bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct healthcare costs of chronic kidney disease management in Italy: What cost‐savings can be achieved with higher biosimilar uptake and more appropriate use of erythropoiesis‐stimulating agents?
Authors: Ingrasciotta Ylenia , Sultana Janet , Formica Dario , Ientile Valentina , Aiello Andrea , Chinellato Alessandro , Tari Daniele Ugo , Gini Rosa , Pastorello Maurizio , Scondotto Salvatore , Cananzi Pasquale , Traversa Giuseppe , Rossi Mariangela , Santoro Domenico , Trifirò Gianluca ,   the Italian Biosimilars Network (I‐BioNetwork)
Published: October 2020

AbstractPurposeErythropoiesis‐stimulating agents (ESAs), are used for treating chronic kidney disease (CKD)‐related anemia, contributing to CKD costs. The study was aimed at investigating direct healthcare costs of CKD patients treated with ESAs and the potential savings achievable by increasing the use of biosimilars and preventing inappropriate ESA use.MethodsA multi‐center, cohort study was conducted using claims databases of five large Italian geographic areas. Yearly mean direct healthcare costs per patient were estimated, stratifying by CKD stage. The total yearly cost and potential savings related to ESA use were estimated: (a) considering 25/50/75% of originator ESA substitution with biosimilars; (b) eliminating inappropriate ESA dispensing.ResultsDuring the study period, the ESA‐related yearly mean cost represented 17% of total yearly costs in stage I‐III, decreasing to 13% in stage IV‐V and 6% in dialysis. Among originator users, assuming a 25% of biosimilar uptake, the annual cost‐savings of ESA treatment would represent 10.5% of total ESA costs in CKD stage I‐V and 7.7% in dialysis. Among incident ESA users for which hemoglobin levels were available, 9% started inappropriately ESA treatment, increasing to 62.0% during the first year of maintenance therapy. Hypothesizing prevention of the first inappropriate ESA dispensing, the total yearly cost‐savings would amount to €35 772, increasing to €167 641 eliminating the inappropriate dispensing during maintenance therapy.ConclusionsHigher use of lowest cost ESA, prevention of inappropriate ESA use as well as other strategies aimed at slowing down the progressive renal impairment are essential for minimizing clinical and economic burden of CKD.
Synthesis and properties of thermoplastic and dissolvable polysiloxanes containing polyhedral oligomeric silsesquioxane
Authors: Guo Ruilu , Liu Yuemin , Zhou Lixia , Li Na , Chen Guangxin , Zhou Zheng , Li Qifang 
Published: October 2020

AbstractThere are many benefits associated with thermoplastic silicones, but very few examples exist: silicone resins or rubbers are normally thermosets. In this article, a facile and efficient approach was reported to prepare thermoplastic silicone by introducing a bulky side siloxane group. Monofunctional polyhedral oligomeric silsesquioxane (POSS), as the bulky siloxane group, was grafted onto the linear polysiloxane backbone via thiol–ene click reaction, endowing the liquid polysiloxane with thermoplastic nature. The POSS‐grafted polysiloxane could be remolded by a hot‐melting or solution casting process. It was worth noting that the novel thermoplastic silicone was composed of both linear siloxane main chains and siloxane side groups, which was distinctly different from previous researches on thermoplastic silicones consisted of siloxane main chains and organic side groups. Thermal analysis, rheological characterization and molecular dynamics simulation results revealed the thermoplastic properties of POSS‐grafted polysiloxane depended on the bulky POSS's hindrance to the movement of the polymer backbone rather than the interaction between the organic side groups.
Tuning the binding interface between Machupo virus glycoprotein and human transferrin receptor
Authors: Sjöström Dick J , Lundgren Anneli , Garforth Scott J , Bjelic Sinisa 
Published: October 2020

AbstractMachupo virus, known to cause hemorrhagic fevers, enters human cells via binding with its envelope glycoprotein to transferrin receptor 1 (TfR). Similarly, the receptor interactions have been explored in biotechnological applications as a molecular system to ferry therapeutics across the cellular membranes and through the impenetrable blood–brain barrier that effectively blocks any such delivery into the brain. Study of the experimental structure of Machupo virus glycoprotein 1 (MGP1) in complex with TfR and glycoprotein sequence homology has identified some residues at the interface that influence binding. There are, however, no studies that have attempted to optimize the binding potential between MGP1 and TfR. In pursuits for finding therapeutic solutions for the New World arenaviruses, and to gain a greater understanding of MGP1 interactions with TfR, it is crucial to understand the structure–sequence relationship driving the interface formation. By displaying MGP1 on yeast surface we have examined the contributions of individual residues to the binding of solubilized ectodomain of TfR. We identified MGP1 binding hot spot residues, assessed the importance of posttranslational N‐glycan modifications, and used a selection with random mutagenesis for affinity maturation. We show that the optimized MGP1 variants can bind more strongly to TfR than the native MGP1, and there is an MGP1 sequence that retains binding in the absence of glycosylation, but with the addition of further amino acid substitutions. The engineered variants can be used to probe cellular internalization or the blood‐brain barrier crossing to achieve greater understanding of TfR mediated internalization.
Examination of Metoprolol Pharmacokinetics and Pharmacodynamics Across CYP2D6 Genotype‐Derived Activity Scores
Authors: Thomas Cameron D. , Mosley Scott A. , Kim Sarah , Lingineni Karthik , El Rouby Nihal , Langaee Taimour Y. , Gong Yan , Wang Danxin , Schmidt Siegfried O. , Binkley Philip F. , Estores David S. , Feng Kairui , Kim Hyewon , Kinjo Minori , Li Zhichuan , Fang Lanyan , Chapman Arlene B. , Cooper-DeHoff Rhonda M. , Gums John G. , Hamadeh Issam S. , Zhao Liang , Schmidt Stephan , Frye Reginald F. , Johnson Julie A. , Cavallari Larisa H. 
Published: October 2020

Recent CYP2D6 phenotype standardization efforts by CYP2D6 activity score (AS) are based on limited pharmacokinetic (PK) and pharmacodynamic (PD) data. Using data from two independent clinical trials of metoprolol, we compared metoprolol PK and PD across CYP2D6 AS with the goal of determining whether the PK and PD data support the new phenotype classification. S‐metoprolol apparent oral clearance (CLo), adjusted for clinical factors, was correlated with CYP2D6 AS (P < 0.001). The natural log of CLo was lower with an AS of 1 (7.6 ± 0.4 mL/minute) vs. 2–2.25 (8.3 ± 0.6 mL/minute; P = 0.012), similar between an AS of 1 and 1.25–1.5 (7.8 ± 0.5 mL/minute; P = 0.702), and lower with an AS of 1.25–1.5 vs. 2–2.25 (P = 0.03). There was also a greater reduction in heart rate with metoprolol among study participants with AS of 1 (−10.8 ± 5.5) vs. 2–2.25 (−7.1 ± 5.6; P < 0.001) and no significant difference between those with an AS of 1 and 1.25–1.5 (−9.2 ± 4.7; P = 0.095). These data highlight linear trends among CYP2D6 AS and metoprolol PK and PD, but inconsistencies with the phenotypes assigned by AS based on the current standards. Overall, this case study with metoprolol suggests that utilizing CYP2D6 AS, instead of collapsing AS into phenotype categories, may be the most precise approach for utilizing CYP2D6 pharmacogenomics in clinical practice.
TRAIL: A novel approach for studying the aerodynamics of ice particles
Authors: McCorquodale M. W. , Westbrook C. D. 
Published: October 2020

AbstractA novel experimental approach for studying the aerodynamics of ice particles is presented. The Trajectory Reconstruction Algorithm implemented through Image anaLysis (TRAIL) produces digital reconstructions of the trajectory and orientation of 3D‐printed analogues of ice particles that fall through a quiescent viscous liquid. Data extracted from this analysis can be used to test fall speed parametrisations and investigate the preferred orientation of analogues with complex irregular geometries. Experiments using thin circular discs are used to validate this approach. Measurements from a case study in which an analogue of an aggregate ice particle is used are also reported. Data extracted from the analysis clearly demonstrate important, but poorly understood, aspects of the aerodynamics of atmospheric ice particles. For example, the orientation that the analogue adopts in free fall is shown to depend not only on the geometric shape of the particle, but also on the Reynolds number at which it falls. In addition, measurements of the drag coefficient indicate that the accuracy of fall speed parametrisations reduces at high Reynolds number due to the onset of unsteady motions.
TRAIL part 2: A comprehensive assessment of ice particle fall speed parametrisations
Authors: McCorquodale M. W. , Westbrook C. D. 
Published: October 2020

AbstractResults are presented from a comprehensive experimental campaign studying the aerodynamics of 3D‐printed analogues of ice particles. Measurements of the drag coefficient of the analogues were acquired by using a novel experimental approach to digitally reconstruct the analogues' trajectory and orientation as they fall through a quiescent viscous liquid, using images acquired by a series of digital cameras. The data are used to evaluate commonly used parametrisations of ice particle fall speeds. We find that the accuracy of each of the parametrisations reduces at Reynolds numbers greater than approximately 100, as a result of effects associated with the onset of unsteady oscillating, fluttering or tumbling motions as the analogues fall. We propose a new fall speed parametrisation that predicts the measured drag coefficients at high Reynolds number with an accuracy consistent with that of the leading parametrisation at low Reynolds number.
Comparison of KD‐SR‐01 robotic partial nephrectomy and 3D‐laparoscopic partial nephrectomy from an operative and ergonomic perspective: A prospective randomized controlled study in porcine models
Authors: Dai Xiaofei , Fan Shubo , Hao Han , Yang Kunlin , Shen Cheng , Xiong Gengyan , Li Xueying , Cui Liang , Li Xuesong , Zhou Liqun 
Published: October 2020

AbstractBackgroundTo investigate the feasibility, validity and security of a new robot platform called KD‐SR‐01 and compare relative merits of KD‐SR‐01 robotic partial nephrectomy (KD‐RPN) and 3D‐Laparoscopic Partial Nephrectomy (3D‐LPN).MethodsTwelve porcine models were randomly and equally divided for KD‐RPN and 3D‐LPN. The perioperative outcomes, physical and mental workload of the surgeon were compared. Physical workload was evaluated with surface electromyography. Mental workload was evaluated with National Aeronautics and Space Administration Task Load Index (NASA‐TLX).ResultsAll surgeries were performed successfully. The average docking time of KD‐RPN was 6 min. The estimated blood loss was lower in KD‐RPN (p < 0.05). There were no differences in all the other operative variables (p > 0.05). KD‐RPN showed advantages in physical workload and was significantly superior in mental workload (p < 0.05).ConclusionsKD‐RPN is technically feasible, valid and safe in porcine models. It's comparable from operative perspective while KD‐RPN had advantages over 3D‐LPN from ergonomic perspective.
Ramsey games near the critical threshold
Authors: Conlon David , Das Shagnik , Lee Joonkyung , Mészáros Tamás 
Published: October 2020

A well‐known result of Rödl and Ruciński states that for any graph H there exists a constant C such that if , then the random graph Gn, p is a.a.s. H‐Ramsey, that is, any 2‐coloring of its edges contains a monochromatic copy of H. Aside from a few simple exceptions, the corresponding 0‐statement also holds, that is, there exists c > 0 such that whenever the random graph Gn, p is a.a.s. not H‐Ramsey. We show that near this threshold, even when Gn, p is not H‐Ramsey, it is often extremely close to being H‐Ramsey. More precisely, we prove that for any constant c > 0 and any strictly 2‐balanced graph H, if , then the random graph Gn, p a.a.s. has the property that every 2‐edge‐coloring without monochromatic copies of H cannot be extended to an H‐free coloring after extra random edges are added. This generalizes a result by Friedgut, Kohayakawa, Rödl, Ruciński, and Tetali, who in 2002 proved the same statement for triangles, and addresses a question raised by those authors. We also extend a result of theirs on the three‐color case and show that these theorems need not hold when H is not strictly 2‐balanced.
Compressive strength of core specimens drilled from concrete test cylinders
Authors: Haavisto Jukka , Husso Ari , Laaksonen Anssi 
Published: October 2020

AbstractThe compressive strength of concrete is highly influenced by the properties of test specimens, such as size and moisture content. This paper presents the results of compression tests on more than 650 test specimens made with four different concrete types, which are mainly air‐entrained. The differences in compressive strength between different types of concrete specimens were investigated with similar compaction and curing conditions. The tested specimens were 50 × 50 mm, 80 × 80 mm, 100 × 100 mm, and 150 × 300 mm cores, which were drilled from the cast cylinders. In addition, 150‐mm cubes, 100 × 100 mm and 150 × 300 mm cylinders were included in the test programme. The ratios of compressive strength between different core sizes and core strength comparability to the cast specimens were found to be strongly dependent on the concrete type. Drilling was found to have a clear weakening effect on obtained compressive strength. The conversion factors for the compressive strength between the core and the same size cast specimen was proposed for 150 × 300 mm and 100 × 100 mm specimen sizes.
CCCDTD5 recommendations on early non cognitive markers of dementia: A Canadian consensus
Authors: Montero‐Odasso Manuel , Pieruccini‐Faria Frederico , Ismail Zahinoor , Li Karen , Lim Andrew , Phillips Natalie , Kamkar Nellie , Sarquis‐Adamson Yanina , Speechley Mark , Theou Olga , Verghese Joe , Wallace Lindsay , Camicioli Richard 
Published: October 2020

AbstractIntroductionCognitive impairment is the hallmark of Alzheimer's disease (AD) and related dementias. However, motor decline has been recently described as a prodromal state that can help to detect at‐risk individuals. Similarly, sensory changes, sleep and behavior disturbances, and frailty have been associated with higher risk of developing dementia. These clinical findings, together with the recognition that AD pathology precedes the diagnosis by many years, raises the possibility that non‐cognitive changes may be early and non‐invasive markers for AD or, even more provocatively, that treating non‐cognitive aspects may help to prevent or treat AD and related dementias.MethodsA subcommittee of the Canadian Consensus Conference on Diagnosis and Treatment of Dementia reviewed areas of emerging evidence for non‐cognitive markers of dementia. We examined the literature for five non‐cognitive domains associated with future dementia: motor, sensory (hearing, vision, olfaction), neuro‐behavioral, frailty, and sleep. The Grading of Recommendations Assessment, Development, and Evaluation system was used to assign the strength of the evidence and quality of the recommendations. We provide recommendations to primary care clinics and to specialized memory clinics, answering the following main questions: (1) What are the non‐cognitive and functional changes associated with risk of developing dementia? and (2) What is the evidence that sensory, motor, behavioral, sleep, and frailty markers can serve as potential predictors of dementia?ResultsEvidence supported that gait speed, dual‐task gait speed, grip strength, frailty, neuropsychiatric symptoms, sleep measures, and hearing loss are predictors of dementia. There was insufficient evidence for recommending assessing olfactory and vision impairments as a predictor of dementia.ConclusionsNon‐cognitive markers can assist in identifying people at risk for cognitive decline or dementia. These non‐cognitive markers may represent prodromal symptoms and several of them are potentially amenable to treatment that might delay the onset of cognitive decline.
Mathematical modeling and fuzzy proportional–integral–derivative scheme to control the yaw motion of a wind turbine
Authors: Campos‐Mercado Eduardo , Cerecero‐Natale Luis F. , Garcia‐Salazar Octavio , Abundis Fong Hugo F. , Wood David 
Published: October 2020

AbstractIn this paper, we present a mathematical model and control strategy to regulate the yaw of a horizontal axis wind turbine. In order to obtain the dynamic equations of the yaw motion, the mathematical model is developed using the Euler–Lagrange formulation and considers the wind turbine as a manipulator robot with three degrees of freedom (DOF). A fuzzy proportional‐integral‐derivative (PID) controller is proposed to manipulate the yaw angle for power regulation. In addition, we have developed a low cost experimental platform to implement the designed controller to obtain experimental results for the dynamic behavior of the closed‐loop system.
The averaged null energy conditions in even dimensional curved spacetimes from AdS/CFT duality
Authors: Iizuka Norihiro , Ishibashi Akihiro , Maeda Kengo 
Published: October 2020

Abstract
We consider averaged null energy conditions (ANEC) for strongly coupled quantum field theories in even (two and four) dimensional curved spacetimes by applying the no-bulk-shortcut principle in the context of the AdS/CFT duality. In the same context but in odd-dimensions, the present authors previously derived a conformally invariant averaged null energy condition (CANEC), which is a version of the ANEC with a certain weight function for conformal invariance. In even-dimensions, however, one has to deal with gravitational conformal anomalies, which make relevant formulas much more complicated than the odd-dimensional case. In two-dimensions, we derive the ANEC by applying the no-bulk-shortcut principle. In four-dimensions, we derive an inequality which essentially provides the lower-bound for the ANEC with a weight function. For this purpose, and also to get some geometric insights into gravitational conformal anomalies, we express the stress-energy formulas in terms of geometric quantities such as the expansions of boundary null geodesics and a quasi-local mass of the boundary geometry. We argue when the lowest bound is achieved and also discuss when the averaged value of the null energy can be negative, considering a simple example of a spatially compact universe with wormhole throat.
Symmetries at null boundaries: two and three dimensional gravity cases
Authors: Adami H. , Sheikh-Jabbari M.M. , Taghiloo V. , Yavartanoo H. , Zwikel C. 
Published: October 2020

AbstractWe carry out in full generality and without fixing specific boundary conditions, the symmetry and charge analysis near a generic null surface for two and three dimensional (2dand 3d) gravity theories. In 2dand 3dthere are respectively two and three charges which are generic functions over the codimension one null surface. The integrability of charges and their algebra depend on the state-dependence of symmetry generators which is a priori not specified. We establish the existence of infinitely many choices that render the surface charges integrable. We show that there is a choice, the “fundamental basis”, where the null boundary symmetry algebra is the Heisenberg⊕Diff(d −2) algebra. We expect this result to be true ford >3 when there is no Bondi news through the null surface.
The action of the Virasoro algebra in the two-dimensional Potts and loop models at generic Q
Authors: Grans-Samuelsson Linnea , Liu Lawrence , He Yifei , Jacobsen Jesper Lykke , Saleur Hubert 
Published: October 2020

Abstract
The spectrum of conformal weights for the CFT describing the two-dimensional critical Q-state Potts model (or its close cousin, the dense loop model) has been known for more than 30 years [1]. However, the exact nature of the corresponding Vir ⊗ $$ \overline{\mathrm{Vir}} $$

Vir
¯

representations has remained unknown up to now. Here, we solve the problem for generic values of Q. This is achieved by a mixture of different techniques: a careful study of “Koo-Saleur generators” [2], combined with measurements of four-point amplitudes, on the numerical side, and OPEs and the four-point amplitudes recently determined using the “interchiral conformal bootstrap” in [3] on the analytical side. We find that null-descendants of diagonal fields having weights (hr,1, hr,1) (with r ∈ ℕ*) are truly zero, so these fields come with simple Vir ⊗ $$ \overline{\mathrm{Vir}} $$

Vir
¯

(“Kac”) modules. Meanwhile, fields with weights (hr,s, hr,−s) and (hr,−s, hr,s) (with r, s ∈ ℕ*) come in indecomposable but not fully reducible representations mixing four simple Vir ⊗ $$ \overline{\mathrm{Vir}} $$

Vir
¯

modules with a familiar “diamond” shape. The “top” and “bottom” fields in these diamonds have weights (hr,−s, hr,−s), and form a two-dimensional Jordan cell for L0 and $$ {\overline{L}}_0 $$

L
¯

0

. This establishes, among other things, that the Potts-model CFT is logarithmic for Q generic. Unlike the case of non-generic (root of unity) values of Q, these indecomposable structures are not present in finite size, but we can nevertheless show from the numerical study of the lattice model how the rank-two Jordan cells build up in the infinite-size limit.
A connection between flavour anomaly, neutrino mass, and axion
Authors: Baek Seungwon 
Published: October 2020

AbstractWe propose a minimal model in which the flavour anomaly in theb → sμ+μ−transition is connected to the breaking of Peccei-Quinn (PQ) symmetry. The flavour anomaly is explained from new physics contribution by introducing one generation of heavy quark and heavy lepton which are vector-like under the standard model (SM) gauge group but charged under a local U(1)Xgroup. They mix with the SM quarks and leptons, inducing flavour-changingZ′couplings, which generates theb → sμ+μ−anomaly at tree level. On the other hand the new fermions are chiral under the global Peccei-Quinn(PQ) symmetry. The pseudo-Goldstone boson coming from the spontaneous breaking of the PQ symmetry becomes an axion, solving the strong CP problem and providing a cold dark matter candidate. The same symmetry prevents the right-handed neutrino from having a Majorana mass term. But the introduction of a neutrino-specific Higgs doublet allows neutrino to have Dirac mass term without fine-tuning problem. The model shows an interplay between axion, neutrino, dark matter, and flavour physics.