bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stopping long‐term treatment with nucleos(t)ide analogues is a favourable option for selected patients with HBeAg‐negative chronic hepatitis B
Authors: van Bömmel Florian , Berg Thomas 
Published: February 2018

AbstractThe immune response against the infection is impaired in patients with chronic hepatitis B, and although HBV DNA can effectively be suppressed by nucleos(t)ide analogues (NA), durable immune control is only established in a minority of patients. This especially applies in HBeAg‐negative patients who usually must receive lifelong NA treatment. Calculated withdrawal of NA leads to a relapse of HBV DNA in most patients. There is evidence that this sudden exposure of viral antigens can trigger immune control in some patients which may result in HBsAg loss or a form of immune control, then sustained low HBV DNA levels and normal alanine aminotransferase (ALT). In the first prospective randomized trial investigating tenofovir treatment cessation in HBeAg‐negative patients, most patients did not need retreatment after NA cessation, although all patients showed a transient relapse in HBV DNA. HBsAg loss was identified in almost 20% nearly 3 years after stopping NA. Further confirmation of these findings is needed in larger randomized trials and patients who are most likely to benefit from finite therapy must be identified to individualize NA stopping strategies. However, these results suggest that in patients without risk factors such as cirrhosis or other severe conditions, NA treatment may be stopped, as long as adequate safety rules for retreatment are followed.
The impact of treatment of hepatitis C with DAAs on the occurrence of HCC
Authors: Roche Bruno , Coilly Audrey , Duclos‐Vallee Jean Charles , Samuel Didier 
Published: February 2018

AbstractHepatitis C virus infection is a major cause of chronic hepatitis resulting in cirrhosis and hepatocellular carcinoma (HCC). The recent introduction of direct acting antivirals (DAA), results in sustained virological response (SVR) rates of >90% in treated patients whatever the stage of liver fibrosis with an excellent safety profile. This major advancement has allowed treatment of a larger number of patients, some with more advanced liver dysfunction and a higher risk of HCC. An SVR is associated with a reduced risk of hepatic decompensation, the need for liver transplantation and both liver‐related and overall mortality. This high rate of SVR has raised hopes that there would be a significant reduction in the incidence of HCC. However, the impact of DAA‐based regimens on the occurrence of HCC in patients with cirrhosis, and in particular the recurrence of HCC following successful curative treatment is controversial. Published studies suggest that DAA does not increase the risk of de novo HCC following SVR. A more controversial topic is the effect of a DAA‐based SVR on the recurrence of HCC following curative treatment of early HCC. Well‐designed studies with robust comparisons are needed to determine the effect of DAA on the recurrence of HCC. At present, patients with HCV cirrhosis who have undergone resection or ablation for HCC should not be dissuaded from receiving DAA therapy to prevent the progression of liver disease. Monitoring for HCC with liver imaging and AFP should be performed twice a year indefinitely post‐SVR in patients with HCV cirrhosis.
Focus on histological abnormalities of intrahepatic vasculature in chronic viral hepatitis
Authors: Guido Maria , Sarcognato Samantha , Russo Francesco P. , Cardin Romilda , Piciocchi Marika , Colloredo Guido , Farinati Fabio 
Published: February 2018

AbstractBackground & AimsThe histological intrahepatic microvasculature lesions have not been deeply investigated outside the setting of portal hypertension. The aim of this study was to analyse the type and the prevalence of microvasculature abnormalities and their correlation with inflammatory activity, fibrosis stage and tissue markers of fibrogenesis, angiogenesis and oxidative DNA damage in liver biopsies obtained from patients with chronic viral hepatitis.MethodsSeventy‐four liver biopsies from untreated patients affected by hepatitis B (22 cases) and C (52 cases) were included. The presence of microvascular changes was correlated with (i) the severity of the activity and fibrosis; (ii) immunohistochemical markers of angiogenesis (CD34) and hepatic stellate cells activation (alpha‐smooth muscle actin); (iii) a tissue marker of oxidative damage (8‐OHdG adducts).ResultsSixty‐five out of 74 biopsies (87.8%) showed vascular lesions. Portal angiomatosis was the most prevalent (62.2%) and it was associated with, on 1 side, the fibrosis stage at both univariate (P < .0001) and multivariate analysis (P = .01, OR = 9.4 [1.6‐54]) and, on the other, with angiogenesis (P = .05) and hepatic stellate cells activation (P = .002). Interestingly, 36/46 cases with portal angiomatosis were at early/intermediate fibrosis stage. The hepatic stellate cells activation was also associated with the presence of aberrant periportal vessels (P = .01).ConclusionsThe histological alterations of intrahepatic microvasculature, usually seen in cirrhosis and portal hypertension, occur in chronic viral hepatitis even at early/intermediate fibrosis stages. Their correlation with angiogenesis and fibrogenesis supports a possible involvement in disease progression.
Multiagent Simulation for Complex Adaptive Modeling of Road Infrastructure Resilience to Sea‐Level Rise
Authors: Batouli Mostafa , Mostafavi Ali 
Published: February 2018

AbstractInfrastructure systems in coastal areas are exposed to episodic flooding exacerbated by sea‐level rise stressors. To enable assessing the long‐term resilience of infrastructure to such chronic impacts of sea‐level rise, the present study created a novel complex system modeling framework that integrates: (i) stochastic simulation of sea‐level rise stressors, based on the data obtained from downscaled climate studies pertaining to future projections of sea level and precipitation; (ii) dynamic modeling of infrastructure conditions by considering regular decay of infrastructure, as well as structural damages caused by flooding; and (iii) a decision‐theoretic modeling of infrastructure management and adaptation processes based on bounded rationality and regret theories. Using the proposed framework and data collected from a road network in Miami, a multiagent computational simulation model was created to assess the long‐term cost and performance of the road network under various sea‐level rise scenarios, adaptation approaches, and network degradation effects. The results showed the capabilities of the proposed computational model for robust planning and scenario analysis to enhance the resilience of infrastructure systems to sea‐level rise impacts.
Intensive care unit nurses' knowledge of medication administration via enteral tubes
Authors: Sari Dilek , Kadifeli Derya , Akbiyik Ayşe , Taşkiran Nihal 
Published: February 2018

ABSTRACTBackgroundMedication administration via enteral tubes is a complex and key application for which nurses in intensive care units are responsible.AimThe aim of this study was to evaluate drug administrations via enteral tubes by nurses in intensive care units.MethodsThis research was conducted using a descriptive and cross‐sectional research design. The study was conducted with 289 nurses at intensive care units in hospitals in İzmir, Turkey. The data of the study were collected with the ‘Sociodemographic Information Form’ and the ‘Enteral Medication Administrations Questionnaire’, which was designed in accordance with the literature and consists of questions on interventions before, during and following medication administrations via enteral tubes.ResultsIt was found that more than half the nurses (62.3%) use nasogastric tubes for medication administrations and that all of them use the enteral way for the administration of medications in the form of tablets, while 58.8% use this method to administer the medications in the form of enteric‐coated tablets. It was determined that approximately half the nurses (52.6%) apply more than one medication separately, and a majority (84.1%) use tap water to wash the enteral tube.ConclusionsEnteral medication administration practices are inconsistent. Some nurses use unsafe practices and may therefore compromise patient care.Relevance to clinical practiceConduction of education programmes on medication administration via enteral tubes for intensive care unit nurses is important in improving nurses' knowledge.
Dentofacial morphology and upper respiratory function in 8‐10‐year‐old children
Authors: Shanker Shiva , Beck Frank M. , Allgair Edwin , Vig Peter S. , Vig Katherine W.L. 
Published: February 2018

Mouth breathing has been associated with many unfavorable sequelae, the most significant of which are features such as excessively long and tapered (dolicofacial) face form, increased lower face height, and narrow maxillary arch form. The aim of this preliminary study was to assess the nature of associations between selected dentofacial morphological variables and respiratory mode as measured by percent nasality (%N), as part of an ongoing longitudinal study. Ninety‐eight normal children (mean age = 8.95 years) were tested using a modified version of the Simultaneous Nasal and Oral Respirometric Technique for determining %N. Selected dentofacial morphological variables including total and lower anterior face heights, face width, and palatal arch width were measured. Statistical analysis was performed to test the strength of association between the measured dentofacial variables and %N.Small associations between morphologic features and respiratory mode were found, but none were statistically significant.
Germination characteristics of Rhinanthus minor influence field emergence, competitiveness and potential use in restoration projects
Authors: Marin M. , Laverack G. , Matthews S. , Powell A. A. 
Published: February 2018

Abstract

The facultative root hemi‐parasite Rhinanthus minor is often used in grassland habitat restoration projects to regulate ecosystem structure and function. Its impact on community productivity and diversity as a function of resource supply, sward composition and management has been widely investigated. However, there is a lack of information about the possible influence of seed quality on the efficacy of the hemi‐parasite.

Ten seed lots from commercial sources were sown in the field and their germination characteristics investigated in the laboratory. Seeds from four lots were also germinated and sown in pots alongside plants of two host species, Lotus corniculatus and Holcus lanatus. Plant establishment, height and flowering density were evaluated for the hemi‐parasite, while plant biomass was measured for both R. minor and its host.

Two aspects of seed quality influenced the field emergence of seed lots of R. minor, the radicle emergence (%) and the length of the lag period from the beginning of imbibition to germination (mean germination time), which indicates seed vigour. A longer lag period (lower vigour) was associated with higher levels of seedling mortality and lower plant vigour, in terms of plant height and biomass accumulation and was also reflected in the parasitic impact of the seed lots.

Seed quality, specifically germination and vigour, can influence the establishment, survival, subsequent plant productivity and parasitic impact of R. minor in vegetation restoration projects. Seed quality is discussed as a key factor to consider when predicting the impact of the hemi‐parasite on community productivity and diversity.
Alpha event‐related synchronization after eye closing differs in Alzheimer's disease and dementia with Lewy bodies: a magnetoencephalography study
Authors: Hata Masahiro , Kurimoto Ryu , Kazui Hiroaki , Ishii Ryouhei , Canuet Leonides , Aoki Yasunori , Ikeda Shunichiro , Azuma Shingo , Suehiro Takashi , Sato Shunsuke , Suzuki Yukiko , Kanemoto Hideki , Yoshiyama Kenji , Iwase Masao , Ikeda Manabu 
Published: February 2018

BackgroundThe electroencephalography (EEG) abnormalities found in patients with dementia with Lewy bodies (DLB) are conflicting. In this study, we used magnetoencephalography, which has higher spatial resolution than electroencephalography, to explore neurophysiological features of DLB that may aid in the differential diagnosis.MethodsSix patients with DLB, 11 patients with Alzheimer's disease, and 11 age‐matched normal subjects were recruited. We investigated alterations in the ratio of event‐related synchronization (ERS) in the alpha band after eye‐closing.ResultsAlthough the averaged ratio change of alpha ERS after eye‐closing appeared predominantly in the posterior brain regions in all study groups, DLB patients had the weakest ratio change of alpha ERS. In particular, DLB patients exhibited a significantly reduced ratio change of alpha ERS in the bilateral inferior temporal gyrus, right occipital pole, and left parieto‐occipital cortex compared to Alzheimer's disease patients or normal controls.ConclusionOur findings indicated that a reduced ratio change of alpha ERS in the posterior brain regions elicited by eye‐closing is a brain electromagnetic feature of DLB.
Characterization of anti‐Müllerian hormone in a case of bovine male pseudohermaphroditism
Authors: Kitahara G , El‐Sheikh Ali H , Teh APP , Hidaka Y , Haneda S , Mido S , Yamaguchi R , Osawa T 
Published: February 2018

ContentsThe current report aimed to characterize plasma anti‐Müllerian hormone (AMH) in bovine male pseudohermaphroditism. The blood AMH concentration in a Japanese Black male pseudohermaphrodite calf was compared with pre‐ and post‐pubertal male and female calves and castrated calves. The concentration in the case was higher than in post‐pubertal males, castrated males, and pre‐ and post‐pubertal female calves (p < .05), but similar to that in pre‐pubertal male calves. After extraction of the testes, the concentration in the case dropped to a certain extent. The extracted testes expressed AMH, as detected by immunohistochemistry. This study is the first to show the characterization of AMH in a male pseudohermaphrodite calf. AMH levels in peripheral blood might be useful to diagnose male pseudohermaphroditism in cattle.
A rare case of Epstein‐Barr virus‐associated hepatosplenic smooth muscle tumors after kidney transplantation
Authors: Pircher C. , Schneeberger S. , Boesmueller C. , Agaimy A. , Zoller H. , Bale R. , Henninger B. , Mayer G. , Neuwirt H. 
Published: February 2018

AbstractA 27‐year old caucasian male was diagnosed 2.7 years after kidney transplantation with Epstein‐Barr virus (EBV)‐associated smooth muscle tumors in liver and spleen. The reduction in immunosuppression and conversion from tacrolimus to sirolimus did not lead to a regression of the tumors. Additionally, the patient developed a cellular rejection of his renal allograft, which was successfully treated. A combined approach with stereotactic radiofrequency ablation (SRFA) and surgical resection was effective in the treatment of the tumors.
Efficacy and safety of sarolaner against generalized demodicosis in dogs in European countries: a non‐inferiority study
Authors: Becskei Csilla , Cuppens Otto , Mahabir Sean P. 
Published: February 2018

BackgroundTreatment of canine demodicosis can be challenging; new treatments are always being sought.ObjectiveThe efficacy of sarolaner was evaluated in comparison with a moxidectin/imidacloprid topical product against generalized demodicosis in dogs in a randomized, single‐masked, multi‐centre field study.AnimalsClient‐owned dogs were treated monthly with oral sarolaner (n= 53) or with weekly/monthly topical moxidectin/imidacloprid (n= 28).MethodsMites were counted monthly in deep skin scrapings and the severity of skin lesions was evaluated. Dogs completed the study when no live mites were found on two consecutive monthly skin scrapings or on day 180 at the latest (study end).ResultsParasitological cure, defined as the first time that no live mites were found in the skin scrapings, was achieved in 92.9% and 100% of the dogs after three and no more than five monthly treatments with sarolaner (respectively). In the moxidectin/imidacloprid group, 77.3% and 91.7% of the dogs were cured after three and six months, respectively. Parasitological cure rate for sarolaner was non‐inferior to moxidectin/imidacloprid on day 60. Mite counts were reduced by 77.2%, 95.0%, 98.5%, 99.0%, 100% and 100% in the sarolaner group and by 68.0%, 88.4%, 91.1%, 92.7%, 73.9% and 82.2% in the moxidectin/imidacloprid group, on days 30, 60, 90, 120, 150 and 180, respectively, compared to pre‐treatment counts. The skin lesions improved throughout the study; the total affected body surface decreased by 94% in the sarolaner and by 72% in the moxidectin/imidacloprid group. There were no treatment‐related adverse events.ConclusionsMonthly oral administration of sarolaner was safe and highly effective in the treatment of generalized demodicosis in dogs.
Probing the Mechanism of Inactivation of the FOX-4 Cephamycinase by Avibactam
Authors: Nukaga Michiyoshi , Papp-Wallace Krisztina M. , Hoshino Tyuji , Lefurgy Scott T. , Bethel Christopher R. , Barnes Melissa D. , Zeiser Elise T. , Johnson J. Kristie , Bonomo Robert A. 
Published: February 2018

ABSTRACT

Ceftazidime-avibactam is a “second-generation” β-lactam–β-lactamase inhibitor combination that is effective against
Enterobacteriaceae
expressing class A extended-spectrum β-lactamases, class A carbapenemases, and/or class C cephalosporinases. Knowledge of the interactions of avibactam, a diazabicyclooctane with different β-lactamases, is required to anticipate future resistance threats. FOX family β-lactamases possess unique hydrolytic properties with a broadened substrate profile to include cephamycins, partly as a result of an isoleucine at position 346, instead of the conserved asparagine found in most AmpCs. Interestingly, a single amino acid substitution at N346 in the
Citrobacter
AmpC is implicated in resistance to the aztreonam-avibactam combination. In order to understand how diverse active-site topologies affect avibactam inhibition, we tested a panel of clinical
Enterobacteriaceae
isolates producing
bla
FOX
using ceftazidime-avibactam, determined the biochemical parameters for inhibition using the FOX-4 variant, and probed the atomic structure of avibactam with FOX-4. Avibactam restored susceptibility to ceftazidime for most isolates producing
bla
FOX
; two isolates, one expressing
bla
FOX-4
and the other producing
bla
FOX-5
, displayed an MIC of 16 μg/ml for the combination. FOX-4 possessed a
k
2
/
K
value of 1,800 ± 100 M
−1
· s
−1
and an off rate (
k
off
) of 0.0013 ± 0.0003 s
−1
. Mass spectrometry showed that the FOX-4–avibactam complex did not undergo chemical modification for 24 h. Analysis of the crystal structure of FOX-4 with avibactam at a 1.5-Å resolution revealed a unique characteristic of this AmpC β-lactamase. Unlike in the
Pseudomonas
-derived cephalosporinase 1 (PDC-1)–avibactam crystal structure, interactions (e.g., hydrogen bonding) between avibactam and position I346 in FOX-4 are not evident. Furthermore, another residue is not observed to be close enough to compensate for the loss of these critical hydrogen-bonding interactions. This observation supports findings from the inhibition analysis of FOX-4; FOX-4 possessed the highest

K
d

(dissociation constant) value (1,600 nM) for avibactam compared to other AmpCs (7 to 660 nM). Medicinal chemists must consider the properties of extended-spectrum AmpCs, such as the FOX β-lactamases, for the design of future diazabicyclooctanes.
Targeting the Nonmevalonate Pathway in Burkholderia cenocepacia Increases Susceptibility to Certain β-Lactam Antibiotics
Authors: Sass Andrea , Everaert Annelien , Van Acker Heleen , Van den Driessche Freija , Coenye Tom 
Published: February 2018

ABSTRACT

The nonmevalonate pathway is the sole pathway for isoprenoid biosynthesis in
Burkholderia cenocepacia
and is possibly a novel target for the development of antibacterial chemotherapy. The goals of the present study were to evaluate the essentiality of
dxr
, the second gene of the nonmevalonate pathway, in
B. cenocepacia
and to determine whether interfering with the nonmevalonate pathway increases susceptibility toward antibiotics. To this end, a rhamnose-inducible conditional
dxr
knockdown mutant of
B. cenocepacia
strain K56-2 (
B. cenocepacia
K56-2
dxr
) was constructed, using a plasmid which enables the delivery of a rhamnose-inducible promoter in the chromosome. Expression of
dxr
is essential for bacterial growth; the growth defect observed in the
dxr
mutant could be complemented by expressing
dxr in trans
under the control of a constitutive promoter, but not by providing 2-
C
-methyl-
d
-erythritol-4-phosphate, the reaction product of DXR (1-deoxy-
d
-xylulose 5-phosphate reductoisomerase).
B. cenocepacia
K56-2
dxr
showed markedly increased susceptibility to the β-lactam antibiotics aztreonam, ceftazidime, and cefotaxime, while susceptibility to other antibiotics was not (or was much less) affected; this increased susceptibility could also be complemented by
in trans
expression of
dxr
. A similarly increased susceptibility was observed when antibiotics were combined with FR900098, a known DXR inhibitor. Our data confirm that the nonmevalonate pathway is essential in
B. cenocepacia
and suggest that combining potent DXR inhibitors with selected β-lactam antibiotics is a useful strategy to combat
B. cenocepacia
infections.