bluuebunny/crossref_metadata_2025 huggingface dataset:
TheENUFmethod—Ewald summation based onnonuniformfast Fourier transform: Implementation, parallelization, and application
Authors: Yang Sheng‐Chun , Li Bin , Zhu You‐Liang , Laaksonen Aatto , Wang Yong‐Lei
Published: August 2020

Computer simulations of model systems are widely used to explore striking phenomena in promising applications spanning from physics, chemistry, biology, to materials science and engineering. The long range electrostatic interactions between charged particles constitute a prominent factor in determining structures and states of model systems. How to efficiently calculate electrostatic interactions in simulation systems subjected to partial or full periodic boundary conditions has been a grand challenging task. In the past decades, a large variety of computational schemes has been proposed, among which the Ewald summation method is the most reliable route to accurately deal with electrostatic interactions between charged particles in simulation systems. In addition, extensive efforts have been done to improve computational efficiencies of the Ewald summation based methods. Representative examples are approaches based on cutoffs, reaction fields, multi‐poles, multi‐grids, and particle‐mesh schemes. We sketched an ENUF method, an abbreviation for the Ewald summation method based on the nonuniform fast Fourier transform technique, and have implemented this method in particle‐based simulation packages to calculate electrostatic energies and forces at micro‐ and mesoscopic levels. Extensive computational studies of conformational properties of polyelectrolytes, dendrimer‐membrane complexes, and ionic fluids demonstrated that the ENUF method and its derivatives conserve both energy and momentum to floating point accuracy, and exhibit a computational complexity ofwith optimal physical parameters. These ENUF based methods are attractive alternatives in molecular simulations where high accuracy and efficiency of simulation methods are needed to accelerate calculations of electrostatic interactions at extended spatiotemporal scales.
The value of circulating long non‐coding RNA maternally expressed gene 3 as a predictor of higher acute respiratory distress syndrome risk and 28‐day mortality in sepsis patients
Authors: Wu Xiaoling , Chen Dan , Yu Li
Published: August 2020

Objective

This study was to evaluate the potential of long non‐coding RNA maternally expressed gene 3 (lncRNA MEG3) in predicting acute respiratory distress syndrome (ARDS) risk and its correlation with prognosis in sepsis patients.

Methods

The plasma samples were obtained from 112 sepsis patients within 24 hours after admission and 100 healthy controls (HCs) at enrollment. The lncRNA MEG3 expression in plasma samples was determined by RT‐qPCR. In sepsis patients, ARDS occurrence was assessed based on Berlin definition of ARDS and 28‐day mortality risk was evaluated.

Results

LncRNA MEG3 expression was increased in sepsis patients compared with HCs. During 28‐day duration, 30 sepsis patients occurred ARDS and 82 sepsis patients did not occur ARDS. LncRNA MEG3 expression was elevated in ARDS sepsis patients compared with non‐ARDS sepsis patients, then the following receiver‐operating characteristic (ROC) curve analysis disclosed that lncRNA MEG3 predicted ARDS risk (area under the curve (AUC) = 0.775), which was further validated as an independent risk factor by multivariate logistic regression. Furthermore, lncRNA MEG3 was positively correlated with chronic obstructive pulmonary disease, respiratory infection, acute physiology and chronic health evaluation II score, sequential organ failure assessment score, white blood cell, and C‐reactive protein, while negatively correlated with albumin in sepsis patients. Additionally, lncRNA MEG3 was elevated in 28‐day deaths compared with 28‐day survivors, and it predicted 28‐day mortality risk in sepsis patients (AUC = 0.708) by ROC curve analysis.

Conclusion

LncRNA MEG3 might represent as a valuable biomarker for individualizing prevention strategies against ARDS and improving prognosis in sepsis.
Structure, development, and evolutive patterns of spermatozoa in rhabditid nematodes (Nematoda: Rhabditida)
Authors: Slos Dieter , Yushin Vladimir V. , Claeys Myriam , Ivanova Elena S. , Kosaka Hajime , Bert Wim
Published: August 2020

Spermatogenesis of five rhabditid nematodes was studied using transmission electron microscopy and is described herein. Structure and development of nematode sperm in all available representatives of the extensive order Rhabditida have been analysed and the main characteristics of each infraorder are discussed. The ancestral sperm of the order Rhabditida was reconstructed using maximum likelihood and Bayesian methods based on 44 ultrastructural sperm characters. The hypothetical ancestral spermatogenesis of the order Rhabditida agrees with the previously suggested “rhabditid” pattern and appears to be conserved throughout the order Rhabditida. Despite the enormous variation of rhabditid nematodes, few groups deviate from the ancestral pattern. This conserved pattern can be informative within the phylum Nematoda at order level, but poses limitations when used in taxonomic and phylogenetic analysis within Rhabditida.
Stress shielding at the bone‐implant interface: Influence of surface roughness and of the bone‐implant contact ratio
Authors: Raffa Maria Letizia , Nguyen Vu‐Hieu , Hernigou Philippe , Flouzat‐Lachaniette Charles‐Henri , Haiat Guillaume
Published: August 2020

Short and long‐term stabilities of cementless implants are strongly determined by the interfacial load transfer between implants and bone tissue. Stress‐shielding effects arise from shear stresses due to the difference of material properties between bone and the implant. It remains difficult to measure the stress field in periprosthetic bone tissue. This study proposes to investigate the dependence of the stress field in periprosthetic bone tissue on (i) the implant surface roughness, (ii) the material properties of bone and of the implant, (iii) the bone‐implant contact ratio. To do so, a microscale two‐dimensional finite element model of an osseointegrated bone‐implant interface was developed where the surface roughness was modeled by a sinusoidal surface. The results show that the isostatic pressure is not affected by the presence of the bone‐implant interface while shear stresses arise due to the combined effects of a geometrical singularity (for low surface roughness) and of shear stresses at the bone‐implant interface (for high surface roughness). Stress‐shielding effects are likely to be more important when the bone‐implant contact ratio value is low, which corresponds to a case of relatively low implant stability. Shear stress reach a maximum value at a distance from the interface comprised between 0 and 0.1 time roughness wavelength λ and tend to 0 at a distance from the implant surface higher than λ, independently from bone‐implant contact ratio and waviness ratio. A comparison with an analytical model allows validating the numerical results. Future work should use the present approach to model osseointegration phenomena.
Barriers and facilitators systematic reviews in health: A methodological review and recommendations for reviewers
Authors: Bach‐Mortensen Anders Malthe , Verboom Ben
Published: August 2020

Background

Systematic reviews cataloguing the barriers to and facilitators of various outcomes are increasingly popular, despite criticisms of this type of review on philosophical, methodological, and practical grounds. The aims of this review are to appraise, analyze, and discuss the reporting and synthesis practices used in recently published barriers and facilitators reviews in health services research.

Methods

All English‐language peer‐reviewed systematic reviews that synthesized research on barriers and facilitators in a health services context were eligible for inclusion. We searched 11 databases over a 13‐month period (1 November 2017‐30 November 2018) using an exhaustive list of search terms for “barrier(s),” “facilitator(s),” and “systematic review.”

Results

One hundred reviews were included. We found a high degree of variation in the synthesis practices used in these reviews, with the majority employing aggregative (rather than interpretive) approaches. The findings echo common critiques of this review type, including concerns about the reduction of complex phenomena to simplified, discrete factors. Although several reviews highlighted the “complexity” of barriers and facilitators, this was usually not analyzed systematically. Analysis of the subsample of reviews that explicitly discussed the barriers and facilitators approach revealed some common issues. These tended to be either conceptual/definitional (eg, ideas about interrelationships and overlap between factors) and methodological/practical (eg, challenges related to aggregating heterogeneous research).

Conclusion

Barriers and facilitators reviews should (a) clearly operationally define “barrier” and “facilitator,” (b) explicitly describe how factors are extracted and subsequently synthesized, and (c) provide critical reflection on the contextual variability and reliability of identified factors.
Supporting role of lignin in immobilization of yeast on sugarcane bagasse for continuous pectinase production
Authors: Ejaz Uroosa , Sohail Muhammad
Published: August 2020

BACKGROUND

Lignocellulosic wastes are pretreated prior to their utilization in fermentation processes. Such pretreatment also alters the topological features of the substrates, and therefore the suitability of pretreated waste as immobilization matrix for microbial cells needs investigation.

RESULTS

In this study, the effect of chemical pretreatment of sugarcane bagasse (SB) for its subsequent utilization as a matrix to immobilize a pectinolytic yeast, Geotrichum candidum AA15, was evaluated using cell retention, concentration of immobilized cells, immobilization efficiency, scanning electron microscopy and Fourier transform infrared spectroscopy of the substrate and pectinase titers obtained after recycling. The results revealed that untreated SB is more efficient for immobilization with higher values of cell retention and pectinase productivity (99.78%) retained for up to six production cycles. It was deduced that removal of lignin by pretreatment negatively influenced the ability of SB to support cell adhesion, as lignin acts as a sealing agent that provides strength to the substrate.

CONCLUSIONS

The strategy of utilizing SB as immobilization matrix was found effective at the laboratory scale as it improved pectinase production and may be investigated further for large‐scale and cost‐effective production. © 2020 Society of Chemical Industry
How to measure the tourism vocation of a territory? Proposal for a composite index
Authors: Casado‐Montilla Jairo , Pulido‐Fernández Juan Ignacio
Published: August 2020

The rapid evolution of the tourism industry has sparked interest among researchers and tourism managers, keen to know which aspects determine whether a territory will become a tourism destination or not. Currently, there is still no clear consensus about the best procedure for doing this. Hence, this paper proposes a composite index resulting from a system of indicators capable of determining the tourism vocation of a territory. Six medium‐sized inland towns in Andalusia (Spain) are analysed, which have, a priori, different degrees of tourism development. The findings show that it is possible to measure the tourism vocation of a territory.
Living standard and Chinese tourism participation
Authors: Bernini Cristina , Fang Ruizhe
Published: August 2020

The paper analyses how the bettering in the living standard affects Chinese households' decision‐making process regarding tourism. The first novelty of this study relays on the role that living standard, proxy by happiness, Internet use and social connection spending, has on the tourism participation and how it impacts tourism expenditures. We estimate hurdle models and calculate income elasticity with respect to living condition; this is the second main novelty of this study. Empirical results show that living standard is associated with likelihood of participating in tourism and is an essential determinant for tourism consumption behaviour. Some recommendations are finally proposed.
Interpolyelectrolyte complexes as effective structure‐forming agents for Chernozem soil
Authors: Panova Irina G. , Demidov Valeriy V. , Shulga Pavel S. , Ilyasov Leonid O. , Butilkina Marina А. , Yaroslavov Alexander A.
Published: August 2020

Chernozems or mollisols/black soils are 'reference soils' with a high content of organic matter, which ensures a high level of crop yield. In the article, we describe the structural characteristics of a typical medium‐thick Chernozem taken from Kursk region and their improvement via treatment by a 1 wt% aqueous solution/suspension of interpolyelectrolyte complex (IPEC), a product of electrostatic interaction between anionic potassium humates and cationic poly(diallyldimethylammonium chloride). The native Chernozem and polymer‐treated chernozem were characterized by laser diffraction, dry and wet sieving methods, transmission electron microscopy, soil washoff in a hydraulic erosion tray, gravimetry, visual control, and vegetation miniaturization in Petri dishes with the following main conclusions: (a) Deposition of a positively charged IPEC over the Chernozem sample led to an increase in a total amount of agronomically valuable 0.25–1 mm aggregates up to 28% in comparison with a 3% content of aggregates in the native Chernozem. (b) An average diameter of the air‐dry aggregates, treated by a cationic IPEC, was of 5.5 mm (cf. with 2.5 mm for the untreated). (c) An average diameter of the IPEC‐treated water‐resistant aggregates was of 2.1 mm (cf. with 0.5 for the untreated). (d) The Chernozem pretreated by the cationic IPEC showed a minimum removal of soil during several cycles of rewatering/drying. (e) All IPEC formulations, stimulated the growth of plants. The results are of interest for preparing low‐toxic polymer formulations capable of effective stabilizing fertile Chernozem soils.
Understanding the role of policy frameworks in developing land degradation in stakeholders perception from a post‐conflict perspective in Bosnia and Herzegovina
Authors: Kapović Solomun Marijana , Ferreira Carla S. S. , Barger Nichole N. , Tošić Radislav , Eremija Saša
Published: August 2020

Bosnia and Herzegovina (BiH) is a developing country facing extensive land degradation. BiH exists as a decentralized state, where all land (e.g., agricultural and forest soils) and water resources are under exclusive jurisdiction of two entities and one district, rather than state‐level legislation. Complex land‐related administration occurs between entities that function independently from each other. The lack of coordination among entities frequently leads to political conflicts over land and limited data exchange which may further exacerbate current land degradation. This article investigates (a) stakeholders' perception of land degradation under complex institutional and policy structures; and (b) the current state of land degradation, with a focus on soil erosion as one important indicator of land degradation across the region. As a consequence of the Civil War that took place in BiH between 1992 and 1995, limited data on soil erosion and land status present additional challenges to those seeking to avoid, reduce, and reverse land degradation. Stakeholders reported that the existence of a policy framework as important to addressing land degradation, but not sufficient if implementation is weak. Decision makers reported that the existing policy frameworks are satisfactory, which was in contrast to other stakeholders. Reliable data are crucial for land degradation assessments and development of strategies and policy frameworks, but also better knowledge and awareness of stakeholder perceptions would foster their implementation. In summary, complex institutional structures underpin the weak communication and cooperation among institutions and stakeholders, which presents significant challenges for sustainable land management in post‐conflict societies.
Ultrafast Epoxy‐Anhydride Photopolyaddition Reaction
Authors: Kavalli Tuba , Wolf Romain , Lalevée Jacques
Published: August 2020

The conventional epoxy/anhydride reaction is quite slow (more than one hour to reach full conversion at room temperature (RT)) and usually requires thermal treatment at rather high temperature. Ideally, the reaction should be triggered by light for on demand systems i.e. very fast polymerizations (in few seconds) can be carried out in mild conditions (at RT with low energy consumption using cheap and safe light emitting diode (LED) light). In this work, a new approach is proposed with an ultrafast epoxy/anhydride photopolyaddition reaction that can be triggered by near‐UV/visible light. Therefore, a photoinitiating system is developed to cure epoxides in presence of anhydrides as hardeners without any external heat and in a short time scale i.e. few seconds upon light vs. hours at RT without light. Excellent polymerization performances can be observed upon LED@405nm irradiation with full epoxy function conversion. The polymerization kinetics are followed both by real‐time FTIR and real‐time photorheology experiments. As example of the high performance of this new photoactivated epoxy/anhydride process, the curing of epoxy/glass fibre composites is presented. Remarkably, an excellent depth of cure can be obtained in only 20 seconds of irradiation with a LED@405 nm.
Interpenetrating Network of Alginate–Human Adipose Extracellular Matrix Hydrogel for Islet Cells Encapsulation
Authors: Wang Jun Kit , Cheam Nicole Mein Ji , Irvine Scott Alexander , Tan Nguan Soon , Venkatraman Subbu , Tay Chor Yong
Published: August 2020

Transplantation of microencapsulated islet cells holds great potential for the treatment of type 1 diabetes mellitus. However, its clinical translation is hampered by the peri‐transplantation loss of islet viability and functionality in the microcapsules. In this work, a novel islet cells biomimetic microencapsulant material that is based on the interpenetrating networks of alginate and extracellular matrix (ECM) hydrogel composite (AEC) is presented. The ECM component is derived from human lipoaspirate. In situ encapsulation of pancreatic β islet cells (MIN6 β‐cells) can be achieved via ionotropic gelation of the alginate matrix and thermal‐induced gelation of the pepsin‐solubilized ECM pre‐gel. Due to the enhanced cell–matrix interaction, islets encapsulated within the AEC microcapsules (≈640 µm) display sevenfold increase in cell growth over 1 week of culture and characteristic glucose‐stimulated insulin response in vitro. The results show that the AEC microcapsule is a potent platform to bioaugment the performance of islet cells.
Ring‐Opening Metathesis Polymerization of endo‐ and exo‐Norbornene Lactones
Authors: Miyasako Narumi , Matsuoka Shin‐ichi , Suzuki Masato
Published: August 2020

New ester‐functionalized bicyclic aliphatic polymers are synthesized through the ring‐opening metathesis polymerization (ROMP) of endo‐ and exo‐norbornene lactones (endo‐NBL and exo‐NBL) and their oxa‐norbornene analogue (exo‐oxa‐NBL) followed by hydrogenation. The polymerizability between endo‐ and exo‐NBLs, and the thermal properties between the six types of polymers before and after hydrogenation are compared and discussed. The ROMP of all three monomers proceeded in a living fashion under optimized conditions, which is confirmed by chain extension experiments. Endo‐NBL shows a much lower homo‐ and copolymerizability than exo‐NBL probably owing to six‐membered chelation to the Ru center and steric hindrance in the ruthenacyclobutane intermediate. Stereo‐block and stereo‐gradient copolymers of poly(endo‐NBL) and poly(exo‐NBL) are also synthesized. The hydrogenation catalyzed by RuHCl(CO)(PPh3)3 in the mixed solvents of o‐xylene and N,N‐dimethyl acetamide (DMAc) results in more than 95% conversion. The obtained hydrogenated polymers, H‐poly(endo‐NBL) and H‐poly(exo‐NBL), are amorphous, soluble in chlorinated aliphatic solvents, and thermally stable until 400 °C without a weight loss. Their glass transition temperatures are 163 and 131 °C, respectively; the values are appropriate in terms of both thermal stability and processing deformation for the application of transparent resin materials.
GBA Variants in Parkinson's Disease: Clinical, Metabolomic, and Multimodal Neuroimaging Phenotypes
Authors: Greuel Andrea , Trezzi Jean‐Pierre , Glaab Enrico , Ruppert Marina C. , Maier Franziska , Jäger Christian , Hodak Zdenka , Lohmann Katja , Ma Yilong , Eidelberg David , Timmermann Lars , Hiller Karsten , Tittgemeyer Marc , Drzezga Alexander , Diederich Nico , Eggers Carsten
Published: August 2020

Background

Alterations in the GBA gene (NM_000157.3) are the most important genetic risk factor for Parkinson's disease (PD). Biallelic GBA mutations cause the lysosomal storage disorder Gaucher's disease. The GBA variants p.E365K and p.T408M are associated with PD but not with Gaucher's disease. The pathophysiological role of these variants needs to be further explored.

Objective

This study analyzed clinical, neuropsychological, metabolic, and neuroimaging phenotypes of patients with PD carrying the GBA variants p.E365K and p.T408M.

Methods

GBA was sequenced in 56 patients with mid‐stage PD. Carriers of GBA variants were compared with noncarriers regarding clinical history and symptoms, neuropsychological features, metabolomics, and multimodal neuroimaging. Blood plasma gas chromatography coupled to mass spectrometry, 6‐[18F]fluoro‐L‐Dopa positron emission tomography (PET), [18F]fluorodeoxyglucose PET, and resting‐state functional magnetic resonance imaging were performed.

Results

Sequence analysis detected 13 heterozygous GBA variant carriers (7 with p.E365K, 6 with p.T408M). One patient carried a GBA mutation (p.N409S) and was excluded. Clinical history and symptoms were not significantly different between groups. Global cognitive performance was lower in variant carriers. Metabolomic group differences were suggestive of more severe PD‐related alterations in carriers versus noncarriers. Both PET scans showed signs of a more advanced disease; [18F]fluorodeoxyglucose PET and functional magnetic resonance imaging showed similarities with Lewy body dementia and PD dementia in carriers.

Conclusions

This is the first study to comprehensively assess (neuro‐)biological phenotypes of GBA variants in PD. Metabolomics and neuroimaging detected more significant group differences than clinical and behavioral evaluation. These alterations could be promising to monitor effects of disease‐modifying treatments targeting glucocerebrosidase metabolism. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Simultaneous multi‐slice spin‐ and gradient‐echo dynamic susceptibility‐contrast perfusion‐weighted MRI of gliomas
Authors: Han Misung , Yang Baolian , Fernandez Brice , Lafontaine Marisa , Alcaide‐Leon Paula , Jakary Angela , Burns Brian L. , Morrison Melanie A. , Villanueva‐Meyer Javier E. , Chang Susan M. , Banerjee Suchandrima , Lupo Janine M.
Published: August 2020

Although combined spin‐ and gradient‐echo (SAGE) dynamic susceptibility‐contrast (DSC) MRI can provide perfusion quantification that is sensitive to both macrovessels and microvessels while correcting for T1‐shortening effects, spatial coverage is often limited in order to maintain a high temporal resolution for DSC quantification. In this work, we combined a SAGE echo‐planar imaging (EPI) sequence with simultaneous multi‐slice (SMS) excitation and blipped controlled aliasing in parallel imaging (blipped CAIPI) at 3 T to achieve both high temporal resolution and whole brain coverage. Two protocols using this sequence with multi‐band (MB) acceleration factors of 2 and 3 were evaluated in 20 patients with treated gliomas to determine the optimal scan parameters for clinical use. ΔR2*(t) and ΔR2(t) curves were derived to calculate dynamic signal‐to‐noise ratio (dSNR), ΔR2*‐ and ΔR2‐based relative cerebral blood volume (rCBV), and mean vessel diameter (mVD) for each voxel. The resulting SAGE DSC images acquired using MB acceleration of 3 versus 2 appeared visually similar in terms of image distortion and contrast. The difference in the mean dSNR from normal‐appearing white matter (NAWM) and that in the mean dSNR between NAWM and normal‐appearing gray matter were not statistically significant between the two protocols. ΔR2*‐ and ΔR2‐rCBV maps and mVD maps provided unique contrast and spatial heterogeneity within tumors.
Postural Tachycardia Syndrome: Nutrition Implications
Authors: Ganesh Ravindra , Bonnes Sara L. R. , DiBaise John K.
Published: August 2020

Postural tachycardia syndrome (POTS) is a syndrome characterized by elevated heart rate without hypotension and most commonly occurs in young females (generally <35 years of age). The prevalence of POTS is on the rise, but the etiology is still under investigation, and there appear to be multiple potential physiologic causes. The majority of these patients experience a multitude of gastrointestinal (GI) and systemic symptoms and conditions that may contribute to functional debility and poor quality of life. Although symptoms generally improve with age, they can still lead to significant issues meeting nutrition and hydration needs. This paper summarizes the understood potential pathophysiology of POTS, associated GI and nutrition issues, general treatment of POTS, and strategies to assess and meet the unique nutrition and hydration needs of these patients.
Enteral Nutrition in Pediatric Short‐Bowel Syndrome
Authors: Channabasappa Nandini , Girouard Sara , Nguyen Van , Piper Hannah
Published: August 2020

Pediatric intestinal failure (IF) is the critical reduction of intestinal mass or function below the amount necessary for normal growth in children. Short‐bowel syndrome (SBS) is the most common cause of IF in infants and children and is caused by intestinal resection. Enteral autonomy and freedom from parenteral nutrition is the mainstay of nutrition management in SBS. The goal is to achieve intestinal adaptation while maintaining proper growth and development. Treatment is variable, and there remains a paucity of evidence to draw well‐informed conclusions for the care of individuals in this complex population. Physiological principles of enteral nutrition and practical recommendations for advancing the diet of patients with pediatric SBS are presented. Emerging trends in nutrition management, such as the growing interest in blending diets and the impact on SBS, are reviewed. Finally, the influence of the microbiome on enteral tolerance and small bowel bacterial overgrowth are considered.
Retracted: Stability analysis of blocky structure system using discontinuity layout optimization
Authors: Jia Cangqin , Huang Qiwu , Wang Guihe
Published: August 2020

The collapse mechanism identification and limit load calculation of block composite structures are essential tasks in practical engineering. In this work, the discontinuity layout optimization (DLO) is utilized to simulate a stable blocky system structure under static and pseudostatic loading by considering soil–structure interaction effects. The program refers to the discretization of the system under consideration by utilizing the potential slip lines to connect nodes. Then, linear programming is applied to identify the critical layout. The DLO procedure is extended to mimic rotations in the approximate simulation of rotational and translational failures along boundaries, thus simulating the mechanism on the rotating block. The simulated failure mechanism and collapse load are consistent with the experimental observations and numerical modeling results. Furthermore, the procedure is applied to two potential practical applications: the stability analysis of a jointed rock slope and concrete masonry retaining wall. The results show that the DLO is a simple but scientific method for identifying the mechanism of the critical failure of blocky structures.
Multiphysics model reduction of symmetric vibro‐acoustic formulation with a priori error estimation criteria
Authors: Kim Soo Min , Chae Soo‐Won , Kim Jin‐Gyun
Published: August 2020

A new multiphysics mode synthesis (MMS) is presented for the construction of reduced‐order models of acoustic fluid‐structure interaction systems. The present acoustic‐structure interaction model is symmetric and consists of the fluid pressure p, the fluid displacement potential φ, and the structural displacement u. In carrying out MMS, the structure is first reduced, which is then applied to the coupling terms in the acoustic (p, φ)‐equations. The fluid parts (p, φ) are then reduced while preserving the coupling effects, resulting in improved accuracy. A combination of a priori modal contribution indicator and cumulative error estimator are derived from the moment matching approach that provides rational criteria for how many structural and fluid modes need to be retained for the construction of reduced models. An iterative MMS algorithm is then proposed by combining the modal indicators and error estimators. The performance of the proposed MMS method is illustrated via numerical examples.
Differences in brain structure and function in children with the FTO obesity‐risk allele
Authors: Lugo‐Candelas Claudia , Pang Yajing , Lee Seonjoo , Cha Jiook , Hong Susie , Ranzenhofer Lisa , Korn Rachel , Davis Haley , McInerny Hailey , Schebendach Janet , Chung Wendy K. , Leibel Rudolph L. , Walsh B. Timothy , Posner Jonathan , Rosenbaum Michael , Mayer Laurel
Published: August 2020

Objective

Noncoding alleles of the fat mass and obesity‐associated (FTO) gene have been associated with obesity risk, yet the underlying mechanisms remain unknown. Risk allele carriers show alterations in brain structure and function, but previous studies have not disassociated the effects of genotype from those of body mass index (BMI).

Methods

Differences in brain structure and function were examined in children without obesity grouped by their number of copies (0,1,2) of the FTO obesity‐risk single‐nucleotide polymorphism (SNP) rs1421085. One hundred five 5‐ to 10‐year‐olds (5th–95th percentile body fat) were eligible to participate. Usable scans were obtained from 93 participants (15 CC [homozygous risk], 31 CT [heterozygous] and 47 TT [homozygous low risk]).

Results

Homozygous C allele carriers (CCs) showed greater grey matter volume in the cerebellum and temporal fusiform gyrus. CCs also demonstrated increased bilateral cerebellar white matter fibre density and increased resting‐state functional connectivity between the bilateral cerebellum and regions in the frontotemporal cortices.

Conclusions

This is the first study to examine brain structure and function related to FTO alleles in young children not yet manifesting obesity. This study lends support to the notion that the cerebellum may be involved in FTO‐related risk for obesity, yet replication and further longitudinal study are required.
Real‐world effectiveness of pembrolizumab in previously treated non‐small cell lung cancer: A population‐based cohort study
Authors: Murteira Rodrigo , Borges Fábio Cardoso , Mendes Gonçalo Pinto , Ramos Catarina , Ramos Adriana , Soares Patrícia , Furtado Cláudia , Miranda Ana , da Costa Filipa Alves ,   The RON Network
Published: August 2020

Purpose

Immunotherapy is promising for lung cancer treatment, although at significant financial impact. The aim of this study was to evaluate the effectiveness and the efficacy‐effectiveness gap of pembrolizumab in previously treated non‐small cell lung cancer (NSCLC).

Methods

A population‐based ambispective cohort study was conducted. Cases of interest were identified through the National Cancer Registry database and additional data sources. Patients aged ≥18 years, diagnosed with NSCLC and exposed to pembrolizumab, between 23 June 2016 and 31 October 2018, as second or later lines of treatment for advanced disease were included. Patients were followed‐up until death or cut‐off date (30 April 2019). Primary outcome was overall survival (OS). Secondary outcomes were progression‐free survival (PFS), event‐free survival (EFS), and adverse events (AEs) leading to treatment discontinuation. The efficacy‐effectiveness gap was evaluated comparing results with clinical trial data.

Results

A total of 181 patients were included. Median age was 63 years (range 33‐94); 74.6% were male. Median treatment duration was 5.6 months (interquartile range: 1.4‐10.4) and, at cut‐off date, treatment had been discontinued in 141 patients, mainly due to disease progression. Median OS was 13.0 months (95% confidence interval [CI] 9.3‐15.9) and 1‐year OS was 53.1% (95% CI 45.2%‐60.3%). Median PFS was 5.6 months (95% CI 4.6‐7.2), median EFS was 4.7 months (95% CI 3.2‐6.0), and treatment was discontinued due to AE in 8.3% of cases (n = 15). The efficacy‐effectiveness gap seems to favor pembrolizumab use in clinical practice.

Conclusion

Real‐world data suggest the performance of pembrolizumab to reflect the clinical trial outcomes in previously treated NSCLC.
Optimizing identification of resistant hypertension: Computable phenotype development and validation
Authors: McDonough Caitrin W. , Babcock Kyle , Chucri Kristen , Crawford Dana C. , Bian Jiang , Modave François , Cooper‐DeHoff Rhonda M. , Hogan William R.
Published: August 2020

Purpose

Computable phenotypes are constructed to utilize data within the electronic health record (EHR) to identify patients with specific characteristics; a necessary step for researching a complex disease state. We developed computable phenotypes for resistant hypertension (RHTN) and stable controlled hypertension (HTN) based on the National Patient‐Centered Clinical Research Network (PCORnet) common data model (CDM). The computable phenotypes were validated through manual chart review.

Methods

We adapted and refined existing computable phenotype algorithms for RHTN and stable controlled HTN to the PCORnet CDM in an adult HTN population from the OneFlorida Clinical Research Consortium (2015‐2017). Two independent reviewers validated the computable phenotypes through manual chart review of 425 patient records. We assessed precision of our computable phenotypes through positive predictive value (PPV) and test validity through interrater reliability (IRR).

Results

Among the 156 730 HTN patients in our final dataset, the final computable phenotype algorithms identified 24 926 patients with RHTN and 19 100 with stable controlled HTN. The PPV for RHTN in patients randomly selected for validation of the final algorithm was 99.1% (n = 113, CI: 95.2%‐99.9%). The PPV for stable controlled HTN in patients randomly selected for validation of the final algorithm was 96.5% (n = 113, CI: 91.2%‐99.0%). IRR analysis revealed a raw percent agreement of 91% (152/167) with Cohen's kappa statistic = 0.87.

Conclusions

We constructed and validated a RHTN computable phenotype algorithm and a stable controlled HTN computable phenotype algorithm. Both algorithms are based on the PCORnet CDM, allowing for future application to epidemiological and drug utilization based research.
Identifying opioid dose reductions and discontinuation among patients with chronic opioid therapy
Authors: Hallvik Sara E. , Johnston Kirbee , Geddes Jonah , Leichtling Gillian , Korthuis P. Todd , Hartung Daniel M.
Published: August 2020

Purpose

To identify and systematically categorize opioid dose reductions and discontinuations in large administrative datasets.

Methods

Using a dataset of Oregon Medicaid beneficiaries linked with prescription drug monitoring program (PDMP) data between 2014 and 2017, we identified patients with high‐dose chronic opioid therapy (COT), ≥84 consecutive days with an average daily MME of ≥50 on each of those days. We categorized patients into four mutually exclusive groups based on the trajectory of opioid use in the year after COT: abrupt discontinuation, dose reduction and discontinuation, dose reduction without discontinuation, and stable or increasing dose. Finally, we examined prescription patterns in each category.

Results

Among individuals with high‐dose COT, 7636 (37.1%) had an abrupt discontinuation, 2577 (12.5%) had a dose reduction and discontinuation, 7739 (37.6%) had a dose reduction without discontinuation, and 2623 (12.8%) had a stable or increasing dose in the year following the COT episode. Among those who discontinued opioid use (n = 10 213, 49.6%), three in four (74.8%) did so without evidence of tapering. Patients who discontinued opioid use were younger, had higher daily MME during COT, and were more likely to have filled a benzodiazepine or had a multiple provider or multiple pharmacy episode compared to patients who did not discontinue opioid use.

Conclusions

Dose reductions and discontinuations after a COT episode can be identified in large administrative datasets. Those with a discontinuation were more likely to have riskier prescription profiles during their COT episode.
Hsp90 chaperones have an energetic hot‐spot for binding inhibitors
Authors: Hoxie Reyal S. , Street Timothy O.
Published: August 2020

Although Hsp90‐family chaperones have been extensively targeted with ATP‐competitive inhibitors, it is unknown whether high affinity is achieved from a few highly stabilizing contacts or from many weaker contacts within the ATP‐binding pocket. A large‐scale analysis of Hsp90α:inhibitor structures shows that inhibitor hydrogen‐bonding to a conserved aspartate (D93 in Hsp90α) stands out as most universal among Hsp90 inhibitors. Here we show that the D93 region makes a dominant energetic contribution to inhibitor binding for both cytosolic and organelle‐specific Hsp90 paralogs. For inhibitors in the resorcinol family, the D93:inhibitor hydrogen‐bond is pH‐dependent because the associated inhibitor hydroxyl group is titratable, rationalizing a linked‐protonation event previously observed by the Matulis group. The inhibitor hydroxyl group pKa associated with the D93 hydrogen‐bond is therefore critical for optimizing the affinity of resorcinol derivatives, and we demonstrate that spectrophotometric measurements can determine this pKa value. Quantifying the energetic contribution of the D93 hotspot is best achieved with the mitochondrial Hsp90 paralog, yielding 3–6 kcal/mol of stabilization (35–60% of the total binding energy) for a diverse set of inhibitors. The Hsp90 Asp93➔Asn substitution has long been known to abolish nucleotide binding, yet puzzlingly, native sequences of structurally similar ATPases, such as Topoisomerasese II, have an asparagine at this same crucial site. While aspartate and asparagine sidechains can both act as hydrogen bond acceptors, we show that a steric clash prevents the Hsp90 Asp93➔Asn sidechain from adopting the necessary rotamer, whereas this steric restriction is absent in Topoisomerasese II.
Head and Neck Immobilization Masks: Increase in Dose Surface Evaluated by EBT3, TLD‐100 and PBC Method
Authors: Verde Nolasco Arnie , de Faria Luiz Oliveira
Published: August 2020

Positioning and immobilization tools are considered essential components of radiotherapy treatments to guarantee that the planned dose distribution can be efficiently reached. However, the benefits brought by their use are met by an apparent increase in the patient skin entrance dose. In the current study, we evaluated the dose surface effects provoked by the use of immobilization thermoplastic masks in head and neck radiotherapy treatments, carried out using a 6‐MV linear accelerator beam. The study was carried out using an anthropomorphic head–neck phantom and three dosimetric techniques: (i) thermoluminescent dosimetry (TL); (ii) radiochromic film dosimetry; and (iii) computational simulation using the pencil beam convolution (PBC) method. For calibration purposes, TLD chips and radiochromic (EBT3) small 2.0‐cm2 strip dosimeters were positioned between two virtual solid water plates, and exposed to absorbed doses ranging from 25 to 200 cGy. The use of an anthropomorphic head–neck phantom allows the dose variation in non‐flat surfaces to be taken into account. TLD chips, positioned on the surface of the supraclavicular fossa anatomical region, covered with a thermoplastic mask, detected an entrance skin dose that was approximately 38.4% higher than that measured without a mask. The EBT3 dosimeters, averaged among all strips used, also detected a medium increase of 58.6%. Both TLD and EBT3 detected increased doses for all measured points, and measured similar averaged surface doses without the use of immobilization masks; that is, 50.5% for EBT3 and 53.7% for TLD‐100. The pencil beam convolution simulation results suggested an increase for most of the measured points; however, no increased, and in some cases even decreased, doses were observed. The surface dose data of three other commercial thermoplastic masks irradiated in a solid water phantom are also provided.
Two‐Qubit State Swap and Entanglement Creation in a Superconducting Circuit QED via Counterdiabatic Drivings
Authors: Yan Run‐Ying , Feng Zhi‐Bo
Published: August 2020

Optimal coherent control of many qubits is critical to quantum information processing. Here, an efficient scheme is proposed for implementing state swap and creating an entanglement with two superconducting qubits in a circuit quantum electrodynamics (QED). Two qutrits of Cooper‐pair box (CPB) circuits are placed into a cavity field and are driven by individual classical microwaves. In the two‐photon resonance with a large detuning, each CPB is reduced into a qubit effectively. Within a composite system composed of qubit states and cavity photons, two‐qubit state swap and entanglement can be fast obtained using the technique of shortcuts to adiabaticity with counterdiabatic drivings. Benefited from the shorter duration times and less sensitivity to timing errors and parameter imperfections, high‐fidelity quantum operations can be performed with the accessible decoherence rates. The present protocol could offer a feasible route towards optimized operations on superconducting qubits in a circuit QED.
A simplified strategy for molecular formula determination of chemical constituents in traditional Chinese medicines based on accurate mass, A + 1 and A + 2 isotopic peaks using Fourier transform ion cyclotron resonance mass spectrometry
Authors: Xu Lu , Zhang Yu , Zhang Qingyu , Wang Xue , Chu Xiaowen , Li Xintong , Sui Wenwen , Han Fei
Published: August 2020

Rationale

Recently, isotopic fine structures derived from Fourier transform ion cyclotron resonance mass spectrometry have been used to determine the molecular formula for unknown compounds in many complex systems. However, a simplified strategy for molecular formula determination of chemical constituents in traditional Chinese medicines (TCMs) based on accurate mass, A + 1 and A + 2 isotopic peaks is necessary.

Methods

Salviae miltiorrhizae was selected as a representative species. First, the chemical constituents were chromatographically separated and their accurate masses were obtained. The A + 1 and A + 2 isotopic peaks of all chemical constituents were then also acquired. Finally, the chemical formulae of the chemical constituents were determined.

Results

In the sample of Salviae miltiorrhizae, the formulae of 38 CHO‐containing chemical constituents were quickly determined, and all chemical constituents were identified using their tandem mass spectrometric data. Moreover, the method was validated by comparison of the A + 1 and A + 2 isotopic peaks, their fragmentation patterns and the retention times of six selected standard substances.

Conclusions

The results demonstrate that the described strategy performs well for molecular formula determination of chemical constituents in TCMs. This also indicates that this method will be meaningful for the structural identification of chemical constituents of TCMs.
Efficient autonomous navigation for planetary rovers with limited resources
Authors: Gerdes Levin , Azkarate Martin , Sánchez‐Ibáñez José Ricardo , Joudrier Luc , Perez‐del‐Pulgar Carlos Jesús
Published: August 2020

Rovers operating on Mars require more and more autonomous features to fulfill their challenging mission requirements. However, the inherent constraints of space systems render the implementation of complex algorithms an expensive and difficult task. In this paper, we propose an architecture for autonomous navigation. Efficient implementations of autonomous features are built on top of the ExoMars path following navigation approach to enhance the safety and traversing capabilities of the rover. These features allow the rover to detect and avoid hazards and perform significantly longer traverses planned by operators on the ground. The efficient navigation approach has been implemented and tested during field test campaigns on a planetary analogue terrain. The experiments evaluated the proposed architecture by autonomously completing several traverses of variable lengths while avoiding hazards. The approach relies only on the optical Localization Cameras stereo bench, a sensor that is found in all current rovers, and potentially allows for computationally inexpensive long‐range autonomous navigation in terrains of medium difficulty.
Mesenchymal stromal cells for sepsis and septic shock: Lessons for treatment of COVID-19
Authors: Laroye Caroline , Gibot Sébastien , Huselstein Céline , Bensoussan Danièle
Published: August 2020

Sepsis is defined as life-threatening organ dysfunction caused by a deregulated immune host response to infection. The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted this multifactorial and complex syndrome. The absence of specific treatment neither against SARS-CoV-2 nor against acute respiratory distress syndrome (ARDS), the most serious stage of this infection, has emphasized the need to find alternative treatments. Several therapeutics are currently being tested, including mesenchymal stromal cells. These cells, already used in preclinical models of ARDS, sepsis, and septic shock and also in a few clinical trials, appear well-tolerated and promising, but many questions remain unanswered.

Significance statement Sepsis is defined as life-threatening organ dysfunction caused by a deregulated immune host response to infection. The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted this multifactorial and complex syndrome. The absence of specific treatment neither against SARS-CoV-2 nor against acute respiratory distress syndrome (ARDS), the most serious stage of this infection, has emphasized the need to find alternative treatments. Several therapeutics are currently being tested, including, mesenchymal stromal cells. These cells, already used in preclinical models of ARDS, sepsis, and septic shock and also in a few clinical trials, appear well-tolerated and promising.