bluuebunny/crossref_metadata_2025 huggingface dataset:
Mucosal concentrations of N‐acetyl‐5‐aminosalicylic acid related to endoscopic activity in ulcerative colitis patients with mesalamine
Authors: Fukuda Tomohiro , Naganuma Makoto , Takabayashi Kaoru , Hagihara Yuya , Tanemoto Shun , Nomura Ena , Yoshimatsu Yusuke , Sugimoto Shinya , Nanki Kosaku , Mizuno Shinta , Mikami Yohei , Fukuhara Kayoko , Sujino Tomohisa , Mutaguchi Makoto , Inoue Nagamu , Ogata Haruhiko , Iwao Yasushi , Abe Takayuki , Kanai Takanori
Published: April 2020

Background and Aim

5‐Aminosalicylic acid (5‐ASA) is a fundamental treatment for mild‐to‐moderate ulcerative colitis (UC). 5‐ASA is taken up into the colonic mucosa and metabolized to N‐acetyl‐5‐ASA (Ac‐5‐ASA). Few studies have assessed whether mucosal 5‐ASA and Ac‐5‐ASA concentrations are associated with endoscopic remission. This study aimed to investigate differences in 5‐ASA and Ac‐5‐ASA concentrations according to endoscopic activity.

Methods

This single‐center, prospective, cross‐sectional study was conducted between March 2018 and February 2019. UC patients who were administered with 5‐ASA medication for at least 8 weeks before sigmoidoscopy were enrolled. Mucosal 5‐ASA and Ac‐5‐ASA concentrations were measured using liquid chromatography with tandem mass spectrometry. The primary endpoint was defined as the difference in mucosal concentrations of 5‐ASA and Ac‐5‐ASA, according to the Mayo endoscopic subscore (MES).

Results

Mucosal concentrations were analyzed in 50 patients. In the sigmoid colon, the median 5‐ASA concentration in patients with MES of 0 (17.3 ng/mg) was significantly higher than MES ≥ 1 (6.4 ng/mg) (P = 0.019). The median 5‐ASA concentrations in patients with Ulcerative Colitis Endoscopic Index of Severity ≤ 1 (16.4 ng/mg) were also significantly higher than in patients with Ulcerative Colitis Endoscopic Index of Severity ≥ 2 (4.63 ng/mg) (P = 0.047). In the sigmoid colon, the concentration of Ac‐5‐ASA was higher in patients with MES of 0 (21.2 ng/mg) than in patients with MES ≥ 1 (5.81 ng/mg) (P = 0.022).

Conclusions

The present study showed that mucosal Ac‐5‐ASA concentrations, as well as 5‐ASA concentrations, are higher in UC patients with endoscopic remission. Ac‐5‐ASA may be useful for a biomarker of 5‐ASA efficacy.
Depression Symptoms and Cognitive Test Performance in Older American Indians: The Strong Heart Study
Authors: Suchy‐Dicey Astrid , Verney Steven P. , Nelson Lonnie A. , Barbosa‐Leiker Celestina , Howard Barbara A. , Crane Paul K. , Buchwald Dedra S.
Published: April 2020

BACKGROUND

American Indians have excess risk of depression, which can contribute to cerebrovascular and cognitive disability, with effects on memory, processing speed, executive function, and visuospatial ability. However, studies examining depression and cognition in American Indians are limited; this study aims to report associations of depression with general cognition, verbal fluency and memory, and processing speed.

DESIGN

Cohort study.

SETTING

The Cerebrovascular Disease and its Consequences in American Indians study was an ancillary examination of Strong Heart Study participants from 3 U.S. regions.

PARTICIPANTS

All eligible were included in this analysis (N=818).

MEASUREMENTS

Participants completed evaluations for depressive symptomology, cognition, and physical function—including Center for Epidemiologic Studies Depression (CESD), Modified Mini‐Mental State Examination (3MSE), Wechsler Adult Intelligence Scale‐Fourth Edition coding (WAIS), Controlled Oral Word Association (COWA), California Verbal and Learning Test, Halstead finger tapping, grip strength, and Short Physical Performance Battery (SPPB) tests. Linear mixed models were adjusted for site, age, sex, education, income, marital status, alcohol, smoking, diabetes, hypertension, obesity, cholesterol, stroke, infarct, and hemorrhage.

RESULTS

Symptoms of depression were common, with 20% (N=138) endorsing CES‐D scores of 16+. More depressive symptoms were associated with older age, female sex, lower education, lower income, non‐married status, not using alcohol, not smoking, hypertension, diabetes, and stroke. In adjusted analyses, processing speed (WAIS: β −0.13, 95%CI −0.25, −0.03), general cognition (3MSE: β −0.10, 95%CI −0.17, −0.03), verbal fluency (COWA: β −0.10, 95%CI −0.19, −0.01), and motor function (SPPB: β −0.05, 95%CI −0.07, −0.03) were significantly associated with more symptoms of depression.

CONCLUSION

These findings maybe informative for health disparities populations, especially those with depressive risk. Clinicians may require particular training in cultural humility. Future studies should validate use of the CES‐D scale in this population; longitudinal studies may focus on causal mechanisms and potential secondary prevention, such as social support. J Am Geriatr Soc 68:1739‐1747, 2020.
Wayfinding Signage for People with Color Blindness
Authors: Lee Heejin , Lee Eunsil , Choi Gyoung–sil
Published: April 2020

Color plays an important role in conveying information through communication systems such as signage and electronic devices. However, people who are color–blind often have difficulties understanding that information because most systems are designed for people who can distinguish colors. The purpose of this study is to propose color combinations for wayfinding signage in public areas that are discriminable and esthetically pleasing for people with and without color blindness. By using a simulation method, this study examined how people with color blindness perceive eight hues of red, green, blue, yellow, orange, purple, cyan, and chartreuse on the natural color system color chart. It also investigated how the current wayfinding signage in Seoul is friendly to the color blind and presented examples of color–blind–friendly color combinations by applying color functions and color harmony theories. This study helps people with color blindness, by offering design professionals insight into more inclusive wayfinding signage that will be of use to people with and without color blindness.
Identification and characterization of long non‐coding RNAs as competing endogenous RNAs in the cold stress response of Triticum aestivum
Authors: Lu Q. , Xu Q. , Guo F. , Lv Y. , Song C. , Feng M. , Yu J. , Zhang D. , Cang J.
Published: April 2020

Long non‐coding RNAs (lncRNAs) play important roles in plant development and stress responses. MicroRNAs (miRNAs) are involved in transcriptional and post‐transcriptional gene regulation. It is not clear how lncRNA‐mediated plant responses to cold stress and how lncRNAs, miRNAs and target mRNAs cooperate subject to the competing endogenous RNA (ceRNA).

We interpreted the function of lncRNAs in the winter wheat cultivar Dongnongdongmai 1 (Dn1). A total of 9970 putative lncRNAs were initially identified from three Dn1 lncRNA libraries (5 °C, −10 °C and −25 °C) using high‐throughput sequencing.

Among the 14,626 genes detected via weighted gene co‐expression network analysis, 7435 lncRNAs were co‐expressed with 7191 mRNAs. We found six modules related to cold resistance in the lncRNA–mRNA weighted co‐expression network, and the functions of mRNAs were similar in each module. Antioxidant systems and hormones played important roles in low‐temperature responses. RNA sequencing analysis revealed that interactions between the 384 lncRNAs and 70 miRNAs were required for ceRNA activity. According to ceRNA activity, 225 lncRNAs, 60 miRNAs and 621 target mRNAs were involved in the regulatory networks of the cold stress response. Notably, a conserved region was found in the complementary regions of lncRNAs and miR164/408 but had reverse expression trends in the ceRNA network.

Our results reveal possible roles of lncRNAs–mRNAs in the regulatory networks associated with tolerance to low temperature and provide useful information for more strategic use of genomic resources in wheat breeding.
Custom Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometric Database for Identification of Environmental Isolates of the Genus
Burkholderia
and Related Genera
Authors: Fergusson Claire H. , Coloma Julienne M. F. , Valentine Mercia C. , Haeckl F. P. Jake , Linington Roger G.
Published: April 2020

The Gram-negative proteobacterial order
Burkholderiales
has emerged as a promising source of novel natural products in recent years. This order includes the genus
Burkholderia
and the newly defined genera
Caballeronia
and
Paraburkholderia
. However, development of this resource has been hampered by difficulties with rapid and selective isolation of
Burkholderiales
strains from the environment. Environmental metagenome sequencing has revealed that the potential for natural products is not evenly distributed throughout the microbial world. Thus, large but targeted microbial isolate libraries are needed to effectively explore the chemical potential of natural products. To study these organisms efficiently, methods to quickly identify isolates to the genus level are required. Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) is already used in clinical settings to reliably identify unknown bacterial pathogens. We have adapted similar methodology using the MALDI Biotyper instrument to rapidly identify environmental isolates of
Burkholderia
,
Caballeronia
, and
Paraburkholderia
for downstream natural product discovery.
Two Ways To Convert a Low-Affinity Potassium Channel to High Affinity: Control of Bacillus subtilis KtrCD by Glutamate
Authors: Krüger Larissa , Herzberg Christina , Warneke Robert , Poehlein Anja , Stautz Janina , Weiß Martin , Daniel Rolf , Hänelt Inga , Stülke Jörg
Published: April 2020

Potassium and glutamate are the major cation and anion, respectively, in every living cell. Due to the high concentrations of both ions, the cytoplasm of all cells can be regarded as a potassium glutamate solution. This implies that the concentrations of both ions need to be balanced. While the control of potassium uptake by glutamate is well established for eukaryotic cells, much less is known about the mechanisms that link potassium homeostasis to glutamate availability in bacteria. Here, we have discovered that the availability of glutamate strongly decreases the minimal external potassium concentration required for the highly abundant Bacillus subtilis potassium channel KtrCD to accumulate potassium. In contrast, the inducible KtrAB and KimA potassium uptake systems have high apparent affinities for potassium even in the absence of glutamate. Experiments with mutant strains revealed that the KtrD subunit responds to the presence of glutamate. For full activity, KtrD synergistically requires the presence of the regulatory subunit KtrC and of glutamate. The analysis of suppressor mutants of a strain that has KtrCD as the only potassium uptake system and that experiences severe potassium starvation identified a mutation in the ion selectivity filter of KtrD (Gly282 to Val) that similarly results in a strongly glutamate-independent increase of the apparent affinity for potassium. Thus, this work has identified two conditions that increase the apparent affinity of KtrCD for potassium, i.e., external glutamate and the acquisition of a single point mutation in KtrD.

IMPORTANCE In each living cell, potassium is required for maintaining the intracellular pH and for the activity of essential enzymes. Like most other bacteria, Bacillus subtilis possesses multiple low- and high-affinity potassium uptake systems. Their activity is regulated by the second messenger cyclic di-AMP. Moreover, the pools of the most abundant ions potassium and glutamate must be balanced. We report two conditions under which the low-affinity potassium channel KtrCD is able to mediate potassium uptake at low external potassium concentrations: physiologically, the presence of glutamate results in a severely increased potassium uptake. Moreover, this is achieved by a mutation affecting the selectivity filter of the KtrD channel. These results highlight the integration between potassium and glutamate homeostasis in bacteria.
Prokaryotic and Viral Community Composition of Freshwater Springs in Florida, USA
Authors: Malki Kema , Rosario Karyna , Sawaya Natalie A. , Székely Anna J. , Tisza Michael J. , Breitbart Mya
Published: April 2020

Aquifer systems may hold up to 40% of the total microbial biomass on Earth. However, little is known about the composition of microbial communities within these critical freshwater ecosystems. Here, we took advantage of Florida’s first-magnitude springs (the highest spring classification based on water discharge), each discharging at least 246 million liters of water each day from the Floridan aquifer system (FAS), to investigate prokaryotic and viral communities from the aquifer. The FAS serves as a major source of potable water in the Southeastern United States, providing water for large cities and citizens in three states. Unfortunately, the health of the FAS and its associated springs has declined in the past few decades due to nutrient loading, increased urbanization and agricultural activity in aquifer recharge zones, and saltwater intrusion. This is the first study to describe the prokaryotic and viral communities in Florida’s first-magnitude springs, providing a baseline against which to compare future ecosystem change.
Visualizing Association of the Retroviral Gag Protein with Unspliced Viral RNA in the Nucleus
Authors: Maldonado Rebecca J. Kaddis , Rice Breanna , Chen Eunice C. , Tuffy Kevin M. , Chiari Estelle F. , Fahrbach Kelly M. , Hope Thomas J. , Parent Leslie J.
Published: April 2020

Retroviruses cause severe diseases in animals and humans, including cancer and acquired immunodeficiency syndromes. To propagate infection, retroviruses assemble new virus particles that contain viral proteins and unspliced vRNA to use as gRNA. Despite the critical requirement for gRNA packaging, the molecular mechanisms governing the identification and selection of gRNA by the Gag protein remain poorly understood. In this report, we demonstrate that the Rous sarcoma virus (RSV) Gag protein colocalizes with unspliced vRNA in the nucleus in the interchromatin space. Using live-cell confocal imaging, RSV Gag and unspliced vRNA were observed to move together from inside the nucleus across the nuclear envelope, suggesting that the Gag-gRNA complex initially forms in the nucleus and undergoes nuclear export into the cytoplasm as a viral ribonucleoprotein (vRNP) complex.
Place-of-death preferences among patients with cancer and family caregivers in inpatient and outpatient palliative care
Authors: Vidal Marieberta , Rodriguez-Nunez Alfredo , Hui David , Allo Julio , Williams Janet L , Park Minjeong , Liu Diane , Bruera Eduardo
Published: April 2020

Objective

Meeting the preferences of patients is considered an important palliative care outcome. Prior studies reported that more than 80% of patients with terminally ill cancer prefer to die at home. The purpose of this study was to determine place-of-death preference among palliative care patients in the outpatient centre and the palliative care unit (PCU) of a comprehensive cancer centre.

Methods

A cross-sectional anonymous questionnaire was administered to patients with advanced cancer and caregivers (PCU and outpatient centre) between August 2012 and September 2014. PCU patients responded when there was no delirium and the primary caregiver responded when the patient was unable to respond. In the case of outpatients, dyads were assessed. The survey was repeated 1 month later.

Results

Overall, 65% preferred home death. There was less preference for home death among PCU patients (58%) than among outpatients (72%). Patient and caregiver agreement regarding preferred place of death for home was 86%. After 1 month, outpatients were significantly more likely than PCU patients to have the same preferred place of death as they had 1 month earlier (96% vs 83%; p=0.003).

Conclusions

Although home was the preferred place of death in our group of patients with advanced cancer and their caregivers, a substantial minority preferred hospital death or had no preference. We speculate that PCU patients’ higher preference for hospital death is likely related to more severe distress because they had already tried home care. Personalised assessment of place of death preference for both patient and caregiver is needed.
Workflow patterns and potential for optimization in endovascular stroke treatment across the world: results from a multinational survey
Authors: Ospel Johanna Maria , Almekhlafi Mohammed A , Menon Bijoy K , Kashani Nima , Chapot René , Fiehler Jens , Hassan Ameer E , Yavagal Dileep , Majoie Charles B L.M , Jayaraman Mahesh V , Hill Michael D , Goyal Mayank
Published: April 2020

Background

The benefit of endovascular treatment (EVT) is highly time-dependent, and treatment delays reduce patients’ chances to achieve a good outcome. In this survey-based study, we aimed to evaluate current in-hospital EVT workflow characteristics across different countries and hospital settings, and to quantify the time-savings that could be achieved by optimizing particular workflow steps.

Methods

In a multinational survey, neurointerventionalists were asked to provide specific information about EVT workflows in their current working environment. Workflow characteristics were summarized using descriptive statistics and stratified by country and physician characteristics, such as age, career stage, personal and institutional caseload.

Results

Among 248 respondents from 48 countries, pre-notification of the neurointerventional team was used in 70% of cases. The emergency department (ED) and CT scanner, and the CT scanner and neuroangiography suite, were on different floors in 23% and 38%, respectively. Redundant procedures in the ED were often routinely performed, such as chest x-rays (in 6%). General anesthesia was the most frequently used anesthesia protocol for EVT (42%), and an anesthesiologist was available in 82% for this purpose. 52% of the participants used a pre-prepared EVT kit.

Conclusion

The current structure of EVT workflows offers possibilities for improvement. While some bottlenecks, such as the spatial department set-up, cannot easily be resolved, pre-notification tools and pre-prepared EVT kits are more straightforward to implement and could help to reduce treatment delays, and thereby improve patient outcomes.
Exploring veterinarians’ use of practices aimed at understanding and providing emotional support to clients during companion animal euthanasia in Ontario, Canada
Authors: Matte Alisha R , Khosa Deep K , Coe Jason B , Meehan Michael , Niel Lee
Published: April 2020

Background

During companion animal euthanasia, support of clients is equally important as the medical care of the companion animal and requires a clear and developed understanding of clients' feelings, needs and expectations. Yet, veterinarians may not be fully exploring such topics.

Methods

A 65‐item online questionnaire was developed and distributed to veterinarians (n=368) in Ontario to explore veterinarians’ use of practices aimed at understanding and providing support during companion animal euthanasia. Measures included veterinarians’ use of previously identified communication and support practices, empathy, years in practice and amount of time scheduled for euthanasia appointments. Data were analysed using descriptive statistics and multivariable regression.

Results

Veterinarians reported consistently providing emotional support but inconsistently implementing practices that may assist in enhancing their understanding of clients’ expectations, previous or emotional experiences. Veterinarians’ empathy scores, years in practice and the amount of time scheduled for euthanasia were positively associated with use of these practices.

Conclusion

Providing adequate time (ideally >30 min) for euthanasia appointments may assist in efforts to understand clients’ experiences, expectations and emotions, and provide support. Combining empathy, hands‐on and self‐care training in veterinary curriculum may also be valuable in improving the comfort level and skill of veterinarians in providing compassionate care.
Heteromorphic seed germination and seedling emergence in the legume Teramnus labialis (L.f.) Spreng (Fabacaeae)
Authors: Acosta Yanier , Pérez Lianny , Escalante Doris , Pérez Aurora , Martínez-Montero Marcos Edel , Fontes Dayamí , Ahmed Lina Qadir , Sershen  , Lorenzo José Carlos
Published: April 2020

Seed heteromorphism can influence germination and ultimately seedling establishment, particularly in disturbed habitats. This study compared seed and seedling traits across three distinctly colored seed morphs (viz. light-brown, brown, and dark-brown) of the forage legume, Teramnus labialis (L.f.) Spreng. The best quality seeds (i.e., un-parasitized, filled and un-cracked) were brown: 389.3 quality seeds per 1000 units compared with <270/1000 units for the other two morphs. Length, width, volume, and water content were lowest in the light-brown and highest in the dark-brown seeds. Seed thickness and mass were lower in the light-brown seeds. Dark-brown seeds imbibed fastest from 2 h onwards. Germination was comparable across the morphs after 7 days but was lowest in the light-brown (17% at 21 days) and highest in the dark-brown seeds (36% at 21 days) at 14 and 21 days. At 7 days, seedling emergence in the dark-brown seeds (15.0%) was higher than in the other two morphs (4%–6%); this remained so at 14 and 21 days. Seedling growth (number of leaves, stem height and diameter, and root length) was superior in the dark-brown seeds. Seed heteromorphism in T. labialis may allow its persistence in disturbed habitats, and the dark-brown seeds are best suited for seeding in revegetation projects, given their superior germination capacity and seedling vigor.
Spatial variability in Ontario Riesling vineyards. II. Berry composition
Authors: Willwerth James J. , Reynolds Andrew G.
Published: April 2020

Spatial variability of berry composition was studied over a 3-yr period in 10 Riesling vineyards in the Niagara Peninsula in Ontario. Vineyards were delineated using global positioning systems (GPS), and 75–80 sentinel vines were georeferenced within a sampling grid for data collection. During 2005–2007, vine water status measurements [leaf water potential (ψ)] were collected biweekly from a subset of these sentinel vines. Data were collected on soil texture and composition, soil water content (SWC; %), leaf ψ, and fruit composition. These variables were mapped using GIS software, and relationships between them were elucidated. Temporal stability in spatial patterns of soil texture and composition, SWC, leaf ψ, soluble solids (Brix), titratable acidity, and monoterpenes were examined. Spatial trends in leaf ψ and (or) SWC showed widespread evidence of temporal stability. Fruit composition variables were not as stable over a 3-yr period. Spatial trends in Brix were temporally stable in seven vineyards, free volatile terpenes were temporally stable in three vineyards, and potentially volatile terpenes were temporally stable in two vineyards. Consistent leaf ψ zones were identified, and these were temporally stable despite different climatic conditions. Furthermore, some soil variables, and particularly vine water status, may contribute significantly to the terroir effect through their effects on vine size and fruit composition. For some vineyards, many viticulture and fruit composition variables were also temporally stable. There was evidence of strong spatial relationships between leaf ψ and fruit composition, suggesting a strong relationship between berry composition and vine water status.
Numerical Methods for the Solution of Population Balance Equations Coupled with Computational Fluid Dynamics
Authors: Shiea Mohsen , Buffo Antonio , Vanni Marco , Marchisio Daniele
Published: April 2020

This review article discusses the solution of population balance equations, for the simulation of disperse multiphase systems, tightly coupled with computational fluid dynamics. Although several methods are discussed, the focus is on quadrature-based moment methods (QBMMs) with particular attention to the quadrature method of moments, the conditional quadrature method of moments, and the direct quadrature method of moments. The relationship between the population balance equation, in its generalized form, and the Euler-Euler multiphase flow models, notably the two-fluid model, is thoroughly discussed. Then the closure problem and the use of Gaussian quadratures to overcome it are analyzed. The review concludes with the presentation of numerical issues and guidelines for users of these modeling approaches.
Microwave Microscopy and Its Applications
Authors: Chu Zhaodong , Zheng Lu , Lai Keji
Published: April 2020

Understanding the nanoscale electrodynamic properties of a material at microwave frequencies is of great interest for materials science, condensed matter physics, device engineering, and biology. With specialized probes, sensitive detection electronics, and improved scanning platforms, microwave microscopy has become an important tool for cutting-edge materials research in the past decade. In this article, we review the basic components and data interpretation of microwave imaging and its broad range of applications. In addition to the general-purpose mapping of permittivity and conductivity, microwave microscopy is now exploited to perform quantitative measurements on semiconductor devices, photosensitive materials, ferroelectric domains and domain walls, and acoustic-wave systems. Implementation of the technique in low-temperature and high-magnetic-field chambers has also led to major discoveries in quantum materials with strong correlation and topological order. We conclude the review with an outlook of the ultimate resolution, operation frequency, and future industrial and academic applications of near-field microwave microscopy.
Neuromodulation of Brain State and Behavior
Authors: McCormick David A. , Nestvogel Dennis B. , He Biyu J.
Published: April 2020

Neural activity and behavior are both notoriously variable, with responses differing widely between repeated presentation of identical stimuli or trials. Recent results in humans and animals reveal that these variations are not random in their nature, but may in fact be due in large part to rapid shifts in neural, cognitive, and behavioral states. Here we review recent advances in the understanding of rapid variations in the waking state, how variations are generated, and how they modulate neural and behavioral responses in both mice and humans. We propose that the brain has an identifiable set of states through which it wanders continuously in a nonrandom fashion, owing to the activity of both ascending modulatory and fast-acting corticocortical and subcortical-cortical neural pathways. These state variations provide the backdrop upon which the brain operates, and understanding them is critical to making progress in revealing the neural mechanisms underlying cognition and behavior.
Annealing Effects on the Band Alignment of ALD SiO2 on (InxGa1−x)2O3 for x = 0.25–0.74
Authors: Fares Chaker , Xian Minghan , Smith David J. , McCartney M. R. , Kneiß Max , von Wenckstern Holger , Grundmann Marius , Tadjer Marko , Ren Fan , Pearton S. J.
Published: April 2020

The band alignment of Atomic Layer Deposited SiO2 on (InxGa1−x)2O3 at varying indium concentrations is reported before and after annealing at 450 °C and 600 °C to simulate potential processing steps during device fabrication and to determine the thermal stability of MOS structures in high-temperature applications. At all indium concentrations studied, the valence band offsets (VBO) showed a nearly constant decrease as a result of 450 °C annealing. The decrease in VBO was −0.35 eV for (In0.25Ga0.75)2O3, −0.45 eV for (In0.42Ga0.58)2O3, −0.40 eV for (In0.60Ga0.40)2O3, and −0.35 eV (In0.74Ga0.26)2O3 for 450 °C annealing. After annealing at 600 °C, the band alignment remained stable, with <0.1 eV changes for all structures examined, compared to the offsets after the 450 °C anneal. The band offset shifts after annealing are likely due to changes in bonding at the heterointerface. Even after annealing up to 600 °C, the band alignment remains type I (nested gap) for all indium compositions of (InxGa1−x)2O3 studied.
Preferential Expression of B7-H6 in Glioma Stem-Like Cells Enhances Tumor Cell Proliferation via the c-Myc/RNMT Axis
Authors: Chen Hanqing , Guo Yundi , Sun Jing , Dong Jun , Bao Qinghua , Zhang Xueguang , Fu Fengqing
Published: April 2020

B7 homologue 6 (B7-H6), a newly identified member of the B7 costimulatory molecule family, is not only a crucial regulator of NK cell-mediated immune responses through binding to NKp30 but also has clinical implications due to its abnormal expression in human cancers. Here, we show that B7-H6 expression is abnormally upregulated in glioma tissue and that B7-H6 is coexpressed with stem cell marker Sox2. Intriguingly, B7-H6 was rarely detected on the surface of glioma cell lines but was abundantly expressed in glioma stem-like cells (GSLCs) that were derived from the glioma cell lines in vitro. Surprisingly, B7-H6 was the only one that was preferentially expressed in the GSLCs among the B7 family members. Functionally, knockdown of B7-H6 in GSLCs by siRNAs led to the inhibition of cell proliferation, with decrease in the expression of the oncogene Myc as well as inactivation of PI3K/Akt and ERK/MAPK signaling pathways. Moreover, we determined that three genes CBL (Casitas B-Lineage Lymphoma Proto-Oncogene), CCNT1 (Cyclin T1), and RNMT (RNA guanine-7 methyltransferase) were coexpressed with B7-H6 and c-myc in glioma tissue samples from the TCGA database and found, however that only RNMT expression was inhibited by the knockdown of B7-H6 expression in the GSLCs, suggesting the involvement of RNMT in the B7-H6/c-myc axis. Extending this to 293T cells, we observed that knocking out of B7-H6 with CRISPR-Cas9 system also suppressed cell proliferation. Thus, our findings suggest B7-H6 as a potential molecule for glioma stem cell targeted immunotherapy.
Combination Use of Tegafur and Apatinib as First-Line Therapy in Treatment of Advanced Gastric Cancer: A Single-Blinded Randomized Study
Authors: Li Chaofeng , Tang Tao , Wang Wenyue
Published: April 2020

Objective. To investigate the efficacy and safety of the combination use of tegafur and apatinib as a first-line therapy strategy in advanced gastric cancer (GC). Methods. The present study included a total of 62 advanced GC patients. The patients were randomized into the combined group (treated with both tegafur and apatinib) and the control group (treated with only tegafur). Treatment efficacy, KPS score, nutrition condition, and progression-free survival time (PFS) were recorded. Results. Both the response and disease control rates were significantly higher in the combined group. The PFS time was remarkably higher and the KPS score was significantly reduced in the combined group after treatment. After treatment, both groups showed significantly increased nutrition risk, but the rates of patients with nutrition risk or innutrition were remarkably higher in the combined group. The ADR rates were also significantly higher in the combined group. Conclusion. The combination use could achieve good efficacy and prolong patients’ PFS time; however, apatinib also reduced the patients’ quality of life and enhanced the nutrition risk and adverse drug reactions.
Discovery of Urinary Proteomic Signature for Differential Diagnosis of Acute Appendicitis
Authors: Zhao Yinghua , Yang Lianying , Sun Changqing , Li Yang , He Yangzhige , Zhang Li , Shi Tieliu , Wang Guangshun , Men Xuebo , Sun Wei , He Fuchu , Qin Jun
Published: April 2020

Acute appendicitis is one of the most common acute abdomens, but the confident preoperative diagnosis is still a challenge. In order to profile noninvasive urinary biomarkers that could discriminate acute appendicitis from other acute abdomens, we carried out mass spectrometric experiments on urine samples from patients with different acute abdomens and evaluated diagnostic potential of urinary proteins with various machine‐learning models. Firstly, outlier protein pools of acute appendicitis and controls were constructed using the discovery dataset (32 acute appendicitis and 41 control acute abdomens) against a reference set of 495 normal urine samples. Ten outlier proteins were then selected by feature selection algorithm and were applied in construction of machine‐learning models using naïve Bayes, support vector machine, and random forest algorithms. The models were assessed in the discovery dataset by leave‐one‐out cross validation and were verified in the validation dataset (16 acute appendicitis and 45 control acute abdomens). Among the three models, random forest model achieved the best performance: the accuracy was 84.9% in the leave‐one‐out cross validation of discovery dataset and 83.6% (sensitivity: 81.2%, specificity: 84.4%) in the validation dataset. In conclusion, we developed a 10‐protein diagnostic panel by the random forest model that was able to distinguish acute appendicitis from confusable acute abdomens with high specificity, which indicated the clinical application potential of noninvasive urinary markers in disease diagnosis.
Biochemical Signals Mediate the Crosstalk between Cartilage and Bone in Osteoarthritis
Authors: Zhou Xuchang , Cao Hong , Yuan Yu , Wu Wei
Published: April 2020

Osteochondral junction is a functional unit comprising the articular cartilage, calcified cartilage, and subchondral bone. Alteration in any component of this composite unit can disrupt the joint integrity and function directly or indirectly. Biochemical signals mediate the crosstalk between tissues and play an essential role in the initiation and progression of osteoarthritis. As osteoarthritis progresses, abnormal subchondral bone remodelling leads to increased angiogenesis and porosity of the subchondral bone plate, which further triggers biochemical signals to mediate the crosstalk between cartilage and bone, contributing to the progression of osteoarthritis. Notably, common biochemical signals include the TGF‐β/Smad, Wnt/β‐catenin, RANK/RANKL/OPG, and MAPK pathways. This biomarker crosstalk network is the basis of osteoarthritis pathogenesis, and some of their key regulators may be potential therapeutic targets for osteoarthritis drug therapy. This review summarised the biochemical crosstalk between cartilage and bone in the pathogenesis of osteoarthritis, which may provide the basis for the discovery of osteoarthritis treatment targets.
RSP5 Positively Regulates the Osteogenic Differentiation of Mesenchymal Stem Cells by Activating the K63-Linked Ubiquitination of Akt
Authors: Liang Changxiang , Liang Guoyan , Zheng Xiaoqing , Huang Yongxiong , Huang Shuaihao , Yin Dong
Published: April 2020

Mesenchymal stem cells (MSCs) are multipotent stem cells that have a strong osteogenic differentiation capacity. However, the molecular mechanism underlying the osteogenic differentiation of MSCs remains largely unknown and thus hinders further development of MSC-based cell therapies for bone repair in the clinic. RSP5, also called NEDD4L (NEDD4-like E3 ubiquitin protein ligase), belongs to the HECT (homologous to E6-AP carboxyl terminus) domain-containing E3 ligase family. Nevertheless, although many studies have been conducted to elucidate the role of RSP5 in various biological processes, its effect on osteogenesis remains elusive. In this study, we demonstrated that the expression of RSP5 was elevated during the osteogenesis of MSCs and positively regulated the osteogenic capacity of MSCs by inducing K63-linked polyubiquitination and activation of the Akt pathway. Taken together, our findings suggest that RSP5 may be a promising target to improve therapeutic efficiency by using MSCs for bone regeneration and repair.
Progressive Rotavirus Infection Downregulates Redox-Sensitive Transcription Factor Nrf2 and Nrf2-Driven Transcription Units
Authors: Patra Upayan , Mukhopadhyay Urbi , Mukherjee Arpita , Sarkar Rakesh , Chawla-Sarkar Mamta
Published: April 2020

Eukaryotic cells adopt highly tuned stress response physiology under threats of exogenous stressors including viruses to maintain cellular homeostasis. Not surprisingly, avoidance of cellular stress response pathways is an essential facet of virus-induced obligatory host reprogramming to invoke a cellular environment conducive to viral perpetuation. Adaptive cellular responses to oxidative and electrophilic stress are usually taken care of by an antioxidant defense system, core to which lies the redox-responsive transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-driven transcriptional cascade. Deregulation of host redox balance and redox stress-sensitive Nrf2 antioxidant defense have been reported for many viruses. In the current study, we aimed to study the modulation of the Nrf2-based host cellular redox defense system in response to Rotavirus (RV) infection in vitro. Interestingly, we found that Nrf2 protein levels decline sharply with progression of RV infection beyond an initial upsurge. Moreover, Nrf2 decrease as a whole was found to be accompanied by active nuclear vacuity of Nrf2, resulting in lowered expression of stress-responsive Nrf2 target genes heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1, and superoxide dismutase 1 both in the presence and absence of Nrf2-driven transcriptional inducers. Initial induction of Nrf2 concurred with RV-induced early burst of oxidative stress and therefore was sensitive to treatments with antioxidants. Reduction of Nrf2 levels beyond initial hours, however, was found to be independent of the cellular redox status. Furthermore, increasing the half-life of Nrf2 through inhibition of the Kelch-like erythroid cell-derived protein with CNC homology- (ECH-) associated protein 1/Cullin3-RING Box1-based canonical Nrf2 turnover pathway could not restore Nrf2 levels post RV-SA11 infection. Depletion of the Nrf2/HO-1 axis was subsequently found to be sensitive to proteasome inhibition with concurrent observation of increased K48-linked ubiquitination associated with Nrf2. Together, the present study describes robust downregulation of Nrf2-dependent cellular redox defense beyond initial hours of RV infection, justifying our previous observation of potent antirotaviral implications of Nrf2 agonists.
Risk Factors of Bacteremia following Multiple Traumas
Authors: Lee Hak-Jae , Choi Eol , Choi Nak-Joon , Sun Hyun-Woo , Lee Jae-Suk , Lee Jeong-Woo , Kim Tae-Yoon , Jung Yoon-Joong , Hong Suk-Kyung
Published: April 2020

Background. Bacteremia is a major nosocomial infection that frequently occurs in trauma patients, increasing morbidity and mortality. The aim of this study was to identify risk factors and to describe epidemiological patterns for early onset (EOB) and late onset (LOB) bacteremia after trauma.Methods. We retrospectively reviewed medical records of all trauma patients admitted to the surgical intensive care unit and general ward between January 2011 and December 2015. The information was collected for each patient and recorded in a computer database: early onset bacteremia (EOB) was defined as when onset occurred within 7 days after trauma, and late onset bacteremia (LOB) was defined as when onset occurred after 7 days from trauma.Results. Thirty-four patients of 859 (4%) developed bacteremia during their hospital stay: 4 (11.8%) developed EOB, 26 (76.4%) LOB, and 4 (11.8%) patients developed both of them. Sixty events of bacteremia happened to these patients: 9 (15.0%) EOB and 51 (85.0%) LOB. Gram-positive cocci were isolated more frequently than Gram-negative bacilli in both groups. Gram-positive cocci were more frequently isolated in EOB than in LOB; otherwise, there was no statistical significance (77.8% vs. 64.7%,p=0.683). Central line-associated blood stream infection (CLABSI) and surgical site infection (SSI) were the most common identified source for LOB. Presence of liver (OR: 2.66,p=0.035) and pelvic injury (OR: 2.25,p=0.038), gastrointestinal tract perforation (OR: 5.48,p=0.002), and massive transfusion (OR: 3.36,p=0.006) represented risk factors for bacteremia.Conclusions. Presence of pelvic and liver injury on arrival in emergency department, gastrointestinal tract perforation, and massive transfusion within the first 24 hours after trauma appears to be significant risk factors for bacteremia.
Physical Activity and Long-term Quality of Life among Colorectal Cancer Survivors—A Population-based Prospective Study
Authors: Eyl Ruth Elisa , Koch-Gallenkamp Lena , Jansen Lina , Walter Viola , Carr Prudence R. , Hoffmeister Michael , Chang-Claude Jenny , Brenner Hermann , Arndt Volker
Published: April 2020

Evidence suggests that physical activity (PA) is positively associated with (health-related) quality of life (QOL) in colorectal cancer survivors. However, little is known regarding long-term effects of PA on QOL and if prediagnosis PA is associated with QOL in the years after diagnosis. Our study aimed to investigate the association of prediagnosis and postdiagnosis PA with long-term QOL in colorectal cancer survivors.

This study is based on a population-based cohort from Germany of 1,781 newly diagnosed colorectal cancer survivors over a 5-year period. PA was assessed at diagnosis and at 5-year follow-up (5YFU). Quality of life was assessed by the European Organisation for Research and Treatment of Cancer C Quality of Life Questionnaire QLQ-C30 at 5YFU. Multivariable linear regression was used to explore associations between prediagnosis and postdiagnosis PA and QOL at 5YFU.

No evidence of a positive association between higher levels of prediagnosis PA and better long-term QOL was found. Higher levels of prediagnosis work-related PA and vigorous PA were even associated with decreased QOL in domains such as cognitive [Beta(β) = −2.52, 95% confidence interval (CI) = −3.77, −1.27; β = −1.92, CI = −3.17, −0.67) and emotional functioning (β = −2.52, CI = −3.84, −1.19; β = −2.12, CI = −3.44, −0.80). In cross-sectional analyses, higher postdiagnosis PA was strongly associated with higher QOL. Survivors physically active at both prediagnosis and postdiagnosis as well as survivors who increased their PA between prediagnosis and postdiagnosis reported significantly higher long-term QOL compared with survivors who remained inactive at prediagnosis and postdiagnosis. In this study, higher prediagnosis PA does not appear to be associated with higher QOL among long-term colorectal cancer survivors but our results support the importance of ongoing PA throughout survivorship.
Anxiety, Depression, and Suicidal Ideation amongst Patients with Facial Dermatoses (Acne, Rosacea, Perioral Dermatitis, and Folliculitis) in Lithuania
Authors: Lukaviciute Laura , Ganceviciene Ruta , Navickas Petras , Navickas Alvydas , Grigaitiene Jurate , Zouboulis Christos C.
Published: April 2020

Background/Objective: Skin diseases, especially those with visible manifestation, are considered to cause a major influence on global mental health. Therefore, we determined the prevalence and severity of anxiety, depression, and suicidal ideation in a large sample of patients with facial dermatoses, namely acne, rosacea, folliculitis, and perioral dermatitis. Methods: The mental health of patients with facial dermatoses and respective controls was assessed using the Hospital Anxiety and Depression Scale and questions concerning suicidal ideation. Results: The study included 543 patients with facial dermatoses and 497 healthy individuals. Anxiety was present in 37.6% of the patients (14.9% of controls), depression in 21.7% (6.8%), and suicidal thoughts in 9.8% (3.2%) (p < 0.001). Acne patients demonstrated the highest anxiety and depression subscale scores (mean ± standard deviation: 7.1 ± 0.25, 95% confidence interval (CI): 6.58–7.56; controls: 5 ± 0.23, 95% CI: 4.57–5.49). In rosacea 30% of the patients had depression symptoms (adjusted odds ratio (OR): 7.216, 95% CI: 4.122–12.632, p < 0.001), while in folliculitis patients 15.4% (OR: 3.138, 95% CI: 1.241–7.936, p = 0.016) had suicidal thoughts. Patients with anxiety symptoms and suicidal thoughts were on average younger than those without (28.3 ± 0.76 vs. 31.2 ± 0.66 years, p = 0.001 and 25.3 ± 0.98 vs. 30.5 ± 0.55 years, p = 0.007, respectively). Conclusion: Acne and rosacea are associated with anxiety, depression, and suicidal ideation in Lithuanian patients. Younger patients are more prone to report such symptoms than older ones.
Urticaria: Collegium Internationale Allergologicum (CIA) Update 2020
Authors: Maurer Marcus , Eyerich Kilian , Eyerich Stefanie , Ferrer Marta , Gutermuth Jan , Hartmann Karin , Jakob Thilo , Kapp Alexander , Kolkhir Pavel , Larenas-Linnemann Désirée , Park Hae-Sim , Pejler Gunnar , Sánchez-Borges Mario , Schäkel Knut , Simon Dagmar , Simon Hans-Uwe , Weller Karsten , Zuberbier Torsten , Metz Martin
Published: April 2020

This update on chronic urticaria (CU) focuses on the prevalence and pathogenesis of chronic spontaneous urticaria (CSU), the expanding spectrum of patient-reported outcome measures (PROMs) for assessing CU disease activity, impact, and control, as well as future treatment options for CU. This update is needed, as several recently reported findings have led to significant advances in these areas. Some of these key discoveries were first presented at past meetings of the Collegium Internationale Allergologicum (CIA). New evidence shows that the prevalence of CSU is geographically heterogeneous, high in all age groups, and increasing. Several recent reports have helped to better characterize two endotypes of CSU: type I autoimmune (or autoallergic) CSU, driven by IgE to autoallergens, and type IIb autoimmune CSU, which is due to mast cell (MC)-targeted autoantibodies. The aim of treatment in CU is complete disease control with absence of signs and symptoms as well as normalization of quality of life (QoL). This is best monitored by the use of an expanding set of PROMs, to which the Angioedema Control Test, the Cholinergic Urticaria Quality of Life Questionnaire, and the Cholinergic Urticaria Activity Score have recently been added. Current treatment approaches for CU under development include drugs that inhibit the effects of signals that drive MC activation and accumulation, drugs that inhibit intracellular pathways of MC activation and degranulation, and drugs that silence MCs by binding to inhibitory receptors. The understanding, knowledge, and management of CU are rapidly increasing. The aim of this review is to provide physicians who treat CU patients with an update on where we stand and where we will go. Many questions and unmet needs remain to be addressed, such as the development of routine diagnostic tests for type I and type IIb autoimmune CSU, the global dissemination and consistent use of PROMs to assess disease activity, impact, and control, and the development of more effective and well-tolerated long-term treatments for all forms of CU.
Value of Hemodynamic Monitoring in Patients With Cardiogenic Shock Undergoing Mechanical Circulatory Support
Authors: Saxena Abhinav , Garan A. Reshad , Kapur Navin K. , O’Neill William W. , Lindenfeld JoAnn , Pinney Sean P. , Uriel Nir , Burkhoff Daniel , Kern Morton
Published: April 2020

The recent widespread availability and use of mechanical circulatory support is transforming the management and outcomes of cardiogenic shock (CS). Clinical decision-making regarding the optimization of therapies for patients with CS can be guided effectively by hemodynamic monitoring with a pulmonary artery catheter (PAC). Because several studies regarding the benefit of PACs are ambiguous, the use of PACs is variable among clinicians treating patients with CS. More notable is that PAC use has not been studied as part of a randomized, controlled trial in patients with CS with or without mechanical circulatory support. Standardized approaches to hemodynamic monitoring in these patients can improve decision-making and outcomes. In this review, we summarize the hemodynamics of CS and mechanical circulatory support with PAC-derived measurements, and provide a compelling rationale for the use of PAC monitoring in patients with CS receiving mechanical circulatory support.