bluuebunny/crossref_metadata_2025_split huggingface dataset:
The concomitant loss of APC and HNF4α in adult hepatocytes does not contribute to hepatocarcinogenesis driven by β‐catenin activation
Authors: Sartor Chiara , Bachelot Laura , Godard Cécile , Lager Franck , Renault Gilles , Gonzalez Frank J. , Perret Christine , Gougelet Angélique , Colnot Sabine 
Published: February 2019

AbstractBackground & AimsLoss of hepatocyte nuclear factor‐4α (HNF4α), a critical factor driving liver development and differentiation, is frequently associated with hepatocellular carcinoma (HCC). Our recent data revealed that HNF4α level was decreased in mouse and human HCCs with activated β‐catenin signalling. In addition, increasing HNF4α level by miR‐34a inhibition slowed tumour progression of β‐catenin‐activated HCC in mice.MethodsWe generated a Hnf4aflox/flox/Apcflox/flox/TTR‐CreERT2 (Hnf4a/Apc∆Hep) mouse line and evaluated the impact of Hnf4a disruption on HCC development and liver homoeostasis.ResultsThere was no significant impact of Hnf4a disruption on tumour onset and progression in Apc∆Hep model. However, we observed an unexpected phenotype in 28% of Hnf4a∆Hep mice maintained in a conventional animal facility, which presented disorganized portal triads, characterized by stenosis of the portal vein and increased number and size of hepatic arteries and bile ducts. These abnormal portal structures resemble the human idiopathic non‐cirrhotic portal hypertension syndrome. We correlated the presence of portal remodelling with a higher expression of protein and mRNA levels of TGFβ and BMP7, a key regulator of the TGFβ‐dependent endothelial‐to‐mesenchymal transition.ConclusionThese data demonstrate that HNF4α does not play a major role during β‐catenin‐driven HCC, thus revealing that the tumour suppressor role of HNF4α is far more complex and dependent probably on its temporal expression and tumour context. However, HNF4α loss in adult hepatocytes could induce abnormal portal structures resembling the human idiopathic non‐cirrhotic portal hypertension syndrome, which may result from endothelial‐ and epithelial‐to‐mesenchymal transitions.
Postglacial ecotype formation under outcrossing and self‐fertilization inArabidopsis lyrata
Authors: Lucek Kay , Hohmann Nora , Willi Yvonne 
Published: February 2019

AbstractThe formation of ecotypes has been invoked as an important driver of postglacial biodiversity, because many species colonized heterogeneous habitats and experienced divergent selection. Ecotype formation has been predominantly studied in outcrossing taxa, while far less attention has been paid to the implications of mating system shifts. Here, we addressed whether substrate‐related ecotypes exist in selfing and outcrossing populations ofArabidopsis lyratasubsp.lyrataand whether the genomic footprint differs between mating systems. The North American subspecies colonized both rocky and sandy habitats during postglacial range expansion and shifted the mating system from predominantly outcrossing to predominantly selfing in a number of regions. We performed an association study on pooled whole‐genome sequence data of 20 selfing or outcrossing populations, which suggested genes involved in adaptation to substrate. Motivated by enriched gene ontology terms, we compared root growth between plants from the two substrates in a common environment and found that plants originating from sand grew roots faster and produced more side roots, independent of mating system. Furthermore, single nucleotide polymorphisms associated with substrate‐related ecotypes were more clustered among selfing populations. Our study provides evidence for substrate‐related ecotypes inA. lyrataand divergence in the genomic footprint between mating systems. The latter is the likely result of selfing populations having experienced divergent selection on larger genomic regions due to higher genome‐wide linkage disequilibrium.
Deciphering the essentiality and function of the anti‐σM factors in Bacillus subtilis
Authors: Zhao Heng , Roistacher Daniel M. , Helmann John D. 
Published: February 2019

SummaryBacteria use alternative sigma factors to adapt to different growth and stress conditions. The Bacillus subtilis extracytoplasmic function sigma factor SigM regulates genes for cell wall synthesis and is crucial for maintaining cell wall homeostasis under stress conditions. The activity of SigM is regulated by its anti‐sigma factor, YhdL, and the accessory protein YhdK. Here, we show that dysregulation of SigM caused by the absence of either component of the anti‐sigma factor complex leads to toxic levels of SigM and severe growth defects. High SigM activity results from a dysregulated positive feedback loop, and can be suppressed by overexpression of the housekeeping sigma, SigA. Using a sigM merodiploid strain, we selected for suppressor mutations that allow survival of yhdL depletion strain. The recovered suppressor mutations map to the beta and beta‐prime subunits of RNA polymerase core enzyme and selectively reduce SigM activity, and in some cases increase the activity of other alternative sigma factors. This work highlights the ability of mutations in RNA polymerase that remodel the sigma‐core interface to differentially affect sigma factor activity, and thereby alter the transcriptional landscape of the cell.
‘Like a human being, I was an equal, I wasn't just a patient’: Service users’ perspectives on their experiences of relationships with staff in mental health services
Authors: Bacha Karin , Hanley Terry , Winter Laura Anne 
Published: February 2019

ObjectivesThe quality of therapeutic relationships in psychiatric services has a significant impact upon the therapeutic outcomes for people diagnosed with a severe mental illness. As previous work has not explicitly explored service users’ in‐depth views about the emotional impact of these relationships, the objective of this work was to bring this perspective to the fore and to gain a greater understanding about which relational components can lead to psychological change.DesignThe project was conducted alongside a service user organization. An interview design was used to qualitatively explore service users’ experiences and perceptions of their relationships with mental health practitioners.MethodsEight individuals who had experience of the mental health system in the United Kingdom were interviewed. Interpretative phenomenological analysis was used to analyse the data.FindingsThree superordinate themes emerged from the analysis. These were (1) Trying to survive: am I a person or just an object in the system?; (2) Traumatic experiences within relationships; and (3) Helpful and transformative relationships. Further, the key transformative components of these relationships were power, safety, and identity.ConclusionsMental health services should be more focused upon care, rather than control. The Power Safety Identity (PSI) model, a reflexive model based upon key relational components highlighted by participants, is proposed for services and professionals to consider their work. The components of this model are managed by mental health practitioners and can determine whether these relationships maintain, increase, or alleviate psychological distress.Practitioner points

Awareness of the relational components of power, safety, and identity has the potential to help practitioners reflect upon the tensions they experience in their relationships with service users.

Mental health services and professionals that are sensitive to issues related to power, safety, and identity when responding to the needs of the service users can improve how individuals perceive the quality of care provided by them.

Relationships between service users and mental health practitioners can encourage recovery if they are consistent, safe, trusting, provide protective power, and mirror a positive sense of self.
Early post‐operative intravenous tacrolimus in pediatric liver transplant recipients is not superior to oral tacrolimus
Authors: Sabra Tarek Abdelazeem , Okajima Hideaki , Yoshizawa Atsushi , Ogawa Eri , Okamoto Shinya , Osman Mohamed Abdelkader , Saad‐Eldin Yasser , Uemoto Shinji 
Published: February 2019

AbstractWe aimed to compare the early results of i.v. with p.o. TAC as a primary immunosuppressant in pediatric patients undergoing LT. This retrospective study enrolled 75 children who underwent LT and received TAC‐steroid regimens as a primary immunosuppressant between September 2011 and October 2015 at our institution. Thirty‐five recipients received TAC i.v. and 40 received TAC p.o. Early results were evaluated and compared, including ACR, EBV, or CMV infection; renal adverse effects; and hospital stay. Comparisons of 90‐day post‐transplant results showed that the rates of overall viral (74% vs 40% P < 0.002), EBV (46% vs 17.5% P < 0.008), and CMV (51% vs 30% P = 0.05) infections were significantly higher in the i.v. than in the p.o. group. Neither regimen has any adverse effects on renal function. There were no between‐group differences in ACR incidence and severity, serum creatinine concentration, and hospital stay. Patient and graft survival rates at 3 months and 1 year did not differ significantly between the two groups. Compared with p.o. treatment, i.v. administration of high TAC concentration did not have beneficial post‐transplant effects on ACR incidence and severity, while increasing the incidence of viral infections in pediatric LT.
Indications and efficacy of conversion from tacrolimus‐ to sirolimus‐based immunosuppression in pediatric patients who underwent liver transplantation for unresectable hepatoblastoma
Authors: Hendrickson Richard J. , Sujka Joseph , Fischer Ryan , Manalang Michelle , Daniel James , Andrews Walter S. 
Published: February 2019

AbstractSRL‐based immunosuppressive strategies in pediatric liver transplantation are not clearly defined, especially within the first year after liver transplant. TAC is the more common, traditional immunosuppressant used. However, SRL may modulate TAC‐associated kidney injury and may also have antiproliferative properties that are valuable in the management of patients following liver transplantation for HB. We sought to determine whether early conversion from TAC to SRL was safe, effective, and beneficial in a subset of liver transplant recipients with unresectable HB exposed to CDDP‐based chemotherapy. Between 2008 and 2013, six patients were transplanted for unresectable HB. All patients received at least one cycle of CDDP‐based chemotherapy prior to transplant. All patients were switched from TAC‐ to SRL‐based immunosuppression within 1 year of transplant. Five patients had improvement in their mGFR, while one patient had a slight decline. The improvement in mGFR was statistically significant. No adverse events were identified. Three patients had BPAR that responded to pulsed steroids. Historical controls showed similar rates of BPAR within the first year after transplant. There were no identified HB recurrences in the follow‐up time period. Conversion from TAC to SRL appears to be safe and effective in this selected group of pediatric liver transplant recipients without adverse reaction or HB recurrences.
Induction of tolerogenic properties by Anisakis larval antigens on murine dendritic cells
Authors: Zamora Vega , Rodero Marta , Andreu‐Ballester Juan Carlos , Mendez Susana , Cuéllar Carmen 
Published: February 2019

SummaryAimsThe objective of this work is to investigate whether Anisakis simplex larval antigens present immunomodulatory properties by the induction of tolerogenic dendritic cells (DCs) from two strains of mice (BALB/c and C57BL/6J).Methods and ResultsWe used mouse bone marrow‐derived DCs. We determined their antigen‐presenting ability by expression of membrane markers (MHC I and MHC II, CD80, CD86) and intracellular expression levels of IL‐10 and IL‐12 cytokines. We also analysed whether stimulation with A simplex larval antigens is enhanced by the co‐administration of the TLR4 and TLR9 agonists [LPS E coli 026B6 and CpG (ODN1826), respectively]. Two differential types of responses were found in the two mouse strains studied: the BALB/c strain showed an acute and inflammatory response, whereas the C57BL/6J mice developed a more discrete and resistant response. This suggests the coexistence of two opposing responses generated by A simplex larval antigens and confirms that the host genetic basis plays a role in the development of a Th2 or Treg response.ConclusionThe study of the mechanisms by which Anisakis manipulates the immune response through anti‐inflammatory molecules is of interest not only for the direct application on the development of anthelmintic strategies, but also for the development of new anti‐inflammatory products.
Stokes waves with constant vorticity: I. Numerical computation
Authors: Dyachenko Sergey A. , Hur Vera Mikyoung 
Published: February 2019

AbstractPeriodic traveling waves are numerically computed in a constant vorticity flow subject to the force of gravity. The Stokes wave problem is formulated via a conformal mapping as a nonlinear pseudodifferential equation, involving a periodic Hilbert transform for a strip, and solved by the Newton‐GMRES method. For strong positive vorticity, in the finite or infinite depth, overhanging profiles are found as the amplitude increases and tend to a touching wave, whose surface contacts itself at the trough line, enclosing an air bubble; numerical solutions become unphysical as the amplitude increases further and make a gap in the wave speed versus amplitude plane; another touching wave takes over and physical solutions follow along the fold in the wave speed versus amplitude plane until they ultimately tend to an extreme wave, which exhibits a corner at the crest. Touching waves connected to zero amplitude are found to approach the limiting Crapper wave as the strength of positive vorticity increases unboundedly, while touching waves connected to the extreme waves approach the rigid body rotation of a fluid disk.
Enterolithic folds in evaporites as microbially induced sedimentary structures: New model of formation and interpretation in the geological record
Authors: Escavy José I. , Herrero María J. 
Published: February 2019

AbstractEnterolithic structures are stratigraphically localized folds in gypsum beds found in certain saline evaporitic sedimentary units in a wide variety of basins. Different models of formation have been proposed, all related to inorganic processes. These models include: diagenetic transformation of gypsum beds producing either displacive growth of crystals or volume changes; mechanical folding caused by compressional stress; and folding produced by slumping. The analysis of three Cenozoic evaporite sequences in Spain reveals that none of the previous models explains their origin and existence. In these outcrops, gypsum enterolithic structures occur in horizontal beds with parallel troughs and crests of the folds. They appear in shoreline facies of lacustrine environments and did not undergo major diagenetic transformations after the primary lithification of the original sediment. Based on these observations, together with the study of a modern analogue in Minorca, Spain, a new model is proposed for the genesis of enterolithic structures. This new model is based on the existence of a microbial mat exposed to brine concentration–dilution cycles and strong wind events. The high wind flow events enhanced folding of the microbial mat that became subaerially exposed and lithified due to subsequent evaporation. Therefore, the presence of enterolithic structures could be used as an indicator of shallow water environmental conditions subject to variations in brine concentration in areas with strong wind flow events. Previous studies of some evaporitic successions should be revisited, taking into account the proposed model, which would imply new depositional environment interpretations. At the same time, the proposed model could explain the existence of Kinneyia‐type structures, also known as wrinkle structures, formed beneath microbial mats in peritidal zones. Moreover, considering enterolithic structures as microbially induced sedimentary structures could be useful as evidence of microbial life in the ancient geological record and on other planets such as Mars.
Scalable statistical inference for averaged implicit stochastic gradient descent
Authors: Fang Yixin 
Published: February 2019

AbstractStochastic gradient descent (SGD) provides a scalable way to compute parameter estimates in applications involving large‐scale data or streaming data. As an alternative version, averaged implicit SGD (AI‐SGD) has been shown to be more stable and more efficient. Although the asymptotic properties of AI‐SGD have been well established, statistical inferences based on it such as interval estimation remain unexplored. The bootstrap method is not computationally feasible because it requires to repeatedly resample from the entire data set. In addition, the plug‐in method is not applicable when there is no explicit covariance matrix formula. In this paper, we propose a scalable statistical inference procedure, which can be used for conducting inferences based on the AI‐SGD estimator. The proposed procedure updates the AI‐SGD estimate as well as many randomly perturbed AI‐SGD estimates, upon the arrival of each observation. We derive some large‐sample theoretical properties of the proposed procedure and examine its performance via simulation studies.
Sequential Requisites Analysis: A New Method for Analyzing Sequential Relationships in Ordinal Data*
Authors: Lindenfors Patrik , Krusell Joshua , Lindberg Staffan I. 
Published: February 2019

ObjectivesThis article presents a new method inspired by evolutionary biology for analyzing longer sequences of requisites for the emergence of particular outcome variables across numerous combinations of ordinal variables in social science analysis.MethodsThe approach is a sorting algorithm through repeated pairwise investigations of states in a set of variables and identifying what states in the variables occur before states in all other variables. We illustrate the proposed method by analyzing a set of variables from version 7.1 of the V‐Dem data set (Coppedge et al. 2017. Varieties of Democracy (V‐Dem) Project; Pemstein et al. 2017. University of Gothenburg, Varieties of Democracy Institute: Working Paper No. 21). With a large set of indicators measured over many years, the method makes it possible to identify and compare long, complex sequences across many variables.ResultsThis affords an opportunity, for example, to disentangle the sequential requisites of failing and successful sequences in democratization, or if requisites are different during different time periods.ConclusionsFor policy purposes, this is instrumental: Which components of democracy occur earlier and which later? Which components of democracy are therefore the ideal targets for democracy promotion at different stages?
Cenozoic thermal history reconstruction of the Dongpu Sag, Bohai Bay Basin: Insights from apatite fission‐track thermochronology
Authors: Tang Xiaoyin , Zuo Yinhui , Kohn Barry , Li Yi , Huang Shaopeng 
Published: February 2019

AbstractKnowledge of the thermal history of the onshore Dongpu Sag (DPS), Bohai Bay Basin is important for understanding its tectonic development within a broader regional context and for elucidating its poorly studied source‐rock maturation history. To unravel DPS time‐temperature development, apatite fission‐track data were acquired from eight sandstone samples in three deep wells. Thermal history modelling indicates continuous heating during the rifting stage (early Eocene to late Oligocene), followed by cooling attributed to tectonic uplift between ~27 and ~16 Ma, which resulted in the removal of ~1,400 to 1,800 m of section. Reheating occurred during the subsidence stage from middle Miocene until present. Unlike typical passive continental margin basins, the DPS experienced accelerated post‐rifting subsidence from ~5.8 Ma, which was especially marked since ~2.6 Ma. This phase was probably triggered by normal fault reactivation, in combination with a variation in the deep heat flow pattern.
Treatment of canine postoperative ocular hypertension with combined latanoprost 0.005% and atropine 1% ophthalmic solutions
Authors: de Linde Henriksen Michala , Lim Christine , Sharp Julia L. 
Published: February 2019

AbstractObjectiveTo compare the effects of topical 0.005% latanoprost (L) vs combined 0.005% latanoprost and 1% atropine (LA) on control of postoperative ocular hypertension (POH), development of posterior synechiae formation, pupil size, and blindness after phacoemulsification surgery in dogs.Animal studiedDogs with postoperative ocular hypertension were included in the study: L‐group, latanoprost (eight dogs, 14 eyes) andLA‐group, latanoprost and atropine (nine dogs, 15 eyes).ProceduresComplete ophthalmic examinations including tonometry were performed at 1, 7, and 21 days following phacoemulsification.ResultsNo significant differences were found between the measured intraocular pressure (IOP) at days 1 and 7 postphacoemulsification surgery in the L‐group and theLA‐group (P = 0.26 [14.12 ± 1.76 mmHg vs 16.96 ± 1.68 mmHg] andP = 0.71 [15.45 ± 1.43 mmHg vs 16.20 ± 1.36 mmHg], respectively). No significant differences were found between pupil sizes at day 7 for the two groups (P = 0.25 [13.83% vs 24.77%]). No significant differences were found between odds of posterior synechiae formation at day 21 (P = 0.92) with a probability ± SEfor L‐group vsLA‐group at 0.27 ± 0.14 vs 0.25 ± 0.13. No significant differences were found in odds of postoperative blindness between groups (P = 0.58) with a probability ± SEof 0.21 ± 0.11 vs 0.13 ± 0.09, respectively for L andLA.ConclusionsCombined topical latanoprost and atropine in dogs maintains normal postoperativeIOPs but does not seem to cause increased mydriasis compared to latanoprost alone.
Eye removal following parotid duct transposition surgery: A survey of current practice among veterinary ophthalmologists
Authors: Zimmer Jennifer L. , Diehl Kathryn A. , Myrna Kathern E. 
Published: February 2019

AbstractObjectiveIdentify dogs that required removal of an eye that had previously undergone a parotid duct transposition (PDT) and secondly to characterize demographics, surgical technique, and outcomes associated with it.ProcedureAn online survey was distributed to American College of Veterinary Ophthalmologists (ACVO) and Veterinary Ophthalmology (VOPH) listservs asking members to report the breed, reason for eye removal, time between surgeries, surgical technique, complications, and additional therapy instituted for dogs requiring removal of an eye subsequent to PDT surgery.ResultsSixteen dogs fit the inclusion criteria. Small breeds (<15 kg) made up 80% of the study population. Time between surgeries was <6 months (1/16), 6 to 12 months (7/16), and ≥1 year (8/16). Reasons for eye removal included: advancing corneal disease (6/16), discomfort (6/16), reaction to saliva (4/16), decreased saliva production (2/16), glaucoma (1/16), orbital neoplasia (1/16), and endophthalmitis (1/16). Surgical techniques included: transection of the parotid duct without ligation (2/16), ligation (9/16), and reversal of the PDT with reimplantation into the mouth (5/16). Complications reported were two dogs who underwent duct ligation experienced prolonged dilation of the duct that resolved with medical therapy (1/2) or without additional therapy (1/2).ConclusionLigation of or reversal of the PDT with reimplantation into the mouth are appropriate adjunctive surgical techniques when removing an eye that previously underwent PDT surgery. Two dogs with nonfunctional PDT had complication‐free eye removal with transection without ligation. Prolonged dilation of the duct is possible after eye removal with duct ligation and may resolve with time or medical management.