bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomised clinical trial: vonoprazan, a novel potassium‐competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis
Authors: Ashida K. , Sakurai Y. , Hori T. , Kudou K. , Nishimura A. , Hiramatsu N. , Umegaki E. , Iwakiri K. 
Published: November 2015

SummaryBackgroundVonoprazan is a novel potassium‐competitive acid blocker which may provide clinical benefit in acid‐related disorders.AimTo verify the non‐inferiority of vonoprazan vs. lansoprazole in patients with erosive oesophagitis (EE), and to establish its long‐term safety and efficacy as maintenance therapy.MethodsIn this multicentre, randomised, double‐blind, parallel‐group comparison study, patients with endoscopically confirmed EE (LA Classification Grades A–D) were randomly allocated to receive vonoprazan 20 mg or lansoprazole 30 mg once daily after breakfast. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 8. In addition, subjects who achieved healed EE in the comparison study were re‐randomised into a long‐term study to investigate the safety and efficacy of vonoprazan 10 or 20 mg as maintenance therapy for 52 weeks.ResultsOf the 409 eligible subjects randomised, 401 completed the comparison study, and 305 entered the long‐term maintenance study. The proportion of patients with healed EE up to week 8 was 99.0% for vonoprazan (203/205) and 95.5% for lansoprazole (190/199), thus verifying the non‐inferiority of vonoprazan (P < 0.0001). Vonoprazan was also effective in patients with more severe EE (LA Classification Grades C/D) and CYP2C19 extensive metabolisers. In the long‐term maintenance study, there were few recurrences (<10%) of EE in patients treated with vonoprazan 10 or 20 mg. Overall, vonoprazan was well‐tolerated.ConclusionsThe non‐inferiority of vonoprazan to lansoprazole in EE was verified in the comparison study, and vonoprazan was well‐tolerated and effective during the long‐term maintenance study.
Combined ursodeoxycholic acid (UDCA) and fenofibrate in primary biliary cholangitis patients with incompleteUDCAresponse may improve outcomes
Authors: Cheung A. C. , Lapointe‐Shaw L. , Kowgier M. , Meza‐Cardona J. , Hirschfield G. M. , Janssen H. L. A. , Feld J. J. 
Published: November 2015

SummaryBackgroundFibrates appear to improve biochemistry in patients with primary biliary cholangitis (PBC), but it is unclear which factors predict response and whether treatment improves transplant‐free survival.AimTo evaluate biochemical profiles, liver‐related outcomes and adverse events following fenofibrate therapy inPBCpatients with incomplete response to ursodeoxycholic acid (UDCA).MethodsA retrospective cohort study was performed at a tertiary centre. Cox regression was used to compare outcomes between patients treated with fibrates andUDCA(FF) orUDCAalone, adjusted for a propensity score to account for treatment selection bias.ResultsA total of 120 patients were included (FFgroupn= 46,UDCAgroupn= 74, median fenofibrate treatment 11 months); 41% vs. 7% met the Toronto criteria for biochemical response [alkaline phosphatase ≤1.67 times the upper limit of normal] in theFFandUDCAgroups, respectively (P= 0.0001). Fenofibrate was also associated with improved decompensation‐free and transplant‐free survival [hazard ratio (HR) 0.09, 95%CI0.03–0.32,P= 0.0002]. However, only fenofibrate use, not biochemical response, was independently associated with improved outcomes on multivariable analysis (HR0.40, 95%CI0.17–0.93,P= 0.03). Twenty‐two percent discontinued fenofibrate due to adverse events (most common: abdominal pain and myalgias). In cirrhotic patients, bilirubin increased more rapidly in theFFgroup (P= 0.005).ConclusionsFenofibrate therapy is associated with significant improvement inalkaline phosphatase, decompensation‐free and transplant‐free survival inPBCpatients with incompleteUDCAresponse. However, fenofibrate should be used cautiously in cirrhosis, with close monitoring for clinical/biochemical decompensation. Additional studies are required to assess the validity ofalkaline phosphataseas an appropriate response criteria for fibrate therapy.
Expression of Forkhead box M1 in soft tissue leiomyosarcoma: Clinicopathologic and in vitro study using a newly established cell line
Authors: Maekawa Akira , Kohashi Kenichi , Setsu Nokitaka , Kuda Masaaki , Iura Kunio , Ishii Takeaki , Matsunobu Tomoya , Nakatsura Tetsuya , Iwamoto Yukihide , Oda Yoshinao 
Published: November 2015

Leiomyosarcoma (LMS) of soft tissue is a sarcoma with smooth‐muscle differentiation, and conventional chemotherapy does not improve its outcome. The application of novel antitumor agents and precise prognostication has been demanded. The expression of the protein Forkhead box M1 (FOXM1), a member of the FOX family, is considered an independent predictor of poor survival in many cancers and sarcomas. However, the expression status of FOXM1 in LMS is poorly understood. The purposes of this study were to examine the correlation between the expression of FOXM1 and clinicopathologic or prognostic factors and to clarify the efficacy of FOXM1 target therapy in LMS. We evaluated the immunohistochemical expressions of FOXM1 using 123 LMS tumor specimens. Univariate and multivariate survival analyses revealed that FOXM1 expression was associated with poor prognosis in LMS. An in vitro study was then carried out to examine the antitumor effect of a FOXM1 inhibitor (thiostrepton) and siRNA on a novel LMS cell line, TC616. We also assessed the efficacy of the combined use of doxorubicin and thiostrepton. Thiostrepton showed dose‐dependent antitumor activity and TC616 cells treated with the combination of thiostrepton and doxorubicin showed lower proliferation compared to those treated with either drug individually. FOXM1 interruption by siRNA decreased cell proliferation and increased chemosensitivity. In conclusion, FOXM1 has potential to be a therapeutic target for LMS.
Contact allergy to chlorhexidine in a tertiary dermatology clinic in Denmark
Authors: Opstrup Morten S. , Johansen Jeanne D. , Zachariae Claus , Garvey Lene H. 
Published: November 2015

SummaryBackgroundChlorhexidine is a widely used disinfectant in the healthcare setting and in cosmetic products. A high prevalence of chlorhexidine contact allergy was reported in Denmark in the 1980s (2.0–5.4% of patients patch tested). It is unknown whether the prevalence is still high, which products cause the contact allergy, and whether accidental re‐exposure occurs in some patients.ObjectivesTo estimate the prevalence of chlorhexidine contact allergy in a tertiary dermatology clinic in Denmark; to investigate whether patch testing with both chlorhexidine diacetate and chlorhexidine digluconate is necessary; to investigate how many patients have combined immediate‐type allergy and contact allergy; and to identify which products cause chlorhexidine contact allergy, and whether patients are accidentally re‐exposed.MethodsThis was a retrospective study including all patients patch tested with chlorhexidine during 2003–2013 at the Department of Dermato‐Allergology at Copenhagen University Hospital Gentofte (n = 8497). All patients with a positive patch test reaction to chlorhexidine were sent a questionnaire comprising questions about the cause of the allergy and re‐exposure.ResultsOverall, 1.0% (n = 82) of all patients patch tested with chlorhexidine were positive. A decrease in the prevalence was observed over time, most likely because of lowering of the test concentration from 1.0 to 0.5% in 2008. Of the 82 patients, 28 (0.3%) had positive test reactions to both chlorhexidine salts, 43 (0.5%) had a positive test reaction only to chlorhexidine diacetate, and 11 (0.1%) had a positive test reaction to chlorhexidine digluconate. Three patients were both patch test‐positive and prick test‐positive. A known cause of the allergy was reported by 19 patients (40%) in the questionnaire: the products used in the healthcare setting were mainly reported, but some reported cosmetic products. Accidental re‐exposure was reported by 15 patients (32%), of whom 13 reported symptoms.ConclusionsThe prevalence of chlorhexidine contact allergy does not seem to be higher in Denmark than in other European countries. Patch testing with both chlorhexidine diacetate and chlorhexidine digluconate may be beneficial. Testing for immediate‐type allergy in patients with a positive patch test reaction to chlorhexidine is recommended. Chlorhexidine‐containing products used in the healthcare setting and in cosmetics are potential causes of sensitization and allergy. Re‐exposure is common, highlighting the fact that patients and healthcare personnel need to be well informed about possible sources of exposure.
In vitro comparison of the effect of two factor XI (FXI) concentrates on thrombin generation in major FXI deficiency
Authors: Pike G. N. , Cumming A. M. , Hay C. R. M. , Sempasa B. , Sutherland M. , Thachil J. , Burthem J. , Bolton‐Maggs P. H. B. 
Published: November 2015

IntroductionBleeding risk in factor XI (FXI) deficiency following surgery may be reduced by treatment with either of two FXI concentrates, but indications for their use are unclear and treatment has been associated with thrombosis.AimTo quantify and compare the effects of two different FXI concentrates on thrombin generation (TG) in major FXI deficiency (FXI:C < 15 IU dL−1).MethodsThrombin generation was measured in controls (n = 50), FXI‐deficient individuals pre and post in vitro spiking with FXI concentrates (n = 10), and in ex vivo samples following treatment with FXI concentrate (n = 3).ResultsThrombin generation was significantly impaired in FXI deficiency but improved following FXI replacement in vitro and in vivo. LFB Hemoleven® had greater effect on TG than BPL FXI concentrate in vitro (equivalent in vivo doses 10, 20 and 30 U kg−1): higher endogenous thrombin potential (ETP) (P < 0.0001), peak height (P < 0.01) velocity (P < 0.0002) and shorter lag time and time to peak (both P < 0.003). Some measurements with LFB Hemoleven® exceeded the reference range. At lower dose (5 U kg−1), BPL FXI concentrate normalized all TG parameters and LFB Hemoleven® normalized the ETP but exceeded the reference range with other parameters.ConclusionBoth FXI concentrates improve TG in vitro in major FXI deficiency but differ in dose response, and for both products, doses lower than previously recommended normalized TG in vitro. Comparison of in vitro spiked and ex vivo samples suggest that in vitro results could be used to estimate an expected in vivo response to FXI replacement.
A wearable wound moisture sensor as an indicator for wound dressing change: an observational study of wound moisture and status
Authors: Milne Stephen D , Seoudi Ihab , Al Hamad Hanadi , Talal Talal K , Anoop Anzila A , Allahverdi Niloofar , Zakaria Zain , Menzies Robert , Connolly Patricia 
Published: November 2015

AbstractWound moisture is known to be a key parameter to ensure optimum healing conditions in wound care. This study tests the moisture content of wounds in normal practice in order to observe the moisture condition of the wound at the point of dressing change. This study is also the first large‐scale observational study that investigates wound moisture status at dressing change. The WoundSense sensor is a commercially available moisture sensor which sits directly on the wound in order to find the moisture status of the wound without disturbing or removing the dressing. The results show that of the 588 dressing changes recorded, 44·9% were made when the moisture reading was in the optimum moisture zone. Of the 30 patients recruited for this study, 11 patients had an optimum moisture reading for at least 50% of the measurements before dressing change. These results suggest that a large number of unnecessary dressing changes are being made. This is a significant finding of the study as it suggests that the protocols currently followed can be modified to allow fewer dressing changes and less disturbance of the healing wound bed.
Advance care planning for nursing home residents with dementia: policy vs. practice
Authors: Ampe Sophie , Sevenants Aline , Smets Tinne , Declercq Anja , Van Audenhove Chantal 
Published: November 2015

AbstractAimsThe aims of this study were: to evaluate the advance care planning policy for people with dementia in nursing homes; to gain insight in the involvement of residents with dementia and their families in advance care planning, and in the relationship between the policy and the actual practice of advance care planning.BackgroundThrough advance care planning, nursing home residents with dementia are involved in care decisions, anticipating their reduced decision‐making capacity. However, advance care planning is rarely realized for this group. Prevalence and outcomes have been researched, but hardly any research has focused on the involvement of residents/families in advance care planning.DesignObservational cross‐sectional study in 20 nursing homes.MethodsThe ACP audit assessed the views of the nursing homes’ staff on the advance care planning policy. In addition, individual conversations were analysed with ‘ACP criteria’ (realization of advance care planning) and the ‘OPTION’ instrument (involvement of residents/families). Data collection: June 2013–September 2013.ResultsNursing homes generally met three quarters of the pre‐defined criteria for advance care planning policy. In almost half of the conversations, advance care planning was explained and discussed substantively. Generally, healthcare professionals only managed to involve residents/families on a baseline skill level. There were no statistically significant correlations between policy and practice.ConclusionThe evaluations of the policy were promising, but the actual practice needs improvement. Future assessment of both policy and practice is recommended. Further research should focus on communication interventions for implementing advance care planning in the daily practice.
Soil microorganisms behave like macroscopic organisms: patterns in the global distribution of soil euglyphid testate amoebae
Authors: Lara Enrique , Roussel‐Delif Ludovic , Fournier Bertrand , Wilkinson David M. , Mitchell Edward A. D. 
Published: November 2015

AbstractAimPatterns of α‐ and β‐diversity of soil protist communities and the factors that shape them remain largely unknown. We undertook a world‐wide survey of forest litter to investigate the patterns of diversity in a group of testate amoebae. We aimed to assess: (1) whether there is a latitudinal gradient in α‐diversity, and (2) whether β‐diversity was correlated solely with environmental factors commonly used in soil biology research or if it was also independently explained by geographical barriers.LocationWorld‐wide.MethodsWe studied the diversity of Euglyphida, a common group of testate amoebae, in 35 samples of forest litter and moss samples from a global survey, using small subunit rRNA gene sequences. We assessed the relationship between sample α‐diversity and latitude using generalized additive models (GAM). Furthermore, we determined the relationships between community composition and geographical models (distance‐based Moran's Eigenvector Maps – db‐MEM) using Generalized UniFrac distances (GUniFrac). We also investigated the relationship between individual measured soil parameters, WorldClim data and diversity (alpha plus beta) using both raw data and synthetic variables obtained through principal components analysis.ResultsWe recorded 245 phylotypes belonging to 6 out of 7 known Euglyphida families, plus four novel deep clades. Euglyphid α‐diversity was positively correlated with temperature and negatively with latitude and litter C/N ratio. Euglyphida community structure was correlated with the spatial eigenvector Db‐MEM31, independently of all measured environmental variables. Db‐MEM31 corresponds to a natural barrier constituted by the Northern Hemisphere desert belt. Beta diversity was correlated with other environmental variables, such as pH, isothermality and temperature in the coldest month of the year.Main conclusionsSoil euglyphid α‐diversity displays a latitudinal gradient, and β‐diversity is not only correlated with climatic and physicochemical parameters but also with geographical barriers. Such patterns of diversity were until recently believed to be characteristic only for macroscopic organisms.
Testosterone Concentrations and Cardiovascular Autonomic Neuropathy in Men with Type 1 Diabetes in the Epidemiology of Diabetes Interventions and Complications Study (EDIC)
Authors: Kim Catherine , Pop-Busui Rodica , Braffett Barbara , Cleary Patricia A. , Bebu Ionut , Wessells Hunter , Orchard Trevor , Sarma Aruna V. 
Published: November 2015

Abstract

Introduction
Previous studies have reported that lower testosterone concentrations are associated with cardiovascular autonomic neuropathy (CAN), a risk factor for cardiovascular events. However, no studies have examined this relationship in men with type 1 diabetes, who are at high risk for CAN.

Aim
The aim of this study was to examine the associations between testosterone concentrations and measures of CAN in a large, well-characterized cohort of men with type 1 diabetes.

Methods
We conducted an analysis of men in the Diabetes Control and Complications Trial (DCCT), a randomized trial of intensive glucose control, and its observational follow-up the Epidemiology of Diabetes Intervention and Complications (EDIC) Study. Testosterone was measured by liquid chromatography mass spectrometry in stored samples from EDIC follow-up years 10 and 17. Regression models were used to assess the cross-sectional relationships between testosterone and CAN measures.

Main Outcome Measures
The main CAN measure from EDIC follow-up year 17 was a standardized composite of R–R variation with paced breathing &lt; 15, or R–R variation 15–20 combined with either a Valsalva ratio ≤ 1.5 or a decrease in diastolic blood pressure &gt; 10 mm Hg upon standing. Continuous R–R variation and Valsalva ratio were secondary outcomes.

Results
Lower total and bioavailable testosterone concentrations at follow-up years 10 and 17 were not associated with the presence of CAN at year 17. In analyses using Valsalva ratio as a continuous measure, higher total (P = 0.01) and bioavailable testosterone concentrations (P = 0.005) were associated with a higher (more favorable) Valsalva ratio after adjustment for covariates including age, body mass index, smoking status, hypertension, and glycemia.

Conclusions
Testosterone levels are not associated with CAN among men with type 1 diabetes. Although testosterone is associated with a higher Valsalva ratio, a more favorable indicator, the clinical significance of this association is not known.
Comparison of lipid profiles of Malassezia pachydermatis strains isolated from dogs with otitis externa and without clinical symptoms of disease
Authors: Czyzewska Urszula , Siemieniuk Magdalena , Pyrkowska Aleksandra , Nowakiewicz Aneta , Bieganska Malgorzata , Dabrowska Iwona , Bartoszewicz Marek , Dobrzyn Pawel , Tylicki Adam 
Published: November 2015

SummaryMalassezia pachydermatis can cause infections of the skin and mucous membranes, especially in animals. It becomes a problem also in medicine. It is considered that metabolic disorders as well as hormonal and immunological status of the host promote diseases caused by M. pachydermatis. Here we consider whether specific features of fungi could also favour infections. We checked whether there are differences in lipid profiles between strains obtained from dogs with otitis externa and strains obtained from healthy dogs. Lipid profiles were determined using thin layer chromatography and gas chromatography–mass spectrometry. All analyses were carried out on 32 strains derived from dogs with otitis externa and 31 strains isolated from dogs without symptoms of disease. The results show that strains isolated from dogs without symptoms of otitis externa are characterised by a higher content of fatty acids. They contain significantly more behenic and lignoceric acids on medium without addition of lipids, and more oleic acid and total monounsaturated fatty acids on medium with lipids supplementation. These strains have also a higher content of esters of ergosterol and triglycerides. Data obtained show differences which may be specific features of M. pachydermatis‐specific strains related to the ability of infection, which could be not directly related of the host condition.
Molecular mechanisms of suberoylanilide hydroxamic acid in the inhibition of TGF‐β1‐mediated canine corneal fibrosis
Authors: Gronkiewicz Kristina M. , Giuliano Elizabeth A. , Sharma Ajay , Mohan Rajiv R. 
Published: November 2015

AbstractObjectiveTo investigate molecular mechanisms mediating anti‐fibrotic effect of SAHA in the canine cornea using an in vitro model. We hypothesized that SAHA attenuates corneal fibrosis by modulating Smad‐dependent and, to a lesser extent, Smad‐independent signaling pathways activated by TGF‐β1, as well as matrix metalloproteinase (MMP) activity.MethodsCultured canine corneal fibroblasts (CCF) were incubated in the presence/absence of TGF‐β1 (5 ng/mL) and SAHA (2.5 μm) for 24 h. Western blot analysis was used to quantify non‐phosphorylated and phosphorylated isoforms of Smad2/3, p38 MAP kinase (MAPK), ERK1/2, and JNK1. Real‐time PCR and zymography were utilized to quantify MMP1, MMP2, MMP8, and MMP9 mRNA expressions and MMP2 and MMP9 protein activities, respectively.ResultsTGF‐β1 treatment caused a significant increase in phospho‐Smad2/3 and phospho‐p38 MAPK. SAHA treatment reduced TGF‐β1‐induced phosphorylation of Smad2/3 but not of p38 MAPK. TGF‐β1 did not modulate the phosphorylation of ERK1/2 or JNK1. SAHA caused a significant reduction in phospho‐ERK1/2 expression regardless of concurrent TGF‐β1 treatment. Neither SAHA alone nor in combination with TGF‐β1 altered phospho‐JNK1 expression. TGF‐β1 significantly increased MMP1 and MMP9 mRNA expressions but did not alter MMP2 mRNA. SAHA treatment attenuated TGF‐β1‐induced MMP9 mRNA expression while significantly enhancing TGF‐β1‐induced MMP1 mRNA expression. Zymography detected reduced expression of MMP2 and MMP9 proteins in untreated control CCF. TGF‐β1 treatment did not alter their expression, but SAHA treatment +/−TGF‐β1 significantly increased MMP2 and MMP9 protein expressions.ConclusionsThe corneal anti‐fibrotic effects of SAHA involve multiple mechanisms including modulation of canonical and non‐canonical components of TGF‐β1 intracellular signaling and MMP activity.
Epidemiology of Invasive Group A Streptococcal Disease in Alaska, 2001 to 2013
Authors: Rudolph Karen , Bruce Michael G. , Bruden Dana , Zulz Tammy , Reasonover Alisa , Hurlburt Debby , Hennessy Thomas 
Published: November 2015

ABSTRACTThe Arctic Investigations Program (AIP) began surveillance for invasive group A streptococcal (GAS) infections in Alaska in 2000 as part of the invasive bacterial diseases population-based laboratory surveillance program. Between 2001 and 2013, there were 516 cases of GAS infection reported, for an overall annual incidence of 5.8 cases per 100,000 persons with 56 deaths (case fatality rate, 10.7%). Of the 516 confirmed cases of invasive GAS infection, 422 (82%) had isolates available for laboratory analysis. All isolates were susceptible to penicillin, cefotaxime, and levofloxacin. Resistance to tetracycline, erythromycin, and clindamycin was seen in 11% (n= 8), 5.8% (n= 20), and 1.2% (n= 4) of the isolates, respectively. A total of 51emmtypes were identified, of whichemm1 (11.1%) was the most prevalent, followed byemm82 (8.8%),emm49 (7.8%),emm12 andemm3 (6.6% each),emm89 (6.2%),emm108 (5.5%),emm28 (4.7%),emm92 (4%), andemm41 (3.8%). The five most commonemmtypes accounted for 41% of isolates. Theemmtypes in the proposed 26-valent and 30-valent vaccines accounted for 56% and 78% of all cases, respectively. GAS remains an important cause of invasive bacterial disease in Alaska. Continued surveillance of GAS infections will help improve understanding of the epidemiology of invasive disease, with an impact on disease control, notification of outbreaks, and vaccine development.