bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viral transmission in honey bees and native bees, supported by a global black queen cell virus phylogeny
Authors: Murray Elizabeth A. , Burand John , Trikoz Natalia , Schnabel Julia , Grab Heather , Danforth Bryan N. 
Published: December 2018

SummaryIn recent decades, we have realized that honey bee viruses are not, in fact, exclusive to honey bees. The potential impact of Apis‐affiliated viruses on native pollinators is prompting concern. Our research addresses the issue of virus crossover between honey bees and native bees foraging in the same localities. We measured the presence of black queen cell virus (BQCV), deformed wing virus (DWV) and sacbrood virus (SBV) in managed Apis mellifera (honey bees) and native Andrena spp. (subgenus Melandrena) bee populations in five commercial orchards. We identified viral presence across sites and bees and related these data to measures of bee community diversity. All viruses were found in both managed and native bees, and BQCV was the most common virus in each. To establish evidence for viral crossover between taxa, we undertook an additional examination of BQCV where 74 samples were sequenced and placed in a global phylogenic framework of hundreds of BQCV strains. We demonstrate pathogen sharing across managed honey bees and distantly related wild bees. This phylogenetic analysis contributes to growing evidence for host switching and places local incidence patterns in a worldwide context, revealing multispecies viral transmission.
MYD88 L265P mutations identify a prognostic gene expression signature and a pathway for targeted inhibition in CLL
Authors: Improgo Ma. Reina , Tesar Bethany , Klitgaard Josephine L. , Magori‐Cohen Reuma , Yu Lijian , Kasar Siddha , Chaudhary Divya , Miao Wenyan , Fernandes Stacey M. , Hoang Kevin , Westlin William F. , Kim Haesook T. , Brown Jennifer R. 
Published: December 2018

SummaryThe L265P somatic mutation in the Myeloid Differentiation Primary Response 88 (MYD88) gene is a recurrent mutation in chronic lymphocytic leukaemia (CLL). This mutation has functional effects in various haematological malignancies but its role in CLL remains to be fully elucidated. Here, we report that MYD88 L265P mutations are associated with mutated immunoglobulin heavy‐chain gene (IGHV‐M) status and that among IGHV‐M patients, the presence of MYD88 L265P is associated with younger age at diagnosis. Using microarray and RNA‐Seq gene expression analysis, we further observe that the MYD88 L265P mutation is associated with a distinctive gene expression signature that predicts both failure‐free survival and overall survival. This association was validated in an independent cohort of patients. To determine whether MYD88 L265P mutations can be therapeutically exploited in CLL, we treated primary cells with an inhibitor of interleukin 1 receptor‐associated kinase 4 (IRAK4), a critical effector of the MYD88 pathway. IRAK4 inhibition decreased downstream nuclear factor‐κB signalling and cell viability in CLL cells, indicating the potential of the MYD88 pathway as a therapeutic target in CLL.
PML/RARA inhibits expression of HSP90 and its target AKT
Authors: Piredda Maria Liliana , Gaur Girish , Catalano Gianfranco , Divona Mariadomenica , Banella Cristina , Travaglini Serena , Puzzangara Maria Carmen , Voso Maria Teresa , Lo‐Coco Francesco , Noguera Nelida Ines 
Published: December 2018

SummaryEssential for cell survival, the 90 kD Heat Shock Proteins (HSP90) are molecular chaperons required for conformational stabilization and trafficking of numerous client proteins. Functional HSP90 is required for the stability of AKT, a serine‐threonine kinase phosphorylated in response to growth factor stimulation. AKT plays a crucial regulatory role in differentiation, cell cycle, transcription, translation, metabolism and apoptosis. Acute promyelocytic leukaemia (APL) is characterized by the presence of the promyelocytic leukaemia/retinoic acid receptor alpha (PML/RARA) fusion protein, which deregulates expression of several genes involved in differentiation and apoptosis. Here, we report inhibition of HSP90AA1 and HSP90AB1 isomer transcription in blasts isolated from patients with APL, associated with reduction of HSP90 protein expression and loss of control on AKT protein phosphorylation. We show that in vitro treatment of PML/RARA expressing cells with all‐trans retinoic acid (ATRA) up‐regulates HSP90 expression and stabilizes AKT. Addition of the HSP90‐inhibitor 17‐(allylamino)‐17‐demethoxygeldanamycin in combination with ATRA, blocks upregulation of AKT protein, indicating that HSP90 is necessary for ATRA action on AKT. This is the first report proving that expression of HSP90 isomers are directly and differentially repressed by PML/RARA, with critical results on cellular homeostasis of target proteins, such as AKT, in APL blasts.
Simvastatin and the Rho‐kinase inhibitor Y‐27632 prevent myofibroblast transformation in Peyronie's disease‐derived fibroblasts via inhibition of YAP/TAZ nuclear translocation
Authors: Milenkovic Uros , Ilg Marcus M. , Zuccato Carola , Ramazani Yasaman , De Ridder Dirk , Albersen Maarten 
Published: December 2018

ObjectivesTo uncover the anti‐myofibroblast (MFB) properties of Rho‐kinase inhibitor (compound Y‐27632) and simvastatin in an in vitro model of Peyronie's disease (PD), a sexually debilitating disease caused by an irreversible fibrotic plaque in the penile tunica albuginea (TA).Materials and MethodsPrimary human fibroblasts (FBs) were isolated from surgically obtained TA tissue from patients with PD. To induce MFB status, cells were stimulated with 3 ng/mL transforming growth factor‐β1 (TGF‐β1). Increasing doses of Y‐27632 and simvastatin were added. Real‐time quantitative PCR was used to assess mRNA expression of α‐smooth muscle actin (α‐SMA), collagen III, elastin and connective tissue growth factor (CTGF) after 72 h. Western blot analysis was used to quantify α‐SMA protein contents, and immunofluorescence (IF) was used to visualize MFB differentiation by staining for α‐SMA after 72 h. A resazurin‐based assay was used to assess cell viability to ensure the anti‐MFB effect of the drugs. A mechanistic study was performed using IF staining for YAP/TAZ nuclear translocation.ResultsAfter 72 h of stimulation with TGF‐β1, a six‐ to 10‐fold upregulation of α‐SMA could be observed. When treated with Y‐27632 or simvastatin, the α‐SMA, collagen III, elastin and CTGF mRNA expression was impeded. Additionally, TGF‐β1 stimulation showed a twofold increase in α‐SMA protein expression, which was reversed to non‐stimulated levels after treatment with Y‐27632 and simvastatin. Using IF, stimulated cells were identified as MFB (α‐SMA+, Vim+) as opposed to the non‐stimulated, Y‐27632‐ and simvastatin‐treated cells (α‐SMA−, Vim+). The resazurin‐based assay confirmed that the cell viability was not compromised by the administered drugs. On stimulation with TGF‐β1, nuclear translocation of YAP/TAZ could be observed, which was prevented by adding the aforementioned compounds.ConclusionTransformation of FBs into the contractile and extracellular matrix‐producing MFBs occurs after TGF‐β1 stimulation. In our experiments, Rho‐kinase inhibition and simvastatin treatment were shown to prevent this in TGF‐β1‐stimulated cells on an RNA and protein level through the inhibition of YAP/TAZ nuclear translocation. Y‐27632 and simvastatin could become a novel treatment option in the early treatment of PD.
Anti‐tumor effects of mAb against l‐type amino acid transporter 1 (LAT1) bound to human and monkey LAT1 with dual avidity modes
Authors: Ueda Shiho , Hayashi Hidemi , Miyamoto Takako , Abe Shinya , Hirai Kana , Matsukura Kanji , Yagi Hideki , Hara Yuta , Yoshida Kinji , Okazaki Shogo , Tamura Masakazu , Abe Yuki , Agatsuma Toshinori , Niwa Shin‐ichiro , Masuko Kazue , Masuko Takashi 
Published: December 2018

l‐Type amino acid transporter 1 (LAT1) disulfide linked to CD98 heavy chain (hc) is highly expressed in most cancer cells, but weakly expressed in normal cells. In the present study, we developed novel anti‐LAT1 mAbs and showed internalization activity, inhibitory effects of amino acid uptake and cell growth and antibody‐dependent cellular cytotoxicity, as well as in vivo antitumor effects in athymic mice. Furthermore, we examined the reactivity of mAbs with LAT1 of Macaca fascicularis to evaluate possible side‐effects of antihuman LAT1 mAbs in clinical trials. Antihuman LAT1 mAbs reacted with ACHN human and MK.P3 macaca kidney‐derived cells, and this reactivity was significantly decreased by siRNAs against LAT1. Macaca LAT1 cDNA was cloned from MK.P3, and only two amino acid differences between human and macaca LAT1 were seen. RH7777 rat hepatoma and HEK293 human embryonic kidney cells expressing macaca LAT1 were established as stable transfectants, and antihuman LAT1 mAbs were equivalently reactive against transfectants expressing human or macaca LAT1. Dual (high and low) avidity modes were detected in transfectants expressing macaca LAT1, MK.P3, ACHN and HCT116 human colon cancer cells, and KA values were increased by anti‐CD98hc mAb, suggesting anti‐LAT1 mAbs detect an epitope on LAT1‐CD98hc complexes on the cell surface. Based on these results, LAT1 may be a promising anticancer target and Macaca fascicularis can be used in preclinical studies with antihuman LAT1 mAbs.
Serum cotinine, vitamin D exposure levels and dental caries experience in U.S. adolescents
Authors: Akinkugbe Aderonke A. , Moreno Oswaldo , Brickhouse Tegwyn H. 
Published: December 2018

AbstractIntroductionEpidemiologic studies of risk and protective factors for poor oral health have mostly been among children and adults, seldom focusing on adolescents. The aims of this study were to examine whether serum cotinine, a marker of tobacco exposure, and serum vitamin D are independently associated with dental caries experience among adolescents.MethodsCross‐sectional data from 2579 adolescent participants in the 2005‐2008 National Health and Nutritional Examination Survey were analysed. The exposures, cotinine and vitamin D, were measured in serum while dental caries experience was determined by screening examination, and a case defined as having ≥1 decayed or filled teeth. Survey‐adjusted logistic regression estimated prevalence odds ratios (POR) and 95% confidence intervals (CI) between the respective exposures and outcome.ResultsThe overall median (IQR) serum cotinine level was 0.15 ng/mL (0.04, 1.80) while the mean (SE) serum vitamin D concentration was 68.2 nmol/L (1.36). In contrast to participants with serum cotinine ≤3 ng/L, those with levels >3 ng/L had covariate‐adjusted estimate of 1.69 (1.16, 2.47) for caries experience. Each additional mean (ng/L) serum cotinine level was associated with an 8% (95% CI = 1.01, 1.16) greater adjusted prevalence odds of having caries experience. In contrast to participants with vitamin D ≥ 50 nmol/L, those with levels of30‐ < 50 nmol/L and <30 nmol/L had non‐statistically significant adjusted estimates of 1.02 (0.72, 1.44) and 1.23 (0.70, 2.16) respectively for caries experience.ConclusionsSerum cotinine is associated with dental caries experience among adolescents and while deficient (<30 nmol/L) levels of vitamin D appear to be associated with greater prevalence odds of caries experience, this association is inconclusive.
How representative of a general type 2 diabetes population are patients included in cardiovascular outcome trials with SGLT2 inhibitors? A large European observational study
Authors: Birkeland Kåre I. , Bodegard Johan , Norhammar Anna , Kuiper Josephina G. , Georgiado Elena , Beekman‐Hendriks Wendy L. , Thuresson Marcus , Pignot Marc , Herings Ron M. C. , Kooy Adriaan 
Published: December 2018

AimsEnrollment criteria vary substantially among cardiovascular outcome trials (CVOTs) of sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2is), which impacts the relationship between a trial population and the general type 2 diabetes (T2D) population. The aim of this study was to evaluate the representativeness of four SGLT‐2i CVOTs of a general T2D population.MethodsT2D patients from Germany, The Netherlands, Norway and Sweden were included in the study. Given the available data per country, key inclusion and exclusion criteria were defined by diagnoses, procedures and drug treatments to facilitate comparability among countries. Representativeness was determined by dividing the number of patients fulfilling the key enrolment criteria of each CVOT (CANVAS, DECLARE‐TIMI 58, EMPA‐REG OUTCOME, VERTIS‐CV) by the total T2D population.ResultsIn 2015, a total T2D population of 803 836 patients was identified in Germany (n = 239 485), in The Netherlands (n = 36 213), in Norway (n = 149 782) and in Sweden (n = 378 356). These populations showed a 25% to 44% cardiovascular (CV) disease baseline prevalence and high CV‐preventive drug use (>80%). The general T2D population had less prevalent CV disease and patients were slightly older than those included in the CVOTs. The DECLARE‐TIMI 58 trial had the highest representativeness, 59% compared to the general T2D population, and this representativeness was almost 2‐, 3‐ and 4‐fold higher compared to the CANVAS (34%), EMPA‐REG OUTCOME (21%) and VERTIS‐CV (17%) trials, respectively.ConclusionsIn large T2D populations within Europe, consistent patterns of representativeness of CVOTs were found when applying the main enrolment criteria. The DECLARE‐TMI 58 trial had the highest representativeness, indicating that it included and examined patients who are most representative of the general T2D patients in the studied countries.
The effects of incretin‐based therapies on β‐cell function and insulin resistance in type 2 diabetes: A systematic review and network meta‐analysis combining 360 trials
Authors: Wu Shanshan , Gao Le , Cipriani Andrea , Huang Yi , Yang Zhirong , Yang Jun , Yu Shuqing , Zhang Yuan , Chai Sanbao , Zhang Zilu , Sun Feng , Zhan Siyan 
Published: December 2018

AimTo evaluate the comparative effects of incretin‐based therapies, including glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and dipeptidyl peptidase‐4 inhibitors (DPP‐4Is), on β‐cell function and insulin resistance in patients with type 2 diabetes mellitus (T2DM).Materials and MethodsMedline, Embase, the Cochrane Library and www.clinicaltrials.gov were searched for randomized controlled trials (RCTs) with a duration of at least 4 weeks. Network meta‐analysis was performed, followed by subgroup analysis and meta‐regression. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the quality of evidence. Outcomes of interest include homeostasis model assessment for β cell function (HOMA‐β) and insulin resistance (HOMA‐IR), fasting C‐peptide and fasting plasma glucose (FPG). Weighted mean difference (WMD) with 95% confidence interval (CI) was calculated as the measure of effect size.ResultsA total of 360 RCTs (74% at least double‐blinded) with 157 696 patients were included. Incretin‐based therapies were compared with six other classes of glucose‐lowering drugs or with placebo. Compared with placebo, a significant increase in HOMA‐β and fasting C‐peptide was detected for GLP‐1RAs (WMD = 20.31 [95% CI, 16.34‐24.39] with low quality; WMD = 0.16 ng/mL [95% CI, 0.03‐0.29] with low quality) and for DPP‐4Is (WMD = 9.90 [95% CI, 8.27‐11.61] with moderate quality; WMD = 0.09 ng/mL [95% CI, 0.04‐0.14] with moderate quality) separately, while a significant reduction in HOMA‐IR and FPG were found in favour of GLP‐1RAs (WMD = −0.67 [95% CI, −1.08 to −0.27] with low quality; WMD = −1.04 mmol/L [95% CI, −1.26 to −0.83] with moderate quality) and DPP‐4Is (WMD = −0.23 [95% CI, −0.38 to −0.08] with low quality; WMD = −0.77 mmol/L [95% CI, −0.98 to −0.57] with moderate quality), respectively.ConclusionsIncretin‐based therapies not only show an increase in HOMA‐β and fasting C‐peptide level, but also achieve a reduction in HOMA‐IR and FPG in comparison with placebo. Although GRADE scores indicate low to moderate for most comparisons, incretin‐based therapies seem to be an advisable option for long‐term treatment to preserve β‐cell function.
Ophiostoma tsotsi and Ophiostoma quercus associated with Platypus cylindrus F. (Coleoptera: Curculionidae) in cork oak stands in Tunisia
Authors: Bellahirech Amani , Inácio Maria L. , Woodward Steve , Ben Jamâa Mohamed L. , Nóbrega Filomena 
Published: December 2018

AbstractAmbrosia beetles, including Platypus cylindrus, commonly act as vectors of Ophiostomatales. In an investigation of fungi associated with P. cylindrus, several species of Ophiostomatales were identified, including two species of Ophiostoma s. str. These two species were characterized based on comparisons of DNA sequences of the internal transcribed spacer regions including the 5.8S gene of rDNA and β‐tubulin gene. Two distinct clades were discernable in the phylogenetic trees, supported by high bootstrap values. One clade included the species Ophiostoma tsotsi, reported herein for the first time in Tunisia, and the species Ophiostoma quercus.
Diplodia sapinea found on Scots pine in Finland
Authors: Müller Michael M. , Hantula Jarkko , Wingfield Michael , Drenkhan Rein 
Published: December 2018

AbstractDiplodia sapinea is an important pathogen of Pinus spp. in many parts of the world's temperate and sub‐tropical zones. In Central Europe, this fungus has been known since its first description in the 19th century. But it was only in 2007 that the fungus was identified using DNA‐markers in northern Europe (in Estonia). Viljo Kujala reported observing D. sapinea on logging debris of Norway spruce in Finland in 1945, but we have not been able to verify the identifications from his herbarium samples. In 2004, we collected cones under asymptomatic Scots pine (Pinus sylvestris) trees at one location near the southern coast of Finland but failed to isolate D. sapinea from the samples. In 2015 and 2016, we collected fallen Scots pine cones in 15 Scots pine stands in various parts of Finland and the fungus was found at five locations in southwestern Finland including the location investigated in 2004. Frequency of cones with pycnidia of D. sapinea varied from 1% to 12% in the infested stands. No symptoms of Diplodia tip blight or resinous cankers were detected in trees in the stands where the cones were collected. The results suggest a recent introduction after 2004 of the D. sapinea in Finland.
Talking about trauma in therapy: Perspectives from young people with post‐traumatic stress symptoms and first episode psychosis
Authors: Tong Janet , Simpson Katrina , Alvarez‐Jimenez Mario , Bendall Sarah 
Published: December 2018

AimDespite recommendations from national guidelines, individuals with first episode psychosis (FEP) are currently unlikely to have the effects of their traumatic experiences assessed and treated within psychosis treatment. This may be due to the mismatch between the objectives of trauma‐specific treatments (directly targeting post‐traumatic stress symptoms by talking about the trauma) and trauma‐informed care (limiting practices that may retraumatise clients). We aimed to gain an understanding of what it was like for young people to talk about trauma in FEP treatment, and how their experiences related to the broad conceptualisations of trauma‐informed and trauma‐specific treatment approaches.MethodsSemi‐structured interviews were conducted with eleven participants (18‐27 years) with FEP and post‐traumatic stress disorder (PTSD) symptoms after the completion of an intervention for the effects of trauma. Transcripts were analysed using an interpretative phenomenological approach.ResultsTwo superordinate themes were identified, each with subordinate themes. 1. Reluctance to approach the trauma memory: 1a. Not wanting to talk about trauma; 1b. Difficulty acknowledging that the trauma had occurred; 1c. Not wanting to re‐experience emotions associated with trauma. 2. Factors aiding the process: 2a. Desire for change; 2b. Not being pushed to talk; 2c. Valuing the case manager; 2d. Time.ConclusionsA majority of participants in the study experienced reluctance when recounting their trauma memories. Being in control of how trauma memories are shared and having time for the therapeutic relationship to develop enhanced participants' readiness for talking about trauma. Incorporating trauma‐informed principles and motivational interviewing could aid in facilitating the processes around talking about trauma.
Prey nutrient content creates omnivores out of predators
Authors: Ugine Todd A. , Krasnoff Stuart B. , Grebenok Robert J. , Behmer Spencer T. , Losey John E. 
Published: December 2018

AbstractThe proximate forces that create omnivores out of herbivores and predators have long fascinated ecologists, but the causal reasons for a shift to omnivory are poorly understood. Determining what factors influence changes in trophic position are essential as omnivory plays a central role in theoretical and applied ecology. We used sevenspotted lady beetles (Coccinella septempunctata) to test how prey nutrient content affects beetles’ propensity to engage in herbivory. We show that beetles consuming an all‐prey diet demonstrate normal growth and development, but suffer a complete loss of fitness (spermatogenic failure) that is restored via herbivory and supplementation with phytosterols and cholesterol. Furthermore, we show that lady beetles possess a state‐dependent sterol‐specific appetite and redressed their sterol deficit by feeding on foliage. These results demonstrate that predators balance their nutrient intake via herbivory when prey quality is low, and reveal a selective force (sterol nutrition) that drives predatory taxa to omnivory.
Novel features for capturing temporal variations of rhythmic limb movement to distinguish convulsive epileptic and psychogenic nonepileptic seizures
Authors: Kusmakar Shitanshu , Karmakar Chandan , Yan Bernard , Muthuganapathy Ramanathan , Kwan Patrick , O'Brien Terence J , Palaniswami Marimuthu Swami 
Published: December 2018

SummaryObjectiveTo investigate the characteristics of motor manifestation during convulsive epileptic and psychogenic nonepileptic seizures (PNES), captured using a wrist‐worn accelerometer (ACM) device. The main goal was to find quantitative ACM features that can differentiate between convulsive epileptic and convulsive PNES.MethodsIn this study, motor data were recorded using wrist‐worn ACM‐based devices. A total of 83 clinical events were recorded: 39 generalized tonic–clonic seizures (GTCS) from 12 patients with epilepsy, and 44 convulsive PNES from 7 patients (one patient had both GTCS and PNES). The temporal variations in the ACM traces corresponding to 39 GTCS and 44 convulsive PNES events were extracted using Poincaré maps. Two new indices—tonic index (TI) and dispersion decay index (DDI)—were used to quantify the Poincaré‐derived temporal variations for every GTCS and convulsive PNES event.ResultsThe TI and DDI of Poincaré‐derived temporal variations for GTCS events were higher in comparison to convulsive PNES events (P < 0.001). The onset and the subsiding patterns captured by TI and DDI differentiated between epileptic and convulsive nonepileptic seizures. An automated classifier built using TI and DDI of Poincaré‐derived temporal variations could correctly differentiate 42 (sensitivity: 95.45%) of 44 convulsive PNES events and 37 (specificity: 94.87%) of 39 GTCS events. A blinded review of the Poincaré‐derived temporal variations in GTCS and convulsive PNES by epileptologists differentiated 26 (sensitivity: 70.27%) of 44 PNES events and 33 (specificity: 86.84%) of 39 GTCS events correctly.SignificanceIn addition to quantifying the motor manifestation mechanism of GTCS and convulsive PNES, the proposed approach also has diagnostic significance. The new ACM features incorporate clinical characteristics of GTCS and PNES, thus providing an accurate, low‐cost, and practical alternative to differential diagnosis of PNES.