bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation with micro‐CT of different anticoagulation strategies during hemodialysis in patients with thrombocytopenia: A randomized crossover study
Authors: Vanommeslaeghe Floris , De Somer Filip , Josipovic Iván , Boone Matthieu , Dhondt Annemieke , Van Biesen Wim , Eloot Sunny 
Published: March 2019

AbstractIn patients with enhanced risk for bleeding, heparin‐free hemodialysis (HD) with conventional dialyzers is routinely used. To explore the potential benefit of using heparin‐coated dialyzers, we used a reference CT‐scanning technique and registered different clotting parameters to quantify coagulation with heparin‐coated versus non‐coated dialyzers. Six HD patients with thrombocytopenia were dialyzed 240 min in a randomized crossover study with Evodial 1.3 or FX600 Cordiax, each without anticoagulation. Blood samples were taken from the vascular access predialysis, and from the dialyzer inlet and outlet at 5 and 240 min after dialysis start. Predialysis blood samples were analyzed for hemoglobin, hematocrit, thrombocytes, fibrinogen, and activated partial thromboplastin time. On dialyzer inlet and outlet blood samples, a viscoelastic measurement of blood coagulation was performed using a Sonoclot analyzer. After dialysis, dialyzers were visually scored, subsequently dried for 24 h, weighed, and scanned with micro‐CT at a resolution of 25 µm. After image reconstruction, the open, non‐coagulated fibers were counted in a representative cross‐section at the dialyzer outlet. No sessions were terminated prematurely for circuit clotting. Heparin‐coated dialyzers had more patent fibers on micro‐CT versus non‐coated dialyzers and also had a better score of subjective visual assessment of fiber clotting. There was no difference in subjective assessment of clotting at the venous drip chamber. With both dialyzers, all ACT values remained in the normal range, and were lower at the dialyzer outlet versus inlet. In conclusion, dialysis with a heparin‐coated versus non heparin‐coated membrane results in substantially less coagulated fibers during 4 h hemodialysis without systemic anticoagulation. Eventual leaching of heparin, immobilized on the fiber membrane, does not result in measurable systemic anticoagulation.
A Bayesian Random Partition Model For Sequential Refinement and Coagulation
Authors: Zanini Carlos Tadeu Pagani , Müller Peter , Ji Yuan , Quintana Fernando A. 
Published: March 2019

Abstract
We analyze time-course protein activation data to track the changes in protein expression over time after exposure to drugs such as protein inhibitors. Protein expression is expected to change over time in response to the intervention in different ways due to biological pathways. We therefore allow for clusters of proteins with different treatment effects, and allow these clusters to change over time. As the effect of the drug wears off, protein expression may revert back to the level before treatment. In addition, different drugs, doses, and cell lines may have different effects in altering the protein expression. To model and understand this process we develop random partitions that define a refinement and coagulation of protein clusters over time. We demonstrate the approach using a time-course reverse phase protein array (RPPA) dataset consisting of protein expression measurements under different drugs, dose levels, and cell lines. The proposed model can be applied in general to time-course data where clustering of the experimental units is expected to change over time in a sequence of refinement and coagulation.
Impact of primary disease on outcome after allogeneic stem cell transplantation for transformed secondary acute leukaemia
Authors: Kröger Nicolaus , Eikema Diderik‐Jan , Köster Linda , Beelen Dietrich , de Wreede Liesbeth C. , Finke Jürgen , Koenecke Christian , Niederwieser Dietger , Bornhäuser Martin , Schoenland Stefan , Potter Victoria , Wolschke Christine , Maertens Johan , Theobald Matthias , Kobbe Guido , Itälä‐Remes Maija , Wulf Gerald , Kahls Peter , Forcade Edouard , Greinix Hildegard , Masszi Tamás , Yakoub‐Agha Ibrahim , Chalandon Yves , Robin Marie ,   on behalf of the Chronic Malignancies Working Party of the European Society for Blood Marrow Transplantation
Published: March 2019

SummaryMyelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) and chronic myelomonocytic leukaemia (CMML) can progress to secondary acute myeloid leukaemia (sAML). We compared the outcome of 4214 sAML patients who received allogeneic haematopoietic stem cell transplantation (allo‐HSCT) from an unrelated (62%) or human leucocyte antigen (HLA)‐identical sibling donor (38%) according the underlying disease: MDS (n = 3541), CMML (n = 251) or MPN (n = 422). After a median follow up of 46·5 months, the estimated 3‐year progression‐free (PFS) and overall survival (OS) for the entire group was 36% (34–37%) and 41% (40–43%), respectively. The cumulative incidence of relapse and non‐relapse mortality (NRM) was 37% (35–39%) and 27% (26–29%), respectively. In a multivariable analysis for OS, besides age (P < 0·001), unrelated donor (P = 0·011), cytomegalovirus ± constellation (P = 0·007), Karnofsky index ≤ 80 (P < 0·001), remission status (P < 0·001), peripheral blood as stem cell source (P = 0·009), sAML from MPN (P = 0·003) remained a significant factor in comparison to sAML from MDS, while worse outcome of sAML from CMML did not reach statistical significance (P = 0·06). This large registry study demonstrates a major impact of the underlying disease on outcome of sAML after allo‐HSCT.
Metabolic control and sex: A focus on inflammatory‐linked mediators
Authors: Henstridge Darren C. , Abildgaard Julie , Lindegaard Birgitte , Febbraio Mark A. 
Published: March 2019

Men and women have many differing biological and physiological characteristics. Thus, it is no surprise that the control of metabolic processes and the mechanisms underlying metabolic‐related diseases have sex‐specific components. There is a clear metabolic sexual dimorphism in that up until midlife, men have a far greater likelihood of acquiring cardio‐metabolic disease than women. Following menopause, however, this difference is reduced, suggestive of a protective role of the female sex hormones. Inflammatory processes have been implicated in the pathogenesis of cardio‐metabolic disease with human studies correlating metabolic disease acquisition or risk with levels of various inflammatory markers. Rodent studies employing genetic modifications or novel pharmacological approaches have provided mechanistic insight into the role of these inflammatory mediators. Sex differences impact inflammatory processes and the subsequent biological response. As a consequence, this may affect how inflammation alters metabolic processes between the sexes. Recently, some of our work in the field of inflammatory genes and metabolic control identified a sexual dimorphism in a preclinical model and caused us to question the frequency and scale of such findings in the literature. This review concentrates on inflammatory‐related signalling in relation to obesity, insulin resistance, and type 2 diabetes and highlights the differences observed between males and females. Differences in the activation and signalling of various inflammatory genes and proteins present another reason why studying both male and female patients or animals is important in the context of understanding and finding therapeutics for metabolic‐related disease.LINKED ARTICLESThis article is part of a themed section on The Importance of Sex Differences in Pharmacology Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.21/issuetoc
The proteostasis network provides targets for neurodegeneration
Authors: Newton Timothy Mark , Duce James Alex , Bayle Elliott David 
Published: March 2019

The production, quality control, and degradation of proteins are a tightly controlled process necessary for cell health. In order to regulate this process, cells rely upon a network of molecular chaperone proteins that bind misfolded proteins and help them fold correctly. In addition, some molecular chaperones can target terminally misfolded proteins for degradation. Neurons are particularly dependent upon this “proteostasis” system, failures in which lead to neurodegenerative disease. In this review, we identify opportunities for modulating molecular chaperone activity with small molecules, which could lower the burden of misfolded protein within neurons, reducing cell death and ameliorating the effects of neurodegeneration.Linked ArticlesThis article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc
S‐nitrosoglutathione inhibits cerebrovascular angiotensin II‐dependent and ‐independent AT1 receptor responses: A possible role of S‐nitrosation
Authors: Bouressam Marie‐Lynda , Lecat Sandra , Raoul Alexandre , Gaucher Caroline , Perrin‐Sarrado Caroline , Lartaud Isabelle , Dupuis François 
Published: March 2019

Background and PurposeAngiotensin II (AngII) and NO regulate the cerebral circulation. AngII AT1 receptors exert ligand‐dependent and ligand‐independent (myogenic tone [MT]) vasoconstriction of cerebral vessels. NO induces post‐translational modifications of proteins such as S‐nitrosation (redox modification of cysteine residues). In cultured cells, S‐nitrosation decreases AngII's affinity for the AT1 receptor. The present work evaluated the functional consequences of S‐nitrosation on both AngII‐dependent and AngII‐independent cerebrovascular responses.Experimental ApproachS‐Nitrosation was induced in rat isolated middle cerebral arteries by pretreatment with the NO donors, S‐nitrosoglutathione (GSNO) or sodium nitroprusside (SNP). Agonist‐dependent activation of AT1 receptors was evaluated by obtaining concentration–response curves to AngII. Ligand‐independent activation of AT1 receptors was evaluated by calculating MT (active vs. passive diameter) at pressures ranging from 20 to 200 mmHg in the presence or not of a selective AT1 receptor inverse agonist.Key ResultsGSNO or SNP completely abolished the AngII‐dependent AT1 receptor‐mediated vasoconstriction of cerebral arteries. GSNO had no impact on responses to other vasoconstrictors sharing (phenylephrine, U46619) or not (5‐HT) the same signalling pathway. MT was reduced by GSNO, and the addition of losartan did not further decrease MT, suggesting that GSNO blocks AT1 receptor‐dependent MT. Ascorbate (which reduces S‐nitrosated compounds) restored the response to AngII but not the soluble GC inhibitor ODQ, suggesting that these effects are mediated by S‐nitrosation rather than by S‐nitrosylation.Conclusions and ImplicationsIn rat middle cerebral arteries, GSNO pretreatment specifically affects the AT1 receptor and reduces both AngII‐dependent and AngII‐independent activation, most likely through AT1 receptor S‐nitrosation.
Exploring rural landowners’ willingness to protect species at risk in Prince Edward Island
Authors: Brown H. Carolyn Peach 
Published: March 2019

Key Messages

On private land the Species at Risk Act in Canada relies on voluntary stewardship as the preferred approach to protecting species at risk.
Private rural landowners in Prince Edward Island have some knowledge of species at risk and feel that they should be protected, but little knowledge of the federal Act.
Study participants say they are willing to change their land management practices in order to protect species at risk, and feel that government should provide education about land management practices to protect species and their habitat.
Echocardiography and monitoring patients receiving dopamine agonist therapy for hyperprolactinaemia: A joint position statement of the British Society of Echocardiography, the British Heart Valve Society and the Society for Endocrinology
Authors: Steeds Richard , Stiles Craig , Sharma Vishal , Chambers John , Lloyd Guy , Drake William 
Published: March 2019

SummaryThis is a joint position statement of the British Society of Echocardiography, the British Heart Valve Society and the Society for Endocrinology on the role of echocardiography in monitoring patients receiving dopamine agonist (DA) therapy for hyperprolactinaemia.

Evidence that DA pharmacotherapy causes abnormal valve morphology and dysfunction at doses used in the management of hyperprolactinaemia is extremely limited. Evidence of clinically significant valve pathology is absent, except for isolated case reports around which questions remain.
Attributing change in degree of valvar regurgitation, especially in mild and moderate tricuspid regurgitation, to adverse effects of DA in hyperprolactinaemia should be avoided if there are no associated pathological changes in leaflet thickness, restriction or retraction. Note must be taken that even where morphological change in leaflet structure and function may be suspected, grading is semi‐quantitative on echocardiography and may vary between different machines, ultrasound settings and operators.
Decisions regarding discontinuation of medication should only be made after review of serial imaging by an echocardiographer experienced in analysing drug‐induced valvulopathy or carcinoid heart disease.
A standard transthoracic echocardiogram should be performed before a patient starts DA therapy for hyperprolactinaemia. Repeat transthoracic echocardiography should then be performed at 5 years after starting cabergoline in patients taking a total weekly dose less than or equal to 2 mg. If there has been no change on the 5‐year scan, repeat echocardiography could continue at 5‐yearly intervals. If a patient is taking more than a total weekly dose of 2 mg, then annual echocardiography is recommended.
A critical assessment of case reports describing absent uterus in subjects with oestrogen deficiency
Authors: Berglund Agnethe , Burt Elizabeth , Cameron‐Pimblett Antoinette , Davies Melanie C. , Conway Gerard S. 
Published: March 2019

SummaryObjectiveThe dual diagnosis of hypoplastic uterus in association with ovarian dysgenesis is regularly reported but the pathogenesis of the association is unclear. The uterus, however, may be invisible to all imaging modalities without at least six months of exogenous oestrogen exposure in complete ovarian failure. We assessed all available case reports in this category to estimate whether the apparent association between primary ovarian insufficiency or Turner syndrome and Mullerian agenesis can be largely accounted for by oestrogen deficiency.DesignA literature review of all cases in which an association between ovarian insufficiency or Turner syndrome and hypoplastic uterus has been reported.PatientsPubMed was searched for all case reports associated with relevant key terms. In total, 22 publications with a total of 25 patients were identified and reviewed; 14 subjects had the normal female karyotype (46,XX), and 11 subjects had Turner Syndrome.MeasurementsProportion of subjects who had been exposed to adequate oestrogen prior to the absent uterine diagnosis.ResultsA diagnosis of absent uterus was made prior to exposure to exogenous oestrogen in 22/25 (88%) of subjects with primary hypogonadism including 14/14 females with normal karyotype and 8/11 females with Turner syndrome.ConclusionsOestrogen deficiency is a possible explanation for most subjects being reported as having Mullerian agenesis in association with Turner syndrome or primary ovarian insufficiency. In the presence of oestrogen deficiency, no conclusion can be made about the status of the uterus until adequate exposure to exogenous oestrogen has been completed and we suggest reassessment of the uterus when full adult dose has been reached towards the end of induction of puberty.
A thermosensitive chitosan‐based hydrogel for sealing and lubricating purposes in dental implant system
Authors: Cao Xiaoxiao , Cai Xinjie , Chen Ruiying , Zhang Huimei , Jiang Tao , Wang Yining 
Published: March 2019

AbstractBackgroundMechanical and biological complications associated with implant systems happen frequently in the clinic.PurposeTo develop a chitosan (CS)‐based thermosensitive hydrogel for sealing and lubricating purposes in dental implant system.Materials and MethodsIn this study, a thermosensitive hydrogel made up of CS, β‐glycerophosphate pentahydrate (β‐GP), and povidone‐iodine (PVP‐I), called CS/β‐GP/PVP‐I thermosensitive hydrogel, was fabricated. Three experimental groups with different volume ratios of CS to β‐GP were prepared, namely 16/4, 13/7, and 10/10 groups. The surface topography of the different groups and their physicochemical characteristics were examined by SEM, FTIR, and X‐ray diffraction analysis. The cytotoxicity of the hydrogel was examined by CCK‐8 test. In vitro antibacterial efficiency was analyzed by the spread plate method. Sealing ability was detected by incubating two‐piece implants in Escherichia coli suspension. Lubricating ability of the hydrogel was evaluated by the removal torque test with a calibrated digital torque meter.ResultsThe CS/β‐GP/PVP‐I thermosensitive hydrogel was fabricated and showed a highly porous structure under SEM. An in vitro cytotoxicity test demonstrated that 13/7 group displayed no cytotoxicity. Furthermore, all three groups showed obviously antibacterial effects. In the sealing ability test, 16/4 group showed the best sealing ability. The removal torque of 16/4 group and 13/7 group was significantly greater than control group.ConclusionsBased on our findings, it could be concluded that the thermosensitive and antibacterial CS/β‐GP/PVP‐I hydrogel with sealing and lubricating ability was successfully prepared. The hydrogel had better sealing and lubricating effects when the volume ratio of CS to β‐GP was 16/4.
Clinical and radiological manifestations of lipoid pneumonia according to etiology: Squalene, omega‐3‐acid ethyl esters, and idiopathic
Authors: Cha Seung‐Ick , Choi Sun Ha , Kim Hyun Jung , Kim Yeon Jae , Lim Jae‐Kwang , Yoo Seung‐Soo , Lee Shin‐Yup , Lee Jaehee , Kim Chang‐Ho , Park Jae‐Yong 
Published: March 2019

AbstractObjectivesClinical manifestations of lipoid pneumonia (LP) vary depending on the causative agents or underlying causes. The aim of the present study was to investigate the clinical and radiological features of LP, classified according to etiologic agents.MethodsThe clinico‐radiological characteristics of LP patients were retrospectively compared among groups: exogenous versus idiopathic and squalene versus omega‐3‐acid ethyl esters (O‐3‐AEE) versus idiopathic. Idiopathic group was defined as LP with no proven or reported etiological evidence.ResultsTwenty‐two patients met the diagnostic criteria for LP: squalene (9 [41%]), O‐3‐AEE (6 [27%]), olive oil (1 [5%]), and idiopathic (7 [32%]). Compared with the exogenous group, the idiopathic group showed a higher recurrence rate; higher frequencies of bronchial anthracofibrosis (BAF) and bronchoalveolar lavage (BAL) lymphocytosis; and a higher rate of crazy‐paving pattern and lower rate of consolidation on computed tomography scan. In three‐group tests, compared with the O‐3‐AEE group, the squalene group exhibited a significantly higher percentage of neutrophils and a higher rate of right middle lobe (RML) involvement.ConclusionsIn comparison with the exogenous group, the idiopathic group demonstrated BAL lymphocytosis, higher rates of recurrence and BAF, and a higher rate of crazy‐paving pattern. Compared with the O‐3‐AEE group, the squlaene group showed a higher percentage of BAL neutrophils and predominant RML involvement.
Which is the best predictor of de novo donor‐specific antibodies in a cohort of non‐sensitized first kidney transplantation: Antigenic, allelic, epitope, or physiochemical HLA mismatches?
Authors: Delion Alexandra , Girerd Sophie , Duarte Kevin , Girerd Nicolas , Schikowski Johan , Kessler Michèle , Frimat Luc , Aarnink Alice 
Published: March 2019

AbstractBackgroundAssessment of human leukocyte antigen (HLA) matching by using high‐resolution allele typing and knowledge of HLA molecule structure may lead to better prediction of de novo donor‐specific antibody (dnDSA) development.MethodsWe conducted a single‐center cohort study among 150 non‐sensitized first kidney transplant recipients to compare the association between antigenic (Ag), allelic (Al), eplet (Ep), amino acid (AAMS) HLA matching and electrostatic (EMS) and hydrophobic (HMS) mismatch scores, and the development of dnDSA.ResultsAfter a mean follow‐up time of 49.3 ± 17.7 months, 18 patients (12%) developed dnDSA. The number of HLA mismatches (MM) was significantly associated with the development of dnDSA. The optimal threshold, determined by Harrell's C‐index, varied according to the method (5 MM for Ag, P = 0.006; 6 for Al, P = 0.009; 22 for Ep, P = 0.005; 42 for AAMS, P = 0.0007; 45 for EMS, P = 0.009 and 44 for HMS, P = 0.026). C‐indices were similar for all matching approaches, suggesting a similar prediction of dnDSA development.ConclusionIn this cohort of low immunological risk transplant patients, the use of Al or Ep matching did not improve the prediction of dnDSA development in comparison with the traditional approach.
Randomised study of evolocumab in patients with type 2 diabetes and dyslipidaemia on background statin: Primary results of the BERSON clinical trial
Authors: Lorenzatti Alberto J. , Eliaschewitz Freddy G. , Chen Yundai , Lu Juming , Baass Alexis , Monsalvo Maria Laura , Wang Nan , Hamer Andrew W. , Ge Junbo 
Published: March 2019

AimTo evaluate the lipid‐lowering efficacy and safety of evolocumab combined with background atorvastatin in patients with type 2 diabetes mellitus (T2DM) and hyperlipidaemia or mixed dyslipidaemia.Materials and methodsBERSON was a double‐blind, 12‐week, phase 3 study (NCT02662569) conducted in 10 countries. Patients ≥18 to ≤80 years with type T2DM received atorvastatin 20 mg/d and were randomised 2:2:1:1 to evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) or placebo Q2W or QM. Co‐primary endpoints were the percentage change in low‐density lipoprotein cholesterol (LDL‐C) from baseline to week 12 and from baseline to the mean of weeks 10 and 12. Additional endpoints included atherogenic lipids, glycaemic measures, and adverse events (AEs).ResultsOverall, 981 patients were randomised and received ≥1 dose of study drug. Evolocumab significantly reduced LDL‐C versus placebo at week 12 (Q2W, −71.8%; QM, −74.9%) and at the mean of weeks 10 and 12 (Q2W, −70.3%; QM, −70.0%; adjusted P < 0.0001 for all) when administered with atorvastatin. Non‐high‐density lipoprotein cholesterol, apolipoprotein B100, total cholesterol, lipoprotein (a), triglycerides, high‐density lipoprotein cholesterol, and very low‐density lipoprotein cholesterol improved significantly with evolocumab versus placebo. The overall incidence of AEs was similar between evolocumab and placebo‐treated patients, and there were no clinically meaningful differences in changes over time in glycaemic variables (fasting serum glucose and HbA1c) between the two groups.ConclusionsIn patients with T2DM and hyperlipidaemia or mixed dyslipidaemia on statin, evolocumab significantly reduced LDL‐C and other atherogenic lipids, was well tolerated, and had no notable impact on glycaemic measures.