bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of ADAM17 as a regulatory checkpoint of CD16A in NK cells and as a potential target for cancer immunotherapy
Authors: Wu Jianming , Mishra Hemant K , Walcheck Bruce 
Published: February 2019

Abstract
Human NK cell antitumor activities involve Ab-dependent cell-mediated cytotoxicity (ADCC), which is a key mechanism of action for several clinically successful tumor-targeting therapeutic mAbs. Human NK cells exclusively recognize these Abs by the Fcγ receptor CD16A (FcγRIIIA), one of their most potent activating receptors. Unlike other activating receptors on NK cells, CD16A undergoes a rapid down-regulation in expression by a proteolytic process following NK cell activation with various stimuli. In this review, the role of a disintegrin and metalloproteinase-17 (ADAM17) in CD16A cleavage and as a regulatory checkpoint is discussed. Several studies have examined the effects of inhibiting ADAM17 or CD16A cleavage directly during NK cell engagement of Ab-coated tumor cells, which resulted in strengthened Ab tethering, decreased tumor cell detachment, and enhanced CD16A signaling and cytokine production. However, the effects of either manipulation on ADCC have varied between studies, which may be due to dissimilar assays and the contribution of different killing processes by NK cells. Of importance is that NK cells under various circumstances, including in the tumor microenvironment of patients, down-regulate CD16A and this appears to impair their function. Considerable progress has been made in the development of ADAM17 inhibitors, including human mAbs that have advantages of high specificity and increased half-life in vivo. These inhibitors may provide a therapeutic means of increasing ADCC potency and/or antitumor cytokine production by NK cells in an immunosuppressive tumor microenvironment, and if used in combination with tumor-targeting Abs or NK cell-based adoptive immunotherapies may improve their efficacy.
Localized synovial sarcoma: A single institutional study of 191 patients with a minimum follow‐up of 5 years for survivors
Authors: Outani Hidetatsu , Nakamura Tomoki , Murata Hiroaki , Stevenson Jonathan , Parry Michael , Gregory Jonathan , Tillman Roger , Jeys Lee , Abudu Adesegun 
Published: February 2019

AbstractPurposeFactors affecting long‐term outcomes of synovial sarcoma (SS) remain unknown. Here, we aimed to investigate the long‐term oncological outcomes and prognostic factors in a large group of patients with surgically‐treated localized SS.Patients and MethodsBetween 1980 and 2011, 191 patients (94 males and 97 females) were treated at a single hospital with a minimum follow‐up of 5 years for survivors. The median age was 35 years (range, 3‐80 years), and the median follow‐up period was 83 months (range, 3‐235 months).ResultsDisease‐specific survival was 76.4% and 60.4% at 5 and 10 years, respectively. Local recurrence occurred in 23 patients at a median of 33 months (range, 6‐158 months), and metastasis occurred in 73 patients at a median of 20 months (range, 2‐166 months). In multivariate analysis, grade 3 tumors sized ≥5 cm were significantly associated with worse survival. Ten patients (5.2%) developed metastasis more than 5 years after surgery.ConclusionTumor size and grade govern prognosis in surgically‐treated localized SS in long‐term settings. If adequately treated patients have not developed metastases for 5 years after surgery, the risk of subsequently developing metastases was lower than previously reported.
Evaluation of the chemical consistency of Yin‐Chen‐Hao‐Tang prepared by combined and separated decoction methods using high‐performance liquid chromatography and quadrupole time‐of‐flight mass spectrometry coupled with multivariate statistical analysis
Authors: Tian Qiang , Liu Fang , Xu Zhou , Liu Huan , Yin Hao , Sun Zhaolin , Chen Mingcang , Li Zhixiong , Ma Lin , Huang Chenggang 
Published: February 2019

AbstractIn this study, Yin‐Chen‐Hao‐Tang prepared by two decoction methods, namely, combined decoction (modern decoction method) and separated decoction (traditional decoction method), was analyzed by high‐performance liquid chromatography with quadrupole time‐of‐flight mass spectrometry. The acquired datasets containing sample codes, tR‐m/z pairs and ion intensities were processed with multivariate statistical analyses, such as principal component analysis and an orthogonal partial least squared discriminant analysis model, to globally compare the chemical differences between the different decoction samples. Then, the chemical differences between the combined and separated decoctions were screened out by S‐plots generated from the orthogonal partial least squared discriminant analysis model and compared with chemical information from an established in‐house library. The six components that contributed the most to the chemical differences were identified as chlorogenic acid, caffeic acid, geniposide, genipin, scopoletin, and 3,5‐dicaffeoylquinic acid. The concentrations of genipin and caffeic acid from the separated decoction were higher than those from the combined decoction, indicating that the separated decoction may present a stronger hepatoprotective effect. However, the results still require further investigation through pharmacological and clinical studies. Our findings not only establish a strategy to evaluate chemical consistency of Yin‐Chen‐Hao‐Tang but also provide the scientific basis for using traditional separated decoction method.
Epidemiology and resource utilization of ludwig's angina ED visits in the United States 2006–2014
Authors: McDonnough Jamiela A. , Ladzekpo Deawodi A. , Yi Iasson , Bond William R. , Ortega Gezzer , Kalejaiye Adedoyin O. 
Published: February 2019

ObjectivesLudwig's angina is a potentially lethal submandibular space infection. We aim to describe the epidemiological characteristics of Ludwig's angina patients presenting to the emergency department (ED) and to examine outcomes and resource utilization to determine their burden on ED and hospitals.MethodsUsing the Nationwide Emergency Department Sample database, a nationally representative all‐payer database, we retrospectively reviewed all ED visits between 2006 and 2014 for patients admitted with a primary diagnosis of Ludwig's angina (International Classification of Diseases, Ninth Revision, 528.3). We collected information including demographics, ED and inpatient charges, airway interventions, length of stay, and mortality.ResultsA total of 5,855 patients met our inclusion criteria. In our study population, the mean age was 44.5 years, with 54% males and 46% females. There were 75% insured and 25% uninsured. Overall median ED charges were $1,352 and median inpatient charges were $18,017.54, with a median length of stay of 3 days. As part of their management, 47.2% of the patients received a surgical drainage procedure, 3.3% required a surgical airway, and 4.6% required a nonsurgical airway. The overall mortality rate was 0.3%.ConclusionLudwig's angina remains a rare and potentially life‐threatening condition. The mortality rate appears to be decreased from previous historical accounts, with airway intervention remaining a significant part of management.Level of Evidence3Laryngoscope, 129:2041–2044, 2019
Multicenter randomized crossover trial evaluating the provox luna in laryngectomized subjects
Authors: Ratnayake Chathura B.B. , Fles Renske , Tan I. Bing , Baijens Laura W.J. , Pilz Walmari , Meeuwis Cees A. , Janssen‐van Det Pauline H.E. , van Son Rob , Van den Brekel Michiel W.M. 
Published: February 2019

ObjectivesThe aim of this study was to compare the relative compliance and the dermatological and pulmonary outcomes when the Provox Luna system (Atos Medical, Malmö, Sweden) is added during the night to the usual tracheastoma care of laryngectomized subjects.MethodsThis was a multicenter randomized crossover trial conducted in the Netherlands Cancer Institute, Erasmus Medical Center, and Maastricht University Medical Center in The Netherlands. The study included 46 laryngectomized subjects with prior heat and moisture exchanger (HME) and adhesive experience.ResultsA significant improvement in the number of compliant individuals was found: Luna: n = 43 of 45 (96%); usual care: n = 35 of 46 (76%), P = 0.02. The Luna period was associated with longer intervals of daily HME use (Luna 23.2 hours [range: 15.6–24.0 hours], usual care [UC]: 21.5 hours [range: 6.0–24.0 hours], P = 0.003) and an increased frequency of skin improvement overnight (Luna 3.9 days [standard deviation (SD)]: 7.0 days), Usual Care: 8.1 days ([SD: 10.8 days], P = 0.008). Fifty‐six percent (n = 26) of participants wanted to continue using the Provox Luna system at the conclusion of the study.ConclusionAn improvement in compliance and skin recovery overnight was observed when the Provox Luna was added to the usual adhesive and HME use. Therefore, there is utility in supplementing the usual post‐total laryngectomy care with the Provox Luna system at night, particularly in the setting of compliance concerns and in subjects who desire dermatological relief overnight.Level of Evidence1bLaryngoscope, 129:2354–2360, 2019
A nomogram to predict osteoradionecrosis in oral cancer after marginal mandibulectomy and radiotherapy
Authors: Renda Levent , Tsai Tsung‐You , Huang Jung‐Ju , Ito Ran , Hsieh Wei‐Chuan , Kao Huang‐Kai , Hung Shao‐Yu , Huang Yenlin , Huang Yu‐Chen , Chang Yu‐Liang , Cheng Ming‐Huei , Chang Kai‐Ping 
Published: February 2019

ObjectiveThere is no useful tool to clinically predict the occurrence of osteoradionecrosis (ORN) of the mandible quantitatively. The aim was to investigate the risk factors, including different modalities of radiotherapy, for developing mandibular ORN in patients undergoing marginal mandibulectomy and postoperative radiotherapy.MethodsBetween January 2006 and December 2012, 167 subjects who underwent marginal mandibulectomy and postoperative radiotherapy with different modalities were enrolled. The association of ORN with mandibular bone measurements and patient variables was analyzed, and a nomogram was established.ResultsFifteen (8.98%) of the 167 patients developed ORN during the follow‐up period, and ORN was significantly associated with diabetes mellitus (DM), body mass index (BMI), remaining bone height, remaining bone height to original bone height ratio, resected bone height to original bone height ratio, and mandibular dose (P: < 0.001, 0.004, 0.042, 0.018, 0.010, 0.020, respectively). Interestingly, the risk of ORN had no significant difference between conformal and intensity modulation radiation therapy (P = 0.407). Multivariate analysis revealed that DM and resected bone height to original bone height ratio ≥ 50% were independent risk factors for postoperative ORN. A nomogram consisting of BMI, DM, resected bone height to original bone height ratio, mandibulotomy, and mandibular dose for predicting the ORN‐free probability was established; and the c‐index of the nomogram for ORN status was 0.803.ConclusionA nomogram based on the risk factors was plotted to strengthen the prediction of ORN quantitatively. Surgeons should be more discrete regarding the treatment plan for patients with higher probability of ORN.Level of Evidence3b Laryngoscope, 130:101–107, 2020
Validation of an MPC Polymer Coating to Attenuate Surface‐Induced Crosstalk between the Complement and Coagulation Systems in Whole Blood in In Vitro and In Vivo Models
Authors: Asif Sana , Asawa Kenta , Inoue Yuuki , Ishihara Kazuhiko , Lindell Björn , Holmgren Robin , Nilsson Bo , Rydén Anneli , Jensen‐Waern Marianne , Teramura Yuji , Ekdahl Kristina N. 
Published: February 2019

AbstractArtificial surfaces that come into contact with blood induce an immediate activation of the cascade systems of the blood, leading to a thrombotic and/or inflammatory response that can eventually cause damage to the biomaterial or the patient, or to both. Heparin coating has been used to improve hemocompatibility, and another approach is 2‐methacryloyloxyethyl phosphorylcholine (MPC)‐based polymer coatings. Here, the aim is to evaluate the hemocompatibility of MPC polymer coating by studying the interactions with coagulation and complement systems using human blood in vitro model and pig in vivo model. The stability of the coatings is investigated in vitro and MPC polymer‐coated catheters are tested in vivo by insertion into the external jugular vein of pigs to monitor the catheters' antithrombotic properties. There is no significant activation of platelets or of the coagulation and complement systems in the MPC polymer‐coated one, which was superior in hemocompatibility to non‐coated matrix surfaces. The protective effect of the MPC polymer coat does not decline after incubation in human plasma for up to 2 weeks. With MPC polymer‐coated catheters, it is possible to easily draw blood from pig for 4 days in contrast to the case for non‐coated catheters, in which substantial clotting is seen.
Consumer responses to corporate social irresponsibility: The role of moral emotions, evaluations, and social cognitions
Authors: Xie Chunyan , Bagozzi Richard P. 
Published: February 2019

AbstractWe investigate the mediating roles of moral emotions and attitudes between perceptions of corporate irresponsible actions, on the one hand, and consumer responses, on the other hand, and further examine their contingencies based on consumer social cognitions. Our findings show that, for corporate transgressions, multiple social cognitions (moral identity, relational and collective self‐concepts, and affective empathy) moderate the elicitation of negative moral emotions (contempt and anger) and overall evaluations (attitudes), which, in turn, lead to negative responses toward the company (negative word of mouth, complaint behaviors, and boycotting). Our study adds to extant research on corporate social irresponsibility by examining three generic reactions people have toward corporate social irresponsibility and demonstrating important boundary conditions. In addition, hypotheses are tested on a sample of adult consumers. Implications for communication by firms are considered.
Design and analysis of a compact omnidirectional UWB slot antenna
Authors: Wang Boning , Yang Deqiang , Sun Kai 
Published: February 2019

AbstractA slot antenna for ultra‐wide band (UWB) application with a compact size, enhanced bandwidth, low profile, flat gain characteristic and omnidirectional radiation pattern is presented in this article. This antenna fed by microstrip to slot line is designed and fabricated on an FR4 substrate with a half‐wavelength rectangular patch as a radiator at low frequency and a pair of quarter‐wavelength long symmetrical slots enhancing the bandwidth at high frequency. This proposed antenna with an overall size of 33 × 10 × 0.8 mm3 (0.33λ0 × 0.1λ0 × 0.008λ0 at 3 GHz) has a |S11| < −10‐dB bandwidth of 3.08‐12.14 GHz (119%), a 1‐dB gain bandwidth of 3.04‐10.5 (110%), and a peak gain of 3.08 dBi at 5.45 GHz in Z direction.
Phase I dose‐finding study for melatonin in pediatric oncology patients with relapsed solid tumors
Authors: Johnston Donna L. , Zupanec Susan , Nicksy Darcy , Morgenstern Daniel , Narendran Aru , Deyell Rebecca J. , Samson Yvan , Wu Bing , Baruchel Sylvain 
Published: February 2019

AbstractBackgroundMelatonin is a natural health product used for sleep disturbances. In preliminary studies of adults with advanced cancer, 20 mg of melatonin daily was associated with reduction in anorexia and weight loss—symptoms that also impact pediatric oncology patients. High doses of melatonin have not been studied in pediatrics.MethodsThis was a multicenter single‐arm phase I dose‐escalation study utilizing a 3 + 3 design to determine the safety and tolerability of escalating doses of melatonin in pediatric oncology patients with relapsed solid tumors. Melatonin was given for 8 weeks at three dose levels—0.075 mg/kg (maximum 5 mg), 0.15 mg/kg (maximum 10 mg), and 0.3 mg/kg (maximum 20 mg).ResultsMelatonin was well tolerated at all three dose levels with no significant adverse events or dose‐limiting toxicities. The only grade 3/4 toxicities were myelosuppression, which was attributed to the concomitant chemotherapy and occurred at all dose levels. Weight gain occurred in seven of nine patients, with a median increase of 1.1 kg (range –3.3 to 4.5) or 3.4% (range –10.2 to 8.7), with two patients losing weight (one in dose level 1 and one level 3).ConclusionsMelatonin is well tolerated at a dose of 0.3 mg/kg (maximum 20 mg), in the pediatric population. This study provides the background for further study of high‐dose melatonin in pediatric oncology patients.
Concurrent Proteomic Fingerprinting and Molecular Analysis of Cyathostomins
Authors: Bredtmann Christina Maria , Krücken Jürgen , Murugaiyan Jayaseelan , Balard Alice , Hofer Heribert , Kuzmina Tetiana A. , von Samson‐Himmelstjerna Georg 
Published: February 2019

AbstractRapid, cost‐effective, efficient, and reliable helminth species identification is of considerable importance to understand host–parasite interactions, clinical disease, and drug resistance. Cyathostomins (Nematoda: Strongylidae) are considered to be the most important equine parasites, yet research on this group is hampered by the large number of 50 morphologically differentiated species, their occurrence in mixed infections with often more than 10 species and the difficulties associated with conventional identification methods. Here, MALDI‐TOF MS, previously successfully applied to identify numerous organisms, is evaluated and compared with conventional and molecular genetic approaches. A simple and robust protocol for protein extraction and subsequent DNA isolation allowing molecular confirmation of proteomic findings is developed, showing that MALDI‐TOF MS can discriminate adult stages of the two closely related cyathostomin species Cylicostephanus longibursatus and Cylicostephanus minutus. Intraspecific variability of proteomic profiles within morphospecies demonstrated an identification of morphospecies with an accuracy of close to 100%. In contrast, three genospecies within C. minutus and sex‐specific profiles within both morphospecies could not be reliably discriminated using MALDI‐TOF MS. In conclusion, MALDI‐TOF MS complemented by the molecular protocol is a reliable and efficient approach for cyathostomin species identification.
Quantitative Proteomic Analysis of Low Linolenic Acid Transgenic Soybean Reveals Perturbations of Fatty Acid Metabolic Pathways
Authors: Islam Nazrul , Bates Philip D. , Maria John K. M. , Krishnan Hari B. , J. Zhang Zhanyuan , Luthria Devanand L. , Natarajan Savithiry S. 
Published: February 2019

AbstractTo understand the effect of fatty acid desaturase gene (GmFAD3) silencing on perturbation of fatty acid (FA) metabolic pathways, the changes are compared in protein profiling in control and low linolenic acid transgenic soybeans using tandem mass tag based mass spectrometry. Protein profiling of the transgenic line unveiled changes in several key enzymes of FA metabolism. This includes enzymes of lower abundance; fabH, fabF, and thioestrase associated with FA initiation, elongation, and desaturation processes and LOX1_5, ACOX, ACAA1, MFP2 associated with β‐oxidation of α‐linolenic acids pathways. In addition, the GmFAD3 silencing results in a significant reduction in one of the major allergens, Gly m 4 (C6T3L5). These results are important for exploring how plants adjust in their biological processes when certain changes are induced in the genetic makeup. A complete understanding of these processes will aid researchers to alter genes for developing value‐added soybeans.
GRGD‐decorated three‐dimensional nanoworm hydrogels for culturing human embryonic stem cells
Authors: Kessel Stefanie , Thakar Nilay , Jia Zhongfan , Wolvetang Ernst J. , Monteiro Michael J. 
Published: February 2019

ABSTRACTHuman embryonic stem cells (hESCs) offer great hope in the development of regenerative medicine. This article demonstrates a method to prepare temperature induced three‐dimensional (3D) hydrogels consisting of soft and flexible polymer nanoworms with a radius of 10 nm and lengths on the micrometer scale. We decorated the surface of the nanoworms with the integrin‐binding peptide (RGD) using our novel physical adsorption process, and show that the resulting gels are able to immobilize and maintain the survival of hESCs. We conclude that the unique PNIPAM nanoworm hydrogels allow binding of undifferentiated hESC through small integrin‐binding peptides. Their temperature sensitivity, biocompatibility, ability to present combinations of multiple ligands and moldability into any desired 3D shape should make this nanoworm system a versatile platform for organoid engineering and regenerative medicine in the future. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1956–1963
The evolution of multiple‐insecticide resistance in UK populations of tomato leafminer, Tuta absoluta
Authors: Grant Charles , Jacobson Rob , Ilias Aris , Berger Madeleine , Vasakis Emmanouil , Bielza Pablo , Zimmer Christoph T , Williamson Martin S , ffrench‐Constant Richard H , Vontas John , Roditakis Emmanouil , Bass Chris 
Published: February 2019

AbstractBACKGROUNDThe tomato leafminer, Tuta absoluta, is an economically important pest of tomatoes in Europe, Africa, Asia and South America. In the UK this species is controlled using an integrated pest management (IPM) programme which incorporates the insecticides spinosad and chlorantraniliprole. In response to UK grower concerns of loss of efficacy of these compounds at certain sites, insecticide bioassays were performed on five populations collected from four commercial glasshouses and potential mechanisms of resistance investigated.RESULTSWe observed high levels of resistance to spinosad in four of the strains, and in two of these tolerance to chlorantraniliprole. Selection of one of these strains with chlorantraniliprole rapidly resulted in a line exhibiting potent resistance to this compound. Sequencing of messenger RNA encoding the nicotinic acetylcholine receptor (nAChR) α6 subunit, target of spinosad, revealed Taα6 transcripts in the spinosad‐resistant strains that lack exon 4 and encode a highly truncated protein, or contain a triplet deletion in the predicted first transmembrane domain resulting in the loss of a highly conserved amino acid. Sequencing of the ryanodine receptor gene, encoding the target of diamide insecticides, of the chlorantraniliprole‐selected line revealed an amino acid substitution (G4903V) that has been previously linked to diamide resistance in populations of T. absoluta in the Mediterranean and South America.CONCLUSIONTaken together our results reveal emerging resistance in UK populations of T. absoluta to two of the most important insecticides used as part of IPM, with significant implications for the control of this species in the UK. © 2019 Society of Chemical Industry