bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac autonomic dysfunction in survivors of childhood acute lymphoblastic leukemia: The St. Jude Lifetime Cohort Study
Authors: Christoffersen Lindsey , Gibson Todd M. , Pui Ching‐Hon , Joshi Vijaya , Partin Robyn E. , Green Daniel M. , Lanctot Jennifer Q. , Howell Carrie R. , Mulrooney Daniel A. , Armstrong Gregory T. , Robison Leslie L. , Hudson Melissa M. , Ness Kirsten K. 
Published: May 2020

AbstractBackgroundCardiac autonomic dysfunction (CAD) is possible following treatment for childhood cancer. The aims of our analyses were to compare the prevalence of CAD between adult survivors of childhood acute lymphoblastic leukemia and controls, compare exercise response among survivors with and without CAD, and identify treatment‐related risk factors for CAD.ProcedureParticipants were treated for childhood acute lymphoblastic leukemia at St. Jude Children's Research Hospital between 1980 and 2003 (N = 338). A comparison group matched for race/ethnicity, age, and sex was also recruited (N = 325). Resting heart rate (HR) was assessed via electrocardiogram, and heart rate recovery (HRR) and exercise capacity were evaluated with submaximal cardiopulmonary exercise testing.ResultsCAD was present in 33.7% of survivors and 27.6% of controls (P = 0.09). Although mean resting HR did not differ between survivors and controls (74 ± 12 vs 72 ± 12 beats per minute (bpm), P = 0.07), survivors had lower mean HRR than controls (22 ± 9 vs 25 ± 10 bpm; P < 0.001). Survivors with CAD had lower peak exercise tolerance (25.7 ± 6.5 vs 21.2 ± 4.9 mL/kg/min, P < 0.001) than those without. Survivors treated with cyclophosphamide in combination with vincristine ≥38 mg/m2 and/or glucocorticoids ≥10 000 mg/m2 were 1.56 (95% CI 1.09‐2.24) times more likely to have CAD than those without this treatment. Obese survivors were 1.78 (95% CI: 1.31‐2.40) times more likely to have CAD than nonobese survivors (P < 0.001).ConclusionCAD was present in over one third of survivors and was associated with lower exercise capacity. Obese survivors and those exposed to cyclophosphamide with high doses of vincristine and/or corticosteroids were at greatest risk.
Human cord blood-derived regulatory T-cell therapy modulates the central and peripheral immune response after traumatic brain injury
Authors: Caplan Henry W. , Prabhakara Karthik S. , Kumar Akshita , Toledano-Furman Naama E. , Martin Cecilia , Carrillo Louis , Moreno Nicolas F. , Bordt Andrea S. , Olson Scott D. , Cox Charles S. 
Published: May 2020

Abstract
Traumatic brain injury (TBI) causes a profound inflammatory response within the central nervous system and peripheral immune system, which contributes to secondary brain injury and further morbidity and mortality. Preclinical investigations have demonstrated that treatments that downregulate microglia activation and polarize them toward a reparative/anti-inflammatory phenotype have improved outcomes in preclinical models. However, no therapy to date has translated into proven benefits in human patients. Regulatory T cells (Treg) have been shown to downregulate pathologic immune responses of the innate and adaptive immune system across a variety of pathologies. Furthermore, cellular therapy has been shown to augment host Treg responses in preclinical models; yet, studies investigating the use of Treg as a therapeutic for TBI are lacking. In a rodent TBI model, we demonstrate that human umbilical cord blood Treg modulate the central and peripheral immune response after injury in vitro and in vivo.

Significance statement This study demonstrates that human regulatory T cells (Treg) expanded from umbilical cord blood can reduce neuroinflammation associated with traumatic brain injury. A single dose of Treg can cause long-term changes in brain microgliosis in chronic TBI.
Detection of Ring and Adatom Defects in Activated Disordered Carbon via Fluctuation Nanobeam Electron Diffraction
Authors: Martin Andrew V. , Bøjesen Espen D. , Petersen Timothy C. , Hu Cheng , Biggs Mark J. , Weyland Matthew , Liu Amelia C. Y. 
Published: May 2020

AbstractHow the structure of disordered porous carbons evolves during their activation is particularly poorly understood. This problem endures primarily because of a lack of high‐resolution 3D techniques for the characterization of amorphous and highly disordered structure. To address this, the measurement of the 3D pair‐angle distribution function using nanodiffraction patterns from high‐energy electrons is demonstrated. These rich multiatom correlations are measured for a disordered carbon and they clearly show the structural evolution during activation. They provide previously inaccessible bond‐angle information and direct evidence for the presence of ring and adatom defects. An increase in the short‐range order and the number of fivefold ring defects with activation are observed, indicating stress relaxation by increasing curvature. These observations support models of disordered porous carbons based on curved graphene networks and explain how large amounts of free volume can be created with surprisingly small changes in the average ratios of tetrahedral to graphitic bonding.
A Dopant Replacement‐Driven Molten Salt Method toward the Synthesis of Sub‐5‐nm‐Sized Ultrathin Nanowires
Authors: Mao Yihua , Yang Xuwen , Gong Wenbin , Zhang Jing , Pan Ting , Sun Hongzhao , Chen Zhigang , Wang Zhen , Zhu Junfa , Hu Jun , Cong Shan , Geng Fengxia , Zhao Zhigang 
Published: May 2020

AbstractThe high‐temperature molten‐salt method is an important inorganic synthetic route to a wide variety of morphological phenotypes. However, its utility is limited by the fact that it is typically incapable of producing ultrathin (<5 nm diameter) nanowires, which have a crucial role in novel nanotechnology applications. Herein, a rapid molten salt‐based synthesis of sub‐5‐nm‐sized nanowires of hexagonal tungsten oxide (h‐WO3) that is critically dependent on a substantial proportion of molybdenum (Mo) dopant is described. This dopant‐driven morphological transition in tungsten oxide (WO3) may be attributable to the collapse of layered structure, followed by nanocluster aggregation, coalescence, and recrystallization to form ultrathin nanowires. Interestingly, due to the structural properties of h‐WO3, the thus‐formed ultrathin nanowires are demonstrated to be excellent photocatalysts for the production of ammonia (NH3) from nitrogen (N2) and water. The ultrathin nanowires exhibit a high photocatalytic NH3‐production activity with a rate of 370 µmol g−1 h−1 and an apparent quantum efficiency of 0.84% at 420 nm, which is more than twice that obtained from the best‐performing Mo‐doped W18O49 nanowire catalysts. It is envisaged that the dopant replacement‐driven synthetic protocol will allow for rapid access to a series of ultrathin nanostructures with intriguing properties and increase potential applications.
The secreted inhibitor of invasive cell growth CREG1 is negatively regulated by cathepsin proteases
Authors: Gomez-Auli Alejandro , Hillebrand Larissa Elisabeth , Christen Daniel , Günther Sira Carolin , Biniossek Martin Lothar , Peters Christoph , Schilling Oliver , Reinheckel Thomas 
Published: May 2020

AbstractPrevious clinical and experimental evidence strongly supports a breast cancer-promoting function of the lysosomal protease cathepsin B. However, the cathepsin B-dependent molecular pathways are not completely understood. Here, we studied the cathepsin-mediated secretome changes in the context of the MMTV-PyMT breast cancer mouse model. Employing the cell-conditioned media from tumor-macrophage co-cultures, as well as tumor interstitial fluid obtained by a novel strategy from PyMT mice with differential cathepsin B expression, we identified an important proteolytic and lysosomal signature, highlighting the importance of this organelle and these enzymes in the tumor micro-environment. The Cellular Repressor of E1A Stimulated Genes 1 (CREG1), a secreted endolysosomal glycoprotein, displayed reduced abundance upon over-expression of cathepsin B as well as increased abundance upon cathepsin B deletion or inhibition. Moreover, it was cleaved by cathepsin B in vitro. CREG1 reportedly could act as tumor suppressor. We show that treatment of PyMT tumor cells with recombinant CREG1 reduced proliferation, migration, and invasion; whereas, the opposite was observed with reduced CREG1 expression. This was further validated in vivo by orthotopic transplantation. Our study highlights CREG1 as a key player in tumor–stroma interaction and suggests that cathepsin B sustains malignant cell behavior by reducing the levels of the growth suppressor CREG1 in the tumor microenvironment.
Note on the existence theory for pseudo-monotone evolution problems
Authors: Kaltenbach A. , Růžička M. 
Published: May 2020

AbstractIn this note, we develop a framework which allows to prove an existence result for nonlinear evolution problems involving time-dependent, pseudo-monotone operators. This abstract existence result is applicable to a large class of concrete problems where the standard theorem on evolutionary pseudo-monotone operators (cf. Theorem 1.3) is not applicable. To this end we introduce the notion of Bochner pseudo-monotonicity, and Bochner coercivity, which are appropriate extensions of the concepts of pseudo-monotonicity and coercivity to the evolutionary setting. Moreover, we give sufficient conditions for these new notions, which are easily and widely applicable.
Stent-Assisted Coiling Using Leo+ Baby Stent
Authors: Luecking Hannes , Struffert Tobias , Goelitz Philipp , Engelhorn Tobias , Brandner Sebastian , Kuramatsu Joji B. , Lang Stefan , Schmidt Manuel , Doerfler Arnd 
Published: May 2020

Abstract
Background
Stent-assisted coiling is well-established for treatment of cerebral aneurysms. The technique enables treatment of wide-neck, bifurcation and recurrent aneurysms with high packing rates. While described in extenso for laser cut stents, the results of patients treated with the Leo+ Baby (Balt, Montmorency, France) braided microstent are presented.

Material and Methods
Patients were included if treated with a Leo+ Baby and with digital subtraction angiography (DSA) follow-up available of at least 6 months. Data were evaluated for successful deployment, aneurysm occlusion according to the modified Raymond-Roy classification (MRRC), stent patency and procedure-related morbidity and mortality.

Results
A total of 81 patients were included and Leo+ Baby deployment was successful in all cases. Coils were used in 80 cases. In 1 case 2 stents were used stent-in-stent without additional coiling. Initial aneurysm occlusion rates were MRRCi1 51.9%, MRRCi2 11.1%, MRRCi3a 24.7% and MRRCi3b 12.3%. Occlusion rates after 6 months were MRRC6m1 78.9%, MRRC6m2 3.9%, MRRC6m3a 6.6% and MRRC6m3b 10.5%. Procedure-related morbidity was 1 case of acute stent thrombosis successfully treated with tirofiban and 1 case with transient hemiparesis due to stent thrombosis after 4 months. There was 1 case of coil-associated subarachnoid hemorrhage (SAH) which caused prolonged hospitalization. No procedure-related mortality was observed.

Conclusion
The results confirm that stent-assisted coiling with the Leo+ Baby stent is safe and efficient for treatment of wide neck or recurrent cerebral aneurysms. Spontaneous progressive aneurysm occlusion over 6 months supports the theory of considerable flow-modulating effects of Leo+ Baby.
Temporal trends in diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes between 2006 and 2016: results from 13 countries in three continents
Authors: Cherubini Valentino , Grimsmann Julia M. , Åkesson Karin , Birkebæk Niels H. , Cinek Ondrej , Dovč Klemen , Gesuita Rosaria , Gregory John W. , Hanas Ragnar , Hofer Sabine E. , Holl Reinhard W. , Jefferies Craig , Joner Geir , King Bruce R. , Mayer-Davis Elizabeth J. , Peña Alexia S. , Rami-Merhar Birgit , Schierloh Ulrike , Skrivarhaug Torild , Sumnik Zdenek , Svensson Jannet , Warner Justin T. , Bratina Nataša , Dabelea Dana 
Published: May 2020

AbstractAims/hypothesisThe aim of this work was to evaluate geographical variability and trends in the prevalence of diabetic ketoacidosis (DKA), between 2006 and 2016, at the diagnosis of childhood-onset type 1 diabetes in 13 countries over three continents.MethodsAn international retrospective study on DKA at diagnosis of diabetes was conducted. Data on age, sex, date of diabetes diagnosis, ethnic minority status and presence of DKA at diabetes onset were obtained from Australia, Austria, Czechia, Denmark, Germany, Italy, Luxembourg, New Zealand, Norway, Slovenia, Sweden, USA and the UK (Wales). Mean prevalence was estimated for the entire period, both overall and by country, adjusted for sex and age group. Temporal trends in annual prevalence of DKA were estimated using logistic regression analysis for each country, before and after adjustment for sex, age group and ethnic minority status.ResultsDuring the study period, new-onset type 1 diabetes was diagnosed in 59,000 children (median age [interquartile range], 9.0 years [5.5–11.7]; male sex, 52.9%). The overall adjusted DKA prevalence was 29.9%, with the lowest prevalence in Sweden and Denmark and the highest in Luxembourg and Italy. The adjusted DKA prevalence significantly increased over time in Australia, Germany and the USA while it decreased in Italy. Preschool children, adolescents and children from ethnic minority groups were at highest risk of DKA at diabetes diagnosis in most countries. A significantly higher risk was also found for females in Denmark, Germany and Slovenia.Conclusions/interpretationDKA prevalence at type 1 diabetes diagnosis varied considerably across countries, albeit it was generally high and showed a slight increase between 2006 and 2016. Increased awareness of symptoms to prevent delay in diagnosis is warranted, especially in preschool children, adolescents and children from ethnic minority groups.
Plasma fatty acids and the risk of vascular disease and mortality outcomes in individuals with type 2 diabetes: results from the ADVANCE study
Authors: Harris Katie , Oshima Megumi , Sattar Naveed , Würtz Peter , Jun Min , Welsh Paul , Hamet Pavel , Harrap Stephen , Poulter Neil , Chalmers John , Woodward Mark 
Published: May 2020

Abstract
Aims/hypothesis
This biomarker study aimed to quantify the association of essential and other plasma fatty acid biomarkers with macrovascular disease, microvascular disease and death in individuals with type 2 diabetes.

Methods
A case-cohort study (N = 3576), including 654 macrovascular events, 341 microvascular events and 631 deaths during 5 years of (median) follow-up, was undertaken as a secondary analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) study (full details of the study design and primary endpoints of the ADVANCE trial and its case-cohort have been published previously). This current study considers new data: fatty acids measured from baseline plasma samples by proton NMR analysis. The fatty acids measured were n-3, docosahexaenoic acid (DHA), n-6, linoleic acid, and polyunsaturated, monounsaturated and saturated fatty acids. HRs were modelled per SD higher (percentage) fatty acid. C statistics and continuous net reclassification improvement were used to test the added value of fatty acids compared with traditional cardiovascular risk factors.

Results
After adjustment for traditional cardiovascular risk factors, an inverse association was observed for n-3 fatty acids and DHA with the risk of macrovascular events (HR [95% CI]: 0.87 [0.80, 0.95] and 0.88 [0.81, 0.96], respectively, per 1 SD higher percentage), and for n-3 fatty acids with the risk of death (HR 0.91 [95% CI 0.84, 0.99] per 1 SD higher percentage). Such associations were also evident when investigating absolute levels of fatty acids. There were no statistically significant associations between any fatty acids and microvascular disease after adjustment. However, there was limited improvement in the predictive ability of models when any fatty acid was added.

Conclusions/interpretation
Plasma n-3 fatty acids and DHA were found to be inversely associated with macrovascular disease, while n-3 fatty acids were also inversely associated with death. These results support the cardioprotective effects of n-3 fatty acids and DHA and further merit testing the role of high-dose supplementation with n-3 fatty acids in individuals with type 2 diabetes.

Trial registration
ClinicalTrials.gov NCT00145925.
Source-related smart suspect screening in the aqueous environment: search for tire-derived persistent and mobile trace organic contaminants in surface waters
Authors: Seiwert Bettina , Klöckner Philipp , Wagner Stephan , Reemtsma Thorsten 
Published: May 2020

AbstractA variant of suspect screening by liquid chromatography–high-resolution mass spectrometry (LC-HRMS) is proposed in this study: Samples of a potential source of contamination and of an environmental sample close to this source are first analyzed in a non-targeted manner to select source-related suspects and to identify them. The suspect list compiled from such an exercise is then applied to LC-HRMS data of environmental samples to ascribe and to identify persistent and mobile contaminants in the water cycle that may originate from the source under study. This approach was applied to tire crumb rubber (source) and road dust (close to source); by comparison of the two data sets, 88% of the features detected in tire leachate could be excluded. Of the 48 suspects remaining, a total of 41 could be tentatively identified as either related to hexamethoxymethyl melamine or cyclic amines, benzothiazoles, or glycols. Subsequently, environmental samples were searched for these suspects: 85% were determined in an urban creek after a combined sewer overflow and 67% in the influent of a municipal wastewater treatment plant (WWTP). These exceptionally high rates of positive findings prove that this source-related smart suspect screening effectively directs the effort of selecting and identifying unknown contaminants to those related to the source of interest. The WWTP effluent and the urban creek during dry weather also showed the presence of numerous contaminants that may stem from tire and road wear particles (TRWP) in road runoff. Contribution from other sources, however, cannot be ruled out.
Dietary calcium intake does not meet the nutritional requirements of children with chronic kidney disease and on dialysis
Authors: McAlister Louise , Silva Selmy , Shaw Vanessa , Shroff Rukshana 
Published: May 2020

AbstractBackgroundAdequate calcium (Ca) intake is required for bone mineralization in children. We assessed Ca intake from diet and medications in children with CKD stages 4–5 and on dialysis (CKD4–5D) and age-matched controls, comparing with the UK Reference Nutrient Intake (RNI) and international recommendations.MethodsThree-day prospective diet diaries were recorded in 23 children with CKD4–5, 23 with CKD5D, and 27 controls. Doses of phosphate (P) binders and Ca supplements were recorded.ResultsMedian dietary Ca intake in CKD4–5D was 480 (interquartile range (IQR) 300–621) vs 724 (IQR 575–852) mg/day in controls (p = 0.00002), providing 81% vs 108% RNI (p = 0.002). Seventy-six percent of patients received < 100% RNI. In CKD4–5D, 40% dietary Ca was provided from dairy foods vs 56% in controls. Eighty percent of CKD4–5D children were prescribed Ca-based P-binders, 15% Ca supplements, and 9% both medications, increasing median daily Ca intake to 1145 (IQR 665–1649) mg/day; 177% RNI. Considering the total daily Ca intake from diet and medications, 15% received < 100% RNI, 44% 100–200% RNI, and 41% > 200% RNI. Three children (6%) exceeded the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) upper limit of 2500 mg/day. None with a total Ca intake < RNI was hypocalcemic, and only one having > 2 × RNI was hypercalcemic.ConclusionsSeventy-six percent of children with CKD4–5D had a dietary Ca intake < 100% RNI. Restriction of dairy foods as part of a P-controlled diet limits Ca intake. Additional Ca from medications is required to meet the KDOQI guideline of 100–200% normal recommended Ca intake.
Ultrasound 3D reconstruction of malignant masses in robotic-assisted partial nephrectomy using the PAF rail system: a comparison study
Authors: Wang Chongyun , Komninos Charalampos , Andersen Stephanie , D’Ettorre Claudia , Dwyer George , Maneas Efthymios , Edwards Philip , Desjardins Adrien , Stilli Agostino , Stoyanov Danail 
Published: May 2020

Abstract
Purpose
In robotic-assisted partial nephrectomy (RAPN), the use of intraoperative ultrasound (IOUS) helps to localise and outline the tumours as well as the blood vessels within the kidney. The aim of this work is to evaluate the use of the pneumatically attachable flexible (PAF) rail system for US 3D reconstruction of malignant masses in RAPN. The PAF rail system is a novel device developed and previously presented by the authors to enable track-guided US scanning.

Methods
We present a comparison study between US 3D reconstruction of masses based on: the da Vinci Surgical System kinematics, single- and stereo-camera tracking of visual markers embedded on the probe. An US-realistic kidney phantom embedding a mass is used for testing. A new design for the US probe attachment to enhance the performance of the kinematic approach is presented. A feature extraction algorithm is proposed to detect the margins of the targeted mass in US images.

Results
To evaluate the performance of the investigated approaches the resulting 3D reconstructions have been compared to a CT scan of the phantom. The data collected indicates that single camera reconstruction outperformed the other approaches, reconstructing with a sub-millimetre accuracy the targeted mass.

Conclusions
This work demonstrates that the PAF rail system provides a reliable platform to enable accurate US 3D reconstruction of masses in RAPN procedures. The proposed system has also the potential to be employed in other surgical procedures such as hepatectomy or laparoscopic liver resection.
E-democracy and the Matter of Scale. Revisiting the Democratic Promises of the Internet in Terms of the Spatial Dimension
Authors: Kneuer Marianne , Datts Mario 
Published: May 2020

AbstractThe emergence of the Internet fueled euphoric—partially utopian—visions that can be summarized as democratic promises. In most cases, the normative and empirical discussion so far has considered e‑democracy tools and their potential, regardless of the scale of interaction—be it local, national, or transnational—as a one-size-fits-all approach, assuming that what is applicable for the national level will be equally true for the subnational and transnational levels. We argue that the question of whether the Internet and digital tools can fulfill the democratic promises must be confronted in a more differentiated way, examiningunder which spatial conditionse‑democracy is more likely to incentivize citizens to engage and to involve more citizens as well as marginalized citizens in public debates and decision making. The article introduces scale as a new element for a better theoretical understanding of e‑democracy. We establish a conceptual framework that enables us to capture scale as distance in terms of territorial, cognitive, and affective distance. The spatial perspective brings an innovative spin to the somewhat petrified positions on the mobilizing or reinforcing effects of digital tools as well as a new theoretical argument for the debate on e‑democracy in general.