bluuebunny/crossref_metadata_2025 huggingface dataset:
Bayesian profiling for cost with zeros to decompose total cost into probability of cost and mean nonzero cost
Authors: Grunwald Gary K. , Arnett James A. , Liu Wenhui , Ho P. Michael
Published: June 2020

Cost of health care can vary substantially across hospitals, centers, or providers. Data from electronic health records provide information for studying patterns of cost variation and identifying high or low cost centers. Cost data often include zero values when patients receive no care, and joint two‐part models have been developed for clustered cost data with zeros. Standard methods for center comparisons, sometimes called profiling, can use these methods to incorporate zero values into total cost. However, zero costs also provide opportunities to further examine sources of cost variation and outliers. For example, a hospital may have high (or low) cost due to frequency of nonzero cost, amount of nonzero cost, or a combination of those. We give methods for decomposing hospital differences in total cost with zeros into components for probability of use (i.e., of nonzero cost) and for cost of use (mean of nonzero cost). The components multiply to total cost and quantify components on the same easily interpreted multiplicative scales. The methods are based on Bayesian hierarchical models and counterfactual arguments, with Markov chain Monte Carlo estimation. We used simulated data to illustrate use, interpretation, and visualization of the methods in diverse situations, and applied the methods to 30,024 patients at 57 US Veterans Administration hospitals to characterize outlier hospitals in one year cost of inpatient care following a cardiac procedure. Twenty eight percent of patients had zero cost. These methods are useful in providing insight into cost variation and outliers for planning future studies or interventions.
Structural and spectroscopic study of Ho3+‐doped nanotitania host prepared using a sol–gel technique
Authors: Ameen Majida A. , Arif Gashaw K.
Published: June 2020

Holmium (Ho3+)‐doped TiO2 solid laser active materials with different concentrations (1, 3, 5, and 7 wt%) of Ho3+ ions were prepared using a sol–gel method. A structural study of the samples using X‐ray diffraction (XRD) revealed the anatase phase of pure and doped TiO2 calcined at 500°C, which is confirmed by (101), (004), (200), (105), (211), (204), (116), (220) and (215) diffraction peaks. XRD analysis showen a deformation along the c‐axis of the anatase lattice constant with doping, and a random change in the grain size of the doped titania with respect to pure samples. The presence of the titania bonds (Ti–O–Ti) and (Ti–O) of pure and Ho3+‐doped samples were confirmed from the FTIR spectroscopy study of the samples. In addition, it was noted that bands around 1338, and 1339 cm−1 belonging to 3, 5, and 7 wt% dopant concentrations, while no band for 1 wt% was observed. UV‐Vis spectrophotometer and spectrofluorophotometer techniques were used to study the optical and spectroscopic characterizations of these samples. It was found that various fluorescence peaks for Ho3+ ions were observed in the UV–vis region under different pump wavelengths. This is a good indication of suitability of the material to be employed as a laser active medium.
Biochemistry course‐based undergraduate research experience: Purification, characterization, and identification of an unknown lactate dehydrogenase isoenzyme
Authors: Chaari Ali , Al‐Ali Dana , Roach James
Published: June 2020

Enzyme purification, characterization, and identification are some of the best ways to introduce undergraduate students to many aspects of biochemistry, particularly as part of project‐based learning (PBL). These kinds of multi‐step laboratory experiments not only help students to better understand basic biochemistry concepts but also serve to introduce them to the scaffolded nature of the research environment. A 13‐week enzyme‐based laboratory project was designed as one of three components associated with the course titled Capstone Laboratory, which is delivered to second‐year undergraduate students at Weill Cornell Medicine in Qatar (WCM‐Q). The project incorporated several fundamental biochemical laboratory techniques, such as chromatography, centrifugation, spectrophotometry, electrophoresis, and kinetic assays, as well as enzyme inhibition and bioinformatic exercises. The aims of the project were to first purify, then to quantify, and finally to study a particular lactate dehydrogenase (LDH) isoenzyme extracted from different chicken organs. LDH was selected for investigation because its inhibition has potential as a therapeutic strategy for cancer treatment. Students enrolled in the Capstone Laboratory course were divided into three groups. Each group conducted experiments associated with one of the project's three aims over consecutive 3‐week periods. Relevant data and materials were passed from one group to the next, with individual students writing reports describing the results from their respective collection of experiments. Students in the third and final group gave presentations summarizing the results of the overall project. In the associated bioinformatic exercises, students assessed the similarities and differences between chicken‐sourced and human‐sourced LDH as well as the interaction between the LDH enzyme and the inhibitors. This PBL in biochemistry is a successful addition to the WCM‐Q premedical curriculum because (a) it affords the second‐year premedical students opportunities to improve and develop content knowledge and technical and communication skills, and also (b) it provides an opportunity to engage many of the undergraduate students in research.
The clinical application value of mixed‐reality‐assisted surgical navigation for laparoscopic nephrectomy
Authors: Li Guan , Dong Jie , Wang Jinbao , Cao Dongbing , Zhang Xin , Cao Zhiqiang , Lu Guangming
Published: June 2020

Purpose

Laparoscopic nephrectomy (LN) has become the preferred method for renal cell carcinoma (RCC). Adequate preoperative assessment or intraoperative navigation is key to the successful implementation of LN. The aim of this study was to evaluate the clinical application value of mixed‐reality–assisted surgical navigation (MRASN) in LN.

Patients and Methods

A total of 100 patients with stage T1N0M0 renal tumors who underwent laparoscopic partial nephrectomy (LPN) or laparoscopic radical nephrectomy (LRN) were prospectively enrolled and divided into a mixed‐reality‐assisted laparoscopic nephrectomy (MRALN) group (n = 50) and a non–mixed‐reality‐assisted laparoscopic nephrectomy (non‐MRALN) group (n = 50). All patients underwent renal contrast‐enhanced CT scans. The CT DICOM data of all patients in the MRALN group were imported into the mixed‐reality (MR) postprocessing workstation and underwent holographic three‐dimensional visualization (V3D) modeling and MR displayed, respectively. We adopted the Likert scale to evaluate the clinical application value of MRASN. The consistency of evaluators was assessed using the Cohen kappa coefficient (k).

Results

No significant differences in patient demographic indicators between the MRALN group and the non‐MRALN group (P > .05). The subjective score of MRASN clinical application value in operative plan formulation, intraoperative navigation, remote consultation, teaching guidance, and doctor‐patient communication were higher in the MRASN group than in the non‐MRASN group (all P < .001). There were significantly more patients for whom LPN was successfully implemented in the MRALN group than in the non‐MRALN group (82% vs 46%, P < .001). The MRALN group had a shorter operative time (OT) and warm ischemia time (WIT) and less estimated blood loss (EBL) than the non‐MRALN group (all P < .001).

Conclusion

MRASN is helpful for operative plan formulation, intraoperative navigation, remote consultation, teaching guidance, and doctor‐patient communication. MRALN may effectively improve the successful implementation rate of LPN and reduce the OT, WIT, and EBL.
A nomogram for prediction of stage III/IV gastric cancer outcome after surgery: A multicenter population‐based study
Authors: Gao Zhiying , Ni Jing , Ding Hui , Yan Caiwang , Ren Chuanli , Li Gang , Pan Feng , Jin Guangfu
Published: June 2020

Most patients with gastric cancer (GC) are first diagnosed at stage III‐IV and surgery resection remains the primary therapeutic modality for these patients. However, clinical staging used for prediction of those patients provides limited information. We collected clinicopathological data and disease‐progression information from 508 patients with stage III‐IV GC at three Chinese hospitals and 1298 patients from the Surveillance, Epidemiology, and End Results database. Based on the stepwise multivariate regression model, we constructed a novel nomogram to predict overall survival (OS). The performance of discrimination for this model was measured using Harrell's concordance index (C‐index) and receiver‐operating characteristic curve (ROC), and was validated using calibration plots. Multivariate Cox regression analyses showed that tumor size, age at diagnosis, N stage, tumor grade, and distant metastases were outstanding independent prognostic factors of stage III‐IV GC. We developed a nomogram based on these five prognostic predictors. In the training set, the C‐index of the nomogram was 0.645 (95% CI: 0.611‐0.679), which was higher than that of the American Joint Committee on Cancer TNM system alone (sixth TNM: 0.544; seventh TNM: 0.575; eighth TNM: 0.568). Similar results were observed in validation cohort. Moreover, calibration blots demonstrated good consistency between the actual and predicted OS probabilities. According to the nomogram, GC individuals could be classified into three groups (low‐, middle‐, and high‐risk) (P < .001). Our nomogram complements the current staging system for prediction of individual prognosis with stage III‐IV GC, and may be helpful for making individualized treatment decisions.
Fabrication of Porous Configurated Ni2P/Ni Foam Catalyst and its Boosted Properties for pH‐universal Hydrogen Evolution Reaction and Efficient Nitrate Reduction
Authors: Huo Siyue , Yang Shuqin , Niu Qianqian , Song Zimo , Yang Fan , Song Laizhou
Published: June 2020

Nickel phosphide (Ni2P) has been widely explored toward hydrogen evolution reaction (HER) for desirable durability and high performance. Tuning the electronic structures and morphologies of Ni2P plays a pivotal role in the improvement of HER performance. In this work, three Ni2P catalysts were fabricated by different strategies and their HER properties were compared. It was found that the bicontinuous porous structured Ni2P on Ni foam (Ni2P /NF−EHP) prepared using coupled electroless nickel‐phosphorus (Ni−P) plating, hydrothermal synthesis and low temperature phosphorization techniques, exhibits the best catalytic activity and a wide pH adaptability. The overpotential at 10 mA cm−2 and Tafel slope are 78 mV and 33 mV dec−1 in 0.5 M H2SO4, those in 1 M PBS are 125 mV and 93 mV dec−1, and 101 mV and 76 mV dec−1 in 1 M KOH. Additionally, the Ni2P/NF−EHP‐catalyzed HER process is also applicable for nitrate reduction with a remarkable removal efficiency of 92.6 %. This catalyst also exhibits a desirable durability both in HER and nitrate reduction. This work offers an efficient strategy to exploit compatible pH‐universal HER catalysts, explores the engineering application of HER process in nitrate reduction.
36‐Nuclearity Organophosphonate‐Functionalized Polyoxomolybdates: Synthesis, Characterization and Selective Catalytic Oxidation of Sulfides
Authors: Xu Qiaofei , Liang Xinmiao , Xu Baijie , Wang Jiawei , He Peipei , Ma Pengtao , Feng Jiwen , Wang Jingping , Niu Jingyang
Published: June 2020

The crown‐shaped 36‐molybdate cluster organophosphonate‐functionalized polyoxomolybdates with the highest nuclearity in organophosphonate‐based polyoxometalate chemistry, (NH4)19Na7H10[Cu(H2O)TeMo6O21{N(CH2PO3)3}]6⋅31 H2O, has been reported for the first time. The synthesized 36‐molybdate cluster was characterized by routine techniques and tested as a heterogeneous catalyst for selective oxidation of sulfides with impressive catalytic and selective performances after heat treatment. High efficiency (TON=15333) was achieved in the selective oxidation of sulfides to sulfoxides, caused by the synergic effect between copper and polyoxomolybdates and the generation of the cuprous species during the heat treatment.
O6‐Alkylguanine DNA Alkyltransferase Mediated Disassembly of a DNA Tetrahedron
Authors: Copp William , Wilds Christopher J.
Published: June 2020

Tetrahedron DNA structures were formed by the assembly of three‐way junction (TWJ) oligonucleotides containing O6‐2′‐deoxyguanosine‐alkylene‐O6‐2′‐deoxyguanosine (butylene and heptylene linked) intrastrand cross‐links (IaCLs) lacking a phosphodiester group between the 2′‐deoxyribose residues. The DNA tetrahedra containing TWJs were shown to undergo an unhooking reaction by the human DNA repair protein O6‐alkylguanine DNA alkyltransferase (hAGT) resulting in structure disassembly. The unhooking reaction of hAGT towards the DNA tetrahedra was observed to be moderate to virtually complete depending on the protein equivalents. DNA tetrahedron structures have been explored as drug delivery platforms that release their payload in response to triggers, such as light, chemical agents or hybridization of release strands. The dismantling of DNA tetrahedron structures by a DNA repair protein contributes to the armamentarium of approaches for drug release employing DNA nanostructures.
Flow Cytometric Quantification of Granulocytic Alkaline Phosphatase Activity in Unlysed Whole Blood
Authors: Bardina Jorge , Rico Laura G. , Ward Michael D. , Bradford Jolene A. , Juncà Jordi , Petriz Jordi
Published: June 2020

Translational research has improved the diagnosis and follow‐up of hematological diseases and malignancies. However, some classical diagnostics used for research and clinical practice that have remain practically unchanged for decades may be better addressed through advances in flow cytometry technology, whereby more precise measurements may be implemented in a straightforward manner. The current method for semiquantitative analysis of granulocytic alkaline phosphatase (GAP) activity is still based on observer‐dependent color‐intensity classification. Here, we describe a novel strategy for flow cytometric quantification of GAP activity in which staining and analytical flow cytometry facilitate the detection and quantification of subpopulations of leukocytes with different GAP activities. Our experiments demonstrate the potential of flow cytometry as a simple and highly sensitive approach for measuring GAP activity in unlysed whole blood. Notably, a comparison of flow cytometry and enzyme cytochemistry techniques showed that enzyme activity scores were not similar, indicating that results needs to be interpreted with caution, given that the enzyme‐substrate binding affinities may differ, as well as the subjective evaluation of the intensity of the precipitated dye. © 2020 Wiley Periodicals LLC.

Basic Protocol: Protocol preparation, sample acquisition, and gating strategy for flow cytometric identification of alkaline phosphatase activity in granulocytes from whole blood samples

Support Protocol 1: Sample preparation for granulocyte alkaline phosphatase determination by flow cytometry using no‐lyse no‐wash methods

Support Protocol 2: Data analysis and formula to calculate the GAP score
A Randomized, Single‐Blind, Placebo‐Controlled, 3‐Way Crossover Study to Evaluate the Effect of Therapeutic and Supratherapeutic Doses of Edaravone on QT/QTc Interval in Healthy Subjects
Authors: Shimizu Hidetoshi , Inoue Shinsuke , Endo Mai , Nakamaru Yoshinobu , Yoshida Kaori , Natori Tomoko , Kakubari Masae , Akimoto Makoto , Kondo Kazuoki
Published: June 2020

This randomized, single‐blind, 3‐way crossover study assessed the effect of edaravone on QT interval, including an exposure‐response analysis. Twenty‐seven healthy Japanese male volunteers, aged 20 to 49 years, were randomly assigned to receive a single intravenous dose of each treatment in 1 of 3 sequences (n = 9 each): ACB, BAC, and CBA, where A was edaravone 60 mg (therapeutic dose), B was edaravone 300 mg (supratherapeutic dose), and C was normal saline (placebo). Electrocardiographs were collected to assess treatment effects. In an exposure‐response analysis, a linear model was determined to be valid and indicated no statistically significant positive slope for the relationship between change from baseline in QTcF (ΔQTcF) and edaravone concentration (0.000155 ms/(ng/mL); P = .1478); upper bounds of 2‐sided 90% confidence intervals after placebo adjustment (ΔΔQTcF) were <10 milliseconds at the geometric mean maximum concentration for each edaravone dose. Overall estimated values by time point of ΔΔQTcF ≤0.9 milliseconds, no outlier values, and no morphologic changes suggestive of repolarization abnormalities were observed. Analysis of heart rate, PR interval, and QRS duration also revealed no adverse findings. These data indicate that edaravone, even at supratherapeutic doses, does not produce clinically meaningful QT prolongation and has no clinically relevant cardiac effects.
Flufenamic acid alleviates sepsis‐induced lung injury by up‐regulating CBR1
Authors: Jiang Qiannan , Chen Zhenzhen , Jiang Hong
Published: June 2020

Investigate the effect of flufenamic acid (FFA) on lung injury of sepsis rats. Rat sepsis model was established using cecal ligation and puncture (CLP). The pathomorphology of lung tissue was detected by Hematoxylin–eosin (H&E) staining. The expression levels of tumor necrosis factor alpha (TNF‐α), interleukin‐6 (IL‐6), and high mobility group box‐1 (HMGB‐1) in serum and TNF‐α, IL‐6, malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) in lung tissues. The viability of RLE‐6TN cells was detected by CCK‐8 assay. The expression of carbonyl reductase 1 (CBR1) in RLE‐6TN cells was analyzed by Western blot analysis and reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) analysis. The inflammatory response was obviously enhanced in CLP‐constructed sepsis rats and alleviated by FFA treatment. Sepsis induced the increase of W/D ratio, promoted the levels of TNF‐α, IL‐6, HMGBR1, and MDA and inhibited the levels of SOD and GSH. FFA could effectively alleviate the sepsis‐induced lung injury. The viability of RLE‐6TN cells induced by LPS was improved with the treatment of FFA. CBR1 expression in LPS‐induced RLE‐6TN cells was decreased and FFA could up‐regulate the CBR1 expression. In addition, LPS‐induced lung injury promoted the inflammatory response in lung tissues, increased the W/D ratio and levels of TNF‐α, IL‐6, HMGBR1, and MDA while inhibited the levels of SOD and GSH. FFA could effectively improve the LPS‐induced lung injury while the effect of FFA on LPS‐induced lung injury was alleviated by CBR1 interference. FFA may alleviate sepsis‐induced lung injury by up‐regulating CBR1.
University dining must take into account students with food allergies
Authors: Charmatz Marc
Published: June 2020

According to a recently filed complaint, a student with celiac disease alleged that a university violated Title II of the Americans with Disabilities Act and Section 504 of the Rehabilitation Act by failing to provide her with a gluten‐free diet, causing her to become seriously ill. See Hannah Smith v. University of Maryland, College Park, No. 8:20‐cv‐00433‐TDC (D. Md. 02/20/20).
Support students’ changing needs throughout the pandemic
Authors: Hope Joan
Published: June 2020

The COVID‐19 pandemic has meant new challenges for Disability Services Offices, and colleges and universities will likely experience the impacts for months, if not years. Members of Disability Compliance for Higher Education’s Advisory Board participated in a conference call to discuss what's been happening at their institutions, how they have addressed the challenges, and what they plan for the future.
Americans increasingly view peers with mental illness as threats
Authors: Sutton Halley
Published: June 2020

Due to the prevalence of mass shootings, Americans increasingly view peers with mental illness as violent threats, despite scientific evidence that points to the contrary, according to a paper published in Health Affairs. “Despite solid evidence that people with mental illness are unlikely to be dangerous, such prejudice can lead to support for inappropriately using legal means to force people into treatment,” the author wrote. The paper examined trends in public perceptions of violence among those with mental health concerns, as well as attitudes about coerced treatment.
Diabetes mellitus induced by immune checkpoint inhibitors
Authors: Zheng Zhenjiang , Liu Ya , Yang Jie , Tan Chunlu , Zhou Li , Wang Xing , Xiao Li , Zhang Shu , Chen Yonghua , Liu Xubao
Published: June 2020

Immune checkpoint inhibitors (ICIs) are widely used in oncology for their favourable antitumor efficacy. ICI therapy is associated with a unique toxicity profile known as immune‐related adverse events (irAEs). One such irAE is ICI‐related diabetes mellitus (DM), which is relatively uncommon but can become extremely severe, leading to irreversible impairment of β‐cells, and even lead to death if not promptly recognised and properly managed. The precise mechanisms of ICI‐related DM are not well understood. In this review, we summarise the clinical characteristics, pathophysiology, and management of this adverse effect caused by ICI therapy. Deeper investigation of ICI‐related DM may contribute to elucidate the molecular mechanisms of classical type 1 DM.
Machine‐learning‐based detection of adaptive divergence of the stream mayfly Ephemera strigata populations
Authors: Li Bin , Yaegashi Sakiko , Carvajal Thaddeus M. , Gamboa Maribet , Chiu Ming‐Chih , Ren Zongming , Watanabe Kozo
Published: June 2020

Adaptive divergence is a key mechanism shaping the genetic variation of natural populations. A central question linking ecology with evolutionary biology is how spatial environmental heterogeneity can lead to adaptive divergence among local populations within a species. In this study, using a genome scan approach to detect candidate loci under selection, we examined adaptive divergence of the stream mayfly Ephemera strigata in the Natori River Basin in northeastern Japan. We applied a new machine‐learning method (i.e., random forest) besides traditional distance‐based redundancy analysis (dbRDA) to examine relationships between environmental factors and adaptive divergence at non‐neutral loci. Spatial autocorrelation analysis based on neutral loci was employed to examine the dispersal ability of this species. We conclude the following: (a) E. strigata show altitudinal adaptive divergence among the populations in the Natori River Basin; (b) random forest showed higher resolution for detecting adaptive divergence than traditional statistical analysis; and (c) separating all markers into neutral and non‐neutral loci could provide full insight into parameters such as genetic diversity, local adaptation, and dispersal ability.
Exploration of the Fluoride Reactivity of Aryltrifluoroborate on Selective Cleavage of Diphenylmethylsilyl Groups
Authors: Fujiki Katsumasa , Tanaka Katsunori
Published: June 2020

The first known report on the fluoride catalytic reactivity of potassium aryltrifluoroborate is described. The fluoride reactivity of phenyltrifluoroborate was controlled by substituents on the trifluoroborate‐attached benzene, such as the methoxy group at the para‐position and the methyl group at the ortho‐position. In addition, the selective aryltrifluoroborate‐catalyzed cleavage of the diphenylmethylsilyl group was achieved.
Epileptic spasms in individuals with Down syndrome: A review of the current literature
Authors: Kats Daniel J. , Roche Katherine J. , Skotko Brian G.
Published: June 2020

Epilepsy can occur in individuals with Down syndrome (DS), with epileptic spasms representing the most frequent seizure type in this population. Epileptic spasms can have devastating consequences on the development of individuals with the condition. This review sought to explore the lifetime prevalence and underlying mechanism of epileptic spasms in this population. We also aimed to review the response rate to various treatments, the relapse rate, and the development of subsequent epilepsy or autism in this population. A comprehensive literature search was conducted for articles discussing the lifetime prevalence, diagnosis, treatment, outcomes, or underlying etiology of epileptic spasms in animal models or individuals with DS. According to available literature, the global clinic‐based lifetime prevalence of epilepsy in individuals with DS ranged from 1.6% to 23.1%, with epileptic spasms representing 6.7%‐66.7% of these cases. Response rate to treatment with adrenocorticotropic hormone/corticosteroids was highest (81%) and has the most literature supporting its use, with other regimens, including vigabatrin and other antiepileptic drugs, having lower response rates. Epileptic spasms occur more frequently in children with DS than in the general population, though more studies are needed to determine the true lifetime prevalence of epileptic spasms in this population. Generally, children with DS and epileptic spasms tend to be more responsive to treatment and have better outcomes than children with epileptic spasms of unknown etiology (ie, without DS), in terms of response and relapse rates as well as the development of intractable epilepsy (eg, Lennox‐Gastaut syndrome).
Energy efficiency enhancement of cell‐free massive multiple‐input multiple‐output network employing threshold‐based beamforming
Authors: Khodkar Zeynab , Abouei Jamshid
Published: June 2020

The downlink of cell‐free massive multiple‐input multiple‐output network is considered. It is assumed that both access points (APs) and users are equipped with multiple antennas. A heuristic threshold‐based‐beamforming (TBF) protocol is proposed, which performs an AP selection algorithm to significantly improve the total energy efficiency (EE) of the network. The beamforming method that fits the model is the maximum eigenmode beamforming (MEB). The threshold level is determined in such a way that the strongest channel eigenmodes contribute in the downlink transmissions. Indeed, power control coefficients are chosen in such a way that the number of users served by each AP is limited according to the TBF‐based AP selection scheme. The spectral efficiency of the proposed method is investigated considering both perfect and imperfect knowledge of the channel state information at transmitters. Simulation results show that the proposed TBF protocol greatly enhances the total EE of the network compared to the MEB, conjugate beamforming, and zero‐force precoding techniques. Furthermore, a modification algorithm is proposed to obtain the minimum per‐user quality of service requirement, which prevents the dramatic reduction in the EE caused by high inter‐user interference levels.
Sensitivity equation method for the Navier‐Stokes equations applied to uncertainty propagation
Authors: Fiorini Camilla , Després Bruno , Puscas Maria Adela
Published: June 2020

This works deals with sensitivity analysis (SA) for the Navier‐Stokes equations. The aim is to provide an estimate of the variance of the velocity field when some of the parameters are uncertain and then to use the variance to compute confidence intervals for the output of the model. First, we introduce the physical model and analyze its stability. The sensitivity equations are derived, and their stability analyzed as well. We propose a finite element‐volume numerical scheme for the state and the sensitivity, which is integrated into the open‐source industrial code TrioCFD. Finally, we present some numerical results: a steady and an unsteady test case for the channel flow problem are investigated. For the steady case, we compare the results to the Monte Carlo method and show how the SA technique succeeds in providing very accurate estimates of the variance. For the unsteady case, a new filtering procedure is proposed to deal with a sensitivity that grows in time. The filtered sensitivity is then used to compute the variance of the output and to provide confidence intervals.
Effects of corn distillers dried grains on dough properties and quality of Chinese steamed bread
Authors: Li Xiaona , Wang Chunyang , Krishnan Padmanaban G.
Published: June 2020

Chinese steamed bread (CSB) accounts for 30% of the wheat end‐use in China. CSB was studied as a platform for fiber and protein enrichment, employing corn distillers dried grains. Food grade distiller's grain (FDDG) processed from co‐products from the corn ethanol industry was used as the enrichment ingredient. Since CSB uses a lean formula with little or no added sugar or fat, it relies entirely on fermentation and steaming for flavor and texture development. FDDG was used to replace 0%–25% all‐purpose flour (APF) in CSB formulations. Effects of FDDG on dough properties and quality of CSB were evaluated by instrumental (Farinograph, Mixolab, and Texture Analyzer), nutritional, and sensory methods. Protein and dietary fiber contents showed significant increases to 18.8% and 15.3%, respectively, for 100 g of steamed bread (25% FDDG db). Fiber in 100 g of fresh FDDG CSB ranged from 2.8 to 7.7 g. FDDG fortified doughs demonstrated higher water absorption, while dough development time, dough stability, and dough extensibility decreased significantly with partial APF replacement. FDDG contributed to increased hardness and adhesiveness in the CSB. Crumb analysis revealed reduced number of gas cells at higher FDDG substitution. FDDG enrichment reduced brightness (L*) of flour blends and CSB. Rheological and sensory analysis showed an upper level of FDDG substitution of 15% was acceptable without detriment to dough functionality, texture, and taste.
Decoding attention control and selection in visual spatial attention
Authors: Hong Xiangfei , Bo Ke , Meyyappan Sreenivasan , Tong Shanbao , Ding Mingzhou
Published: June 2020

Event‐related potentials (ERPs) are used extensively to investigate the neural mechanisms of attention control and selection. The univariate ERP approach, however, has left important questions inadequately answered. We addressed two questions by applying multivariate pattern classification to multichannel ERPs in two cued visual spatial attention experiments (N = 56): (a) impact of cueing strategies (instructional vs. probabilistic) on attention control and selection and (b) neural and behavioral effects of individual differences. Following cue onset, the decoding accuracy (cue left vs. cue right) began to rise above chance level earlier and remained higher in instructional cueing (~80 ms) than in probabilistic cueing (~160 ms), suggesting that unilateral attention focus leads to earlier and more distinct formation of the attention control set. A similar temporal sequence was also found for target‐related processing (cued target vs. uncued target), suggesting earlier and stronger attention selection under instructional cueing. Across the two experiments: (a) individuals with higher cue‐related decoding accuracy showed higher magnitude of attentional modulation of target‐evoked N1 amplitude, suggesting that better formation of anticipatory attentional state leads to stronger modulation of target processing, and (b) individuals with higher target‐related decoding accuracy showed faster reaction times (or larger cueing effects), suggesting that stronger selection of task‐relevant information leads to better behavioral performance. Taken together, multichannel ERPs combined with machine learning decoding yields new insights into attention control and selection that complement the univariate ERP approach, and along with the univariate ERP approach, provides a more comprehensive methodology to the study of visual spatial attention.
The impact of drug quality ratings from health technology assessments on the adoption of new drugs by physicians in Germany
Authors: Blankart Katharina Elisabeth , Stargardt Tom
Published: June 2020

Payers are increasingly calling for the value of new drugs to be measured explicitly. We analyze how the availability of drug quality ratings by health technology assessment (HTA) agencies affects the adoption of new drugs by physicians in Germany. We combine data from drug quality ratings, promotional spending, and a physician panel. In a latent utility model, time to adoption is specified as a function of quality rating, promotional spending by manufacturers, and physician‐specific variables. As expected, drugs with a positive rating were adopted faster (p < 0.001) than those without. However, our results suggest that it was the publication of the quality rating itself that affected adoption. Indeed, before a quality rating was published, drugs that went on to receive a positive quality rating were not adopted significantly faster than drugs that went on to receive a negative quality rating. In contrast, after the publication of the HTA quality rating, drugs with a positive rating were adopted significantly faster than those without (p < 0.05). The per physician value of a positive quality rating was EUR 393.50. Our results suggest that there are returns from HTAs beyond their use in price negotiations.
miR‐448‐3p alleviates diabetic vascular dysfunction by inhibiting endothelial–mesenchymal transition through DPP‐4 dysregulation
Authors: Guan Guo‐Ying , Wei Nan , Song Tao , Zhao Chao , Sun Yang , Pan Ru‐Xin , Zhang Lu‐lu , Xu Ying‐Ying , Dai Ya‐mei , Han Hui
Published: June 2020

Diabetes mellitus (DM) often causes vascular endothelial damage and alters vascular microRNA (miR) expression. miR‐448‐3p has been reported to be involved in the development of DM, but whether miR‐448‐3p regulates diabetic vascular endothelial dysfunction remains unclear. To investigate the molecular mechanism of diabetic vascular endothelial dysfunction and the role of miR‐448‐3p therein, Sprague‐Dawley rats were injected with streptozotocin (STZ) to establish diabetic animal model and the rat aortic endothelial cells were treated with high glucose to establish diabetic cell model. For the treatment group, after the induction of diabetes, the miR‐448‐3p levels in vivo and in vitro were upregulated by adeno‐associated virus serotype 2 (AAV2)‐miR‐448‐3p injection and miR‐448‐3p mimic transfection, respectively. Our results showed that AAV2‐miR‐448‐3p injection alleviated the body weight loss and blood glucose level elevation induced by STZ injection. The miR‐448‐3p level was significantly decreased and the dipeptidyl peptidase‐4 (DPP‐4) messenger RNA level was increased in diabetic animal and cell models, which was reversed by miR‐448‐3p treatment. Moreover, the diabetic rats exhibited endothelial damage and endothelial–mesenchymal transition (EndMT), while AAV2‐miR‐448‐3p injection relieved those situations. In vitro experiments demonstrated that miR‐448‐3p overexpression in endothelial cells alleviated endothelial damage by inhibiting EndMT through blocking the transforming growth factor‐β/Smad pathway. We further proved that miR‐448‐3p negatively regulated DPP‐4 by binding to its 3′‐untranslated region, and DPP‐4 overexpression reversed the effect of miR‐448‐3p overexpression on EndMT. Overall, we conclude that miR‐448‐3p overexpression inhibits EndMT via targeting DPP‐4 and further ameliorates diabetic vascular endothelial dysfunction, indicating that miR‐448‐3p may serve as a promising therapeutic target for diabetic endothelial dysfunction.
LncRNA 0003250 accelerates heart autophagy and binds to miR‐17‐5p as a competitive endogenous RNA in chicken induced by selenium deficiency
Authors: Yang Jie , Shi Guangliang , Gong Yafan , Cai Jingzeng , Zheng Yingying , Zhang Ziwei
Published: June 2020

Long noncoding RNAs (LncRNAs) have been demonstrated to be associated with a variety of myocardial diseases, but how LncRNAs regulate autophagy in selenium (Se)‐deficient myocardial injury is infrequently reported. Here, we screened out a novel long noncoding RNA, microRNA, and ATG7 through transcriptomic results. We employed a Se‐deficient chicken model in vivo, and primary cultured cardiomyocytes treated by correlation in vitro. The results showed that Se deficiency upregulated the expression of ATG7, and miR‐17‐5p inhibited cardiomyocyte autophagy by targeting ATG7. Furthermore, we found that LncRNA 0003250 regulated miR‐17‐5p, and thus affected the expression of ATG7 and autophagic cell death. Our present study proposed a novel model for the regulation of cardiomyocytes autophagy, which includes LncRNA 0003250, miR‐17‐5p and ATG7 in the chicken heart. Our conclusions may provide a feasible diagnostic tool for Se‐deficient cardiomyocyte injury.
Fibroblast growth factor inducible 14 signaling facilitates anti‐dsDNA IgG penetration into mesangial cells
Authors: Li Ruilian , Jia Fangyan , Ren Kaixuan , Luo Mai , Min Xiaoyun , Xiao Shengxiang , Xia Yumin
Published: June 2020

Anti‐double‐stranded DNA (dsDNA) antibodies induce renal damage in patients with systemic lupus erythematosus by triggering fibrotic processes in kidney cells. However, the precise mechanism underlying penetration of anti‐dsDNA immunoglubolin G (IgG) into cells remains unclear. This study was designed to investigate the effect of tumor necrosis factor‐like weak inducer of apoptosis (TWEAK)/fibroblast growth factor inducible 14 (Fn14) signaling on anti‐dsDNA IgG penetration into cells. Mesangial cells were cultured in vitro, and stimulated with TWEAK and anti‐dsDNA IgG. The results revealed that TWEAK dose‐dependently enhanced cellular internalization of anti‐dsDNA IgG and the expression of high‐mobility group box 1 (HMGB1). In addition, TWEAK and anti‐dsDNA IgG synthetically downregulate suppressor of cytokine signaling 1, and induce the expression of various fibrotic factors. Furthermore, inhibition of HMGB1 attenuates the enhancement effect of TWEAK on anti‐dsDNA IgG internalization. The TWEAK upregulation of HMGB1 involves the nuclear factor‐κB and phosphatidylinositide 3‐kinase/protein kinase B pathways. Therefore, TWEAK/Fn14 signaling contributes to the penetration of anti‐dsDNA IgG and relevant fibrotic processes in mesangial cells.
Protein kinase C‐δ interacts with and phosphorylates ARD1
Authors: Chun Kwang‐Hoon , Cho Seung‐Ju , Lee Ji‐Won , Seo Ji Hae , Kim Kyu‐Won , Lee Seung‐Ki
Published: June 2020

Protein kinase C‐δ (PKCδ) is a diacylglycerol‐dependent, calcium‐independent novel PKC isoform that is engaged in various cell signaling pathways, such as cell proliferation, apoptosis, inflammation, and oxidative stress. In this study, we searched for proteins that bind PKCδ using a yeast two‐hybrid assay and identified murine arrest‐defective 1 (mARD1) as a binding partner. The interaction between PKCδ and mARD1 was confirmed by glutathione S‐transferase pull‐down and co‐immunoprecipitation assays. Furthermore, recombinant PKCδ phosphorylated full‐length mARD1 protein. The NetPhos online prediction tool suggested PKCδ phosphorylates Ser80, Ser108, and Ser114 residues of mARD1 with the highest probability. Based on these results, we synthesized peptides containing these sites and examined their phosphorylations using recombinant PKCδ. Autoradiography confirmed these sites were efficiently phosphorylated. Consequent mass spectrometry and peptide sequencing in combination with MALDI‐TOF MS/MS confirmed that Ser80 and Ser108 were major phosphorylation sites. The alanine mutations of Ser80 and Ser108 abolished the phosphorylation of mARD1 by PKCδ in 293T cells supporting these observations. In addition, kinase assays using various PKC isotypes showed that Ser80 of ARD1 was phosphorylated by PKCβI and PKCζ isotypes with the highest selectivity, while Ser108 and/or Ser114 were phosphorylated by PKCγ with activities comparable to that of the PKCδ isoform. Overall, these results suggest the possibility that PKCδ transduces signals by regulating phosphorylation of ARD1.
Microwave assisted synthesis and antimicrobial evaluation of novel substituted thiosemicarbazide derivatives of pyrimidine
Authors: Panneerselvam Theivendren , Mandhadi Jithendar Reddy
Published: June 2020

A new series of antimicrobial thiosemicarbazide substituted pyrimidine derivatives were synthesized by using thiosemicarbazide and ethyl 2‐((2‐amino‐5‐carbamoyl‐6‐[substituted benzyl] pyrimidin‐4‐yl)oxy)acetate derivatives and subsequent addition of acetaldehyde and acetone. The designed compounds were screened for Antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, Micrococcus luteus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumonia in comparison with the standard drugs Ciprofloxacin and antifungal effect against Aspergillus niger and Aspergillus fumigates in comparison with the standard drug Ketoconazole reveal the potency of synthesized derivatives. In accordance with the data obtained from antimicrobial activity, all the synthesized derivatives have shown good activity against the tested microbes. Among them, compound bearing 2‐hydroxy and 3‐chloro derivatives of thiosemicarbazide substituted pyrimidine has shown good activity against all the tested organisms.
Impact of Fiberoptic Endoscopic Evaluation of Swallowing Outcomes and Dysphagia Management in Neurodegenerative Diseases
Authors: Tye Cooper B. , Gardner Philip A. , Dion Gregory R. , Simpson C. Blake , Dominguez Laura M.
Published: June 2020

Objectives/Hypothesis

To determine the incidence of abnormal fiberoptic endoscopic evaluation of swallowing (FEES) findings in patients with progressive neurologic disorders and identify the most commonly implemented dysphagia management strategies.

Study Design

Retrospective Review.

Methods

A retrospective review was performed of patients with neurodegenerative disease who underwent FEES at a tertiary‐care center between 2008 and 2019. Patient demographics, diagnosis, and Eating Assessment Tool‐10 (EAT‐10) scores were recorded. Rates of penetration, aspiration, and functional change in management (FCIM) to include dietary modifications, home exercises, swallow therapy, surgical intervention (injection augmentation or esophageal dilation), or alternative means of nutrition (i.e., percutaneous enteral gastrostomy [PEG] tube) were calculated.

Results

Two hundred nine FEES assessments were performed in 178 patients with a mean age of 64.8 years (standard deviation = ±14). The most common diagnoses were amyotrophic lateral sclerosis (32%) followed by Parkinson's disease or Parkinsonism (26%). FEES demonstrated penetration in 72.5% of patients and aspiration in 14.6%. Mean EAT‐10 scores differed between patients with aspiration versus penetration versus normal FEES (24.7 vs. 14.9 vs. 13.9, respectively, P < .001). An FCIM was recommended in 88% of patients and most commonly included self‐directed modifications (43%). Overall, 4.5% of patients underwent surgical intervention. A PEG tube was recommended for either supplemental or sole form of nutrition in 19% of the entire cohort.

Conclusions

Most patients with neurodegenerative diseases presenting with dysphagia demonstrated abnormal FEES findings necessitating an FCIM, suggesting early dysphagia evaluation may be warranted in this cohort. These findings correlate with worsened EAT‐10 scores in patients with aspiration or penetration on FEES.

Level of Evidence

4 Laryngoscope, 131:726–730, 2021
Electron Energy Loss Spectroscopy of Singular Plasmonic Metasurfaces
Authors: Yang Fan , Huidobro Paloma Arroyo , Pendry J. B.
Published: June 2020

Singular plasmonic metasurfaces, which feature sharp edges or ultra‐small gaps, are characterized by a continuous excitation spectrum that results in broadband light‐harvesting properties. In this paper, an analytical study of the electron energy loss spectroscopy (EELS) of this kind of metasurfaces is presented. Making use of transformation optics, the response of singular metasurfaces is studied when interacting with a moving electron both in the frequency and time domains. This allows gaining a deeper understanding of the surface plasmon compression at the singularities, which is responsible for the broadband spectra, as well as of the effect of blunt singularities and nonlocality in the metal. Two instances of singular metasurfaces are considered: one with sharp singularities in the form of sharp angle grooves, and one with smooth singularities in the form of two nearly touching surfaces.
Transforming public health using value lens and extended partner networks
Authors: Tanniru Mohan R.
Published: June 2020

Introduction

Organizational transformations have focused on creating and fulfilling value for customers, leveraging advanced technologies. Transforming public health (PH) faces an interesting challenge. The value created (preventive practices) to fulfill policy makers’ desire to reduce healthcare costs is realized by several external partners with varying goals and is practiced by the public (value in use), which often places low priority on prevention.

Methods

This paper uses value lens to argue that PH transformation strategy must align the goals of all stakeholders involved. This may include allowing partners and the public to contextualize the preventive practices to see the value in near term and as relevant. It also means extending the number of partners PH uses and helping them connect with the public to seek shared alignment in shared goals of value fulfillment and value‐in‐use.

Results

Using lessons from Covid‐19 and PH experience with partners in four different sectors: business, healthcare, public and community, the paper illustrates how PH transformation strategy can be implemented going forward.

Conclusions

We conclude the paper with five distinct directions for future research to create and sustain value using the framework of learning health systems.
COQ8B nephropathy: Early detection and optimal treatment
Authors: Song Xiaoxiang , Fang Xiaoyan , Tang Xiaoshan , Cao Qi , Zhai Yihui , Chen Jing , Liu Jialu , Zhang Zhiqing , Xiang Tianchao , Qian Yanyan , Wu Bingbing , Wang Huijun , Zhou Wenhao , Liu Cuihua , Shen Qian , Xu Hong , Rao Jia
Published: June 2020

Background

Mutations in COQ8B (*615567) as a defect of coenzyme Q10 (CoQ10) cause steroid resistant nephrotic syndrome (SRNS).

Methods

To define the clinical course and prognosis of COQ8B nephropathy, we retrospectively assessed the genotype and phenotype in patients with COQ8B mutations from Chinese Children Genetic Kidney Disease Database. We performed the comparing study of renal outcome following CoQ10 treatment and renal transplantation between early genetic detection and delayed genetic detection group.

Results

We identified 20 (5.8%) patients with biallelic mutations of COQ8B screening for patients with SRNS, non‐nephrotic proteinuria, or chronic kidney disease (CKD) of unknown origin. Patients with COQ8B mutations showed a largely renal‐limited phenotype presenting with proteinuria and/or advanced CKD at the time of diagnosis. Renal biopsy uniformly showed focal segmental glomerulosclerosis. Proteinuria was decreased, whereas the renal function was preserved in five patients following CoQ10 administration combined with angiotensin‐converting enzyme (ACE) inhibitor. The renal survival analysis disclosed a significantly better outcome in early genetic detection group than in delayed genetic detection group (Kaplan–Meier plot and log rank test, p = .037). Seven patients underwent deceased donor renal transplantation without recurrence of proteinuria or graft failure. Blood pressure showed decreased significantly during 6 to 12 months post transplantation.

Conclusions

COQ8B mutations are one of the most common causes of adolescent‐onset proteinuria and/or CKD of unknown etiology in the Chinese children. Early detection of COQ8B nephropathy following CoQ10 supplementation combined with ACE inhibitor could slow the progression of renal dysfunction. Renal transplantation in patients with COQ8B nephropathy showed no recurrence of proteinuria.