bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accelerating CFD solver computation time with reduced‐order modeling in a multigrid environment
Authors: Karcher Niklas , Wallraff Marcel 
Published: July 2020

SummaryReduced‐order models (ROMs) are more and more considered for use in aerodynamic applications. Benefits of these methods can be expected for optimization problems or predicting aerodynamic loads for the entire flight envelope. For these applications it is often possible to perform computations for various parameter combinations before any ROM evaluations are needed. The order reduction of the CFD solutions in this article is done using proper orthogonal decomposition. Coupled with an interpolation method predictions for unknown parameter combinations can be made. The CFD solutions are computed using a discontinuous Galerkin finite element method combined with a nonlinear multigrid scheme. The nonlinear multigrid solver algorithms depend on a good initial guess of the flow field to be computed. Typically, the initial guess on a fine mesh is obtained by solving the problem on a agglomerated mesh. Alternatively, an initial guess could be obtained from a ROM prediction, if available. The main objective is to identify the benefits of using a ROM in a higher‐order multigrid environment. Integral as well as distributed surface quantities of the ROM predictions originating from several multigrid levels will be compared with fully converged flow solutions on the top level of the multigrid algorithm. Furthermore, initializing the flow solver with predictions from several multigrid levels will be analyzed in comparison to full multigrid computations as well as to a scenario where already converged solutions for similar parameter combinations are used as initial flow solutions on the top multigrid level.
Activation of PLAG1 and HMGA2 by gene fusions involving the transcriptional regulator gene NFIB
Authors: Afshari Maryam Kakay , Fehr André , Nevado Paloma Tejera , Andersson Mattias K. , Stenman Göran 
Published: July 2020

AbstractThe pleomorphic adenoma (PA), which is the most common salivary gland neoplasm, is a benign tumor characterized by recurrent chromosome rearrangements involving 8q12 and 12q14‐15. We have previously shown that the PLAG1 and HMGA2 oncogenes are the targets of these rearrangements. Here, we have identified previously unrecognized subsets of PAs with ins(9;8)/t(8;9) (n = 5) and ins(9;12)/t(9;12) (n = 8) and breakpoints located in the vicinity of the PLAG1 and HMGA2 loci. RNA‐sequencing and reverse transcriptase (RT)‐PCR analyses of a case with an ins(9;8) revealed a novel NFIB‐PLAG1 fusion in which NFIB exon 4 is linked to PLAG1 exon 3. In contrast to the developmentally regulated PLAG1 gene, NFIB was highly expressed in normal salivary gland, indicating that PLAG1 in this case, as in other variant fusions, is activated by promoter swapping. RT‐PCR analysis of three PAs with t(9;12) revealed two tumors with chimeric transcripts consisting of HMGA2 exon 4 linked to NFIB exons 9 or 3 and one case with a fusion linking HMGA2 exon 3 to NFIB exon 9. The NFIB fusion events resulted in potent activation of PLAG1 and HMGA2. Analysis of the chromatin landscape surrounding NFIB revealed several super‐enhancers in the 5′‐ and 3′‐parts of the NFIB locus and its flanking sequences. These findings indicate that PLAG1 and HMGA2, similar to MYB in adenoid cystic carcinoma, may be activated by enhancer‐hijacking events, in which super‐enhancers in NFIB are translocated upstream of PLAG1 or downstream of HMGA2. Our results further emphasize the role of NFIB as a fusion partner to multiple oncogenes in histopathologically different types of salivary gland tumors.
ACSIS Atlantic Ocean medium resolution SST dataset: Reconstructed 5‐day, ½‐degree, Atlantic Ocean SST (1950‐2014)
Authors: Williams Simon David Paul , Berry David I. 
Published: July 2020

AbstractA new dataset, the ACSIS Atlantic Ocean medium resolution SST dataset, is presented. This new dataset spans the period 1950–2014 at a 5‐day, ½‐degree resolution and covers the Atlantic Ocean. The dataset is based on in situ sea surface temperature (SST) observations from the International Comprehensive Ocean‐Atmosphere Data Set interpolated using Kriging to infill gaps and is available from the Centre for Environmental Data Analysis (CEDA) archive. Compared to existing datasets, the resolution is increased by a factor of 4 spatially and 6 temporally.
Intestinal Virome in Patients With Alcoholic Hepatitis
Authors: Jiang Lu , Lang Sonja , Duan Yi , Zhang Xinlian , Gao Bei , Chopyk Jessica , Schwanemann Leila K. , Ventura‐Cots Meritxell , Bataller Ramon , Bosques‐Padilla Francisco , Verna Elizabeth C. , Abraldes Juan G. , Brown Robert S. , Vargas Victor , Altamirano Jose , Caballería Juan , Shawcross Debbie L. , Ho Samuel B. , Louvet Alexandre , Lucey Michael R. , Mathurin Philippe , Garcia‐Tsao Guadalupe , Kisseleva Tatiana , Brenner David A. , Tu Xin M. , Stärkel Peter , Pride David , Fouts Derrick E. , Schnabl Bernd 
Published: July 2020

Background and Aims
Alcoholic hepatitis (AH) is a severe manifestation of alcohol‐associated liver disease (ALD) with high mortality. Although gut bacteria and fungi modulate disease severity, little is known about the effects of the viral microbiome (virome) in patients with ALD.

Approach and Results
We extracted virus‐like particles from 89 patients with AH who were enrolled in a multicenter observational study, 36 with alcohol use disorder (AUD), and 17 persons without AUD (controls). Virus‐like particles from fecal samples were fractionated using differential filtration techniques, and metagenomic sequencing was performed to characterize intestinal viromes. We observed an increased viral diversity in fecal samples from patients with ALD, with the most significant changes in samples from patients with AH. Escherichia‐, Enterobacteria‐, and Enterococcus phages were over‐represented in fecal samples from patients with AH, along with significant increases in mammalian viruses such as Parvoviridae and Herpesviridae. Antibiotic treatment was associated with higher viral diversity. Specific viral taxa, such as Staphylococcus phages and Herpesviridae, were associated with increased disease severity, indicated by a higher median Model for End‐Stage Liver Disease score, and associated with increased 90‐day mortality.

Conclusions
In conclusion, intestinal viral taxa are altered in fecal samples from patients with AH and associated with disease severity and mortality. Our study describes an intestinal virome signature associated with AH.
Role of pharmacists in improving accessibility of antiretrovirals to support the United States President's Emergency Plan for AIDS Relief: Impact on the patient, program, and market
Authors: Malati Christine Y. 
Published: July 2020

AbstractThe United States President's Emergency Plan for AIDS Relief (PEPFAR) is the largest commitment by any nation to combat a single disease through prevention and treatment initiatives; pharmacists play a critical role in improving the accessibility of antiretrovirals (ARVs). When determining the potential use of a medication for a human immunodeficiency virus (HIV) program, it is helpful to consider decisions through the (a) Perspective of a patient, (b) Perspective of the overarching HIV program providing care, and (c) Perspective of the ARV market. Pharmacists are uniquely positioned to contribute to decisions from these three perspectives. At the beginning of PEPFAR, the price of ARVs was cost prohibitive; however, after 17 years since its inception, through the work of pharmacists and other public health professionals, the price to treat one patient for one year is currently 63 USD. This article describes the impact of pharmacists at the U.S. Agency for International Development (USAID) and the Food and Drug Administration (FDA) in facilitating a dramatic reduction in the cost of ARVs, through the use of an expedited approval process and through pooling procurement of ARVs from a limited formulary.
Biophotonics methods for functional monitoring of complications of diabetes mellitus
Authors: Zharkikh Elena , Dremin Viktor , Zherebtsov Evgeny , Dunaev Andrey , Meglinski Igor 
Published: July 2020

AbstractThe prevalence of diabetes complications is a significant public health problem with a considerable economic cost. Thus, the timely diagnosis of complications and prevention of their development will contribute to increasing the length and quality of patient life, and reducing the economic costs of their treatment. This article aims to review the current state‐of‐the‐art biophotonics technologies used to identify the complications of diabetes mellitus and assess the quality of their treatment. Additionally, these technologies assess the structural and functional properties of biological tissues, and they include capillaroscopy, laser Doppler flowmetry and hyperspectral imaging, laser speckle contrast imaging, diffuse reflectance spectroscopy and imaging, fluorescence spectroscopy and imaging, optical coherence tomography, optoacoustic imaging and confocal microscopy. Recent advances in the field of optical noninvasive diagnosis suggest a wider introduction of biophotonics technologies into clinical practice and, in particular, in diabetes care units.
Antibacterial activity of nitric oxide‐releasing carboxymethylcellulose against periodontal pathogens
Authors: Feura Evan S. , Yang Lei , Schoenfisch Mark H. 
Published: July 2020

AbstractThe prevalence of periodontal disease poses a significant global health burden. Treatments for these diseases, primarily focused on removal and eradication of dental plaque biofilms, are challenging due to limited access to periodontal pockets where these oral pathogens reside. Herein, we report on the development and characterization of nitric oxide (NO)‐releasing carboxymethylcellulose (CMC) derivatives and evaluate their in vitro bactericidal efficacy against planktonic Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, two prominent periodontopathogens. Bactericidal exposure assays revealed that three of the synthesized NO‐releasing polymers were capable of reducing bacterial viability of both species by 99.9% in 2 hr at concentrations of 4 mg ml−1 or lower, reflecting NO's potent and rapid bactericidal action. The NO‐releasing CMCs elicited minimal toxicity to human gingival fibroblasts at their bactericidal concentrations following 24‐hr exposure.
Strontium substitution of gelatin modified calcium hydrogen phosphates as porous hard tissue substitutes
Authors: Kruppke Benjamin , Heinemann Christiane , Gebert Annett , Rohnke Marcus , Weiß Manuel , Henß Anja , Wiesmann Hans‐Peter , Hanke Thomas 
Published: July 2020

AbstractAiming at the generation of a high strontium‐containing degradable bone substitute, the exchange of calcium with strontium in gelatin‐modified brushite was investigated. The ion substitution showed two mineral groups, the high‐calcium containing minerals with a maximum measured molar Ca/Sr ratio of 80%/20% (mass ratio 63%/37%) and the high‐strontium containing ones with a maximum measured molar Ca/Sr ratio of 21%/79% (mass ratio 10%/90%). In contrast to the high‐strontium mineral phases, a high mass loss was observed for the calcium‐based minerals during incubation in cell culture medium (alpha‐MEM), but also an increase in strength owing to dissolution and re‐precipitation. This resulted for the former in a decrease of cation concentration (Ca + Sr) in the medium, while the pH value decreased and the phosphate ion concentration rose significantly. The latter group of materials, the high‐strontium containing ones, showed only a moderate change in mass and a decrease in strength, but the Ca + Sr concentration remained permanently above the initial calcium concentration in the medium. This might be advantageous for a future planned application by supporting bone regeneration on the cellular level.
A multilayered scaffold for regeneration of smooth muscle and connective tissue layers
Authors: Garrison Carly M. , Singh‐Varma Anya , Pastino Alexandra K. , Steele Joseph A. M. , Kohn Joachim , Murthy N. Sanjeeva , Schwarzbauer Jean E. 
Published: July 2020

AbstractTissue regeneration often requires recruitment of different cell types and rebuilding of two or more tissue layers to restore function. Here, we describe the creation of a novel multilayered scaffold with distinct fiber organizations—aligned to unaligned and dense to porous—to template common architectures found in adjacent tissue layers. Electrospun scaffolds were fabricated using a biodegradable, tyrosine‐derived terpolymer, yielding densely‐packed, aligned fibers that transition into randomly‐oriented fibers of increasing diameter and porosity. We demonstrate that differently‐oriented scaffold fibers direct cell and extracellular matrix (ECM) organization, and that scaffold fibers and ECM protein networks are maintained after decellularization. Smooth muscle and connective tissue layers are frequently adjacent in vivo; we show that within a single scaffold, the architecture supports alignment of contractile smooth muscle cells and deposition by fibroblasts of a meshwork of ECM fibrils. We rolled a flat scaffold into a tubular construct and, after culture, showed cell viability, orientation, and tissue‐specific protein expression in the tube were similar to the flat‐sheet scaffold. This scaffold design not only has translational potential for reparation of flat and tubular tissue layers but can also be customized for alternative applications by introducing two or more cell types in different combinations.
Burden of Illness in Adults With Hypophosphatasia: Data From the Global Hypophosphatasia Patient Registry
Authors: Seefried Lothar , Dahir Kathryn , Petryk Anna , Högler Wolfgang , Linglart Agnès , Martos-Moreno Gabriel Ángel , Ozono Keiichi , Fang Shona , Rockman-Greenberg Cheryl , Kishnani Priya S 
Published: July 2020

ABSTRACT
Hypophosphatasia (HPP) is a rare, inherited, metabolic disease caused by deficient tissue non-specific alkaline phosphatase activity. This study aims to assess patient-reported pain, disability and health-related quality of life (HRQoL) in a real-world cohort of adults with HPP who were not receiving asfotase alfa during the analysis. Adults (≥18 years old) with HPP (confirmed by ALPL gene mutation and/or low serum alkaline phosphatase activity for age/sex) were identified from the Global HPP Registry (NCT02306720). Demographics, clinical characteristics, and data on patient-reported pain, disability, and HRQoL (assessed by Brief Pain Inventory Short Form [BPI-SF], Health Assessment Questionnaire Disability Index [HAQ-DI], and 36-Item Short-Form Health Survey version 2 [SF-36v2], respectively) were stratified by pediatric- and adult-onset HPP and summarized descriptively. Of the 304 adults included (median [min, max] age 48.6 [18.8, 79.8] years; 74% women), 45% had adult-onset HPP and 33% had pediatric-onset HPP (unknown age of onset, 22%). Of those with data, 38% had experienced ≥5 HPP manifestations and 62% had a history of ≥1 fracture/pseudofracture. Median (Q1, Q3) BPI-SF scores were 3.5 (1.5, 5.3) for pain severity and 3.3 (0.9, 6.2) for pain interference. Median (Q1, Q3) disability on the HAQ-DI was 0.3 (0.0, 0.7). Median (Q1, Q3) physical and mental component summary scores on the SF-36v2 were 42.4 (32.7, 49.9) and 45.3 (36.3, 54.8), respectively. Greater numbers of HPP manifestations experienced/body systems affected correlated significantly with poorer scores on the BPI-SF, HAQ-DI, and SF-36v2 (all p &lt; 0.05). No significant differences between adults with pediatric- and adult-onset HPP were observed for patient-reported outcomes, except for disability and the BPI-SF question “pain at its worst,” which were significantly higher among adults with pediatric- versus adult-onset HPP (p = 0.03 and 0.04, respectively). These data from the Global HPP Registry show that adults with HPP have a substantial burden of illness that is associated with reduced patient-reported HRQoL, regardless of age of disease onset. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Enolase‐phosphatase 1 acts as an oncogenic driver in glioma
Authors: Wang Bo , Xu Xin , Liu Xi , Wang Dong , Zhuang Hao , He Xin , Han Tong , Hong Jian 
Published: July 2020

AbstractEnolase‐phosphatase 1 (ENOPH1), a newly identified enzyme involved in l‐methionine biosynthesis, is associated with anxiety and depression. In this study, ENOPH1 was found to play a crucial role in promoting the proliferation and migration of glioma cells. Among high‐grade glioma patients, the overall survival of the group showing high ENOPH1 expression was shorter than that of the group showing low ENOPH1 expression. ENOPH1 knockdown inhibited glioma cell proliferation and migration. In parallel, ENOPH1 knockdown suppressed tumor growth capacity and prolonged survival in an orthotopic glioma model. Mechanistically, we found that ENOPH1 activates the PI3K/AKT/mTOR signaling pathway by regulating THEM4. In conclusion, ENOPH1 is an important mediator that promotes glioma cell proliferation and migration.
Diagnostic potential of presepsin in bacterial infection following hepato‐biliary‐pancreatic surgery: A prospective observational study
Authors: Yao Siyuan , Kaido Toshimi , Uozumi Ryuji , Hirata Masaaki , Iwamura Sena , Miyachi Yosuke , Macshut Mahmoud , Sharshar Mohamed , Yagi Shintaro , Uemoto Shinji 
Published: July 2020

AbstractBackground/PurposeThe aim in the present study was to elucidate the diagnostic ability of presepsin for postoperative infectious complications following major hepato‐biliary‐pancreatic (HBP) surgery.MethodsBetween 2017 and 2019, 50 patients with major hepatectomy and 55 patients with pancreatoduodenectomy were enrolled. Presepsin, the neutrophil‐to‐lymphocyte ratio (NLR), C‐reactive protein (CRP), and procalcitonin (PCT) were prospectively measured for the first 2 weeks after surgery. The diagnostic abilities of these biomarkers were compared multidirectionally.ResultsAll biomarkers returned to normal ranges within 2 weeks after surgery. However, presepsin, unlike the other biomarkers, showed less nonspecific elevation in response to the invasiveness of the surgical procedure immediately after surgery. Receiver operating characteristic curve analysis revealed that presepsin (area under the curve (AUC), 0.959) had a greater ability to discriminate bacterial infection than PCT (AUC, 0.723), CRP (AUC, 0.800), and the NLR (AUC, 0.804). A very high sensitivity of 93.3% and a specificity of 89.2% were achieved at the cutoff value of 620 pg/mL. Multivariable analysis revealed that presepsin on day 3 (P = .013) independently predicted bacterial infection after HBP surgery.ConclusionsPresepsin may have a better predictive ability than existing biomarkers for infection following major HBP surgery, which may help us achieve faster and more accurate detection of bacterial infections.
Prediction of the progression of walled‐off necrosis in patients with acute pancreatitis on whole pancreatic perfusion CT
Authors: Yamamiya Akira , Kitamura Katsuya , Yoshida Hitoshi , Ishii Yu , Mitsui Yuta , Irisawa Atsushi 
Published: July 2020

AbstractBackground/PurposeThis study investigated whether measuring pancreatic blood volume (PBV) on whole pancreatic perfusion computed tomography (P‐CT) can predict the progression of walled‐off necrosis (WON) in patients with acute pancreatitis (AP).MethodsA single‐center, retrospective cohort study was conducted between December 2015 and December 2016. The participants were divided into two groups: 14 patients with WON and 15 patients without WON. PBV was measured within 72 hours after the diagnosis of AP, and the final diagnosis of WON was made by contrast‐enhanced CT (CE‐CT) or endoscopic ultrasonography (EUS) 4 weeks after the onset of AP.ResultsThe minimum CT value did not differ significantly between the two groups. On the other hand, the minimum PBV was significantly lower in the WON group than in the without WON group (1.4 (0.9–9.9) vs 19.8 (8.2–21.7) mL/100 mL, respectively; P = .02). The cutoff value of the minimum PBV for WON was 16.5 mL/100 mL (sensitivity 100%, specificity 67%, AUC 0.85; P = .001).ConclusionsWhole pancreatic P‐CT can evaluate pancreatic ischemia visually and quantitatively. The minimum PBV measurement on whole pancreatic P‐CT within 72 hours after the diagnosis of AP contributes to the prediction of progression of WON.
Metabolic epilepsies amenable to ketogenic therapies: Indications, contraindications, and underlying mechanisms
Authors: Gavrilovici Cezar , Rho Jong M. 
Published: July 2020

AbstractMetabolic epilepsies arise in the context of rare inborn errors of metabolism (IEM), notably glucose transporter type 1 deficiency syndrome, succinic semialdehyde dehydrogenase deficiency, pyruvate dehydrogenase complex deficiency, nonketotic hyperglycinemia, and mitochondrial cytopathies. A common feature of these disorders is impaired bioenergetics, which through incompletely defined mechanisms result in a wide spectrum of neurological symptoms, such as epileptic seizures, developmental delay, and movement disorders. The ketogenic diet (KD) has been successfully utilized to treat such conditions to varying degrees. While the mechanisms underlying the clinical efficacy of the KD in IEM remain unclear, it is likely that the proposed heterogeneous targets influenced by the KD work in concert to rectify or ameliorate the downstream negative consequences of genetic mutations affecting key metabolic enzymes and substrates—such as oxidative stress and cell death. These beneficial effects can be broadly grouped into restoration of impaired bioenergetics and synaptic dysfunction, improved redox homeostasis, anti‐inflammatory, and epigenetic activity. Hence, it is conceivable that the KD might prove useful in other metabolic disorders that present with epileptic seizures. At the same time, however, there are notable contraindications to KD use, such as fatty acid oxidation disorders. Clearly, more research is needed to better characterize those metabolic epilepsies that would be amenable to ketogenic therapies, both experimentally and clinically. In the end, the expanded knowledge base will be critical to designing metabolism‐based treatments that can afford greater clinical efficacy and tolerability compared to current KD approaches, and improved long‐term outcomes for patients.
Failure in Systems and Culture: Barriers That Prevent Implementation of Evidence‐Based Fasting Times for Patients in the Acute Care Setting
Authors: Carey Sharon , Hogan Sophie 
Published: July 2020

AbstractBackgroundThere is strong evidence supporting fasting guidelines of 6 hours’ fast from solids and 2 hours’ fast from fluids prior to surgery. Despite this, patients spend prolonged periods of time fasting for surgery with a lack of research to support translating this evidence into practice, particularly for emergency surgical theater lists. This study aims to explore barriers and enablers to reduce prolonged fasting for patients on emergency surgical lists in the acute care setting.MethodsQualitative interviews were undertaken with 22 health professionals on acute surgical wards within a quaternary referral hospital in Sydney, Australia. Semistructured interviews explored barriers and enablers to implementing evidence‐based fasting practices for patients on emergency surgical lists, using a theoretical domains framework. Interviews were transcribed verbatim and analyzed using an inductive thematic approach.ResultsKey barriers to implementing reduced fasting included unpredictable, inflexible systems; cultural concerns; and gaps in knowledge. Major enablers to reducing fasting times are the recognition of patient distress caused by excessive fasting and desire by all 22 interviewees to address the problem.ConclusionsThis research is the first to explore barriers and enablers to implementing interventions to address excessive fasting. This research highlights the complexity of the issue and the need for a multifaceted translational intervention addressing limitations in systems and cultural barriers.