bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cystatin C may be better than creatinine for digoxin dosing in older adults with atrial fibrillation
Authors: Šálek Tomáš , Vodička Martin , Gřiva Martin 
Published: June 2020

AbstractBackgroundPatients taking digoxin are older with high probability of having low muscle mass, and current clinical practice in digoxin dosing relies only on estimated glomerular filtration rate from serum creatinine (eGFRcrea). The aim of the study is to compare eGFRcrea and estimated glomerular filtration rate from serum cystatin C (eGFRcys) in older adult patients with atrial fibrillation (AF) overdosed with digoxin.MethodsA total of 80 consecutive patients overdosed with digoxin and 33 controls with AF from Department of Internal Medicine were included in the prospective observational study. The median of age of participants was 81 years in both the overdosed and the control group. The eGFRs were calculated using The Chronic Kidney Disease Epidemiology (CKD‐ EPI) equations using standardized methods for serum creatinine and cystatin C measurement.ResultsThe median (IQR) of eGFRcrea was higher than that of eGFRcys (45 mL/min/1.73 m2 (35‐59) vs 30 (21‐38), respectively; P < .0001) in overdosed patients. The median (IQR) of eGFRcrea was higher than that of eGFRcys (61 mL/min/1.73 m2 (49‐72) vs 40 (30‐56), respectively; P < .0001) in control group of patients. Serum predose digoxin concentration in overdosed patients was inversely associated with eGFRcys (ρ = −0.26, P < .05).ConclusionPhysicians should consider GFR when changing digoxin dosing. eGFRcys was lower in both the overdosed and the control group. eGFRcys would lead to lower digoxin doses and thus prevent overdose.
Prevalence of protein intake below recommended in community‐dwelling older adults: a meta‐analysis across cohorts from the PROMISS consortium
Authors: Hengeveld Linda M. , Boer Jolanda M.A. , Gaudreau Pierrette , Heymans Martijn W. , Jagger Carol , Mendonça Nuno , Ocké Marga C. , Presse Nancy , Sette Stefania , Simonsick Eleanor M. , Tapanainen Heli , Turrini Aida , Virtanen Suvi M. , Wijnhoven Hanneke A.H. , Visser Marjolein 
Published: June 2020

AbstractBackgroundLower protein intake in older adults is associated with loss of muscle mass and strength. The present study aimed to provide a pooled estimate of the overall prevalence of protein intake below recommended (according to different cut‐off values) among community‐dwelling older adults, both within the general older population and within specific subgroups.MethodsAs part of the PRevention Of Malnutrition In Senior Subjects in the EU (PROMISS) project, a meta‐analysis was performed using data from four cohorts (from the Netherlands, UK, Canada, and USA) and four national surveys [from the Netherlands, Finland (two), and Italy]. Within those studies, data on protein and energy intake of community‐dwelling men and women aged ≥55 years were obtained by either a food frequency questionnaire, 24 h recalls administered on 2 or 3 days, or food diaries administered on 3 days. Protein intake below recommended was based on the recommended dietary allowance of 0.8 g/kg body weight (BW)/d, by using adjusted BW (aBW) instead of actual BW. Cut‐off values of 1.0 and 1.2 were applied in additional analyses. Prevalences were also examined for subgroups according to sex, age, body mass index (BMI), education level, appetite, living status, and recent weight loss.ResultsThe study sample comprised 8107 older persons. Mean ± standard deviation protein intake ranged from 64.3 ± 22.3 (UK) to 80.6 ± 23.7 g/d [the Netherlands (cohort)] or from 0.94 ± 0.38 (USA) to 1.17z ± 0.30 g/kg aBW/d (Italy) when related to BW. The overall pooled prevalence of protein intake below recommended was 21.5% (95% confidence interval: 14.0–30.1), 46.7% (38.3–55.3), and 70.8% (65.1–76.3) using the 0.8, 1.0, and 1.2 cut‐off value, respectively. A higher prevalence was observed among women, individuals with higher BMI, and individuals with poor appetite. The prevalence differed only marginally by age, education level, living status, and recent weight loss.ConclusionsIn community‐dwelling older adults, the prevalence of protein intake below the current recommendation of 0.8 g/kg aBW/d is substantial (14–30%) and increases to 65–76% according to a cut‐off value of 1.2 g/kg aBW/d. To what extent the protein intakes are below the requirements of these older people warrants further investigation.
Social frailty predicts worse outcomes in patients with multiple myeloma: A novelty in an old approach
Authors: Terao Toshiki , Tsushima Takafumi , Miura Daisuke , Narita Kentaro , Takeuchi Masami , Matsue Kosei 
Published: June 2020

AbstractSocial frailty, defined as the loss of social roles and networks in the community, has never been evaluated in patients with multiple myeloma (MM). This study aimed to evaluate the usefulness of social frailty as a predictor of survival in MM. We retrospectively reviewed 237 consecutive patients with MM from 2009 to 2019. Activities of daily living (ADL), the instrumental ADL score, the Charlson Comorbidity Index, and factors to evaluate social relationships were routinely assessed at the time of initial diagnosis and first hospitalization at our center by hematological clinicians, nurses, and rehabilitation staff. Social frailty was evaluated using five social factors and was defined as a score of at least 2 points. Overall, 69 (30.0%) patients were defined as socially frail, with a median score of 0. Those who were socially frail showed significantly shorter progression‐free and overall survival than those who were not. Using the International Staging System, International Myeloma Working Group frailty score, and social frailty, we developed two staging systems, and these further demonstrated the importance of assessing frail patients with MM. Our findings have identified the usefulness for evaluating social frailty; however, to confirm our results, an independent study with larger patient numbers with an entirely prospective assessment is needed to confirm their results.
Consecutive false‐negative rRT‐PCR test results for SARS‐CoV‐2 in patients after clinical recovery from COVID‐19
Authors: Wang Guan , Yu Na , Xiao Weimin , Zhao Chen , Wang Zhenning 
Published: June 2020

AbstractThis study reviewed the serial real‐time reverse‐transcription polymerase chain reaction (rRT‐PCR) results of 37 patients admitted to our hospital in Wuhan, China, who had three or more sequential negative results before discharge. Of these 37 patients, 14 (~38%) had a positive rRT‐PCR result after a negative result during convalescence, and 5 (~14%) had a positive rRT‐PCR result after two consecutive negative results during convalescence. These results suggest that it may be necessary to require that patients have three consecutive negative results before discharge, to ensure that they do not spread infection among members of their household, or in the community. We believe that our study makes a significant contribution to the literature because it is not currently the standard of care to require patients to have three consecutive negative results before discharge. Our results suggest that a relatively high proportion of patients may continue to shed severe acute respiratory syndrome coronavirus 2 after they have clinically recovered, and thus may transmit the infection to others.
Characterization of the seasonal variation of soil moisture in Argentina
Authors: Fernández‐Long María Elena , Peretti Mercedes , Carnelos Danilo , Della‐Chiesa Tomás , Spescha Liliana 
Published: June 2020

AbstractSoil moisture is an essential variable for both the agricultural production and the functioning of natural ecosystems, as well as one of the main variables regulating the climate system. Like precipitation, soil moisture has a marked annual cycle that depends mainly on the behaviour of precipitation and evapotranspiration. In this study, we developed a methodology that allows describing and characterizing the annual cycle of soil moisture in Argentina. For this purpose, we estimated soil moisture at 121 sites of Argentina by means of a simple hydrological balance (the BHOA, an acronym for its name in Spanish: “Balance Hidrológico Operativo para el Agro”) and analysed its intra‐annual variability by means of different indices. This methodology allowed recognizing five different annual behaviours, with a consistent geographical pattern throughout Argentina. The characterization was based mainly on the time of occurrence of the annual maximum and minimum values of soil moisture, and secondly by the annual soil moisture content and seasonality. The northwest and part of the centre of Argentina present the minimum soil moisture values in spring and the maximum ones in autumn, while the east and south present the minimum values in summer and the maximum ones in winter. In general, sites with higher soil water content were found to have lower seasonality and vice‐versa.
Evaluation of the van Deemter equation in terms of open‐ended flow to chromatography
Authors: Andersen Jens E.T. , Mukami Hawa W. , Maina Irene W. 
Published: June 2020

AbstractPlate theory and adsorption theory are the main tools available for understanding chromatographic experiments. Both theories predict a Gaussian distribution of solute molecules within the tubular system. However, Gaussian concentration distributions are observed predominantly at slow linear flow rates, while asymmetric concentration distributions are observed at the linear flow rates most used in chromatography. Allegedly, this asymmetry originates from an inhomogeneous distribution of grain sizes in the column and column overload. However, it is an experimental fact that the distribution of chemicals within an injected volume of solute changes as a function of time, while the response is measured simultaneously. Accordingly, the obtained signal cannot be compared to the theory before some type of time‐based deconvolution of the data has been performed. Adjustments to high‐performance liquid chromatography data were thus proposed through empirical equations that describe the relevant time values, peak height, peak area, and parameters of the van Deemter equation. It was proposed that the transfer of solute from the front to the rear part of the pulse during laminar open‐ended flow occurs at rate that depends on the linear flow rate, and to a lesser extent, on properties of the response function.
Increased Expression of PD‐1 and PD‐L1 in Patients With Laryngotracheal Stenosis
Authors: Davis Ruth J. , Lina Ioan , Ding Dacheng , Engle Elizabeth L. , Taube Janis , Gelbard Alexander , Hillel Alexander T. 
Published: June 2020

ObjectivesLaryngotracheal stenosis (LTS) is a fibrotic condition of the upper airway. Recent evidence suggests dysregulated host immunity plays a role in LTS development and progression. The programmed death‐1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) axis, targeted by paradigm‐shifting immunotherapies for cancer treatment, has also recently been implicated in the pathogenesis of fibrotic pulmonary disease. However, a role for the PD‐1/PD‐L1 axis in the proximal airway fibrosis seen in LTS patients has not been explored.Study DesignControlled ex vivo study.MethodsExpression of PD‐1, PD‐L1, CD4, and CD8 were evaluated using immunohistochemical staining of cricotracheal resection specimens from postintubation iatrogenic laryngotracheal stenosis (iLTS), idiopathic subglottic stenosis (iSGS) patients, and normal controls derived from rapid autopsy (n = 8 per group). Fibroblasts derived from iLTS scar were also treated with transforming growth factor beta 1 (TGFβ1) and analyzed for PD‐L1 expression by quantitative real‐time polymerase chain reaction (n = 6).ResultsiLTS specimens exhibited increased expression of PD‐1, PD‐L1, and CD4 (all P < .0167) compared to controls, whereas iSGS specimens exhibited increased expression of PD‐1 and CD4 (P < .0167) compared to controls. PD‐1, PD‐L1, and CD4 showed periepithelial patterns of expression in both disease cohorts. TGFβ1 treatment of iLTS fibroblasts increased expression of PD‐L1 (the cognate ligand for PD‐1).ConclusionExpression of both PD‐1 and its ligand PD‐L1 are significantly greater in patients with iLTS compared to controls, and PD‐1 expression is also elevated in patients with iSGS. Given published evidence implicating the PD‐1/PD‐L1 axis in pulmonary fibrosis, this suggests a possible role for checkpoint inhibitors targeting the PD‐1/PD‐L1 axis for the treatment of LTS.Level of EvidenceN/A Laryngoscope, 131:967–974, 2021
Variable clinical expression of Stickler Syndrome: A case report of a novel COL11A1 mutation
Authors: Brizola Evelise , Gnoli Maria , Tremosini Morena , Nucci Paolo , Bargiacchi Sara , La Barbera Andrea , Giglio Sabrina , Sangiorgi Luca 
Published: June 2020

AbstractBackgroundStickler Syndrome is a rare connective tissue disorder, characterized by clinical, and genetic heterogeneity. The clinical expression is highly variable, including moderate to severe myopia in childhood, hearing loss, facial dysmorphic features, cleft palate, and early osteoarthritis. COL2A1, COL11A1, and COL11A2 mutations account of the majority of autosomal dominant Stickler Syndrome and, in particular, a heterozygous mutation in COL11A1 gene is identified in about 10 to 20% of Stickler Syndrome patients.MethodsHerein, we report a case of an 8‐year‐ old child with Stickler Syndrome, presenting with early‐onset of myopia with vitreal abnormalities, facial dysmorphic characteristics, and mild hearing loss later in childhood. To identify the underlying genetic cause, Whole Exome Sequencing was carried out for COL11A1 gene.ResultsA novel de novo heterozygous splice site variant (NM_001854: c.1845 + 5G> C) of the COL11A1 gene, which had not been previously reported, was identified by Whole Exome Sequencing.ConclusionWe reported a novel COL11A1 mutation in a child with Stickler Syndrome presenting a phenotype of early‐onset of ocular anomalies and mild hearing loss later in childhood. Our findings confirm the variability of the expression of the disease, even in the contest of the same gene‐related disorder, thus, contributing to improve the knowledge on clinical and molecular basis of this rare disease.
A variational discrete element method for quasistatic and dynamic elastoplasticity
Authors: Marazzato Frédéric , Ern Alexandre , Monasse Laurent 
Published: June 2020

SummaryWe propose a new discrete element method supporting general polyhedral meshes. The method can be understood as a lowest‐order discontinuous Galerkin method parametrized by the continuous mechanical parameters (Young's modulus and Poisson's ratio). We consider quasistatic and dynamic elastoplasticity, and in the latter situation, a pseudoenergy conserving time‐integration method is employed. The computational cost of the time‐stepping method is moderate since it is explicit and used with a naturally diagonal mass matrix. Numerical examples are presented to illustrate the robustness and versatility of the method for quasistatic and dynamic elastoplastic evolutions.
Moving Profiling Spatial Proteomics Beyond Discrete Classification
Authors: Crook Oliver M. , Smith Tom , Elzek Mohamed , Lilley Kathryn S. 
Published: June 2020

AbstractThe spatial subcellular proteome is a dynamic environment; one that can be perturbed by molecular cues and regulated by post‐translational modifications. Compartmentalization of this environment and management of these biomolecular dynamics allows for an array of ancillary protein functions. Profiling spatial proteomics has proved to be a powerful technique in identifying the primary subcellular localization of proteins. The approach has also been refashioned to study multi‐localization and localization dynamics. Here, the analytical approaches that have been applied to spatial proteomics thus far are critiqued, and challenges particularly associated with multi‐localization and dynamic relocalization is identified. To meet some of the current limitations in analytical processing, it is suggested that Bayesian modeling has clear benefits over the methods applied to date and should be favored whenever possible. Careful consideration of the limitations and challenges, and development of robust statistical frameworks, will ensure that profiling spatial proteomics remains a valuable technique as its utility is expanded.
Structural compliance: A new metric for protein flexibility
Authors: Scaramozzino Domenico , Khade Pranav M. , Jernigan Robert L. , Lacidogna Giuseppe , Carpinteri Alberto 
Published: June 2020

AbstractProteins are the active players in performing essential molecular activities throughout biology, and their dynamics has been broadly demonstrated to relate to their mechanisms. The intrinsic fluctuations have often been used to represent their dynamics and then compared to the experimental B‐factors. However, proteins do not move in a vacuum and their motions are modulated by solvent that can impose forces on the structure. In this paper, we introduce a new structural concept, which has been called the structural compliance, for the evaluation of the global and local deformability of the protein structure in response to intramolecular and solvent forces. Based on the application of pairwise pulling forces to a protein elastic network, this structural quantity has been computed and sometimes is even found to yield an improved correlation with the experimental B‐factors, meaning that it may serve as a better metric for protein flexibility. The inverse of structural compliance, namely the structural stiffness, has also been defined, which shows a clear anticorrelation with the experimental data. Although the present applications are made to proteins, this approach can also be applied to other biomolecular structures such as RNA. This present study considers only elastic network models, but the approach could be applied further to conventional atomic molecular dynamics. Compliance is found to have a slightly better agreement with the experimental B‐factors, perhaps reflecting its bias toward the effects of local perturbations, in contrast to mean square fluctuations. The code for calculating protein compliance and stiffness is freely accessible at https://jerniganlab.github.io/Software/PACKMAN/Tutorials/compliance.
A simple immersed boundary forcing for flows over steep and complex orography
Authors: Allen T. , Zerroukat M. 
Published: June 2020

AbstractSimulation and parametrization of flow over the Earth's orographic features is an important element of any climate or weather model. With increasing resolution, especially in the limited‐area context, the orographic features are not only becoming better resolved but, importantly for numerical stability, the slopes are becoming ever steeper and the currently employed terrain‐following coordinates can cause convergence issues as the curvilinear terms become relatively large. This paper discusses this specific issue and suggests a possible solution based upon an immersed boundary forcing method for representing steep and complex terrain. The method is simple and straightforward to incorporate into any atmospheric model.
What can we learn from N2O isotope data? – Analytics, processes and modelling
Authors: Yu Longfei , Harris Eliza , Lewicka‐Szczebak Dominika , Barthel Matti , Blomberg Margareta R.A. , Harris Stephen J. , Johnson Matthew S. , Lehmann Moritz F. , Liisberg Jesper , Müller Christoph , Ostrom Nathaniel E. , Six Johan , Toyoda Sakae , Yoshida Naohiro , Mohn Joachim 
Published: June 2020

The isotopic composition of nitrous oxide (N2O) provides useful information for evaluating N2O sources and budgets. Due to the co‐occurrence of multiple N2O transformation pathways, it is, however, challenging to use isotopic information to quantify the contribution of distinct processes across variable spatiotemporal scales. Here, we present an overview of recent progress in N2O isotopic studies and provide suggestions for future research, mainly focusing on: analytical techniques; production and consumption processes; and interpretation and modelling approaches.Comparing isotope‐ratio mass spectrometry (IRMS) with laser absorption spectroscopy (LAS), we conclude that IRMS is a precise technique for laboratory analysis of N2O isotopes, while LAS is more suitable for in situ/inline studies and offers advantages for site‐specific analyses. When reviewing the link between the N2O isotopic composition and underlying mechanisms/processes, we find that, at the molecular scale, the specific enzymes and mechanisms involved determine isotopic fractionation effects. In contrast, at plot‐to‐global scales, mixing of N2O derived from different processes and their isotopic variability must be considered. We also find that dual isotope plots are effective for semi‐quantitative attribution of co‐occurring N2O production and reduction processes. More recently, process‐based N2O isotopic models have been developed for natural abundance and 15N‐tracing studies, and have been shown to be effective, particularly for data with adequate temporal resolution.Despite the significant progress made over the last decade, there is still great need and potential for future work, including development of analytical techniques, reference materials and inter‐laboratory comparisons, further exploration of N2O formation and destruction mechanisms, more observations across scales, and design and validation of interpretation and modelling approaches. Synthesizing all these efforts, we are confident that the N2O isotope community will continue to advance our understanding of N2O transformation processes in all spheres of the Earth, and in turn to gain improved constraints on regional and global budgets.
Graphical calibration curves and the integrated calibration index (ICI) for survival models
Authors: Austin Peter C. , Harrell Frank E. , van Klaveren David 
Published: June 2020

AbstractIn the context of survival analysis, calibration refers to the agreement between predicted probabilities and observed event rates or frequencies of the outcome within a given duration of time. We aimed to describe and evaluate methods for graphically assessing the calibration of survival models. We focus on hazard regression models and restricted cubic splines in conjunction with a Cox proportional hazards model. We also describe modifications of the Integrated Calibration Index, of E50 and of E90. In this context, this is the average (respectively, median or 90th percentile) absolute difference between predicted survival probabilities and smoothed survival frequencies. We conducted a series of Monte Carlo simulations to evaluate the performance of these calibration measures when the underlying model has been correctly specified and under different types of model mis‐specification. We illustrate the utility of calibration curves and the three calibration metrics by using them to compare the calibration of a Cox proportional hazards regression model with that of a random survival forest for predicting mortality in patients hospitalized with heart failure. Under a correctly specified regression model, differences between the two methods for constructing calibration curves were minimal, although the performance of the method based on restricted cubic splines tended to be slightly better. In contrast, under a mis‐specified model, the smoothed calibration curved constructed using hazard regression tended to be closer to the true calibration curve. The use of calibration curves and of these numeric calibration metrics permits for a comprehensive comparison of the calibration of competing survival models.