bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppressive effects of methylthiouracil on polyphosphate‐mediated vascular inflammatory responses
Authors: Min Gahee , Ku Sae‐Kwang , Jeong Seongdo , Baek Moon‐Chang , Bae Jong‐Sup 
Published: July 2016

AbstractDrug repositioning is used to discover drug candidates to treat human diseases, through the application of drugs or compounds that are approved for the treatment of other diseases. This method can significantly reduce the time required and cost of discovering new drug candidates for human diseases. Previous studies have reported pro‐inflammatory responses of endothelial cells to the release of polyphosphate (PolyP). In this study, we examined the anti‐inflammatory responses and mechanisms of methylthiouracil (MTU), which is an antithyroid drug, and its effects on PolyP‐induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behaviour of human neutrophils and vascular permeability were determined in PolyP‐activated HUVECs and mice. MTU suppressed the PolyP‐mediated vascular barrier permeability, up‐regulation of inflammatory biomarkers, adhesion/migration of leucocytes, and activation and/or production of nuclear factor‐κB, tumour necrosis factor‐α and interleukin‐6. Furthermore, MTU demonstrated protective effects on PolyP‐mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of MTU on various systemic inflammatory diseases, such as sepsis or septic shock.
The expression of Lamin A mutant R321X leads to endoplasmic reticulum stress with aberrant Ca2+ handling
Authors: Carmosino Monica , Gerbino Andrea , Schena Giorgia , Procino Giuseppe , Miglionico Rocchina , Forleo Cinzia , Favale Stefano , Svelto Maria 
Published: July 2016

AbstractMutations in the Lamin A/C gene (LMNA), which encodes A‐type nuclear Lamins, represent the most frequent genetic cause of dilated cardiomyopathy (DCM). This study is focused on a LMNA nonsense mutation (R321X) identified in several members of an Italian family that produces a truncated protein isoform, which co‐segregates with a severe form of cardiomyopathy with poor prognosis. However, no molecular mechanisms other than nonsense mediated decay of the messenger and possible haploinsufficiency were proposed to explain DCM. Aim of this study was to gain more insights into the disease‐causing mechanisms induced by the expression of R321X at cellular level. We detected the expression of R321X by Western blotting from whole lysate of a mutation carrier heart biopsy. When expressed in HEK293 cells, GFP‐ (or mCherry)‐tagged R321X mislocalized in the endoplasmic reticulum (ER) inducing the PERK‐CHOP axis of the ER stress response. Of note, confocal microscopy showed phosphorylation of PERK in sections of the mutation carrier heart biopsy. ER mislocalization of mCherry‐R321X also induced impaired ER Ca2+ handling, reduced capacitative Ca2+ entry at the plasma membrane and abnormal nuclear Ca2+ dynamics. In addition, expression of R321X by itself increased the apoptosis rate. In conclusion, R321X is the first LMNA mutant identified to date, which mislocalizes into the ER affecting cellular homeostasis mechanisms not strictly related to nuclear functions.
A nurse‐led interdisciplinary approach to promote self‐management of type 2 diabetes: a process evaluation of post‐intervention experiences
Authors: Whitehead Lisa C. , Crowe Marie T. , Carter Janet D. , Maskill Virginia R. , Carlyle Dave , Bugge Carol , Frampton Chris M. A. 
Published: July 2016

AbstractRationale, aims and objectivesSelf‐management of type 2 diabetes through diet, exercise and for many medications, are vital in achieving and maintaining glycaemic control in type 2 diabetes. A number of interventions have been designed to improve self‐management, but the outcomes of these are rarely explored from a qualitative angle and even fewer through a process evaluation.MethodA process evaluation was conducted using a qualitative design with participants randomized to an intervention. Seventy‐three people living with type 2 diabetes and hyperglycaemia for a minimum of 1 year, randomized to one of two interventions (n = 34 to an education intervention and n = 39 to an education and acceptance and commitment therapy intervention) completed stage one of the process evaluation, immediately following the intervention through written feedback guided by open‐ended questions. A purposive sample of 27 participants completed semi‐structured interviews at 3 and 6 months post intervention. Interview data were transcribed and data analysed using a thematic analysis.ResultsThe majority of participants described an increase in knowledge around diabetes self‐management and an increased sense of personal responsibility. Participants also described changes in self‐management activities and reflected on the challenges in instigating and maintaining change to improve diabetes management.ConclusionThe complexities of implementing change in daily life to improve glycaemic control indicate the need for ongoing support post intervention, which may increase and maintain the effectiveness of the intervention.
Emergence of a new rhabdovirus associated with mass mortalities in eelpout (Zoarces viviparous) in the Baltic Sea
Authors: Axén C , Hakhverdyan M , Boutrup T S , Blomkvist E , Ljunghager F , Alfjorden A , Hagström Å , Olesen N J , Juremalm M , Leijon M , Valarcher J‐F 
Published: July 2016

AbstractWe report the first description of a new Rhabdoviridae tentatively named eelpout rhabdovirus (EpRV genus Perhabdovirus). This virus was associated with mass mortalities in eelpout (Zoarces viviparous, Linnaeus) along the Swedish Baltic Sea coast line in 2014. Diseased fish showed signs of central nervous system infection, and brain lesions were confirmed by histology. A cytopathogenic effect was observed in cell culture, but ELISAs for the epizootic piscine viral haemorrhagic septicaemia virus (VHSV), infectious pancreas necrosis virus (IPNV), infectious haematopoietic necrosis virus (IHNV) and spring viraemia of carp virus (SVCV) were negative. Further investigations by chloroform inactivation, indirect fluorescence antibody test and electron microscopy indicated the presence of a rhabdovirus. By deep sequencing of original tissue suspension and infected cell culture supernatant, the full viral genome was assembled and we confirmed the presence of a rhabdovirus with 59.5% nucleotide similarity to the closest relative Siniperca chuatsi rhabdovirus. The full‐genome sequence of this new virus, eelpout rhabdovirus (EpRV), has been deposited in GenBank under accession number KR612230. An RT‐PCR based on the L‐gene sequence confirmed the presence of EpRV in sick/dead eelpout, but the virus was not found in control fish. Additional investigations to characterize the pathogenicity of EpRV are planned.
Prokinetic effects of a new 5‐HT4 agonist, YKP10811, on gastric motility in dogs
Authors: Yin Jieyun , Xu Xiaohong , Song Gengqing , Han Hyun Sil , Kim Hong Wook , Chen Jiande D Z 
Published: July 2016

AbstractBackground and AimProkinetics have been considered the first‐line medicine for treating delayed gastric emptying. The aim of this study was to explore the effects and mechanisms of a new 5‐HT4 receptor agonist, YKP10811, on gastric motility in dogs.MethodsFour experiments were performed in dogs: (i) dose–response effects of YKP10811 on liquid gastric emptying; (ii) effects and mechanisms of YKP10811 on solid gastric emptying delayed by glucagon; (iii) effects of low‐dose YKP10811 on antral contractions; and (iv) effects of low‐dose YKP10811 on gastric accommodation.ResultsNo adverse events or cardiac dysrhythmia was noted. (i) High‐dose YKP10811 (30 mg/kg) accelerated liquid gastric emptying from 15 to 90 min without inducing adverse events or cardiac dysrhythmia. YKP10811 at low doses (0.3, 1, and 3 mg/kg) accelerated gastric emptying in a dose‐dependent manner. (ii) YKP10811 (0.1 mg/kg), but not tegaserod (0.3 mg/kg), significantly accelerated glucagon‐induced delayed gastric emptying of solid, and the effect was completely blocked by GR113808. (iii) YKP10811 (0.3 mg/kg) enhanced antral contractions. (iv) YKP10811 did not alter gastric accommodation.ConclusionsYKP10811 seems to improve antral contractions and accelerate gastric emptying without altering gastric accommodation in dogs via the 5‐HT4 mechanism and is substantially more potent than tegaserod. No adverse events were noted at a dose 300 times the lowest effective dose. YKP10811 may have a therapeutic potential for gastroparesis.
Nucleoside diphosphate‐linked moiety X‐type motif 15 C415T variant as a predictor for thiopurine‐induced toxicity in Indian patients
Authors: Shah Swarup A V , Paradkar Minal , Desai Devendra , Ashavaid Tester F 
Published: July 2016

AbstractBackground and AimInterindividual variation seen in the thiopurine metabolism is attributed to the genetic variant in thiopurine methyltransferase (TPMT) gene leading to myelosuppression. In Asians, the thiopurine‐induced toxicity is not completely explained by TPMT variants. Literature indicates that a newer genetic variant in nucleoside diphosphate‐linked moiety X‐type motif 15 (NUDT15) gene is associated with thiopurine intolerance. We aimed to determine the risk allele frequency of NUDT15 genetic variant and its association with thiopurine‐induced toxicity in Indian patients.MethodsIn this pilot study, 69 patients on thiopurine therapy were analyzed. The frequencies of thiopurine‐induced leukopenia were recorded. NUDT15 (C415T) and TPMT (*2, *3A, *3B, and *3C) genotyping was performed using amplification refractory mutation system–polymerase chain reaction and restriction fragment length polymorphism technique. Results were validated by DNA sequencing.ResultsThe NUDT15 CC, CT, and TT genotypes were found to be 86.9%, 11.5%, and 1.5%, respectively, whereas TPMT genetic variants were absent. Of 60 patients without NUDT15 variant, none developed leukopenia, whereas of nine patients with NUDT15 variant, six developed leukopenia (P‐value < 0.0001). The mean thiopurine dose of 1.01 and 0.73 mg/kg/day for patients with wild and mutant NUDT15 alleles, respectively, was statistically significant (P < 0.01). The sensitivity and specificity for NUDT15 variant were 100% and 95.2%, respectively.ConclusionsThe NUDT15 risk allele frequency was 7.2%. There are 6/69 (8.7%) patients who developed leukopenia and harbored NUDT15 variant, thus showing a strong association for thiopurine‐induced toxicity. Hence, NUDT15 genotyping may be considered before thiopurine therapy in Indian patients.
Is This Broken Bone Because of Abuse? Characteristics and Comorbid Diagnoses in Older Adults with Fractures
Authors: Gironda Melanie W. , Nguyen Annie L. , Mosqueda Laura M. 
Published: July 2016

ObjectivesTo examine the relationship between individual characteristics and potential correlates of elder abuse in older adults who present with fractures.DesignCross‐sectional analysis of deidentified data extracted from medical records.SettingAcademic medical center.ParticipantsIndividuals aged 65 and with a primary diagnosis of any fracture admitted to an outpatient department or emergency department (ED) in a single southern California medical center over a 36‐month period (N = 652).MeasurementsParticipant characteristics included demographic characteristics, number of medical visits, and point of service. Corresponding International Classification of Diseases, Ninth Revision (ICD‐9) codes, E‐codes, and V‐codes were extracted to identify cause, location, and type of fracture. The presence of 13 potential correlates of abuse as captured by ICD‐9 codes were extracted and summed. Descriptive statistics and regression models were used for analyses.ResultsMean age of participants was 77.2, 58% were female (58%), 60% were white (60%), and 46% had one or more potential correlates of abuse. In bivariate analyses, older age (≥80), dementia, seeking care in the ED (vs inpatient or outpatient clinics), only one visit to a medical facility (vs multiple visits) in the 36‐month study period, cause of fracture as something other than a fall, and fractures of the head or face were more likely to have at least one correlate of abuse. In logistic regression, dementia (B = 0.794, standard error (SE) = 0.280); seeking care in the ED (vs outpatient or outpatient clinics) (B = 1.86, SE = 0.302); at least two visits to a medical facility (vs multiple visits) (B = −0.585, SE = 0.343); and fracture of the back (B = 0.730, SE = 0.289), head (B = 1.22, SE = 0.333), and face (B = 1.28, SE = 0.474) were associated with the presence of at least one correlate of abuse.ConclusionCertain characteristics in older adults with fracture are associated with potential correlates of abuse. Medical practitioners should have a heightened awareness when these signs are present.
A simple technique to repair a hand fracture in a captive Siamang
Authors: Piga Sara , Negro Francesco , Meda Stefano , Bertuglia Andrea 
Published: July 2016

AbstractA 5‐year‐old female Siamang (Hylobates syndactilus) in captivity sustained a displaced closed fracture of the proximal phalanx of the middle digit, resulting in finger deformity and hand functional disability. Anatomical reduction and stabilization of the fracture were obtained surgically using two multifilament wire sutures. The primate had a successful functional recovery.
The intermediate filament protein vimentin is essential for axonotrophic effects of Clostridium botulinum C3 exoenzyme
Authors: Adolf Andrej , Leondaritis George , Rohrbeck Astrid , Eickholt Britta Johanna , Just Ingo , Ahnert‐Hilger Gudrun , Höltje Markus 
Published: July 2016

AbstractThe type III intermediate filament protein vimentin was recently identified to mediate binding and uptake of Clostridium botulinum C3 exoenzyme (C3bot) in two cell lines. Here, we used primary neuronal cultures from vimentin knockout (Vim−/−) mice to study the impact of vimentin on axonal growth and internalization of C3bot. In contrast to wild type, vimentin knockout neurons were insensitive to C3bot. Application of extracellular vimentin to Vim−/− neurons completely restored the growth‐promoting effects of C3bot. In line with this uptake of C3bot into Vim−/− neurons was strongly decreased resulting in reduced ADP‐ribosylation of RhoA and B as detected by an antibody recognizing selectively ADP‐ribosylated RhoA/B. Again, uptake of C3bot into Vim−/− neurons was rescued by addition of extracellular vimentin. In addition, in purified embryonic stem cell‐derived motor neurons that are devoid of glial cells C3bot elicited axonotrophic effects confining neuronal vimentin as a binding partner.
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Primary neuronal cultures from vimentin knockout (KO) mice were used to study the impact of vimentin on axonal growth and internalization of C3bot. In contrast to wild type, vimentin knockout neurons were insensitive to the axonotrophic effects of C3bot. Application of extracellular vimentin (recombinant vimentin) to vimentin KO neurons completely restored the growth‐promoting effects of C3bot. In line with this uptake of C3bot into vimentin KO neurons was strongly decreased resulting in reduced ADP‐ribosylation of RhoA and B as detected by an antibody recognizing selectively ADP‐ribosylated RhoA/B.
Prognostic significance of VEGF‐C in predicting micrometastasis and isolated tumour cells in N0 oral squamous cell carcinoma
Authors: Kazakydasan Sarvambika , Rahman Zainal Ariff Abdul , Ismail Siti Mazlipah , Abraham Mannil Thomas , Kallarakkal Thomas George 
Published: July 2016

BackgroundLymph node metastasis in oral squamous cell carcinoma (OSCC) is a well‐known independent prognostic factor. However, the identification of occult tumour cells within the lymph nodes has remained a challenge for the pathologist as well as the clinician.ObjectiveThe aim of this study was to determine the prevalence of micrometastasis and isolated tumour cells (ITCs) in pathologically staged N0 OSCC of the tongue and buccal mucosa and to assess its correlation with vascular endothelial growth factor C, (VEGF‐C) expression in the primary tumour.MethodsThirty‐four cases of N0 OSCC comprising of 17 cases each from the tongue and buccal mucosa were evaluated by immunohistochemistry for VEGF‐C expression. The corresponding lymph nodes from levels I and II were pathologically examined and cross‐detected for micrometastasis and ITCs with desmoglein 3 (DSG3).ResultsThe prevalence of micrometastasis and ITCs in OSCC of the tongue and buccal mucosa was 23.5% and 17.6%, respectively. A total of 12 out of 151 lymph nodes contained micrometastatic tumour foci and ITCs. A higher expression of VEGF‐C in the primary tumour was associated with a greater probability for the occurrence of micrometastasis and ITCs in the lymph nodes.ConclusionHigh expression of VEGF‐C in the primary tumour may be a good determinant for detection of occult tumour cells in the lymph nodes of OSCC cases.
Metabolizable energy intake of client‐owned adult dogs
Authors: Thes M. , Koeber N. , Fritz J. , Wendel F. , Dillitzer N. , Dobenecker B. , Kienzle E. 
Published: July 2016

SummaryA post hoc analysis of the metabolizable energy (ME) intake of privately owned pet dogs from the authors' nutrition consultation practice (Years 2007–2011) was carried out to identify if currentMErecommendations are suitable for pet dogs. Data on 586 adult dogs were available (median age 5.5, median deviation from ideal weight 0.0), 55 of them were healthy; the others had various diseases. For ration calculation, a standardized questionnaire and the software diet‐check Munich™was used.MEwas predicted according toNRC(2006). Data were evaluated for the factors disease, breed, size, age, gender and type of feeding. The meanMEintake of all adult dogs amounted to 0.410 ± 0.121MJ/kg metabolic body weight (BW0.75) (n = 586). There was no effect of size and disease. Overweight dogs ate 0.360 ± 0.121MJ/kgBW0.75, and underweight dogs ate 0.494 ± 0.159MJ/kgBW0.75. Older dogs (>7 years,n = 149, 0.389 ± 0.105MJ/kgBW0.75) had a lowerMEintake than younger ones (n = 313, 0.419 ± 0.121MJ/kgBW0.75), and intact males had a higherMEintake than the others (p < 0.001). Some breeds were above average: Jack Russell Terrier, Dalmatian, small Munsterlander and Magyar Viszla, Bearded Collies, Sight Hounds, German Boxers, English foxhounds, Rhodesian Ridgebacks and Flat‐Coated Retrievers with a meanMEintake of 0.473 ± 0.121MJ/kgBW0.75. The following breeds were below average: Dachshunds, Bichons, West highland White Terrier, Collies except Bearded Collies, Airedale Terriers, American Staffordshire terriers and Golden Retrievers with a meanMEintake of 0.343 ± 0.096MJ/kgBW0.75. The mean maintenance energy requirements of pet dogs are similar to that of kennel dogs which do not exercise very much. These results suggest that opportunity and stimulus to exercise provided for pet dogs are lower than for kennel dogs. Lower activity in pet dogs may reduce part of potential effects of breed, medical history and age groups.
Comparative Study on Physical–Chemical and Biological Characteristics of Grass Carp Reovirus From Different Genotypes
Authors: Wang Qing , Zeng Weiwei , Yin Liang , Wang Yingying , Liu Chun , Li Yingying , Zheng Shucheng , Shi Cunbin 
Published: July 2016

AbstractGrass carp reovirus (GCRV) was first isolated in 1983. In China, the virus caused severe hemorrhagic disease with significant losses of fingerling and yearling grass carp,Cyenopharyngodon idellus. Clade analysis of the differentGCRVisolates from China indicates there are three distinct branches, which represent genotypesI,II, andIII. However, little is known about the physical–chemical and biological characteristics of viruses from these three genotypes. In this study, the morphologic characteristics ofJX‐0901 (genotype I),HZ08(genotypeII), and Hubei grass carp disease reovirus (genotypeIII) were determined using electron microscopy which revealed morphological similarities but viral particles of the isolates arrayed in different ways. A comparison of selected viruses was performed for physical and chemical properties, including stability under differentpHconditions, treatment with ether and trypsin, and repeated freeze–thaw cycles. Three isolates showed similar resistance to treatment with ether or trypsin and were stable betweenpH3 andpH10. The viruses exhibited different proliferation curves in the Grass carp swimming bladder cell. No postinfection mortalities or histological lesions were observed in infected rare minnow. Furthermore, cross‐protection assays revealed low cross protection between different genotype viruses. This study contributes to the body of knowledge concerning disease control and vaccine development for grass carp hemorrhagic disease.
Molecular Characterization and Dietary Regulation of the AlaSerCys Transporter 2 in Grass Carp, Ctenopharyngodon idella
Authors: Hu Rong , Wang Yonghong , Qu Fufa , Tang Jianzhou , Zhou Yi , Lu Shuangqing , Zhang Jianshe , Liu Zhen , Zhou Zhigang , Guo Xinhong 
Published: July 2016

AbstractAlaSerCys Transporter 2 (ASCT2), a glutamine/amino acid transporter, plays an important role in the absorption of neutral amino acids. In this study, we cloned the full‐length cDNA of ASCT2 from grass carp, Ctenopharyngodon idella, which encodes a 541‐amino‐acid protein. Phylogenetic analysis revealed that the ASCT2 sequence of grass carp clustered with the ASCT2 from Danio rerio. ASCT2 mRNA was differentially expressed in different tissues, with a gradient expression from high to low in tissues of the liver, gill, muscle, midgut, hypophysis, hindgut, kidney, heart, foregut, brain, spleen, and gonad. Meanwhile, the quantitative real‐time polymerase chain reaction results showed that 22% crude protein diets could significantly stimulate ASCT2 gene expression. In addition, ASCT2 was expressed in higher quantities in the soybean meal group than in the fishmeal group. Furthermore, 7.5 g/kg glutamine and 2.5 g/kg glutamine dipeptide remarkably improved the expression of ASCT2. These results suggested that ASCT2 expression is regulated by the dietary protein levels and sources, as well as appropriate concentration of glutamine and glutamine dipeptide additives.
Differential Laser‐Induced Perturbation Spectroscopy for Analysis of Mixtures of the Fluorophores l‐Phenylalanine, l‐Tyrosine and l‐Tryptophan Using a Fluorescence Probe
Authors: Oztekin Erman K. , Hahn David W. 
Published: July 2016

AbstractQuantitative detection of common endogenous fluorophores is accomplished using differential laser‐induced perturbation spectroscopy (DLIPS) with a 193‐nm UV fluorescence probe and various UV perturbation wavelengths. In this study, DLIPS is explored as an alternative to traditional fluorescence spectroscopy alone, with a goal of exploring natural fluorophores pursuant to biological samples and tissue analysis. To this end, aromatic amino acids, namely, l‐phenylalanine, l‐tyrosine and l‐tryptophan are mixed with differing mass ratios and then classified with various DLIPS schemes. Classification with a traditional fluorescence probe is used as a benchmark. The results show a 20% improvement in classification performance of the DLIPS method over the traditional fluorescence method using partial least squares (PLS) analysis. Additional multivariate analyses are explored, and the relevant photochemistry is elucidated in the context of perturbation wavelengths. We conclude that DLIPS is a promising biosensing approach with potential for in vivo analysis given the current findings with fluorophores relevant to biological tissues.