bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-1β (Interleukin-1β) and TNF-α (Tumor Necrosis Factor-α) Impact Abdominal Aortic Aneurysm Formation by Differential Effects on Macrophage Polarization
Authors: Batra Rishi , Suh Melissa K. , Carson Jeffrey S. , Dale Matthew A. , Meisinger Trevor M. , Fitzgerald Matthew , Opperman Patrick J. , Luo Jiangtao , Pipinos Iraklis I. , Xiong Wanfen , Baxter B. Timothy 
Published: December 2017

Objective—
Abdominal aortic aneurysms are inflammatory in nature and are associated with some risk factors that also lead to atherosclerotic occlusive disease, most notably smoking. The purpose of our study was to identify differential cytokine expression in patients with abdominal aortic aneurysm and those with atherosclerotic occlusive disease. Based on this analysis, we further explored and compared the mechanism of action of IL (interleukin)-1β versus TNF-α (tumor necrosis factor-α) in abdominal aortic aneurysm formation.

Approach and Results—

IL-1β was differentially expressed in human plasma with lower levels detected in patients with abdominal aortic aneurysm compared with matched atherosclerotic controls. We further explored its mechanism of action using a murine model and cell culture. Genetic deletion of IL-1β and IL-1R did not inhibit aneurysm formation or decrease MMP (matrix metalloproteinase) expression. The effects of IL-1β deletion on M1 macrophage polarization were compared with another proinflammatory cytokine, TNF-α. Bone marrow-derived macrophages from IL-1β
−/−
and TNF-α
−/−
mice were polarized to an M1 phenotype. TNF-α deletion, but not IL-1β deletion, inhibited M1 macrophage polarization. Infusion of M1 polarized TNF-α
−/−
macrophages inhibited aortic diameter growth; no inhibitory effect was seen in mice infused with M1 polarized IL-1β
−/−
macrophages.

Conclusions—
Although IL-1β is a proinflammatory cytokine, its effects on aneurysm formation and macrophage polarization differ from TNF-α. The differential effects of IL-1β and TNF-α inhibition are related to M1/M2 macrophage polarization and this may account for the differences in clinical efficacy of IL-1β and TNF-α antibody therapies in management of inflammatory diseases.
Macrophage-Associated Lipin-1 Enzymatic Activity Contributes to Modified Low-Density Lipoprotein–Induced Proinflammatory Signaling and Atherosclerosis
Authors: Vozenilek Aimee E. , Navratil Aaron R. , Green Jonette M. , Coleman David T. , Blackburn Cassidy M.R. , Finney Alexandra C. , Pearson Brenna H. , Chrast Roman , Finck Brian N. , Klein Ronald L. , Orr A. Wayne , Woolard Matthew D. 
Published: December 2017

Objective—
Macrophage proinflammatory responses induced by modified low-density lipoproteins (modLDL) contribute to atherosclerotic progression. How modLDL causes macrophages to become proinflammatory is still enigmatic. Macrophage foam cell formation induced by modLDL requires glycerolipid synthesis. Lipin-1, a key enzyme in the glycerolipid synthesis pathway, contributes to modLDL-elicited macrophage proinflammatory responses in vitro. The objective of this study was to determine whether macrophage-associated lipin-1 contributes to atherogenesis and to assess its role in modLDL-mediated signaling in macrophages.

Approach and Results—
We developed mice lacking lipin-1 in myeloid-derived cells and used adeno-associated viral vector 8 expressing the gain-of-function mutation of mouse proprotein convertase subtilisin/kexin type 9 (adeno-associated viral vector 8-proprotein convertase subtilisin/kexin type 9) to induce hypercholesterolemia and plaque formation. Mice lacking myeloid-associated lipin-1 had reduced atherosclerotic burden compared with control mice despite similar plasma lipid levels. Stimulation of bone marrow–derived macrophages with modLDL activated a persistent protein kinase Cα/βII–extracellular receptor kinase1/2–jun proto-oncogene signaling cascade that contributed to macrophage proinflammatory responses that was dependent on lipin-1 enzymatic activity.

Conclusions—
Our data demonstrate that macrophage-associated lipin-1 is atherogenic, likely through persistent activation of a protein kinase Cα/βII–extracellular receptor kinase1/2–jun proto-oncogene signaling cascade that contributes to foam cell proinflammatory responses. Taken together, these results suggest that modLDL-induced foam cell formation and modLDL-induced macrophage proinflammatory responses are not independent consequences of modLDL stimulation but rather are both directly influenced by enhanced lipid synthesis.
Loss of Vascular Myogenic Tone in miR-143/145 Knockout Mice Is Associated With Hypertension-Induced Vascular Lesions in Small Mesenteric Arteries
Authors: Holmberg Johan , Bhattachariya Anirban , Alajbegovic Azra , Rippe Catarina , Ekman Mari , Dahan Diana , Hien Tran Thi , Boettger Thomas , Braun Thomas , Swärd Karl , Hellstrand Per , Albinsson Sebastian 
Published: December 2017

Objective—
Pressure-induced myogenic tone is involved in autoregulation of local blood flow and confers protection against excessive pressure levels in small arteries and capillaries. Myogenic tone is dependent on smooth muscle microRNAs (miRNAs), but the identity of these miRNAs is unclear. Furthermore, the consequences of altered myogenic tone for hypertension-induced damage to small arteries are not well understood.

Approach and Results—
The importance of smooth muscle–enriched microRNAs, miR-143/145, for myogenic tone was evaluated in miR-143/145 knockout mice. Furthermore, hypertension-induced vascular injury was evaluated in mesenteric arteries in vivo after angiotensin II infusion. Myogenic tone was abolished in miR-143/145 knockout mesenteric arteries, whereas contraction in response to calyculin A and potassium chloride was reduced by ≈30%. Furthermore, myogenic responsiveness was potentiated by angiotensin II in wild-type but not in knockout mice. Angiotensin II administration in vivo elevated systemic blood pressure in both genotypes. Hypertensive knockout mice developed severe vascular lesions characterized by vascular inflammation, adventitial fibrosis, and neointimal hyperplasia in small mesenteric arteries. This was associated with depolymerization of actin filaments and fragmentation of the elastic laminae at the sites of vascular lesions.

Conclusions—
This study demonstrates that miR-143/145 expression is essential for myogenic responsiveness. During hypertension, loss of myogenic tone results in potentially damaging levels of mechanical stress and detrimental effects on small arteries. The results presented herein provide novel insights into the pathogenesis of vascular disease and emphasize the importance of controlling mechanical factors to maintain structural integrity of the vascular wall.
The Croatia v. Slovenia Arbitration: The Silver Lining
Authors: Meshel Tamar 
Published: December 2017

Abstract
Much controversy has surrounded the recent arbitration between Croatia and Slovenia. Nonetheless, the proceedings represent a welcome step in the right direction in terms of the perception and use of arbitration as a quasi-diplomatic interstate dispute resolution mechanism. Such an approach to arbitration is evident both in the parties’ arbitration agreement and in the arbitral tribunal’s final award in this case. The article first explains the proper use of interstate arbitration in its original form as a quasi-diplomatic process. This process produces a final and binding decision that respects international law yet does not necessarily rely solely on it. The article then examines how this original quasi-diplomatic nature of interstate arbitration is reflected in certain aspects of the Croatia v. Slovenia case.
Procedural Developments at the International Court of Justice
Authors: Bordin Fernando Lusa 
Published: December 2017

Abstract
The present column covers procedural developments at the International Court of Justice for the period spanning from 1 July 2015 to 31 March 2017. Those developments involve the existence of a dispute as a condition for the Court’s jurisdiction; the interpretation of compromissory clauses; the interpretation of declarations made under Article 36(2) of the icj Statute (the “Optional Clause”); the principles of res judicata, ne bis in idem and exhaustion of treaty processes; the indispensable third parties doctrine; the admissibility of requests to enforce judgments of the Court; issues of admissibility arising from multilateral disputes; and allocation of costs under Article 64 of the Statute.
Res judicata, Jurisdiction ratione materiae and Legal Reasoning in the Dispute between Nicaragua and Colombia before the International Court of Justice
Authors: Sarzo Matteo 
Published: December 2017

Abstract
With the aim of barring Nicaragua’s fresh request for the delimitation of the continental shelf beyond 200 nautical miles, Colombia raised the issue of the res judicata effect of the previous decision of 2012, rendered in the Territorial and Maritime Dispute, whereby the icj had apparently settled the case and dismissed on the merits the same request. In the Judgment on preliminary objections of 2016, relating to the “new” case Question of the Delimitation of the Continental Shelf between Nicaragua and Colombia beyond 200 nautical miles from the Nicaraguan Coast, the icj held that no binding force attached to the operative part of the 2012 ruling. The outcome of the incidental proceedings was not predictable as one might have expected, given that the decision was taken with the casting vote of the President and prompted a strong dissent among some judges. This occurrence gives clear evidence of the interplay between several intertwined issues of international law, which the majority was called upon to deal with and balance in the present case, such as the interpretation of Article 76, paragraph 8 of the unclos, the principles of res judicata and jurisdiction ratione materiae and the duty to give reasons. The article aims to demonstrate that the Court dismissed Colombia’s third preliminary objection for underlying reasons of judicial policy, namely to secure its previous judgment of 2012 from any potential claim relating to inadequate reasoning, if construed as a final rejection on the merits.
The Impact of Airborne Radio Occultation Observations on the Simulation of Hurricane Karl (2010)
Authors: Chen X. M. , Chen S.-H. , Haase J. S. , Murphy B. J. , Wang K.-N. , Garrison J. L. , Chen S. Y. , Huang C. Y. , Adhikari L. , Xie F. 
Published: December 2017

Abstract
This study evaluates, for the first time, the impact of airborne global positioning system radio occultation (ARO) observations on a hurricane forecast. A case study was conducted of Hurricane Karl during the Pre-Depression Investigation of Cloud-Systems in the Tropics (PREDICT) field campaign in 2010. The assimilation of ARO data was developed for the three-dimensional variational (3DVAR) analysis system of the Weather Research and Forecasting (WRF) Model version 3.2. The impact of ARO data on Karl forecasts was evaluated through data assimilation (DA) experiments of local refractivity and nonlocal excess phase (EPH), in which the latter accounts for the integrated horizontal sampling along the signal ray path. The tangent point positions (closest point of an RO ray path to Earth’s surface) drift horizontally, and the drifting distance of ARO data is about 2 to 3 times that of spaceborne RO, which was taken into account in these simulations.
Results indicate that in the absence of other satellite observations, the assimilation of ARO EPH resulted in a larger impact on the analysis than local refractivity did. In particular, the assimilation of ARO observations at the actual tangent point locations resulted in more accurate forecasts of the rapid intensification of the storm. Among all experiments, the best forecast was obtained by assimilating ARO data with the most accurate geometric representation, that is, the use of nonlocal EPH operators with tangent point drift, which reduced the error in the storm’s predicted minimum sea level pressure (SLP) by 43% beyond that of the control experiment.
How Well Can the Met Office Unified Model Forecast Tropical Cyclones in the Western North Pacific?
Authors: Short Chris J. , Petch Jon 
Published: December 2017

AbstractConvection-permitting numerical weather prediction models are a key tool for forecasting tropical cyclone (TC) intensities, intensity changes, and precipitation. The Met Office has been routinely running a regional (4.4-km grid spacing), explicit convection version of its Unified Model (UM) over the Philippines since August 2014, driven by its operational global model. The principal aim of this study is to assess the performance of this model relative to the driving global model. By evaluating over a year’s worth of operational TC forecasts, it is shown that the Philippines regional model offers clear benefits for TC forecasting compared with the Met Office global model. In particular, it provides much improved predictions for the intensities of strong storms (category 3 and above) and can successfully capture some rapid intensification (RI) events, whereas the global model cannot predict RI at all. The spatial location of rainfall within intense TCs is also more skillfully predicted by the regional model, and the statistical distribution of rain rates is closer to that observed. Although the regional model adds value, notable biases are also identified, highlighting areas for future work to develop and improve the model.
Probiotic supplementation in sports and physical exercise: Does it present any ergogenic effect?
Authors: Coqueiro Audrey Yule , de Oliveira Garcia Amanda Beatriz , Rogero Marcelo Macedo , Tirapegui Julio 
Published: December 2017

Background: Probiotics are live microorganisms that promote health benefits to the host. Evidence indicates that some probiotic strains play an immunomodulatory role and reduce the incidence of respiratory and gastrointestinal infections in athletes and in physical activity practitioners. For this reason, probiotic supplementation could indirectly improve exercise performance. However, recent studies have observed direct ergogenic effects of probiotics, but the mechanisms of action are poorly elucidated. Objective: In this study, we aim to synthesize available knowledge on the effect of probiotics on physical exercise, identify the mechanisms of action by which probiotics could improve performance directly and indirectly, and verify whether probiotics have any ergogenic effect. Methods: The study was performed in the PubMed database in February 2017, without limitation as to the publication period. The keyword combinations used were: ‘Probiotics’ and ‘Sports’ ( n = 17 articles), ‘Probiotics’ and ‘Exercise’ ( n = 26 articles) and ‘Probiotics’ and ‘Athletes’ ( n = 11 articles). Results: Of the 16 studies evaluated, only six applied performance tests, of which only two demonstrated that probiotic supplementation increases performance, but one of them was performed with mice. Conclusions: According to the studies evaluated, probiotic supplementation does not present ergogenic effect, however, considering the small number of studies, this subject should be better investigated.
The design and rationale of an interdisciplinary, non-prescriptive, and Health at Every Size®-based clinical trial: The “Health and Wellness in Obesity” study
Authors: Ulian Mariana D , Gualano Bruno , Benatti Fabiana B , de Campos-Ferraz Patricia Lopes , Coelho Desire , Roble Odilon J , Sabatini Fernanda , Perez Isabel , Aburad Luiz , Pinto Ana Jéssica , Vessoni André , Victor Jhessica Campos , Lima Victoria Kupper , Unsain Ramiro Fernandez , de Morais Sato Priscila , Rogero Marcelo Macedo , Toporcov Tatiana Natasha , Scagliusi Fernanda B 
Published: December 2017

Background: This manuscript describes the design and rationale of a clinical trial that aims to investigate the multiple physiological, attitudinal, nutritional, and behavioral effects of a new interdisciplinary intervention based on the Health at Every Size® (HAES®) approach in obese women. Methods: This will be a prospective, 7-month, randomized (2:1), mixed-method clinical trial. Obese women will be recruited and randomly allocated into two groups. The intervention group (I-HAES®; proposed n = 40) will undertake a novel HAES®-based intervention. Participants will take part in an exercise program, nutrition counseling sessions, and philosophical workshops, all aligned with the principles of the HAES® approach. The control group (CTRL; proposed n = 20) will participate in a program using a traditional HAES®-based group format, characterized by bimonthly lectures about the same topics offered to the experimental group, encouraging the adoption of a healthy lifestyle. The following multiple quantitative outcomes will be assessed pre and post intervention: health-related quality of life, cardiovascular risk factors, anthropometric assessments, physical activity level, physical capacity and function, and psychological and behavioral assessments. Qualitative analysis will be used to evaluate the experiences of the participants throughout the intervention, as assessed by focus groups and semi-structured interviews. Conclusions: The interdisciplinary research team leading this study has varied and complementary expertise. The knowledge arising from this study will help to guide new interdisciplinary interventions with the potential to holistically improve the health of obese individuals. This trial is registered at Clinicaltrials.gov (NCT02102061).
Creatine supplementation elicits greater muscle hypertrophy in upper than lower limbs and trunk in resistance-trained men
Authors: Nunes João Pedro , Ribeiro Alex S , Schoenfeld Brad J , Tomeleri Crisieli M , Avelar Ademar , Trindade Michele CC , Nabuco Hellen CG , Cavalcante Edilaine F , Junior Paulo Sugihara , Fernandes Rodrigo R , Carvalho Ferdinando O , Cyrino Edilson S 
Published: December 2017

Background: Creatine (Cr) supplementation associated with resistance training produces greater muscular strength improvements in the upper compared with the lower body; however, no study has investigated if such region-specific results are seen with gains in muscle mass. Aim: We aimed to evaluate the effect of Cr supplementation in combination with resistance training on lean soft tissue changes in the upper and lower limbs and trunk in resistance-trained young adult men. Methods: In a randomized, double-blind and placebo-controlled design, 43 resistance-trained men (22.7 ± 3.0 years, 72.9 ± 8.7 kg, 177.9 ± 5.7 cm, 23.0 ± 2.5 kg/m2) received either creatine (Cr, n = 22) or placebo (PLA, n = 21) over an 8-week study period. The supplementation protocol included a loading phase (7 days, four doses of 0.3 g/kg per day) and a maintenance phase (7 weeks, single dose of 0.03 g/kg per day). During the same period, subjects performed resistance training four times per week using the following two-way split routine: Monday and Thursday = pectoral, shoulders, triceps, and abdomen, Tuesday and Friday = back, biceps, thighs, and calves. Lean soft tissue of the upper limbs (ULLST), lower limbs (LLLST), and trunk (TLST) was assessed by dual-energy X-ray absorptiometry before and after the intervention. Results: Both groups showed significant ( p < 0.001) improvements in ULLST, LLLST, TLST, and the Cr group achieved greater ( p < 0.001) increases in these outcomes compared with PLA. For the Cr group, improvements in ULLST (7.1 ± 2.9%) were higher than those observed in LLLST (3.2 ± 2.1%) and TLST (2.1 ± 2.2%). Otherwise, for PLA group there was no significant difference in the magnitude of segmental muscle hypertrophy (ULLST = 1.6 ± 3.0%; LLLST = 0.7 ± 2.8%; TLST = 0.7 ± 2.8%). Conclusion: Our results suggest that Cr supplementation can positively augment muscle hypertrophy in resistance-trained young adult men, particularly in the upper limbs.
In vivo and ex vivo analyses of amyloid toxicity in the Tc1 mouse model of Down syndrome
Authors: Naert Gaëlle , Ferré Valentine , Keller Emeline , Slender Amy , Gibbins Dorota , Fisher Elizabeth MC , Tybulewicz Victor LJ , Maurice Tangui 
Published: December 2017

Rationale: The prevalence of Alzheimer’s disease is increased in people with Down syndrome. The pathology appears much earlier than in the general population, suggesting a predisposition to develop Alzheimer’s disease. Down syndrome results from trisomy of human chromosome 21, leading to overexpression of possible Alzheimer’s disease candidate genes, such as amyloid precursor protein gene. To better understand how the Down syndrome context results in increased vulnerability to Alzheimer’s disease, we analysed amyloid-β [25-35] peptide toxicity in the Tc1 mouse model of Down syndrome, in which ~75% of protein coding genes are functionally trisomic but, importantly, not amyloid precursor protein. Results: Intracerebroventricular injection of oligomeric amyloid-β [25-35] peptide in three-month-old wildtype mice induced learning deficits, oxidative stress, synaptic marker alterations, activation of glycogen synthase kinase-3β, inhibition of protein kinase B (AKT), and apoptotic pathways as compared to scrambled peptide-treated wildtype mice. Scrambled peptide-treated Tc1 mice presented high levels of toxicity markers as compared to wildtype mice. Amyloid-β [25-35] peptide injection in Tc1 mice induced significant learning deficits and enhanced glycogen synthase kinase-3β activity in the cortex and expression of apoptotic markers in the hippocampus and cortex. Interestingly, several markers, including oxidative stress, synaptic markers, glycogen synthase kinase-3β activity in the hippocampus and AKT activity in the hippocampus and cortex, were unaffected by amyloid-β [25-35] peptide injection in Tc1 mice. Conclusions: Tc1 mice present several toxicity markers similar to those observed in amyloid-β [25-35] peptide-treated wildtype mice, suggesting that developmental modifications in these mice modify their response to amyloid peptide. However, amyloid toxicity led to severe memory deficits in this Down syndrome mouse model.
Exploring Perceived Barriers to Medication Adherence and the Use of Mobile Technology in Underserved Patients With Chronic Conditions
Authors: Hincapie Ana L. , Gupta Vasudha , Brown Stephenne A. , Metzger Anne H. 
Published: December 2017

Background and Objective: Evidence suggests that the prevalence of medication nonadherence is greater in medically underserved, low-income communities. There is paucity of qualitative data examining the potential use of mobile health (mHealth) in underserved patients. This study aimed to explore barriers to medication adherence and identify opportunities and challenges for the potential use of mHealth adherence interventions in an underserved population. Methods: A qualitative cross-sectional focus group was conducted. Focus groups were conducted with underserved patients recruited at a federally qualified health center. The Health Belief Model was used as theoretical framework to develop the focus group guide. Audio-recorded data were transcribed and thematically analyzed to identify common themes across the data set. Results: Seventeen patients participated in 4 focus groups. Findings were organized by the following themes: (1) perceived barriers to medication adherence, (2) everyday practices used to improve medication adherence, and (3) perceived benefits and barriers to technology use. Use of text messages seemed beneficial; however, not carrying a phone always was a significant barrier for patients. Some patients expressed willingness to try smartphone applications but stated that they would not be able to afford them. Changes in daily routine and complexity of medication regimens were seen as barriers to medication adherence. Conclusions: Findings underscore the importance of considering diverse experiences when engaging patients in mHealth for medication adherence. Providing patient-centered approaches to assist patients construct their individualized medication adherence strategies may lead to better outcomes.