to a thick layer of mesoglea at polyp-stolon junctions. The myonemes of these myoepithelial cells extend from the thickened mesoglea to the rigid perisarc on the outside of the colony. The perisarc thus anchors the myoepithelial cells and allows them to pull against the mesoglea and open the lumen of the polyp-stolon junction, while relaxation of these cells closes the lumen.
Local motion detectors are required for the computation of expansion flow-fields
Authors: Schilling Tabea , Borst Alexander 
Published: August 2015

ABSTRACTAvoidance of predators or impending collisions is important for survival. Approaching objects can be mimicked by expanding flow-fields. Tethered flying fruit flies, when confronted with an expansion flow-field, reliably turn away from the pole of expansion when presented laterally, or perform a landing response when presented frontally. Here, we show that the response to an expansion flow-field is independent of the overall luminance change and edge acceleration. As we demonstrate by blocking local motion-sensing neurons T4 and T5, the response depends crucially on the neural computation of appropriately aligned local motion vectors, using the same hardware that also controls the optomotor response to rotational flow-fields.
Estradiol Preferentially Induces Progestin Receptor-A (PR-A) Over PR-B in Cells Expressing Nuclear Receptor Coactivators in the Female Mouse Hypothalamus
Authors: Acharya Kalpana D. , Finkelstein Sarah D. , Bless Elizabeth P. , Nettles Sabin A. , Mulac-Jericevic Biserka , Conneely Orla M. , Mani Shaila K. , Tetel Marc J. 
Published: August 2015

AbstractEstrogens act in brain to profoundly influence neurogenesis, sexual differentiation, neuroprotection, cognition, energy homeostasis, and female reproductive behavior and physiology through a variety of mechanisms, including the induction of progestin receptors (PRs). PRs are expressed as two isoforms, PR-A and PR-B, that have distinct functions in physiology and behavior. Because these PR isoforms cannot be distinguished using cellular resolution techniques, the present study used isoform-specific null mutant mice that lack PR-A or PR-B for the first time to investigate whether 17β-estradiol benzoate (EB) regulates the differential expression of the PR isoforms in the ventromedial nucleus of the hypothalamus (VMN), arcuate nucleus, and medial preoptic area, brain regions that are rich in EB-induced PRs. Interestingly, EB induced more PR-A than PR-B in all three brain regions, suggesting that PR-A is the predominant isoform in these regions. Given that steroid receptor coactivator (SRC)-1 and SRC-2 are important in estrogen receptor (ER)-dependent transcription in brain, including PR induction, we tested whether the expression of these coactivators was correlated with PR isoform expression. The majority of EB-induced PR cells expressed both SRC-1 and SRC-2 in the three brain regions of all genotypes. Interestingly, the intensity of PR-A immunoreactivity correlated with SRC-2 expression in the VMN, providing a potential mechanism for selective ER-mediated transactivation of PR-A over PR-B in a brain region-specific manner. In summary, these novel findings indicate that estrogens differentially regulate PR-A and PR-B expression in the female hypothalamus, and provide a mechanism by which steroid action in brain can selectively modulate behavior and physiology.