bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of novel “LOCGEF” isoforms of ARHGEF18 in eosinophils
Authors: Turton Keren B , Wilkerson Emily M , Hebert Alex S , Fogerty Frances J , Schira Hazel M , Botros Fady E , Coon Joshua J , Mosher Deane F
Published: March 2018

Genomic, transcriptomic and proteomic databases indicate that the N-terminal 322 residues encoded by the presumptive LOC100996504 gene, which is adjacent to the ARHGEF18 guanine nucleotide exchange factor gene on chromosome 19, constitute the N-terminal portion of a 1361-residue isoform of ARHGEF18, dubbed LOCGEF-X3. LOCGEF-X3 arises from the use of a leukocyte-specific alternative transcriptional start site and splicing that bypasses the initial noncoding exon of the canonical 1015-residue ARHGEF18 isoform, p114. Eosinophil LOCGEF-X3 was amplified and cloned, recombinant LOCGEF-X3 was expressed, and anti-ARHGEF18 antibody was found to recognize a band in immunoblots of eosinophil lysates that co-migrates with recombinant LOCGEF-X3. PCR of eosinophils revealed minor amounts of transcripts for X4 and X5 isoforms of LOCGEF that arise from differential splicing and differ from the X3 isoform at their extreme N-termini. No p114 transcript or protein band was detected in eosinophils. Immunostaining with anti-ARHGEF18 antibody revealed relocalization of LOCGEF and RHOA from the periphery of round unstimulated eosinophils to the 2 poles of eosinophils polarized by treatment with IL5, CCL11, or IL33 in suspension. Canonical p114 ARHGEF18 has been implicated in maintenance of epithelial cell polarity. We suggest that the “LOC” portion of LOCGEF, which is unlike any other protein domain, has unique functions in control of polarity in activated eosinophils and other leukocytes.

A set of ARHGEF18 isoforms is specific for eosinophils and other leukocytes.
Frontline Science: Specialized proresolving lipid mediators inhibit the priming and activation of the macrophage NLRP3 inflammasome
Authors: Lopategi Aritz , Flores-Costa Roger , Rius Bibiana , López-Vicario Cristina , Alcaraz-Quiles José , Titos Esther , Clària Joan
Published: March 2018

The prototypic proinflammatory cytokine IL-1β plays a central role in innate immunity and inflammatory disorders. The formation of mature IL-1β from an inactive pro-IL-1β precursor is produced via nonconventional multiprotein complexes called the inflammasomes, of which the most common is the nucleotide-binding domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome composed by NLRP3, (ASC) apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (CARD), and caspase-1. Specialized proresolving mediators (SPMs) promote resolution of inflammation, which is an essential process to maintain host health. SPMs prevent excessive inflammation by terminating the inflammatory response and returning to tissue homeostasis without immunosupression. This study tested the hypothesis that modulation of the NLRP3 inflammasome in macrophages is one mechanism involved in the SPM-regulated processes during resolution. Our findings demonstrate that the SPM resolvin D2 (RvD2) suppressed the expression of pro-IL-1β and reduced the secretion of mature IL-1β in bone marrow-derived macrophages challenged with LPS+ATP (classical NLRP3 inflammasome model) or LPS+palmitate (lipotoxic model). Similar findings were observed in thioglycolate-elicited peritoneal macrophages, in which RvD2 remarkably reduced ASC oligomerization, inflammasome assembly, and caspase-1 activity. In vivo, in a self-resolving zymosan A-induced peritonitis model, RvD2 blocked the NLRP3 inflammasome leading to reduced release of IL-1β into the exudates, repression of osteopontin, and MCP-1 expression and induction of M2 markers of resolution (i.e., CD206 and arginase-1) in peritoneal macrophages. RvD2 inhibitory actions were receptor mediated and were abrogated by a selective GPR18 antagonist. Together, these findings support the hypothesis that SPMs have the ability to inhibit the priming and to expedite the deactivation of the NLRP3 inflammasome in macrophages during the resolution process.

Resolvin D2 modulates the NLRP3 inflammasome and the production of IL-1β in macrophages during resolution of inflammation.
Frontline Science: Elevated nuclear lamin A is permissive for granulocyte transendothelial migration but not for motility through collagen I barriers
Authors: Yadav Sandeep Kumar , Feigelson Sara W , Roncato Francesco , Antman-Passig Merav , Shefi Orit , Lammerding Jan , Alon Ronen
Published: March 2018

Transendothelial migration (TEM) of lymphocytes and neutrophils is associated with the ability of their deformable nuclei to displace endothelial cytoskeletal barriers. Lamin A is a key intermediate filament component of the nuclear lamina that is downregulated during granulopoiesis. When elevated, lamin A restricts nuclear squeezing through rigid confinements. To determine if the low lamin A expression by leukocyte nuclei is critical for their exceptional squeezing ability through endothelial barriers, we overexpressed this protein in granulocyte-like differentiated HL-60 cells. A 10-fold higher lamin A expression did not interfere with chemokinetic motility of these granulocytes on immobilized CXCL1. Furthermore, these lamin A high leukocytes exhibited normal chemotaxis toward CXCL1 determined in large pore transwell barriers, but poorly squeezed through 3 μm pores toward identical CXCL1 gradients. Strikingly, however, these leukocytes successfully completed paracellular TEM across inflamed endothelial monolayers under shear flow, albeit with a small delay in nuclear squeezing into their sub-endothelial pseudopodia. In contrast, CXCR2 mediated granulocyte motility through collagen I barriers was dramatically delayed by lamin A overexpression due to a failure of lamin A high nuclei to translocate into the pseudopodia of the granulocytes. Collectively, our data predict that leukocytes maintain a low lamin A content in their nuclear lamina in order to optimize squeezing through extracellular collagen barriers but can tolerate high lamin A content when crossing the highly adaptable barriers presented by the endothelial cytoskeleton.

Differential effects of nuclear stiffness on chemokine-driven leukocyte squeezing through endothelial and extracellular collagenous barriers.
Regulation of immune cell signaling by activated protein C
Authors: Healy Laura D , Rigg Rachel A , Griffin John H , McCarty Owen J T
Published: March 2018

Innate immune cells are an essential part of the host defense response, promoting inflammation through release of proinflammatory cytokines or formation of neutrophil extracellular traps. While these processes are important for defense against infectious agents or injury, aberrant activation potentiates pathologic inflammatory disease. Thus, understanding regulatory mechanisms that limit neutrophil extracellular traps formation and cytokine release is of therapeutic interest for targeting pathologic diseases. Activated protein C is an endogenous serine protease with anticoagulant activity as well as anti-inflammatory and cytoprotective functions, the latter of which are mediated through binding cell surface receptors and inducing intracellular signaling. In this review, we discuss certain leukocyte functions, namely neutrophil extracellular traps formation and cytokine release, and the inhibition of these processes by activated protein C.
Myocardial fibrosis evaluated by diffusion‐weighted imaging and its relationship to 3D contractile function in patients with hypertrophic cardiomyopathy
Authors: Wu Rui , An Dong‐Aolei , Shi Ruo‐Yang , Chen Bing‐hua , Jiang Meng , Bacyinski Andrew , Han Tong‐Tong , Hu Jiani , Xu Jian‐Rong , Wu Lian‐Ming
Published: March 2018

Background

Previous studies have shown that diffusion‐weighted imaging (DWI) is sensitive to myocardial fibrosis in ischemic and nonischemic cardiomyopathy.

Purpose

To explore the prognostic value of apparent diffusion coefficient (ADC) for detecting myocardial fibrosis and its relationship to the contractile function in hypertrophic cardiomyopathy (HCM).

Study Type

Prospective.

Population

A total of 45 HCM patients and 20 controls.

Field Strength/Sequence

3.0T cardiac MRI. The cardiac MR sequences included cine, T1 mapping, and DWI.

Assessment

According to the presence of late gadolinium enhancement (LGE) and the extracellular volume (ECV) values (+2 SD of control subjects), respectively, reader W and reader J assessed the value of ADC of each segment for detecting myocardial fibrosis and its relationship to impaired contractile function in HCM patients.

Statistical Tests

Independent sample t‐test, Pearson analysis, and intraclass correlation (ICC).

Results

The value of ECV was 23.6 ± 3.0% for control. ECV ≥ 29.6% and ECV < 29.6% groups were classified. ADC values in the ECV ≥ 29.6% group were significantly increased compared to the ECV < 29.6% group, (2.41 ± 0.23 μm2/ms vs. 2.03 ± 0.16 μm2/ms, P < 0.005). Compared to the LGE – group, ECV (32.1 ± 2.3% vs. 29.0 ± 2.8%, P < 0.005) and ADC (2.60 ± 0.18 μm2/ms vs. 2.10 ± 0.07 μm2/ms, P < 0.005) values were significantly increased in the LGE + group. ADC values were linearly associated with ECV values (R2 = 0.65) in HCM patients. ADC values were linearly associated with circumferential and longitudinal strain (R2 = 0.60, R2 = 0.46), as well as circumferential, longitudinal, and radial strain rate (R2 = 0.13, R2 = 0.25, R2 = 0.17, respectively).

Data Conclusion

Contractile dysfunction in HCM is predominantly associated with ADC, which is a feasible alternative to ECV and LGE for detecting myocardial fibrosis.

Level of Evidence: 1

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2018;48:1139–1146.
Colorectal carcinoma: Ex vivo evaluation using q‐space imaging; Correlation with histopathologic findings
Authors: Yamada Ichiro , Hikishima Keigo , Yoshino Norio , Sakamoto Junichiro , Miyasaka Naoyuki , Yamauchi Shinichi , Uetake Hiroyuki , Yasuno Masamichi , Saida Yukihisa , Tateishi Ukihide , Kobayashi Daisuke , Eishi Yoshinobu
Published: March 2018

Background

Although the prognosis of colorectal carcinoma (CRC) patients depends on the histologic grade (HG) and lymph node metastasis (LNM), accurate preoperative assessment of these prognostic factors is often difficult.

Purpose

To assess the HG and extent of LNM by q‐space imaging (QSI) for preoperative diagnosis of CRC.

Study Type

Prospective.

Specimen

A total of 20 colorectal tissue samples containing adenocarcinomas and resected lymph nodes (LNs).

Field Strength/Sequence

QSI was performed with a 3T MRI system using a diffusion‐weighted echo‐planar imaging sequence: repetition time, 10,000 msec; echo time, 216 or 210 msec; field of view, 113 × 73.45 mm; matrix, 120 × 78; section thickness, 4 mm; and 11 b values ranging from 0 to 9000 s/mm2.

Assessment

The mean displacement (MDP; μm), zero‐displacement probability (ZDP; arbitrary unit [a.u.]), kurtosis (K; a.u.), and apparent diffusion coefficient (ADC) were analyzed by two observers and compared with histopathologic findings.

Statistical Tests

Spearman's rank correlation coefficient, Mann–Whitney U‐test, and ROC curve analyses.

Results

For all 20 carcinomas, the MDP, ZDP, K, and ADC were 8.87 ± 0.37 μm, 82.0 ± 6.2 a.u., 74.3 ± 3.0 a.u., and 0.219 ± 0.040 × 10−3 mm2/s, respectively. The MDP (r = –0.768; P < 0.001), ZDP (r = 0.768; P < 0.001), and K (r = 0.785; P < 0.001) were significantly correlated with the HG of CRC, but not the ADC (r = 0.088; P = 0.712). There were also significant differences in the MDP, ZDP, and K between metastatic and nonmetastatic LNs (all, P < 0.001), but not the ADC (P = 0.082). In the HG of CRC and LNM, the area under the curve was significantly greater for MDP, ZDP, and K than for ADC.

Data Conclusion

QSI provides useful diagnostic information to assess the HG and extent of LNM in CRC.

Level of Evidence: 1

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2018;48:1059–1068.
Formation of cyanide compounds during preparation of gold surfaces evidenced by surface‐enhanced Raman spectroscopy
Authors: Merlen A. , Pardanaud C. , Coussan S. , Panagiotopoulos C. , Grauby O. , Ruiz Carmen M.
Published: March 2018

We report surface‐enhanced Raman spectroscopy (SERS) measurements on nanostructured gold surfaces prepared using a primary vacuum sputtering technique. Even if no molecules have been deposited on the metallic surface, a clear Raman signal is observed. A very intense and sharp peak around 2,100 cm−1 together with low‐wavenumber modes are visible. The comparison between the experimental spectra and those obtained using density functional theory calculations confirms that these new modes are associated with the cyanide compound Au(CN)2−. This proves the high sensitivity of SERS for the chemical analysis of metallic surfaces. It also shows that the pollution should be carefully taken into account in SERS analysis. We also demonstrate that high power laser illumination transforms these toxic compounds into carbon species; this method can be used to clean SERS substrates.
The performance of five fruit‐derived and freeze‐dried potentially probiotic Lactobacillus strains in apple, orange, and grape juices
Authors: Garcia Estefânia Fernandes , de Oliveira Araújo Amanda , Luciano Winnie Alencar , de Albuquerque Thatyane Mariano Rodrigues , de Oliveira Arcanjo Narciza Maria , Madruga Marta Suely , dos Santos Lima Marcos , Magnani Marciane , Saarela Maria , de Souza Evandro Leite
Published: March 2018

BACKGROUND

This study assessed the survival of the fruit‐derived and freeze‐dried L. plantarum 49, L. brevis 59, L. paracasei 108, L. fermentum 111 and L. pentosus 129 strains during frozen storage and when incorporated into apple, orange, and grape juice stored under refrigeration. Physicochemical parameters of juices containing the freeze‐dried Lactobacillus strains and the survival of the test strains in the fruit juices during in vitro digestion were also evaluated.

RESULTS

No decreases in survival rates (log N/log N0) of the freeze‐dried cells were observed in up to 1 month of storage. The survival rates of the freeze‐dried strains L. plantarum 49 and L. paracasei 108 were > 0.75 in up to 4 months of storage. All freeze‐dried strains exhibited survival rates of >0.75 in up to 2 weeks of storage in apple juice; only L. plantarum 49 and L. paracasei 108 showed similar survival rates in orange and grape juices in up to 2 weeks of storage. The contents of the monitored organic acids or sugars during storage varied depending on the added strain and the type of fruit juice. At the end of in vitro digestion, L. brevis 59, L. paracasei 108 and L. fermentum 111 showed survival rates of >0.80 in apple juice.

CONCLUSION

Apple juice was the best substrate for the survival of the tested freeze‐dried Lactobacillus strains over time. L. paracasei 108 and L. plantarum 49 were the strains presenting the best performance for incorporation in potentially probiotic fruit juices. © 2018 Society of Chemical Industry
Live delivery of neurosurgical operating theater experience in virtual reality
Authors: Salmimaa Marja , Kimmel Jyrki , Jokela Tero , Eskolin Peter , Järvenpää Toni , Piippo Petri , Müller Kiti , Satopää Jarno
Published: March 2018

A system for assisting in microneurosurgical training and for delivering interactive mixed reality surgical experience live was developed and experimented in hospital premises. An interactive experience from the neurosurgical operating theater was presented together with associated medical content on virtual reality eyewear of remote users. Details of the stereoscopic 360‐degree capture, surgery imaging equipment, signal delivery, and display systems are presented, and the presence experience and the visual quality questionnaire results are discussed. The users reported positive scores on the questionnaire on topics related to the user experience achieved in the trial.
Programmed death‐ligand 1 (PD‐L1) expression in pleomorphic carcinoma of the lung
Authors: Imanishi Naoko , Hirai Ayako , Yoneda Kazue , Shimajiri Shohei , Kuwata Taiji , Tashima Yuko , Takeuchi Masahiro , Iwai Yoshiko , Ichiki Yoshinobu , Tanaka Fumihiro
Published: March 2018

Background and Objectives

Pulmonary pleomorphic carcinoma (PPC) is a rare and aggressive subtype of lung cancer. Programmed cell death‐ligand 1 (PD‐L1) expression may be induced in a variety of malignant tumors, but its prognostic implication in PPC remains unclear.

Methods

Twenty‐six patients with surgically resected PPC were retrospectively reviewed. Immuno‐histochemical staining was used to detect PD‐L1 expression, and PD‐L1 status was classified into “high” or “low” according to the percentage of tumor cells (TCs) expressing PD‐L1 (tumor proportion score, TPS).

Results

PD‐L1 expression was positive in 20 (76.9%) patients at the cut‐off TPS value of 1%. A receiver‐operating characteristic (ROC) analysis showed that the optimal cut‐off value was 15% for prediction of cancer‐specific death with the area under ROC curve of 0.701 (P = 0.107). High PD‐L1 expression was associated with a favorable overall survival (100% vs 45.9% at 5 years; P = 0.046) as well as a favorable cancer‐specific survival (88.9% vs 37.5% at 5 years; P = 0.012). A multivariate analysis indicated a trend toward a favorable prognosis associated with high PD‐L1 expression (hazard ratio [HR], 0.254 [95% confidence interval, 0.054‐1.200]; P = 0.084).

Conclusions

PD‐L1 expression was positive in most PPC cases, and high PD‐L1 expression may predict a favorable prognosis in resected PPC.
Preparation and evaluation of open‐tubular capillary column combining a metal–organic framework and a brush‐shaped polymer for liquid chromatography
Authors: Chen Kai , Zhang Lingyi , Zhang Weibing
Published: March 2018

In this work, an open‐tubular capillary liquid‐phase column was prepared by modifying chain polymer on the inner surface of capillary and chemical bonding of metal organic frameworks, NH2‐UiO‐66, to the brushes of chain polymer (poly(glycidyl methacrylate)). Besides advantages of facial preparation and good permeability, the chain polymer effectively increases the modification amount of NH2‐UiO‐66 nanoparticles to increase the phase ratio of open‐tubular capillary column and enhance the interactions with analytes. The results of scanning electron microscope energy‐dispersive X‐ray spectra indicated that NH2‐UiO‐66 nanoparticles were successfully bonded to the chain polymer. Because of the hydrophobic interaction and hydrogen bonding interaction between the analytes and the ligand of NH2‐UiO‐66, different analytes were well separated on the NH2‐UiO‐66‐modified poly(glycidyl methacrylate) capillary (1.12 m × 25 μm id × 365 μm od) with the high absolute column efficiency reaching 121 477 plates, benefiting from an open‐tubular column and low mass transfer resistance provided by polymer brush and metal–organic framework crystal. The relative standard deviations of the retention time for run‐to‐run, day‐to‐day, and column‐to‐column (n = 3) runs are below 4.28%, exhibiting good repeatability. Finally, the column was successfully applied to separation of flavonoids in licorice.
Tourism industry career prospects and the business environment: Evidence from Canada and Macau
Authors: Tung Vincent Wing Sun , Tang Mei Fung Candy , King Brian Edward Melville
Published: March 2018

Previous researchers have undertaken detailed examinations of the factors impacting on aspirant perceptions of tourism and hospitality careers. This paper moves beyond personal and internal dimensions to explore business conditions in the cities where hospitality and tourism students are studying or where recent graduates are making their careers. By examining the prevalent business environments in cities in both North America (Calgary) and in Asia (Macau), the researchers show how such settings influence the perceptions of hospitality and tourism aspirants towards their industry futures, including peer influence.
Patenting patterns in the tourism industry: Evidence from Italy
Authors: Succurro Marianna , Boffa Federico
Published: March 2018

We study patent applications in the Italian hospitality sector. We analyze (a) the determinants of patenting behavior in the Italian accommodation sector and (b) the impact of innovation—measured through firms' patenting activity—on firms' performance. Using microdata from the Orbis database (Bureau van Dijk), we find that the firms' innovative performance in the Italian hospitality sector—measured through the number of successful patents applications—varies based on firms' size, age, intangible assets, and legal form. Moreover, patenting activity is positively and significantly associated to different measures of firms' performance.
Identifying holes in the greater sage‐grouse conservation umbrella
Authors: Carlisle Jason D. , Keinath Douglas A. , Albeke Shannon E. , Chalfoun Anna D.
Published: March 2018

The umbrella species concept, wherein multiple species are indirectly protected under the umbrella of a reserve created for one, is intended to enhance conservation efficiency. Although appealing in theory and common in practice, empirical tests of the concept have been scarce. We used a real‐world, semi‐protected reserve established to protect a high‐profile umbrella species (greater sage‐grouse [Centrocercus urophasianus]) to investigate 2 potential mechanisms underlying the concept's successful application: reserve size and species similarity. We estimated how much habitat protection the established reserve provided to 52 species of conservation concern associated with vegetation communities where greater sage‐grouse occur. To illustrate the importance of reserve size, we compared the effectiveness of the established reserve to alternative greater sage‐grouse reserves of various sizes and to simulated reserves of equal size but sited with no regard for greater sage‐grouse. We further assessed whether key species’ traits were associated with different levels of protection under the umbrella reserve. The established umbrella reserve protected 82% of the state's greater sage‐grouse population and 0–63% of the habitat of the background species examined. The reserve outperformed equally sized, simulated reserves for only 12 of 52 background species. As expected, larger alternative reserves served as better umbrellas, but regardless of reserve size, not all species received equal protection. The established reserve was most effective at protecting the habitat of species that were most similar to the umbrella species (i.e., avian species, those highly associated with sagebrush plant communities, and those with widespread habitat). In contrast, the habitat of species with restricted distributions, particularly when combined with vegetation associations not closely matching the umbrella species, was not protected as well by the umbrella reserve. Such species require additional, targeted attention to achieve conservation objectives. Successful application of the umbrella species concept requires careful consideration of the characteristics of the umbrella species, the reserve delineated on its behalf, and the similarity of the umbrella species to its purported background species. © 2018 The Wildlife Society.
Cost‐effectiveness of sialendoscopy versus medical management for radioiodine‐induced sialadenitis
Authors: Kowalczyk David M. , Jordan J. Randall , Stringer Scott P.
Published: March 2018

Objectives/Hypothesis

The medical management and radiographic identification of radioiodine‐induced sialadenitis (RAIS) is challenging. This study utilizes a cost‐effectiveness analysis to compare upfront sialendoscopy as both a diagnostic and therapeutic option versus multiple modalities of diagnostic radiography along with medical management.

Study Design

Literature review and cost‐effectiveness analysis.

Methods

A literature review was performed to identify the outcomes of medical management, sialendoscopy, diagnostic radiography, and surgical complications. All charges were obtained from the University of Mississippi Budget Office in 2017 US dollars and converted to costs using the 2017 Medicare Cost‐to‐Charge Ratio for urban medical centers. A cost‐effectiveness analysis was used to evaluate the four treatment arms—sialendoscopy, medical management– ultrasound, medical management–computed tomography (CT) sialography, and medical management–magnetic resonance (MR) sialography. Sensitivity analyses were used to evaluate the confidence levels of the economic evaluation.

Results

The incremental cost‐effectiveness ratio for upfront sialendoscopy versus medical management–ultrasound was $30,402.30, which demonstrates that sialendoscopy is the more cost‐effective option given a willingness‐to‐pay threshold of $50,000. The probability that this decision is correct at a willingness‐to‐pay of $50,000 is 64.5%. Sialendoscopic improvement was the most sensitive variable requiring a threshold of 0.70. Of the three imaging modalities, ultrasound dominated MR and CT sialography, both of which required a willingness‐to‐pay of greater than $90,000 to realize a difference.

Conclusions

Upfront sialendoscopy is more cost‐effective compared to medical management utilizing diagnostic ultrasound assuming a willingness‐to‐pay threshold of $50,000. There is a clear cost‐effectiveness to using ultrasound with medical management over CT and MR sialography in the diagnosis and management of RAIS.

Level of Evidence

NA. Laryngoscope, 1822–1828, 2018
The age of water and carbon in lake‐catchments: A simple dynamical model
Authors: Duffy Christopher J. , Dugan Hilary A. , Hanson Paul C.
Published: March 2018

The rate at which water and carbon move through lake‐catchments influences carbon metabolism, storage, and transport to down‐stream ecosystems. This article focuses on conceptual‐mathematical modeling of the “age” of water and carbon in lake‐catchment systems, where “age” is defined as the time since the water parcel and environmental tracer entered the system. We test a framework for implementing models and data for the Lake Mendota lake‐catchment system. We show that the lake‐catchment system provides the basis for predicting time varying age of carbon along flow paths, and the residence times of dissolved organic carbon (DOC) leaving each compartment, which further helps to provide a deeper understanding of fundamental biogeochemical dynamic processes of carbon and water cycling within the lake‐catchment system. Three scenarios illustrate how the age of DOC might evolve from climate or land cover change that alters the hydrologic water balance through increases or decreases in lake‐catchment precipitation and evapotranspiration.
“Bottom‐Up” Fabrication of BODIPY‐Functionalized Fluorescent Hyperbranched Glycopolymers for Hepatoma‐Targeted Imaging
Authors: Sun Pei , Deng Hongping , Zhou Linzhu , Wu Yan , Jin Xin , Tong Gangsheng , Yu Xuemei
Published: March 2018

A novel type of multivalent and highly specific fluorescent hyperbranched glycopolymers h‐P(GalEA‐co‐VBPT‐co‐BYMA) (hPGVB) is designed and prepared successfully via a facile “bottom‐up” strategy. The acetylated hPGVB is prepared by one‐pot reversible addition‐fragmentation chain transfer (RAFT) copolymerization of acrylate‐type galactose monomers AcGalEA and methacrylate‐type fluorescent monomers BYMA in presence of an inimer‐type RAFT chain transfer agent. After deacetylation, the resulting amphiphilic hPGVB can self‐assemble into stable nanoparticles in aqueous media, showing strong green fluorescence with relative high quantum yields and good photostability. The cell viability study indicates the excellent biocompatibility of the hPGVB fluorescent nanoparticles (FNPs) against HepG2 and NIH3T3 cells. More importantly, comparing with the galactose‐free fluorescent hyperbranched polymers h‐P(OEGMA‐co‐VBPT‐co‐BYMA), hPEVB FNPs can be selectively internalized by asialoglycoprotein (ASGP) receptor‐rich HepG2 cells, indicating their potential application in the bioimaging fields.
Obliquely‐arranged double skin paddles: A novel design to reconstruct extensive head and neck defects with a single fibula or peroneal flap
Authors: Lin Ying‐Sheng , Liu Wen‐Chung , Wang Kuan‐Ying , Lin Yaoh‐Shiang , Yang Kuo‐Chung
Published: March 2018

Objective

To reconstruct extensive head and neck defects usually necessitates double free flaps, which require a time‐and‐manpower‐consuming surgical procedure. We present using a single fibula or peroneal flap with the novel design of obliquely‐arranged double skin paddles to reconstruct an extensive head and neck defect.

Methods

From 1998 to 2016, eight patients with the age of 52.25 (35–71) years old had extensive head and neck defects after oral cancer ablation. All of the defects were through and through with the size of 16.25 (12–24) cm × 8.8 (4.5–11) cm. Six of the defects were due to buccal cancer. One was due to tongue cancer, and another one was due to gingiva cancer. All the defects were reconstructed with obliquely‐arranged double‐paddle free fibula or peroneal flaps. The long axis of the skin paddles was arranged at certain angle (30–45 degrees) to the long axis of lower leg, and the two separate skin paddles were used as the form of island flaps by isolating the cutaneous perforators to create a true chimeric flap.

Results

The skin paddle sizes were 14 cm × 3 cm–24 cm × 11 cm and 9.5 cm × 4.5 cm–13 cm × 8 cm. The average length of harvested fibula was 19 (10–30) cm. All of the eight flaps survived without obvious donor site morbidity. One patient had partial skin necrosis over recipient site, requiring surgical debridements and closure. One patient had superficial necrosis over the edge of outer skin paddle, which healed spontaneously. After the follow‐up periods of 1 month to 3 year and 8 months, two patients died of sepsis. Six of them could resume soft diet and had no saliva drooling. The remaining two remained nasogastric diet and had saliva drooling.

Conclusion

With the design of obliquely‐arranged double paddles, we may maximize the harvested skin area of lateral lower leg to reconstruct an extensive head and neck defect with a single free flap.
Evaluation of Kinase Inhibitor Selectivity Using Cell‐based Profiling Data
Authors: Miljković Filip , Bajorath Jürgen
Published: March 2018

Kinases are among the most heavily investigated drug targets and inhibition of kinases and kinase‐dependent signaling has become a paradigm for therapeutic intervention. Kinase inhibitors and associated activity data have increasing ‘big data’ character, which presents challenges for computational analysis, but also unprecedented opportunities for learning from compound data and for data‐driven medicinal chemistry. Herein, publicly available kinase inhibitor data are evaluated and a number of characteristics are discussed. In addition, selectivity of clinical kinase inhibitors is explored computationally on the basis of recently reported cell‐based profiling data. For inhibitors shared by pairs of kinases, selectivity profiles were generated and a variety of selective inhibitors were identified. Uni‐directional selectivity profiles revealed inhibitors that were selective for one kinase over the other, while bi‐directional profiles uncovered compounds with inverted selectivity for paired kinases.
Analysis of positive solution and Hyers‐Ulam stability for a class of singular fractional differential equations with p‐Laplacian in Banach space
Authors: Khan Hasib , Chen Wen , Sun Hongguang
Published: March 2018

This paper deals with 2 core aspects of fractional calculus including existence of positive solution and Hyers‐Ulam stability for a class of singular fractional differential equations with nonlinear p‐Laplacian operator in Caputo sense. For these aims, the suggested problem is converted into an integral equation via Green function
, for ε∈(n−1,n], where n≥4. Then, the Green function is examined whether it is increasing or decreasing and positive or negative function. After these properties, some classical fixed‐point theorems are used for the existence of positive solution. Hyers‐Ulam stability of the proposed problem is also considered. For the application of the results, an expressive example is included.
Rare manifestations of spinal tuberculosis in the Robert J. Terry Anatomical Skeletal Collection (National Museum of Natural History, Smithsonian Institution, Washington, DC, USA)
Authors: Spekker O. , Hunt D.R. , Váradi O.A. , Berthon W. , Molnár E. , Pálfi G.
Published: March 2018

Today, osteoarticular tuberculosis (TB) is a rare extrapulmonary manifestation of TB, developing in about 1–3% of patients. Although any part of the skeleton can be affected by tuberculosis, the spine represents the most common site of involvement (~50%). Spinal TB or tuberculous spondylitis typically affects 2 or more contiguous vertebrae, predominantly in the lower thoracic (40–50%) and upper lumbar (35–40%) regions. In the minority of patients (less than 10%), multilevel noncontiguous involvement occurs. By the location of lesions in the vertebra, 5 main types of spinal TB can be distinguished: paradiscal, central, anterior subligamentous, posterior, and articular forms, with the first being the most common type (90–95%). In the palaeopathological literature, the majority of the described spinal TB cases represent the paradiscal form affecting 2 or more contiguous vertebrae in the thoracolumbar region. The aim of our paper is to provide 3 example cases of known age at death, sex, and cause of death from the Terry Collection that show vertebral alterations indicative of rare manifestations of tuberculous spondylitis, and to interpret the observed lesions with regard to their diagnostic value in the palaeopathological practice. Terry No. 468 (23‐year‐old, male, died of pulmonary and spinal TB) exhibited bony changes presumably attributed to the anterior subligamentous form, whereas Terry No. 902 (c. 36‐year‐old, male, died of pulmonary TB) very likely represents the articular and anterior subligamentous types. The vertebral lesions recorded in the skeleton of Terry No. 1124R (49‐year‐old, female, died of pulmonary TB) are suggestive of the paradiscal form with multilevel noncontiguous involvement. Our paper provides palaeopathologists with a stronger basis for identifying tuberculosis in ancient human remains that reveal unusual vertebral alterations resembling that of our cases and, therefore, with a more sensitive means of assessing TB prevalence in past populations.
Chromatographic characterisation of 11 phytocannabinoids: Quantitative and fit‐to‐purpose performance as a function of extra‐column variance
Authors: Noestheden Matthew , Friedlander Gareth , Anspach Jason , Krepich Scott , Hyland K. C. , Zandberg Wesley F.
Published: March 2018

Introduction

Cannabis sativa L. (cannabis) is utilised as a therapeutic and recreational drug. With the legalisation of cannabis in many countries and the anticipated regulation of potency that will accompany legalisation, analytical testing facilities will require a broadly applicable, quantitative, high throughput method to meet increased demand. Current analytical methods for the biologically active components of cannabis (phytocannabinoids) suffer from low throughput and/or an incomplete complement of relevant phytocannabinoids.

Objective

To develop a rapid, quantitative and broadly applicable liquid chromatography–tandem mass spectrometry analytical method for 11 phytocannabinoids in cannabis with acidic and neutral character.

Methodology

Bulk diffusion coefficients were calculated using the Taylor–Aris open tubular method, with four reference compounds used to validate the experimental set‐up. Three columns were quantitatively evaluated using van Deemter plots and fit‐to‐purpose performance metrics. Low (1.2 μL2) and standard (3.6 μL2) extra‐column variance ultra‐high pressure liquid chromatography (UPLC) configurations were contrasted. Method performance was demonstrated with methanolic cannabis flower extracts.

Results

Bulk diffusion coefficients and van Deemter plots for 11 phytocannabinoids are reported. The developed chromatographic method includes the challenging Δ8/Δ9‐tetrahydrocannabinol isobars and, at 6.5 min, is faster than existing methods targeting similar panels of biologically active phytocannabinoids.

Conclusions

The bulk diffusion coefficients and van Deemter curves informed the development of a rapid quantitative method and will facilitate potential expansion to include additional compounds, including synthetic cannabinoids. The developed method can be implemented with low or standard extra‐column variance UPLC configurations.
Anticholinergics Influence Transition from Normal Cognition to Mild Cognitive Impairment in Older Adults in Primary Care
Authors: Campbell Noll L. , Lane Kathleen A. , Gao Sujuan , Boustani Malaz A. , Unverzagt Fred
Published: March 2018

Study Objective

To determine the influence of anticholinergic medications on transitions in cognitive diagnosis of older adults in primary care.

Design

This observational cohort study was conducted over a mean follow‐up of 3.2 years. Anticholinergic exposure was defined by pharmacy dispensing and claims records. Cognitive diagnosis was performed by an expert panel at baseline and annually up to 4 years.

Data Source

Medication exposure and other clinical data were extracted from the Indiana Network for Patient Care (INPC). The cognitive diagnosis was derived from a cognitive screening and diagnosis study.

Participants

A total of 350 adults 65 years and older without dementia and receiving primary care in a safety net health care system.

Measurement and Main Results

Cognitive diagnosis followed a two‐phase screening and consensus‐based neuropsychiatric examination to determine a baseline diagnosis as normal cognition, mild cognitive impairment (MCI), or dementia, with a follow‐up neuropsychiatric examination and consensus‐based diagnosis repeated annually. The Anticholinergic Cognitive Burden scale was used to identify anticholinergics dispensed up to 10 years before enrollment and annually throughout the study. A total standard daily dose of anticholinergics was calculated by using pharmacy dispensing data from the INPC. Among 350 participants, a total of 978 diagnostic assessments were completed over a mean follow‐up of 3.2 years. Compared with stable cognition, increasing use of strong anticholinergics calculated by total standard daily dose increased the odds of transition from normal cognition to MCI (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01–1.31, p = 0.0342). Compared with stable MCI, strong anticholinergics did not influence the reversion of MCI to normal cognition (OR 0.95, 95% CI 0.86–1.05, p = 0.3266).

Conclusion

De‐prescribing interventions in older adults with normal cognition should test anticholinergics as potentially modifiable risk factors for cognitive impairment.
Health care costs of depression in patients diagnosed with cancer
Authors: Mausbach Brent T. , Yeung Philip , Bos Taylor , Irwin Scott A.
Published: March 2018

Objective

Depression is common among patients diagnosed with cancer. Patients with cancer and depression use more health care services compared with nondepressed cancer patients. The current study seeks to estimate the added cost of depression in cancer patients in the first year after cancer diagnosis.

Methods

Health care charges were obtained for 2051 depressed and 11 182 nondepressed patients with an International Classification of Diseases, Ninth Revision, diagnosis of cancer in the 2014 calendar year from the University of California San Diego Healthcare System. The annual health care charges for cancer patients with and without depression were analyzed using generalized linear models with a log‐link function and gamma distribution, covarying for age, sex, race/ethnicity, comorbid diseases, and presence of metastatic disease. Total cost data were broken down into several categories including ambulatory care, emergency department visits, and hospital visits.

Results

Depressed cancer patients had total annual health care charges that were 113% higher than nondepressed cancer patients (B = 0.76; P < .001). The estimated mean charges for depressed patients were $235 337 compared with $110 650 for nondepressed patients. Depressed cancer patients incurred greater charges than nondepressed patients in ambulatory care (B = 0.70; P < .001), emergency department charges (B = 0.31; P < .001), and hospital charges (B = 0.39; P < .001).

Conclusions

Depressed cancer patients incur significantly higher health care charges across multiple cost categories including ambulatory care, emergency department visits, and hospital visits. Future research should investigate if interventions for detecting and treating depression are effective for reducing health care use and costs in cancer patients.
A fluorescently labeled undecapeptide derived from a protein in royal jelly of the honeybee—royalisin—for specific detection of oxidized low‐density lipoprotein
Authors: Sato Akira , Unuma Hiroto , Yamazaki Yoji , Ebina Keiichi
Published: March 2018

The probes for detection of oxidized low‐density lipoprotein (ox‐LDL) in plasma and in atherosclerotic plaques are expected to facilitate the diagnosis, prevention, and treatment of atherosclerosis. Recently, we have reported that a heptapeptide (Lys‐Trp‐Tyr‐Lys‐Asp‐Gly‐Asp, KP6) coupled through the ε‐amino group of N‐terminal Lys to fluorescein isothiocyanate (FITC), (FITC)KP6, can be useful as a fluorescent probe for specific detection of ox‐LDL. In the present study, to develop a novel fluorescent peptide for specific detection of ox‐LDL, we investigated the interaction (with ox‐LDL) of an undecapeptide corresponding to positions 41 to 51 of a potent antimicrobial protein (royalisin, which consists of 51 residues; from royal jelly of honeybees), conjugated at the N‐terminus to FITC in the presence of 6‐amino‐n‐caproic acid (AC) linker, (FITC‐AC)‐royalisin P11, which contains both sequences, Phe‐Lys‐Asp and Asp‐Lys‐Tyr, similar to Tyr‐Lys‐Asp in (FITC)KP6. The (FITC‐AC)‐royalisin P11 bound with high specificity to ox‐LDL in a dose‐dependent manner, through the binding to major lipid components in ox‐LDL (lysophosphatidylcholine and oxidized phosphatidylcholine). In contrast, a (FITC‐AC)‐shuffled royalisin P11 peptide, in which sequences Phe‐Lys‐Asp and Asp‐Lys‐Tyr were modified to Lys‐Phe‐Asp and Asp‐Tyr‐Lys, respectively, hardly bound to LDL and ox‐LDL. These findings strongly suggest that (FITC‐AC)‐royalisin P11 may be an effective fluorescent probe for specific detection of ox‐LDL and that royalisin from the royal jelly of honeybees may play a role in the treatment of atherosclerosis through the specific binding of the region at positions 41 to 51 to ox‐LDL.
The Influence of Trace Elements (In, Sn) on the Hardening Process of Al–Cu Alloys
Authors: Lotter Frank , Petschke Danny , Staab Torsten E. M. , Rohrmann Urban , Schubert Thomas , Sextl Gerhard , Kieback Bernd
Published: March 2018

Adding trace elements (Cd, In, Sn) to Al‐Cu‐based alloys can significantly improve their strength by the growth of small and finely distributed θ′ precipitates. However, the underlying atomic mechanisms of their nucleation are so far only superficially understood. We follow the precipitation process, that is changes in the microstructure, by different methods: differential scanning calorimetry (DSC), giving information on formation and dissolution of precipitates, 3D atom probe tomography (3DAP), giving information on size and density of precipitates and finally, positron annihilation lifetime spectroscopy (PALS), being sensitive especially to quenched‐in vacancies and their interaction with alloying elements. By the use of these complementary methods we obtain information on vacancy binding to the alloying elements and also on structure, kind and distribution of precipitates while correlating this with hardness measurements.
Structured H∞‐control of infinite‐dimensional systems
Authors: Apkarian P. , Noll D.
Published: March 2018

We develop a novel frequency‐based H∞‐control method for a large class of infinite‐dimensional linear time‐invariant systems in transfer function form. A major benefit of our approach is that reduction or identification techniques are not needed, which avoids typical distortions. Our method allows to exploit both state‐space or transfer function models and input/output frequency response data when only such are available. We aim for the design of practically useful H∞‐controllers of any convenient structure and size. We use a nonsmooth trust‐region bundle method to compute arbitrarily structured locally optimal H∞‐controllers for a frequency‐sampled approximation of the underlying infinite‐dimensional H∞‐problem in such a way that (i) exponential stability in closed loop is guaranteed and that (ii) the optimal H∞‐value of the approximation differs from the true infinite‐dimensional value only by a prior user‐specified tolerance. We demonstrate the versatility and practicality of our method on a variety of infinite‐dimensional H∞‐synthesis problems, including distributed and boundary control of partial differential equations, control of dead‐time and delay systems, and using a rich testing set.
Understanding the effects of river regulation on Atlantic salmon fry: The importance of channel morphology
Authors: Millidine K.J. , Fryer R.J. , Malcolm I.A.
Published: March 2018

River regulation influences hydrological regime, channel hydraulics, and habitat quality for freshwater biota. Environmental flow assessments typically require river managers to incorporate the requirements of different freshwater species and life stages in designing discharge regimes. However, these requirements can often conflict or be poorly quantified. There is therefore increasing interest in adaptive management whereby the ecological effects of changing flow regime can be monitored and assessed. This study investigated the effects of flow regulation on Atlantic salmon fry below an impoundment. The flow regime incorporated a compensation flow with an atypical seasonal profile where higher discharges were released in the summer than autumn and a spring high flow (freshet) to facilitate downstream migration of smolts through the dam. Saturation stocking and electrofishing were combined with hydraulic and habitat models to predict the effects of discharge on habitat quality and standardized fry densities. The discharge at which the highest standardized fry densities were observed varied depending on reach morphology, particularly channel roughness. Low fry survival was consistent with predictions of consistently low habitat quality during the spring freshet. Fish locations observed during electrofishing were not always consistent with contemporary flows and may reflect the influence of antecedent flows and high site fidelity. The combination of saturation stocking, hydraulic, and habitat models provides a valuable approach for assessing the effects of regulation. It is recommended that future freshets operate at night, that uninterrupted periods of high flow are avoided during the spring, and that compensation flows reflect natural seasonal patterns.