bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the patient's body weight on the efficacy and adverse events of valganciclovir for cytomegalovirus reactivation after hematopoietic stem cell transplantation
Authors: Misaki Yukiko , Kimura Shun‐ichi , Kawamura Masakatsu , Kawamura Shunto , Takeshita Junko , Yoshino Nozomu , Yoshimura Kazuki , Gomyo Ayumi , Matsumi Shimpei , Akahoshi Yu , Tamaki Masaharu , Kusuda Machiko , Kameda Kazuaki , Wada Hidenori , Kawamura Koji , Sato Miki , Terasako‐Saito Kiriko , Tanihara Aki , Nakasone Hideki , Kako Shinichi , Kanda Yoshinobu
Published: February 2020

While the dose of ganciclovir (GCV) is decided base on patients' body weight (BW), that of valganciclovir (VGCV) is fixed as 900 or 1800 mg/d regardless of the patient's BW in preemptive therapy for cytomegalovirus (CMV) reactivation in hematopoietic stem cell transplantation. We analyzed the impact of the patient's BW on the effectiveness and adverse events (AEs) of VGCV. From March 2004 to February 2017, 27 patients received VGCV as a first‐line treatment for CMV reactivation. As a historical control group, we extracted 17 patients who started to receive GCV at a similar timing. We used the following definitions of outcomes: speed of reduction of CMV antigenemia (CMV‐AG) as a measure of effectiveness, ratios of baseline and minimum value for white blood cell (WBC) and platelet counts, and ratio of baseline and maximum values for serum creatinine (sCr) as measures of AEs. As a result, there was no significant correlation between average daily dose of VGCV with or without adjusting for the patient's BW and speed of reduction of CMV‐AG. On the other hand, the decreases in WBC and platelets and the increase in sCr were significantly correlated with the cumulative dose of VGCV. However, the absolute values of the correlation coefficients did not increase when we analyzed the correlations between the BW‐adjusted cumulative dose of VGCV and factors associated with adverse events. There were no significant differences in efficacies or AE parameters between the GCV and VGCV groups. In conclusion, the patient's BW did not significantly affect the effectiveness or adverse events of VGCV.
Cerebrovascular reactivity to carbon dioxide is not influenced by variability in the ventilatory sensitivity to carbon dioxide
Authors: Howe Connor A. , Caldwell Hannah G. , Carr Jay , Nowak‐Flück Daniela , Ainslie Philip N. , Hoiland Ryan L.
Published: February 2020

New Findings

What is the central question of this study?

Do differing magnitudes of ventilation influence cerebrovascular CO2 reactivity and the cerebral blood flow response to increases in arterial carbon dioxide?

What is the main finding and its importance?

While a greater ventilation, through voluntary hyperventilation, is associated with a higher anterior cerebral blood flow during carbon dioxide breathing, this elevated cerebral blood flow is due to a higher blood pressure and not ventilation per se. A greater ventilation, through voluntary hyperventilation, does not influence global or posterior cerebral blood flow during carbon dioxide breathing. Cerebrovascular reactivity to carbon dioxide is not influenced by an individual's ventilatory sensitivity to carbon dioxide.

Recent work demonstrated an influence of ventilation on cerebrovascular reactivity to CO2; however, the concomitant influence of changes in mean arterial blood pressure (MAP) on ventilation‐induced differences in cerebral blood flow (CBF) has yet to be examined in this context. Healthy participants (n = 15; 25 ± 3 years of age; 179 ± 6 cm height; 74 ± 10 kg weight; 3 female) underwent end‐tidal forcing to increase their partial pressure of end‐tidal CO2 by +3, +6 and +9 mmHg above baseline in 5‐min sequential steps while maintaining iso‐oxia. This protocol was then repeated twice, with participants hyperventilating and hypoventilating by ∼30% compared to the first trial. Intra‐cranial and extra‐cranial CBF were measured using ultrasound. The MAP (finger photo‐plethysmography) was higher during the hyperventilation and hypoventilation trials compared to normal ventilation (main effects, P < 0.05 for both). While internal carotid artery blood flow was higher during the hyperventilation trial compared to normal ventilation (P = 0.01), this was due to a higher MAP, as indicated by analysis of conductance values (P = 0.68) or inclusion of MAP in covariate analysis (P = 0.11). Global CBF (P = 0.11) and vertebral artery blood flow (P = 0.93) were unaffected by the magnitude of ventilation. Further, CO2 reactivity was not affected by the different breathing trials (P > 0.05 for all). Retrospective analysis of a larger data set (n = 53) confirmed these observations and demonstrated no relationships between the ventilatory and global CBF response to hypercapnia (r2 = 0.04; P = 0.14). Therefore, when differences in MAP are accounted for, cerebrovascular CO2 reactivity (assessed via end‐tidal forcing) is independent of the magnitude of ventilation.
A Probabilistic Design Reuse Index for Engineering Designs
Authors: Vasantha Gokula , Corney Jonathan , Stuart Struan , Sherlock Andrew , Quigley John , Purves David
Published: February 2020

Many companies offer a range of related products that are constructed using similar components and processes. This enables them to meet customer expectations of product variety while minimizing the overheads (e.g., development and manufacturing costs). To support the management of product variety several indices have been proposed in the literature that measure the degree to which component use is standardized across products within the same product family. However, the derivation of some of these statistics can be laborious to calculate due to the effort required to assemble the necessary information. In this paper, we develop an index more suited to the automated data-mining of a company’s product portfolio, which is derived from the Kullback–Leibler divergence. The new measure provides an easily computed probabilistic measure that can be used to characterize the degree of component reuse within a single product, across a family of products, and at the individual component family level. To illustrate their applications, the indices and several existing measures are calculated for two contrasting product types; using the non-differentiating components of two flat-pack furniture ranges and the components of a range of bicycles.
Ultrasonographic elastography, no longer for the “select few”
Authors: Lupsor-Platon Monica
Published: February 2020

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Stability of hexafluoroacetylacetone molecules on metallic and oxidized nickel surfaces in atomic-layer-etching processes
Authors: Basher Abdulrahman H. , Krstić Marjan , Takeuchi Takae , Isobe Michiro , Ito Tomoko , Kiuchi Masato , Karahashi Kazuhiro , Wenzel Wolfgang , Hamaguchi Satoshi
Published: February 2020

Adsorption of enol hexafluoroacetylacetone (hfacH) on nickel oxide (NiO) fcc (100) and metallic Ni fcc (100) surfaces and the stability of the adsorbate was examined using first-principles quantum mechanical simulations. It was shown that an hfacH molecule can be unstable and dissociate on an Ni metal surface. On an NiO surface; however, an hfacH molecule can be deprotonated and form a hexafluoroacetylacetonate anion (hfac−) bonded stably with positively charged Ni atoms of the surface. The results are consistent with observations of the interaction of hfacH with NiO and Ni surfaces in earlier experiments. The results also explain the mechanisms of the adsorption steps in the thermal atomic layer etching of Ni based on the cyclic processes of surface oxidation and formation of volatile organo-nickel complexes.
Flexible Al2O3/plasma polymer multilayer moisture barrier films deposited by a spatial atomic layer deposition process
Authors: Kim Sun Jung , Yong Sang Heon , Choi You Jin , Hwangbo Hyeok , Yang Woo-Young , Chae Heeyeop
Published: February 2020

Al2O3/plasma polymer multilayers were developed and characterized for the moisture barrier films of flexible organic devices. The inorganic Al2O3 thin films were deposited by a spatial atomic layer deposition process and the organic layers were deposited by plasma polymerization in the same chamber using CHF3, benzene, and cyclohexane precursors. The deposition rate, light transmittance, and surface roughness of the plasma polymer films obtained from the three precursors were investigated. The three plasma polymer layers were introduced between Al2O3 layers and their effect on the water permeability and flexibility of each Al2O3/plasma polymer multilayer structure was evaluated. The multilayer structure with hydrocarbon from cyclohexane shows better flexibility than that with fluorocarbon by CHF3 and hydrocarbon by benzene. Polymer interlayers with plasma thicker than 20 nm are necessary for reasonable flexibility. The authors increased the number of layers up to 21 to improve the water permeability and flexibility. The water vapor transmission rate (WVTR) of a 100 nm-thick Al2O3/plasma polymer was reduced to 8.5 × 10−5 g/m2 day with the 21-layer structure. This WVTR value is 58% lower than that of the 100 nm-thick single-layer Al2O3. The WVTR of a 100 nm-thick single-layer Al2O3 increased by 900% when it was bent 1000 times with a bending radius of 1 cm due to film cracks, while, under the same conditions, the 21-layer structure showed only a 32% increase in the WVTR. These results indicate that the nanometer-scale-thick plasma polymer can be an effective solution for multilayer moisture barrier films.
Direct plasma-enhanced atomic layer deposition of aluminum nitride for water permeation barriers
Authors: Fischer David Dustin , Knaut Martin , Reif Johanna , Nehm Frederik , Albert Matthias , Bartha Johann W.
Published: February 2020

Oxygen-free, transparent, and insulating thin films at fabrication temperatures below 100 °C are important for sensitive materials and interfaces, like organic electronics. In this work, a capacitive coupled plasma-enhanced atomic layer deposition process of aluminum nitride with trimethylaluminum as a precursor and a mixture of hydrogen/nitrogen as the reactive gas was studied at 80 and 200 °C. The film properties were characterized by spectroscopic ellipsometry, x-ray photoelectron spectroscopy, scanning electron microscopy, and electrical measurements. The growth per cycle stayed constant at around 1 Å, and the refractive index decreased slightly from 1.97 at 200 °C to 1.93 at 80 °C. While the AFM surface roughness was below 0.5 nm at 80 °C deposition temperature, scanning electron microscopy images reveal blister generation at 200 °C on silicon. The x-ray photoemission spectroscopy measurements show a layer composition of Al:N of 1.0:0.9 with a few percent of oxygen and carbon, indicating good air stability and reasonable stoichiometry. The metal-insulator-metal capacitance measurements showed a dielectric constant of 11 at both temperatures. The water vapor transmission rate for a 20 nm thick film on polyethylene naphthalate films was lower than 0.5 mg/(m2⋅day) at 38 °C/90%.
Autotoxic Ginsenoside Disrupts Soil Fungal Microbiomes by Stimulating Potentially Pathogenic Microbes
Authors: Li Yunlong , Dai Shenyan , Wang Baoying , Jiang Yuting , Ma Yanyu , Pan Leilv , Wu Kai , Huang Xinqi , Zhang Jinbo , Cai Zucong , Zhao Jun
Published: February 2020

Sanqi ginseng [
Panax notoginseng
(Burk.) F. H. Chen] is geoauthentically produced in a restricted area of southwest China, and successful replanting requires a rotation cycle of more than 15 to 30 years. The increasing demand for Sanqi ginseng and diminishing arable land resources drive farmers to employ consecutive monoculture systems. Replant failure has severely threatened the sustainable production of Sanqi ginseng and causes great economic losses annually. Worse still, the acreage and severity of replant failure are increased yearly, which may destroy the Sanqi ginseng industry in the near future. The significance of this work is to decipher the mechanism of how autotoxic ginsenosides promote the accumulation of soilborne pathogens and disrupt the equilibrium of soil fungal microbiomes. This result may help us to develop effective approaches to successfully conquer the replant failure of Sanqi ginseng.
De Novo
Purine Biosynthesis Is Required for Intracellular Growth of Staphylococcus aureus and for the Hypervirulence Phenotype of a
purR
Mutant
Authors: Goncheva Mariya I. , Flannagan Ronald S. , Heinrichs David E.
Published: February 2020

Staphylococcus aureus
is a noted human and animal pathogen. Despite decades of research on this important bacterium, there are still many unanswered questions regarding the pathogenic mechanisms it uses to infect the mammalian host. This can be attributed to it possessing a plethora of virulence factors and complex virulence factor and metabolic regulation. PurR, the purine biosynthesis regulator, was recently also shown to regulate virulence factors in
S. aureus
, and mutations in
purR
result in derepression of fibronectin binding proteins (FnBPs) and extracellular toxins, required for a so-called hypervirulent phenotype.
Fitness Trade-Offs Resulting from Bacteriophage Resistance Potentiate Synergistic Antibacterial Strategies
Authors: Mangalea Mihnea R. , Duerkop Breck A.
Published: February 2020

Bacteria that cause life-threatening infections in humans are becoming increasingly difficult to treat. In some instances, this is due to intrinsic and acquired antibiotic resistance, indicating that new therapeutic approaches are needed to combat bacterial pathogens. There is renewed interest in utilizing viruses of bacteria known as bacteriophages (phages) as potential antibacterial therapeutics. However, critics suggest that similar to antibiotics, the development of phage-resistant bacteria will halt clinical phage therapy.
The Lyme Disease Biobank: Characterization of 550 Patient and Control Samples from the East Coast and Upper Midwest of the United States
Authors: Horn Elizabeth J. , Dempsey George , Schotthoefer Anna M. , Prisco U. Lena , McArdle Matthew , Gervasi Stephanie S. , Golightly Marc , De Luca Cathy , Evans Mel , Pritt Bobbi S. , Theel Elitza S. , Iyer Radha , Liveris Dionysios , Wang Guiqing , Goldstein Don , Schwartz Ira
Published: February 2020

Lyme disease (LD) is an increasing public health problem. Current laboratory testing is insensitive in early infection, the stage at which appropriate treatment is most effective in preventing disease sequelae. The Lyme Disease Biobank (LDB) collects samples from individuals with symptoms consistent with early LD presenting with or without erythema migrans (EM) or an annular, expanding skin lesion and uninfected individuals from areas of endemicity. Samples were collected from 550 participants (298 cases and 252 controls) according to institutional review board-approved protocols and shipped to a centralized biorepository.
Proposal of a Taxonomic Nomenclature for the Bacillus cereus Group Which Reconciles Genomic Definitions of Bacterial Species with Clinical and Industrial Phenotypes
Authors: Carroll Laura M. , Wiedmann Martin , Kovac Jasna
Published: February 2020

Historical species definitions for many prokaryotes, including pathogens, have relied on phenotypic characteristics that are inconsistent with genome evolution. This scenario forces microbiologists and clinicians to face a tradeoff between taxonomic rigor and clinical interpretability. Using the
Bacillus cereus
group as a model, a conceptual framework for the taxonomic delineation of prokaryotes which reconciles genomic definitions of species with clinically and industrially relevant phenotypes is presented. The nomenclatural framework outlined here serves as a model for genomics-based bacterial taxonomy that moves beyond arbitrarily set genomospecies thresholds while maintaining congruence with phenotypes and historically important species names.
Scratching the Surface: Bacterial Cell Envelopes at the Nanoscale
Authors: Viljoen Albertus , Foster Simon J. , Fantner Georg E. , Hobbs Jamie K. , Dufrêne Yves F.
Published: February 2020

The bacterial cell envelope is essential for viability, the environmental gatekeeper and first line of defense against external stresses. For most bacteria, the envelope biosynthesis is also the site of action of some of the most important groups of antibiotics. It is a complex, often multicomponent structure, able to withstand the internally generated turgor pressure. Thus, elucidating the architecture and dynamics of the cell envelope is important, to unravel not only the complexities of cell morphology and maintenance of integrity but also how interventions such as antibiotics lead to death.
Autoantibody-Mediated Erythrophagocytosis Increases Tuberculosis Susceptibility in HIV Patients
Authors: Dai Youchao , Cai Yi , Wang Xin , Zhu Jialou , Liu Xiaoqian , Liu Houming , Li Linghua , Zhang Yinze , Liu Shengze , Wen Zhihua , Feng Carl G. , Chen Xinchun , Tang Xiaoping
Published: February 2020

HIV infection significantly increases TB susceptibility due to CD4 T-cell loss and macrophage dysfunction. Although it is relatively clear that CD4 T-cell loss represents a direct effect of HIV infection, the mechanism underlying how HIV infection dampens macrophage function is unknown. Here, we show that HIV infection enhances autoantibody-mediated erythrophagocytosis, which dampens macrophage bactericidal activity against TB by inhibiting HO-1-associated autophagy. Our findings reveal a novel mechanism explaining how HIV infection increases susceptibility to TB. We propose that DAT could be a potential measure to identify HIV patients who are at high TB risk and who would be suitable for anti-TB chemotherapy preventive treatment.
Screening for infection in unaccompanied asylum-seeking children and young people
Authors: Williams Bhanu , Boullier Mary , Cricks Zoe , Ward Allison , Naidoo Ronelle , Williams Amanda , Robinson Kim , Eisen Sarah , Cohen Jonathan
Published: February 2020

We aimed to evaluate a screening programme for infection in unaccompanied asylum seeking children and young people against national guidance and to described the rates of identified infection in the cohort. The audit was conducted by retrospective case note review of routinely collected, anonymised patient data from all UASC referred between January 2016 and December 2018 in two paediatric infectious diseases clinics.There were 252 individuals from 19 countries included in the study, of these 88% were male, and the median age was 17 years (range 11–18). Individuals from Afghanistan, Eritrea and Albania constituted the majority of those seen. Median time between arriving in the UK and infection screening was 6 months (IQR 4–10 months, data available on 197 UASC). There were 94% (238/252) of cases tested for tuberculosis (TB), of whom 23% (55/238) were positive, including three young people with TB disease. Of those tested for hepatitis B, 4.8% (10/210) were positive, 0.5% (1/121) were positive for hepatitis C and of 252 tested, none were positive for HIV. Of the 163 individuals who were tested for schistosomiasis, 27 were positive (16%).The majority of patients were appropriately tested for infections with a high rate of identification of treatable asymptomatic infection. Infections were of both individual and public health significance. Our findings of clinically significant rates of treatable infections in UASC highlight the importance of infection screening for all in this vulnerable patient group.
Exploring geographic variation of and influencing factors for utilization of four diabetes management measures in Swiss population using claims data
Authors: Wei Wenjia , Gruebner Oliver , von Wyl Viktor , Dressel Holger , Ulyte Agne , Brüngger Beat , Blozik Eva , Bähler Caroline , Braun Julia , Schwenkglenks Matthias
Published: February 2020

Introduction

Four strongly recommended diabetes management measures are biannual glycated hemoglobin (HbA1c) testing, annual eye examination, kidney function examination, and low-density lipoprotein (LDL) testing in patients below 75 years. We aimed to describe regional variation in the utilization of the four measures across small regions in Switzerland and to explore potential influencing factors.

Research design and methods

We conducted a cross-sectional study of adult patients with drug-treated diabetes in 2014 using claims data. Four binary outcomes represented adherence to the recommendations. Possible influencing factors included sociodemographics, health insurance preferences, and clinical characteristics. We performed multilevel modeling with Medstat regions as the higher level. We calculated the median odds ratio (MOR) and checked spatial autocorrelation in region level residuals using Moran’s I statistic. When significant, we further conducted spatial multilevel modeling.

Results

Of 49 198 patients with diabetes (33 957 below 75 years), 69.6% had biannual HbA1c testing, 44.3% each had annual eye examination and kidney function examination, and 55.5% of the patients below 75 years had annual LDL testing. The effects of health insurance preferences were substantial and consistent. Having any supplementary insurance (ORs across measures were between 1.08 and 1.28), having supplementary hospital care insurance (1.08–1.30), having chosen a lower deductible level (eg, SFr2500 compared with SFr300: 0.57–0.69), and having chosen a managed care model (1.04–1.17) were positively associated with recommendations adherence. The MORs (1.27–1.33) showed only moderate unexplained variation, and we observed inconsistent spatial patterns of unexplained variation across the four measures.

Conclusion

Our findings indicate that the uptake of strongly recommended measures in diabetes management could possibly be optimized by providing further incentives to patients and care providers through insurance scheme design. The absence of marked regional variation implies limited potential for improvement by targeted regional intervention, while provider-specific promotion may be more impactful.
Using internet search data to explore the global public concerns in ankylosing spondylitis
Authors: Mei Yong-Jun , Mao Yan-Mei , Cao Fan , Wang Tao , Li Zhi-Jun
Published: February 2020

Objective

This study explored the changes of global public interest in internet search of ankylosing spondylitis (AS) based on Google Trends (GT) data, in order to reflect the characteristics of AS itself.

Methods

GT was used to obtain the search popularity scores of the term ’AS’ on a global scale, between January 2004 and December 2018, under the ’health’ classification. Based on the global search data of AS provided by GT, the cosinor analysis was used to test whether there was seasonality in AS.

Results

In general, AS related search volume demonstrated a decreasing trend from January 2004 to December 2014 and then remain stable from January 2015 to December 2018. No obvious seasonal variations were detected in AS related search volume (amplitude=1.54; phase: month=3.9; low point: month=9.9; p>0.025), which peaked in April and bottomed out in October. The top 17 rising topics were adalimumab, spondylolisthesis, Morbus, Vladimir Mikhailovich Bekhterev, autoimmune disease, rheumatoid arthritis, ankylosis, HLA- B27 positive, Crohn’s disease, rheumatology, spondylosis, arthritis, uveitis, rheumatism, sacroiliac, psoriatic arthritis and spondylitis.

Conclusions

Globally, there is no significant seasonal variation in GT for AS. The top fast-growing topics related to AS may be beneficial for doctors to provide targeted health education of the disease to patients and their families.
Division probability for quaternion algebras over fields
Authors: Jindal Leena , Khurana Anjana
Published: February 2020

Let [Formula: see text] be a field of [Formula: see text] with finitely many square classes. In this paper, we define a new rational valued invariant of [Formula: see text], and call it the division probability of [Formula: see text]. We compute it for all fields of elementary type. Further, we show that [Formula: see text], where [Formula: see text] is the number of Witt-equivalence classes of fields with [Formula: see text], and [Formula: see text] is the count of rational numbers that appear as division probabilities for fields [Formula: see text] of elementary type with [Formula: see text]. In the paper, we also determine [Formula: see text] for all [Formula: see text] and show that rational numbers of type [Formula: see text] always occur as division probability for a suitable field [Formula: see text].
IMMEDIATE AND LONGER-TERM STOCK PRICE DYNAMICS FOLLOWING LARGE STOCK PRICE CHANGES
Authors: KUDRYAVTSEV ANDREY
Published: February 2020

The study explores the correlation between the immediate and the longer-term stock returns following large daily price moves. Following the previous literature, which documents a tendency for price reversals after initial large price moves, I suggest that if a large stock price move is immediately followed by a short-term price drift, then it may indicate that the company-specific shock is more completely incorporated in the stock price, significantly increasing the probability of subsequent longer-term price reversal. Analyzing a vast sample of large stock price moves, I document that negative (positive) longer-term stock price reversals after large price increases (decreases) are significantly more pronounced if the latter are immediately followed by relatively high (low) short-term cumulative abnormal returns, that is, by short-term price drifts. The effect remains significant after accounting for additional company-specific (size, market model beta, historical, or conditional volatility) and event-specific (stock’s return and trading volume on the event day) factors.
Effects of Scaling and Sequence on Performance of Dynamic Bimanual Path Following Tasks
Authors: Boehm Jacob R. , Fey Nicholas P. , Fey Ann Majewicz
Published: February 2020

Bimanual coordination plays a vital role in many haptic and robotic system operations. However, theories in bimanual human motor control are rarely integrated into the control system for human-in-the-loop robots, potentially limiting the usability and collaborative potential between the human and robot, particularly for complex tasks such as robotic surgery. To inform future integration, we investigate unknown manual performance relationships regarding the scaling (the size of one hand’s motions compared to the other) and sequence (the order in which the hands move) of complex bimanual path following tasks. For scaling variations, either the left or right hand desired trajectory amplitude was increased. For sequence, the task was split so that the hands moved sequentially or simultaneously. The experiment is performed by 11 inexperienced, able bodied subjects (all right-handed) in a virtual environment while using haptic devices. Results show significant ([Formula: see text]) decreased manual performance for one hand when the opposite hand is scaled, thus suggesting an increase in the scale of one hand will decrease the performance of the contralateral. Results also show a significant decrease in performance for the left hand when moving simultaneous with the right, but the right hand does not show such a decrease in performance. This might suggest that only the nondominant hand suffers from simultaneous motion conditions. These results may lead to unique opportunities to integrate theories related to human motor control into the control system for haptic and robotic systems used in complex bimanual upper-limb tasks.
Editing self-image
Authors: Fried Ohad , Jacobs Jennifer , Finkelstein Adam , Agrawala Maneesh
Published: February 2020

Technologies for manipulating our digital appearance alter the way the world sees us as well as the way we see ourselves.
Above the line, below the line
Authors: Cook Richard I.
Published: February 2020

The resilience of Internet-facing systems relies on what is above the line of representation.
Evolution of Plant NLRs: From Natural History to Precise Modifications
Authors: Tamborski Janina , Krasileva Ksenia V.
Published: February 2020

Nucleotide-binding leucine-rich repeat receptors (NLRs) monitor the plant intracellular environment for signs of pathogen infection. Several mechanisms of NLR-mediated immunity arose independently across multiple species. These include the functional specialization of NLRs into sensors and helpers, the independent emergence of direct and indirect recognition within NLR subfamilies, the regulation of NLRs by small RNAs, and the formation of NLR networks. Understanding the evolutionary history of NLRs can shed light on both the origin of pathogen recognition and the common constraints on the plant immune system. Attempts to engineer disease resistance have been sparse and rarely informed by evolutionary knowledge. In this review, we discuss the evolution of NLRs, give an overview of previous engineering attempts, and propose how to use evolutionary knowledge to advance future research in the generation of novel disease-recognition capabilities.
Circulating and tissue matricellular RNA and protein expression in calcific aortic valve disease
Authors: Kossar Alexander P. , Anselmo Wanda , Grau Juan B. , Liu Yichuan , Small Aeron , Carter Samuel L. , Salvador Lisa , Zhao Lei , Cvijic Mary Ellen , Li Zhuyin , Yarde Melissa , Rioux Nancy , Rader Daniel J. , Levy Robert J. , Ferrari Giovanni
Published: February 2020

Aortic valve sclerosis is a highly prevalent, poorly characterized asymptomatic manifestation of calcific aortic valve disease and may represent a therapeutic target for disease mitigation. Human aortic valve cusps and blood were obtained from 333 patients undergoing cardiac surgery ( n = 236 for severe aortic stenosis, n = 35 for asymptomatic aortic valve sclerosis, n = 62 for no valvular disease), and a multiplex assay was used to evaluate protein expression across the spectrum of calcific aortic valve disease. A subset of six valvular tissue samples ( n = 3 for asymptomatic aortic valve sclerosis, n = 3 for severe aortic stenosis) was used to create RNA sequencing profiles, which were subsequently organized into clinically relevant gene modules. RNA sequencing identified 182 protein-encoding, differentially expressed genes in aortic valve sclerosis vs. aortic stenosis; 85% and 89% of expressed genes overlapped in aortic stenosis and aortic valve sclerosis, respectively, which decreased to 55% and 84% when we targeted highly expressed genes. Bioinformatic analyses identified six differentially expressed genes encoding key extracellular matrix regulators: TBHS2, SPARC, COL1A2, COL1A1, SPP1, and CTGF. Differential expression of key circulating biomarkers of extracellular matrix reorganization was observed in control vs. aortic valve sclerosis (osteopontin), control vs. aortic stenosis (osteoprotegerin), and aortic valve sclerosis vs. aortic stenosis groups (MMP-2), which corresponded to valvular mRNA expression. We demonstrate distinct mRNA and protein expression underlying aortic valve sclerosis and aortic stenosis. We anticipate that extracellular matrix regulators can serve as circulating biomarkers of early calcific aortic valve disease and as novel targets for early disease mitigation, pending prospective clinical investigations.
Development of an Enriched Polyphenol (Natural Antioxidant) Extract from Orange Juice (Citrus sinensis) by Adsorption on Macroporous Resins
Authors: Campone Luca , Celano Rita , Rizzo Serena , Piccinelli Anna Lisa , Rastrelli Luca , Russo Mariateresa
Published: February 2020

Orange (Citrus sinensis) juice contains a high amount of antioxidant compounds, such as polyphenols and vitamins. The aim of this work was to develop an adsorption procedure for the quantitative recovery of polyphenols from fresh orange juice. Different macroporous resins have been selected to evaluate their affinity for phenolic compound in order to purify the antioxidant compounds from the orange juice. The main compounds of orange juice were firstly characterized using an UPLC-UV-HRMS to define the metabolite profile, and subsequently three different types of adsorbent (XAD-2, XAD-4, and XAD-16N) were tested to concentrate these bioactive compounds. The time of contact was selected based on kinetic studies, and subsequently the adsorption and elution conditions were optimized in order to maximize the recovery of phenolic compounds to obtain an extract rich of bioactive compounds. Lastly, antioxidant capacity of the orange juice extract of selected macroporous resin, obtained under optimized conditions, was determined by in vitro antioxidant assays.
Research on Degradation of GaN-Based Blue LED Caused by γ Radiation under Low Bias
Authors: Zhao Qifeng , Lu Xiangyang , Yu Fajun , Xu Jinglei , Fang Zeping , Liu Xiao-yong
Published: February 2020

GaN multiquantum-well blue light-emitting diodes (LEDs) were radiated with 60Co γ-rays for accumulated doses up to 2.5 Mrad (SiO2). The radiation-induced current and 1/f noise degradations were studied when the devices operate at the low bias voltage. The current increased by 2.31 times, and the 1/f noise increased by 275.69 times after a dose of 2.5 Mrad (SiO2). Based on Hurkx’s trap-assisted tunneling model, the degradation of current was explained. γ radiation created defects in the space-charge region of LEDs. These defects as generation-recombination centers lead to the increase in the current. In addition, based on the quantum l/f noise theory, the degradation of 1/f noise might be also attributed to these defects, which caused an increase in the Hooge constant and a decrease in the carrier lifetimes. The current and 1/f noise degradations can be attributed to the same physical origin. Compared to the current, the 1/f noise parameter is more sensitive, so it may be used to evaluate the radiation resistance capability of GaN blue LEDs.
Glucose-Regulated Protein 78 in the Aqueous Humor of Patients with Diabetic Macular Edema
Authors: Choi Moon Young , Kwon Jin-woo
Published: February 2020

Purpose. We identified the associations between levels of aqueous glucose-regulated protein 78 (GRP78) and systemic or ocular factors in patients with center-involving diabetic macular edema (CIDME). Methods. We measured the aqueous concentrations of GRP78, interleukin- (IL-) 1β, IL-2, IL-8, IL-10, and IL-17, placental growth factor, and vascular endothelial growth factor (VEGF). We explored the associations between aqueous GRP78 levels and those of other aqueous factors, optical coherence tomography (OCT) findings, and systemic parameters in CIDME patients. Results. In multivariate regression analysis, aqueous GRP78 levels were associated with aqueous VEGF levels (p=0.007), length of EZ disruption (p<0.001), and duration of diabetes (p=0.002). However, no significant relationship was observed between GRP78 levels and those of other systemic and ocular factors including inflammatory cytokines in the aqueous humor. In terms of responsiveness, the number of hyperreflective foci (≥8) was significantly associated with the responsiveness of three consecutive monthly intravitreal bevacizumab injections (OR=0.34, p=0.046), but not the aqueous GRP78 levels. Conclusions. Aqueous GRP78 levels correlated with VEGF levels in the aqueous humor and EZ disruption on OCT. However, GRP78 levels were not associated with those of inflammatory biomarkers in the aqueous humor or OCT findings. Additionally, GRP78 could not serve as a biomarker to predict short-term prognosis of anti-VEGF agent.
Multivariate Statistical Analysis Reveals the Heterogeneity of Lacustrine Tight Oil Accumulation in the Middle Permian Jimusar Sag, Junggar Basin, NW China
Authors: Wang Yuce , Cao Jian , Tao Keyu , Gao Xiuwei , Li Erting , Shi Chunhua
Published: February 2020

Tight oil and gas accumulation commonly has heterogeneities within the reservoir formation. This heterogeneity, however, is hard to investigate by conventional geological and (organic) geochemical tools and thus is critical and challenging to study. Here, we attempted multivariate statistical analysis to reveal the heterogeneity based on a case study in the lacustrine tight oil accumulation in the middle Permian Lucaogou Formation of the Jimusar sag, Junggar Basin, NW China. Clustering heat maps and multi-dimensional scaling analysis revealed the heterogeneity of tight oil accumulation. The heterogeneity is reflected by the complex relationship between the two reservoir sweet spots as well as the oil migration and accumulation vertically and spatially, rather than the previous thoughts that it is a closed system associated with proximal hydrocarbon accumulation patterns. Multiple biomarkers show that the source rocks and reservoirs have similar characteristics in the lower part of the formation, reflecting a proximal hydrocarbon accumulation pattern in the lower sweet spot (near-source accumulation, abbreviated as NA). This represents a relatively closed system. However, the upper sweet spot and the middle section mudstone sequence intervening the two sweet spots are not a completely closed system in a strict sense. These sequences can be divided into three tight oil segments, i.e., lower, middle, and upper from deep to shallow. The lower segment is sited in the lower part of the middle section mudstone sequence. The middle segment is composed of the upper part of the middle section mudstone sequence and the lower part of the upper sweet spot. The upper segment is composed of the upper part of the upper sweet spot and the overlying upper Permian Wutonggou Formation reservoirs. Oils generated in the lower segment migrated vertically to upper sweet spot reservoirs through faults/fractures, and laterally to distal reservoirs. Oils generated in the middle segment were preserved in reservoirs of the upper sweet spot. Oils in the upper segment require accumulation by vertical and lateral migration through faults/fractures. As such, the tight oil accumulation is complex in the Lucaogou Formation. From base to top, the accumulation mechanisms in the Lucaogou Formation were NA, VLMA (vertical and lateral migration and accumulation), NA and VLMA, thereby showing strong heterogeneities. Our data suggest that these processes might be typical of tight oil accumulations universally, and are important for future exploration and exploitation in the region to consider the heterogeneities rather than a closed system. The multivariate statistical analysis is an effective tool for investigating complex oil-source correlations and accumulation in petroleum basins.
High Glucose Induces Endothelial COX2 and iNOS Expression via Inhibition of Monomethyltransferase SETD8 Expression
Authors: Qi Jie , Wu Qichao , Cheng Qian , Chen Xiangyuan , Zhu Minmin , Miao Changhong
Published: February 2020

Cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS) overexpression results in endothelial apoptosis, thus mediating vascular endothelial injury in hyperglycaemia. E26 transformation-specific sequence transcription factor-1 (ESE-1), which belongs to the E26 transformation-specific family of transcription factors, has been demonstrated to be involved in COX2 and iNOS gene transcription. Our previous study indicated that SET domain-containing protein 8 (SETD8) downregulation is involved in high glucose-mediated endothelial inflammation in human umbilical vein endothelial cells (HUVECs). Here, we report that SETD8 plays a major role in hyperglycaemia-induced COX2 and iNOS expression. In HUVECs, upregulation of ESE-1 expression was related to high glucose-mediated apoptosis and COX2 and iNOS expression. High glucose inhibited SETD8 expression, and overexpression of SETD8 diminished the effects of high glucose treatment. Consistently, RNA silencing of SETD8 led to the opposite effect. Furthermore, SETD8 was found to interact with specificity protein 1 (SP1). Blockade of SP1 protected against high glucose-mediated endothelial injury. Mechanistically, we showed that H4K20me1, a downstream target of SETD8, and SP1 were enriched at the ESE-1 promoter region by ChIP assay. Luciferase reporter assays indicated that SETD8 overexpression attenuated ESE-1 promoter activity and augmented the inhibitory effect of siSP1 on ESE-1 promoter activity. In general, our data indicate that SETD8 interacts with SP1 to coregulate ESE-1 expression, which is involved in hyperglycaemia-mediated endothelial apoptosis in HUVECs.
FAM64A Promotes Osteosarcoma Cell Growth and Metastasis and Is Mediated by miR-493
Authors: Jiang Ying , Zhou Chunlei , Gao Qiang , Yin Zhi-Qi , Wang Jingwen , Mu Hong , Yan Jun
Published: February 2020

Aberrant expression of FAM64A was correlated with cell proliferation in various cancer types. We examined the expression of FAM64A and the upstream gene miR-493 in OS. The functions of miR-493 were revealed through extensive experiments. We found an increase of FAM64A gene and protein in OS tissues. Overexpression of FAM64A resulted in promoting tumor proliferation, migration, and invasion. The miR-493 targeted and negatively regulated FAM64A. Our data showed that upregulation of FAM64A in OS correlated with poor prognosis.
Tanshinone IIA Alleviates CCL2‐Induced Leaning memory and Cognition Impairment in Rats: A Potential Therapeutic Approach for HIV‐Associated Neurocognitive Disorder
Authors: Liao Yuan-jun , Chen Jian-min , Long Jiang-yi , Zhou Yi-jun , Liang Bing-yu , Zhou Yan
Published: February 2020

Chemokine CC motif ligand 2 (CCL2) is one of the most recognized proinflammatory chemokines, and the expression of CCL2 in the cerebrospinal fluid of patients infected with HIV‐1 is significantly higher than that of healthy people. As such, it is seen as an important cause of HIV‐associated neurocognitive disorder (HAND). Our previous investigation has confirmed the pathological role of CCL2 in mediating brain damage leading to cognitive dysfunction. Currently, however, research on therapeutic drugs for the central nervous system targeting CCL2 is very limited. Our present study used brain stereotactic technology to induce cognitive impairment in rats by injecting CCL2 (5 ng) into the bilateral hippocampus. To investigate the protective effect and mechanism of Tanshinone IIA (25, 50, 75 mg/kg/d) on CCL2‐induced learning memory and cognitive impairment in rats, we performed the Morris water maze (MWM) and novel object recognition tests (NORT) on the rats. The results showed that Tanshinone IIA significantly alleviated CCL2‐induced learning memory and cognitive dysfunction. Further studies on the hippocampal tissue of the rats revealed that Tanshinone IIA treatment significantly increased the activity of SOD and GSH‐Px while the level of MDA decreased compared to the model group. Additionally, the relative expression of apoptosis‐associated genes caspase‐3, caspase‐8, and caspase‐9 and inflammation‐associated genes IL‐1β and IL‐6 in Tanshinone IIA‐treated rats was lower than that in model rats. Finally, we confirmed hippocampal neuron loss and apoptosis by Nissl staining and TdT‐mediated dUTP Nick end labeling (TUNEL). Taken together, these data imply that Tanshinone IIA can ameliorate CCL2‐induced learning memory and cognitive impairment by impacting oxidative stress, inflammation, and apoptosis. Tanshinone IIA may be a potential therapeutic agent for the treatment of HAND.
Bone Transport for Treatment of Traumatic Composite Tibial Bone and Soft Tissue Defects: Any Specific Needs besides the Ilizarov Technique?
Authors: Li Runguang , Zhu Guozheng , Chen Chaojie , Chen Yirong , Ren Gaohong
Published: February 2020

Objective. To evaluate the surgical efficacy of bone transport (Ilizarov technique) plus “shortening‐lengthening,” “flap surgery,” and “open bone transport” as individualized treatments for traumatic composite tibial bone and soft tissue defects. Methods. We retrospectively analyzed sixty‐eight cases (mean age: 35.69 years, (range, 16–65)) treated from July 2014 to June 2017, including 29 middle, 18 distal, and 21 proximal tibial bone defects (4–18 cm, mean: 7.97 cm) with soft tissue defects (2.5 cm × 4.0 cm to 30.0 cm × 35.0 cm after debridement). We adopted the bone transport external fixator to fix the fracture after debriding the defect parts. In the meantime, we adopted the “shortening‐lengthening technique,” “flap surgery,” and “open bone transport” as individualized treatment based on the location, range, and severity of the composite tibial bone and soft tissue defects. Postoperative follow‐up was carried out. Surgical efficacy was assessed based on (1) wound healing; (2) bone defect healing rate; (3) external fixation time and index; (4) incidence/recurrence of deep infection; (5) postoperative complications; and (6) Association for the Study and Application of the Methods of Ilizarov (ASAMI) score. Results. The mean duration from injury to reconstruction was 22 days (4–80 d), and the mean postoperative follow‐up period was 30.8 months (18–54 m). After the repair and reconstruction, 2 open bone transport patients required infected bone removal first before continuing the bone transport treatment. No deep infection (osteomyelitis) occurred or recurred in the remaining patients, and no secondary debridement was required. Some patients had complications after surgery. All the postoperative complications, including flap venous crisis, nail channel reaction, bone nonunion, mechanical axis deviation, and refracture, were improved or alleviated. External fixation time was 12.5 ± 3.41 months, and the index was 1.63 ± 0.44. According to the ASAMI score, 76.47% of the outcomes were good/excellent. Conclusion. The Ilizarov technique yields satisfactory efficacy for composite tibial bone and soft tissue defects when combined with “shortening‐lengthening technique,” “flap surgery,” and “open bone transport” with appropriate individualized treatment strategies.
Fixation Methods for Mandibular Advancement and Their Effects on Temporomandibular Joint: A Finite Element Analysis Study
Authors: Demircan Sabit , Uretürk Erdoğan Utku , Apaydın Ayşegül , Şen Sinan
Published: February 2020

Objectives. Bilateral sagittal split osteotomy (BSSO) is a common surgical procedure to correct dentofacial deformities that involve the mandible. Usually bicortical bone fixation screw or miniplates with monocortical bone fixation screw were used to gain stability after BSSO. On the other hand, the use of resorbable screw materials had been reported. In this study, our aim is to determine first stress distribution values at the temporomandibular joint (TMJ) and second displacement amounts of each mandibular bone segment. Methods. A three‐dimensional virtual mesh model of the mandible was constructed. Then, BSSO with 9 mm advancement was simulated using the finite element model (FEM). Fixation between each mandibular segment was also virtually performed using seven different combinations of fixation materials, as follows: miniplate only (M), miniplate and a titanium bicortical bone fixation screw (H), miniplate and a resorbable bicortical bone fixation screw (HR), 3 L‐shaped titanium bicortical bone fixation screws (L), 3 L‐shaped resorbable bicortical bone fixation screws (LR), 3 inverted L‐shaped titanium bicortical bone fixation screws (IL), and 3 inverted L‐shaped resorbable bicortical bone fixation screws (ILR). Results. At 9 mm advancement, the biggest stress values at the anterior area TMJ was seen at M fixation and LR fixation at posterior TMJ. The minimum stress values on anterior TMJ were seen at L fixation and M fixation at posterior TMJ. Minimum displacement was seen in IL method. It was followed by L, H, HR, M, ILR, and LR, respectively. Conclusion. According to our results, bicortical screw fixation was associated with more stress on the condyle. In terms of total stress value, especially LR and ILR lead to higher amounts.