bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholecalciferol Supplementation Attenuates Bone Loss in Incident Kidney Transplant Recipients: A Prespecified Secondary Endpoint Analysis of a Randomized Controlled Trial
Authors: Tsujita Makoto , Doi Yohei , Obi Yoshitsugu , Hamano Takayuki , Tomosugi Toshihide , Futamura Kenta , Okada Manabu , Hiramitsu Takahisa , Goto Norihiko , Isaka Yoshitaka , Takeda Asami , Narumi Shunji , Watarai Yoshihiko 
Published: November 2021

ABSTRACT
Vitamin D deficiency, persistent hyperparathyroidism, and bone loss are common after kidney transplantation (KTx). However, limited evidence exists regarding the effects of cholecalciferol supplementation on parathyroid hormone (PTH) and bone loss after KTx. In this prespecified secondary endpoint analysis of a randomized controlled trial, we evaluated changes in PTH, bone metabolic markers, and bone mineral density (BMD). At 1 month post-transplant, we randomized 193 patients to an 11-month intervention with cholecalciferol (4000 IU/d) or placebo. The median baseline 25-hydroxyvitamin D (25[OH]D) level was 10 ng/mL and 44% of participants had osteopenia or osteoporosis. At the end of the study, the median 25(OH)D level was increased to 40 ng/mL in the cholecalciferol group and substantially unchanged in the placebo group. Compared with placebo, cholecalciferol significantly reduced whole PTH concentrations (between-group difference of −15%; 95% confidence interval [CI] −25 to −3), with greater treatment effects in subgroups with lower 25(OH)D, lower serum calcium, or higher estimated glomerular filtration rate (pint &lt; 0.05). The percent change in lumbar spine (LS) BMD from before KTx to 12 months post-transplant was −0.2% (95% CI −1.4 to 0.9) in the cholecalciferol group and −1.9% (95% CI −3.0 to −0.8) in the placebo group, with a significant between-group difference (1.7%; 95% CI 0.1 to 3.3). The beneficial effect of cholecalciferol on LS BMD was prominent in patients with low bone mass pint &lt; 0.05). Changes in serum calcium, phosphate, bone metabolic markers, and BMD at the distal radius were not different between groups. In mediation analyses, change in whole PTH levels explained 39% of treatment effects on BMD change. In conclusion, 4000 IU/d cholecalciferol significantly reduced PTH levels and attenuated LS BMD loss after KTx. This regimen has the potential to eliminate vitamin D deficiency and provides beneficial effects on bone health even under glucocorticoid treatment. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Evaluation of changes in prescription among Japanese elderly patients before and after transition to home care
Authors: Masumoto Shoichi , Sato Mikiya , Yamakawa Tomotsugu , Hamada Shuhei , Inaba Takashi , Kataoka Yoshihiro , Ozone Sachiko , Yokoya Shoji , Hamano Jun 
Published: November 2021

AbstractBackgroundMost patients receiving home care have multimorbidity and tend to be prescribed multiple drugs with the complicated regimen. Family physicians (FPs) are responsible for patients' prescriptions after transition to home care. This study aimed to assess changes in medication regimen complexity and potentially inappropriate medications (PIMs) made by FPs before and after transition to home care.MethodsA retrospective cohort study was conducted in six home care clinics in Ibaraki Prefecture, Japan. Data from patients aged 65 years and older taking any medication who initiated home care between April 2018 and March 2019 were collected using medical records. The medication regimen complexity index‐Japanese version (MRCI‐J) score and the presence of PIMs were assessed before and 3 months after transition to home care.ResultsThe mean age of 169 patients was 84.0 years. MRCI‐J score and percentage of PIMs remained unchanged between before and 3 months after home care initiation. However, MRCI‐J score significantly decreased among patients with polypharmacy, but significantly increased among patients with nonpolypharmacy. In multiple regression analysis, a greater number of medications before home care initiation was associated with a decreasing MRCI‐J score, but pharmacist home visit services were not associated with changes in MRCI‐J score.ConclusionsOur results suggest that FPs involved in home care are trying to adjust prescriptions by simplifying the medication regimen of patients with polypharmacy, and adding symptomatic drugs to those with nonpolypharmacy.
A comparative study of metatranscriptomic assessment methods to characterize Microcystis blooms
Authors: Pound Helena L. , Gann Eric R. , Wilhelm Steven W. 
Published: November 2021

AbstractHarmful algal blooms are increasing in duration and severity globally, resulting in increased research interest. The use of genetic sequencing technologies has provided a wealth of opportunity to advance knowledge, but also poses a risk to that knowledge if handled incorrectly. The vast numbers of sequence processing tools and protocols provide a method to test nearly every hypothesis, but each method has inherent strengths and weaknesses. Here, we tested six methods to classify and quantify metatranscriptomic activity from a harmful algal bloom dominated by Microcystis spp. Three online tools were evaluated (Kaiju, MG‐RAST, and GhostKOALA) in addition to three local tools that included a command line BLASTx approach, recruitment of reads to individual Microcystis genomes, and recruitment to a combined Microcystis composite genome generated from sequenced isolates with complete, closed genomes. Based on the analysis of each tool presented in this study, two recommendations are made that are dependent on the hypothesis to be tested. For researchers only interested in the function and physiology of Microcystis spp., read recruitments to the composite genome, referred to as “Frankenstein's Microcystis,” provided high total estimates of transcript expression. However, for researchers interested in the entire bloom microbiome, the online GhostKOALA annotation tool, followed by subsequent read recruitments, provided functional and taxonomic characterization, in addition to transcript expression estimates. This study highlights the critical need for careful evaluation of methods before data analysis.
Genetic manipulation of trehalose‐6‐phosphate synthase results in changes in the soluble sugar profile in transgenic sugarcane stems
Authors: Gabriel Casey , Fernhout Jean‐Jacque , Fichtner Franziska , Feil Regina , Lunn John E. , Kossmann Jens , Lloyd James R. , van der Vyver Christell 
Published: November 2021

AbstractTrehalose is a non‐reducing disaccharide widely distributed in nature. The trehalose biosynthetic intermediate, trehalose 6‐phosphate (Tre6P) is an essential regulatory and signaling molecule involved in both regulation of carbon metabolism and photosynthesis. To investigate the effect of altered trehalose synthesis on sucrose accumulation in sugarcane (Saccharum spp. hybrid), we independently overexpressed the Escherichia coli otsA (trehalose‐6‐phosphate synthase; TPS) and otsB (trehalose‐6‐phosphate phosphatase; TPP) genes and additionally partially silenced native TPS expression. In mature cane, sucrose levels in the otsA transgenic plants were lowered, whereas sucrose levels in the otsB transgenic plants were increased. Partial silencing of TPS expression in sugarcane transformed with a TPS‐targeted microRNA recombinant construct was confirmed in leaf and mature internode tissue of transgenic plants. Most of the silencing transgenic lines accumulated trehalose at lower levels than the wild‐type (WT) plants. The immature stalk tissue of these transgenic lines had lower levels of glucose and fructose, whereas the mature internode tissue had lower sucrose and glucose levels, when compared with the WT. Furthermore, various minor metabolites and sugars were detected in the sugarcane plants, which mostly decreased as the stalk tissue of the cane matured. The results demonstrate that manipulation of Tre6P/trehalose metabolism has the potential to modify the profile of soluble sugars accumulated in sugarcane stems.
Tomato and cotton G protein beta subunit mutants display constitutive autoimmune responses
Authors: Ninh Thi Thao , Gao Wei , Trusov Yuri , Zhao Jing‐Ruo , Long Lu , Song Chun‐Peng , Botella Jose Ramon 
Published: November 2021

AbstractHeterotrimeric G protein Gβ‐deficient mutants in rice and maize display constitutive immune responses, whereas Arabidopsis Gβ mutants show impaired defense, suggesting the existence of functional differences between monocots and dicots. Using CRISPR/Cas9, we produced one hemizygous tomato line with a mutated SlGB1 Gβ gene. Homozygous slgb1 knockout mutants exhibit all the hallmarks of autoimmune mutants, including development of necrotic lesions, constitutive expression of defense‐related genes, and high endogenous levels of salicylic acid (SA) and reactive oxygen species, resulting in early seedling lethality. Virus‐induced silencing of Gβ in cotton reproduced the symptoms observed in tomato mutants, confirming that the autoimmune phenotype is not limited to monocot species but is also shared by dicots. Even though multiple genes involved in SA and ethylene signaling are highly induced by Gβ silencing in tomato and cotton, co‐silencing of SA or ethylene signaling components in cotton failed to suppress the lethal phenotype, whereas co‐silencing of the oxidative burst oxidase RbohD can repress lethality. Despite the autoimmune response observed in slgb1 mutants, we show that SlGB1 is a positive regulator of the pathogen‐associated molecular pattern (PAMP)‐triggered immunity (PTI) response in tomato. We speculate that the phenotypic differences observed between Arabidopsis and tomato/cotton/rice/maize Gβ knockouts do not necessarily reflect divergences in G protein‐mediated defense mechanisms.
Performance on the American Board of Physical Medicine and Rehabilitation certifying examinations: Rural and urban physicians
Authors: Murphy Kevin P. , Raddatz Mikaela M. , Robinson Lawrence R. 
Published: November 2021

AbstractBackgroundOver 60 million people in the United States live in a rural community making up approximately 20% of the population. Data are minimal about the physiatrists who serve this rural population, their performance on certification examinations and how the American Board of Physical Medicine and Rehabilitation (ABPM&R) serves their ongoing educational, assessment, and practice needs.ObjectiveTo compare the performance of rural and urban physicians on the Part I, Part II, and maintenance of certification (MOC) examinations along with subspecialty preference and continuance of primary certification.DesignRetrospective cross‐sectional study.SettingBoard‐eligible PM&R physicians and certified diplomates of the ABPM&R.ParticipantsPhysicians who participated in an initial certification or maintenance of certification examination with the ABPM&R between 2010 and 2019.MethodsComparisons of physician pass rates, mean scaled scores (aggregates), and program pass rates on ABPM&R certifying examinations were completed. Cross‐reference to national database and ABPM&R practice site zip codes provided sociogeographic linkage.InterventionsNot applicableMain Outcome MeasuresPhysician mean scaled scores, pass rates, subspecialty preferences, and primary certification status.ResultsThere were no meaningful differences in performance on the ABPM&R Part I, II, and MOC examinations between rural and urban physiatrists. Most common subspecialty is the pain medicine certification whose diplomates most frequently drop their primary certification. Pediatric rehabilitation medicine certification is rare in rural localities and a health care disparity.ConclusionThe study found no meaningful differences in the performance of rural and urban physicians on the ABPM&R certifying examinations.
Normal variation of the gut microbiota affects hepatic cytochrome P450 activity in mice
Authors: Togao Masao , Tajima Shinnosuke , Kurakawa Takashi , Wagai Gaku , Otsuka Jun , Kado Shoichi , Kawakami Koji 
Published: November 2021

AbstractSeveral studies revealed that substantial artificial changes in the gut microbiota resulted in modification of hepatic cytochrome P450 3a (Cyp3a) in mice. Consequently, we hypothesized that “normal” variation of the gut microbiota might also alter hepatic Cyp activity and lead to individual differences in drug metabolism. Therefore, this study investigated the effects of normal gut microbiota variation on hepatic Cyp activity under the same genetic and environmental conditions using ex‐germ‐free mice. Using the feces of three breeder BALB/c mice (Jcl, Slc, and Crj), germ‐free BALB/cYit mice were conventionalized (Yit‐Jcl, Yit‐Slc, and Yit‐Crj). The gut microbiota composition and hepatic Cyp activity of these donors and recipients were evaluated. 16S rRNA sequencing revealed clear differences of the gut microbiota among donors and among recipients. Cyp3a activity was significantly higher in Slc mice than in Jcl and Crj mice. Notably, among recipients, Cyp3a activity was significantly higher in Yit‐Slc and Yit‐Crj mice than in Yit‐Jcl mice. Cyp2b activity was significantly higher in Slc mice than in Jcl and Crj mice. Cyp2b activity was significantly higher in Yit‐Slc mice than in Yit‐Jcl mice. Additionally, in correlation analysis, some genera displayed significant positive or negative correlations with Cyp activity, particular the strong positive correlation between Clostridium sensu stricto 1 with Cyp3a activity. In conclusion, this study demonstrated that normal variation of the gut microbiota affected hepatic Cyp3a and Cyp2b activity, which might result in individual differences of drug metabolism.
SIL‐3, SIL‐2, and unicorns (there is a high probability your SIL 2 and SIL 3 SIFs have no better performance than SIL 1)
Authors: Dowell Arthur M. (Art) , Bridges William , Thomas Hal W. (Hal) , Massello Matias 
Published: November 2021

AbstractSafety instrumented system (SIS) standards improved the definition of interlocks and introduced requirements for improved management systems to enforce independence from other independent protection layers (IPLs). SIS standards require verification that the performance of each safety instrumented function (SIF) will be met during its lifetime, where the performance criterion is documented as the target safety integrity level (SIL) or risk reduction factor for the SIF. The SIL is in turn tied to specific values of probability of failure on demand (PFD). The current SIS standards and the TR (Technical Reports, from ISA) that explain how to do SIL verification calculations do not include accounting for specific human error probabilities—this is a major deficiency as even the probability of a single human error can be much larger than the target PFD of 0.001 for a SIL 3 and oftentimes a little larger than the PFD of 0.01 for a SIL 2. The SIL verification methods outlined in the standards and technical reports like ANSI/ISA TR84.00.02 facilitate consistency for the component‐only failure rates. As user companies seek to obtain greater risk reduction from their SIS to satisfy their corporate risk criteria, failure to adequately address potential specific human failures can lead to overly optimistic results and a misallocation of resources intended to reduce risk.
Osmotic management of distributed complex systems: A declarative decentralised approach
Authors: Forti Stefano , Lera Isaac , Guerrero Carlos , Brogi Antonio 
Published: November 2021

AbstractOsmotic computing encompasses emerging Cloud‐Internet of Things (IoT) computing paradigms, by featuring the possibility for application services to adapt into different functionally equivalent flavours, depending on the contextually available resources and on specific requirements of running applications. This article proposes a fully decentralised declarative framework that enables both application and infrastructure operators to declare management policies for the service instances and the nodes they manage, respectively. Policies are composed of a simple and well‐defined set of management operations, declared in Prolog, which trigger based on locally available contextual information on application requests and infrastructure resources. A prototype implementation of the framework is showcased and assessed via simulation over a lifelike Smart Campus use case with multiple applications, at increasing infrastructure sizes and number of mobile users. Experimental results show that the proposed management framework scales to large infrastructure sizes and suits the needs of multiflavoured Osmotic applications in dynamic deployment conditions, by improving the trade‐off between their response times and suitable service usage.
Zum Kriechen von Sandwichelementen unter axialer Belastung
Authors: Hörnel‐Metzger Beate , Naujoks Bernd 
Published: November 2021

AbstractBei der Berechnung von Sandwichelementen, die neben Flächenlasten senkrecht zur Ebene und einem Temperaturgradienten auch durch Drucknormalkräfte beansprucht werden, müssen die Effekte nach Theorie II. Ordnung beachtet werden. Die Verformungen aus der Ebene werden unter Berücksichtigung der Schubverformungen des Kernmaterials ermittelt. Dabei ist der Einfluss des Kriechens des Kernmaterials erheblich. Für rein auf Biegung beanspruchte Elemente werden vom jeweiligen Hersteller Kriechbeiwerte für unterschiedliche Belastungsdauern deklariert, da diese je nach Zusammensetzung des Kernmaterials stark variieren. Fraglich ist, auf welche Weise diese Werte für die Bemessung druckbeanspruchter Elemente verwendet werden können. Dazu wurden am Institut für Sandwichtechnik (iS‐mainz) der Hochschule Mainz axiale Kriechversuche durchgeführt. Basierend auf den Ergebnissen aus diesem Forschungsvorhaben sowie aus dem FP7‐Projekt EASIE unter Leitung des iS‐mainz wird ein Bemessungsvorschlag für axial belastete Sandwichelemente unter Berücksichtigung des Kriechverhaltens der Kernschicht vorgestellt, der im Entwurf der prEN 1993‐7 Design of steel structures – Sandwich Panels enthalten sein wird.
Dark moments for the Standard Model?
Authors: Rizzo Thomas G. 
Published: November 2021

Abstract
If dark matter (DM) interacts with the Standard Model (SM) via the kinetic mixing (KM) portal, it necessitates the existence of portal matter (PM) particles which carry both dark and SM quantum numbers that will appear in vacuum polarization-like loop graphs. In addition to the familiar ∼ eϵQ strength, QED-like interaction for the dark photon (DP), in some setups different loop graphs of these PM states can also induce other coupling structures for the SM fermions that may come to dominate in at least some regions of parameter space regions and which can take the form of ‘dark’ moments, e.g., magnetic dipole-type interactions in the IR, associated with a large mass scale, Λ. In this paper, motivated by a simple toy model, we perform a phenomenological investigation of a possible loop-induced dark magnetic dipole moment for SM fermions, in particular, for the electron. We show that at the phenomenological level such a scenario can not only be made compatible with existing experimental constraints for a significant range of correlated values for Λ and the dark U(1)D gauge coupling, gD, but can also lead to quantitatively different signatures once the DP is discovered. In this setup, assuming complex scalar DM to satisfy CMB constraints, parameter space regions where the DP decays invisibly are found to be somewhat preferred if PM mass limits from direct searches at the LHC and our toy model setup are all taken seriously. High precision searches for, or measurements of, the e+e− → γ + DP process at Belle II are shown to provide some of the strongest future constraints on this scenario.
Optimal integrability threshold for Gibbs measures associated with focusing NLS on the torus
Authors: Oh Tadahiro , Sosoe Philippe , Tolomeo Leonardo 
Published: November 2021

AbstractWe study an optimal mass threshold for normalizability of the Gibbs measures associated with the focusing mass-critical nonlinear Schrödinger equation on the one-dimensional torus. In an influential paper, Lebowitz et al. (J Stat Phys 50(3–4):657–687, 1988) proposed a critical mass threshold given by the mass of the ground state on the real line. We provide a proof for the optimality of this critical mass threshold. The proof also applies to the two-dimensional radial problem posed on the unit disc. In this case, we answer a question posed by Bourgain and Bulut (Ann Inst H Poincaré Anal Non Linéaire 31(6):1267–1288, 2014) on the optimal mass threshold. Furthermore, in the one-dimensional case, we show that the Gibbs measure is indeed normalizable at the optimal mass threshold, thus answering an open question posed by Lebowitz et al. (1988). This normalizability at the optimal mass threshold is rather striking in view of the minimal mass blowup solution for the focusing quintic nonlinear Schrödinger equation on the one-dimensional torus.
Efficient adjoint-based well-placement optimization using flow diagnostics proxies
Authors: Krogstad Stein , Nilsen Halvor Møll 
Published: November 2021

AbstractModel-based optimization of placement and trajectories of wells in petroleum reservoirs by the means of reservoir simulation forecasts is computationally demanding due to the high number of simulations typically required to achieve a local optimum. In this work, we develop an efficient flow-diagnostics proxy for net-present-value (NPV) with adjoint capabilities for efficient computation of well control gradients and approximate sensitivities with respect to placement/trajectory parameters. The suggested flow-diagnostic proxy consists of numerically solving a single pressure equation for the given scenario and the solution of a few inter-well time-of-flight and steady-state tracer equations, typically achieved in a few seconds for a reservoir model of medium size. Although the proxy may not be a particularly good approximation for the full reservoir simulation response, we find that for the cases considered, the correlation is very good and hence the proxy is suitable for use in an optimization loop. The adjoint simulation for the proxy model which provides control gradients and placement sensitivities is of similar computational complexity as the forward proxy model (a few seconds). We employ a version of the generalized reduced gradient for handling individual well constraints (e.g., bottom-hole-pressures and rates). As a result, the individual well constraints are enforced within the flow-diagnostics computations, and hence every parameter update becomes feasible without sacrificing gradient information. We present two numerical experiments illustrating the efficiency and performance of the approach for well placement problems involving trajectories and simulation models of realistic complexity. The suggested placements are evaluated using full simulations. We conclude by discussing limitations and possible enhancements of the methodology.