bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sarcopenia is a poor prognostic factor following hepatic resection in patients aged 70 years and older with hepatocellular carcinoma
Authors: Harimoto Norifumi , Yoshizumi Tomoharu , Shimokawa Masahiro , Sakata Kazuhito , Kimura Kouichi , Itoh Shinji , Ikegami Toru , Ikeda Tetsuo , Shirabe Ken , Maehara Yoshihiko 
Published: February 2016

AimThe present study investigated the effect of sarcopenia on short‐ and long‐term surgical outcomes and identified potential prognostic factors for hepatocellular carcinoma (HCC) following hepatectomy among patients 70 years of age and older.MethodsPatient data were retrospectively collected for 296 consecutive patients who underwent hepatectomy for HCC with curative intent. Patients were assigned to two groups according to age (younger than 70 years, and 70 years and older), and the presence of sarcopenia. The clinicopathological, surgical outcome, and long‐term survival data were analyzed.ResultsSarcopenia was present in 112 of 296 (37.8%) patients with HCC, and 35% of patients aged 70 years and older. Elderly patients had significantly lower serum albumin levels, prognostic nutrition index, percentage of liver cirrhosis, and histological intrahepatic metastasis compared with patients younger than 70 years. Overall survival and disease‐free survival rates in patients with sarcopenia correlated with significantly poor prognosis in the group aged 70 years and older. Multivariate analysis revealed that sarcopenia was predictive of an unfavorable prognosis.ConclusionThis retrospective analysis revealed that sarcopenia was predictive of worse overall survival and recurrence‐free survival after hepatectomy in patients 70 years of age and older with HCC.
Effect of cocoa in diabetes: the potential of the pancreas and liver as key target organs, more than an antioxidant effect?
Authors: Mellor Duane D. , Naumovski Nenad 
Published: February 2016

SummaryIncreasingly, type 2 diabetes mellitus is being linked to metabolic abnormalities within the liver and pancreas, associated with fat deposition and oxidative stress. Cocoa and chocolate have been seen to improve oxidative stress and enhance insulin sensitivity. Recent in vitro and animal model studies have begun to investigate the potential of cocoa and cocoa extracts in modulating fatty liver and pancreatic function. Evidence from these studies has highlighted a number of mechanisms, which facilitate insulin secretion and enhanced survival in pancreatic beta cells. Whilst in liver, improved effect of insulin was observed with some improvements in fatty infiltration. However, what was seen as a common effect was an increase in endogenous antioxidant capability. The potential of cocoa products in the management of fatty liver and supporting pancreatic function in humans is likely to be limited by their macronutrient and energy profile or palatability, unless taken as cocoa extract supplements.
MicroRNA‐132 and microRNA‐223 control positive feedback circuit by regulating FOXO3a in inflammatory bowel disease
Authors: Kim Hye‐Youn , Kwon Hyeok Yi , Ha Thi Huyen Trang , Lee Ho Jae , Kim Gwang Il , Hahm Ki‐Baek , Hong Suntaek 
Published: February 2016

AbstractBackground and AimAlthough many progresses have been achieved for inflammatory bowel disease (IBD), it is still remained as idiopathic disease to be completely controlled. MicroRNAs (miRNAs) have been identified as key players in many human diseases through degradation or translational inhibition of target genes. Because role of miRNAs in IBD is not completely understood yet, we need to identify miRNAs as novel targets for treatment of IBD.MethodsMicroarray analysis for miRNAs was performed using dextran sulfate sodium‐induced colitis samples and selected differentially regulated miRNAs. Candidate genes were validated using in vitro system and IBD patient samples. Molecular mechanism for regulation of inflammatory signaling was identified using gene modulation system of miRNAs.ResultsWe selected 14 upregulated and 15 downregulated miRNAs through microarray analysis. Among candidate miRNAs, significant upregulation of miR‐132 and miR‐223 was confirmed in inflamed mouse tissues as well as human IBD patient tissues. Through bioinformatics analysis, we identified FOXO3a as direct target of miRNAs and confirmed regulatory mechanism using luciferase assay. Expression of miRNAs clearly suppressed the level of IκBα through downregulation of FOXO3a, leading to enhanced NF‐κB signaling to promote the production of pro‐inflammatory cytokines. The downregulation of FOXO3a concurrent with upregulation of cytokines was significantly reversed by sequestration of miRNAs with miRNA sponges.ConclusionsOur findings provided the evidences that miR‐132 and 223 are critical mediators in positive circuit for pathogenesis of IBD by negatively regulating FOXO3a to enhance the expression of inflammatory cytokines and can be a good therapeutic target for IBD treatment.
Efficacy of an ethanol/guar/triclosan/glycerine gel on bacteria and yeast loads in canine pododermatitis: a pilot study
Authors: Ortalda C. , Noli C. , Cena T. 
Published: February 2016

OBJECTIVESTo assess efficacy of a gel compound containing guar, glycerine, triclosan and ethanol (Pawcare®, JOKER Technologies, Kerzers, Switzerland) in decreasing bacterial and yeast loads on the paws of dogs with erythematous, greasy and/or malodorous pododermatitis.METHODSIn 20 dogs, each with at least two affected paws, semiquantitative Malassezia species counts were performed on 10 oil‐immersion fields (range: 0 to 30) from acetate tapes pressed on the palmar/plantar surface of one paw. Half of the area was sampled before and the other half immediately after the application of Pawcare®. With a similar procedure, swab samples were collected from the other paw for bacterial culture, identification and evaluation of colony‐forming units before and immediately after treatment. Statistical evaluation of pre‐ and posttreatment counts was performed with the Wilcoxon signed‐rank test.RESULTSNine dogs were positive for Malassezia species Mean acetate tape preparation counts decreased significantly from 8·78 (±8·03) to 5·668 (±6·65) (P=0·0039) after treatment. Twenty‐five bacterial isolates of 11 different species were cultured in 19 dogs. Posttreatment cultures were sterile in 8 dogs that had an initial zero or low number (1 to 2 log counts) of colony‐forming units. In cases with a higher pre‐treatment number of colony forming units (2 to 6 log counts), there was a significant decrease – by a mean of 1·16 log counts (pre 3·12 ±1·69, post 1·96 ±1·57) (P=0·0002).CLINICAL SIGNIFICANCEThe findings of the present study support the use of PawCare ® gel to decrease bacterial and yeast loads in dogs affected by chronic diseases involving the inter‐digital spaces.
The roles of the hybrid cluster protein, Hcp and its reductase, Hcr, in high affinity nitric oxide reduction that protects anaerobic cultures of Escherichia coli against nitrosative stress
Authors: Wang Jing , Vine Claire E. , Balasiny Basema K. , Rizk John , Bradley Charlene L. , Tinajero‐Trejo Mariana , Poole Robert K. , Bergaust Linda L. , Bakken Lars R. , Cole Jeffrey A. 
Published: February 2016

SummaryThe hybrid cluster protein, Hcp, contains a 4Fe‐2S‐2O iron‐sulfur‐oxygen cluster that is currently considered to be unique in biology. It protects various bacteria from nitrosative stress, but the mechanism is unknown. We demonstrate that the Escherichia coli Hcp is a high affinity nitric oxide (NO) reductase that is the major enzyme for reducing NO stoichiometrically to N2O under physiologically relevant conditions. Deletion of hcp results in extreme sensitivity to NO during anaerobic growth and inactivation of the iron‐sulfur proteins, aconitase and fumarase, by accumulated cytoplasmic NO. Site directed mutagenesis revealed an essential role in NO reduction for the conserved glutamate 492 that coordinates the hybrid cluster. The second gene of the hcp‐hcr operon encodes an NADH‐dependent reductase, Hcr. Tight interaction between Hcp and Hcr was demonstrated. Although Hcp and Hcr purified individually were inactive or when recombined, a co‐purified preparation reduced NO in vitro with a Km for NO of 500 nM. In an hcr mutant, Hcp is reversibly inactivated by NO concentrations above 200 nM, indicating that Hcr protects Hcp from nitrosylation by its substrate, NO.
Influence of Parenting Behavior on Psychosocial Adjustment in Early Adolescence: Mediated by Anger Regulation and Moderated by Gender
Authors: Rueth Jana Elisa , Otterpohl Nantje , Wild Elke 
Published: February 2016

AbstractEmotion regulation (ER)—one of the most important developmental tasks in early adolescence—has been proposed to mediate the relation between parenting and adolescents’ psychosocial adjustment. The aim of this study was to examine the influence of parental psychological control and autonomy support on adolescents’ problem and prosocial behavior (Strengths and Difficulties Questionnaire), as well as to examine the mediating role of adolescents’ anger regulation and the moderating effect of gender. We collected three‐year longitudinal questionnaire data from N = 923 parents and their (at first assessment) 9‐ to 13‐year‐old children. Path‐analysis results mainly support the mediating role of adolescents’ adaptive and maladaptive anger regulation and suggest parental autonomy support to be beneficial for regulatory abilities and psychosocial adjustment, whereas the opposite was found for psychological control. Gender differences were found for parent report data, but not for adolescent report data. Practical and theoretical implications are discussed.
Numerical Simulation of the Structural Response of Al/Graphite Composites Using Unit Cell Models and Different Interface Conditions
Authors: Hernández-Rivera J. L. , Medellín-Castillo H. I. , de Lange D. F. , Mejía-Rodríguez Gilberto 
Published: February 2016

The advantages of using graphite as reinforcement in aluminum composites have been addressed by several authors, e.g. Warner et al. [1]. The addition of graphite has been demonstrated to improve the relation strength to density ratio because of the low weight of graphite. Also a significant hardening caused by the difference in the thermal expansion coefficient between graphite and Al matrix have been observed [2]. Furthermore, the presence of graphite has been demonstrated to reduce the wear and abrasion of tools. The structural response of metal matrix composites (MMC) has been studied recently to evaluate the elastic and plastic performance by using Finite Element Method (FEM) [3, 4].
In this paper an analysis of the structural response of Al\graphite composites is presented. The analysis is based on the Finite Element Method (FEM) in the elastic and plastic regions. Several Al\graphite composites with different graphite contents were considered. A FEM model based on a unit cell was proposed and two different Al/graphite interface conditions were assumed: 1) strongly bonded interface, and 2) sliding-friction interface. Also, both regular and irregular arrays of graphite particles in the aluminum were considered in the model. The results in the elastic region are evaluated in terms of the effective elastic modulus and compared with some theoretical models in the literature [5]. From these results it has been observed that when a friction-sliding interface is considered, a slightly smaller elastic modulus is obtained, compared with the strongly-bonded interface condition. Regarding the numerical simulation in the plastic region, the results were compared with theoretical models [6] and experimental data obtained from compression tests.
Clofazimine Inhibits the Growth of Babesia and Theileria Parasites
In Vitro
and
In Vivo
Authors: Tuvshintulga Bumduuren , AbouLaila Mahmoud , Davaasuren Batdorj , Ishiyama Aki , Sivakumar Thillaiampalam , Yokoyama Naoaki , Iwatsuki Masato , Otoguro Kazuhiko , Ōmura Satoshi , Igarashi Ikuo 
Published: February 2016

ABSTRACT

The present study evaluated the growth-inhibitory effects of clofazimine, currently used for treating leprosy, against
Babesia bovis
,
B. bigemina
,
B. caballi
, and
Theileria equi
in
in vitro
culture and against
Babesia microti
in mice. The 50% inhibitory concentrations (IC
50
s) of clofazimine against the
in vitro
growth of
B. bovis
,
B. bigemina
,
B. caballi
, and
T. equi
were 4.5, 3, 4.3, and 0.29 μM, respectively. In mice infected with
B. microti
, treatment with 20 mg/kg of body weight of clofazimine administered orally resulted in a significantly lower peak parasitemia (5.3%) than that in the control group (45.9%), which was comparable to the subcutaneous administration of 25 mg/kg diminazene aceturate, the most widely used treatment for animal piroplasmosis. Although slight anemia was observed in both clofazimine- and diminazene aceturate-treated infected mice, the level and duration of anemia were lower and shorter, respectively, than those in untreated infected mice. Using blood transfusions and PCR, we also examined whether clofazimine completely killed
B. microti
. On day 40 postinfection, when blood analysis was performed, parasites were not found in blood smears; however, the DNA of
B. microti
was detected in the blood of clofazimine-treated animals and in several tissues of clofazimine- and diminazene aceturate-treated mice by PCR. The growth of parasites was observed in mice after blood transfusions from clofazimine-treated mice. In conclusion, clofazimine showed excellent inhibitory effects against
Babesia
and
Theileria in vitro
and
in vivo
, and further study on clofazimine is required for the future development of a novel chemotherapy with high efficacy and safety against animal piroplasmosis and, possibly, human babesiosis.
Longitudinal Analysis of the Effect of Inflammation on Voriconazole Trough Concentrations
Authors: Encalada Ventura M. A. , van Wanrooy M. J. P. , Span L. F. R. , Rodgers M. G. G. , van den Heuvel E. R. , Uges D. R. A. , van der Werf T. S. , Kosterink J. G. W. , Alffenaar J. W. C. 
Published: February 2016

ABSTRACT

Voriconazole (VCZ) exhibits great inter- and intrapatient variability. The latter variation cannot exclusively be explained by concomitant medications, liver disease or dysfunction, and genetic polymorphisms in cytochrome P450 2C19 (CYP2C19). We hypothesized that inflammatory response in patients under VCZ medication might also influence this fluctuation in concentrations. In this study, we explored the association between inflammation, reflected by the C-reactive protein (CRP) concentration, and VCZ trough concentrations over time. A retrospective analysis of data was performed for patients with more than one steady-state VCZ trough concentration and a CRP concentration measured on the same day. A longitudinal analysis was used for series of observations obtained from many study participants over time. The approach involved inclusion of random effects and autocorrelation in linear models to reflect within-person cross-time correlation. A total of 50 patients were eligible for the study, resulting in 139 observations (paired VCZ and CRP concentrations) for the analysis, ranging from 2 to 6 observations per study participant. Inflammation, marked by the CRP concentration, had a significant association with VCZ trough concentrations (
P
< 0.001). Covariates such as age and interacting comedication ([es]omeprazole), also showed a significant correlation between VCZ and CRP concentrations (
P
< 0.05). The intrapatient variation of trough concentrations of VCZ was 1.401 (confidence interval [CI], 0.881 to 2.567), and the interpatient variation was 1.756 (CI, 0.934 to 4.440). The autocorrelation between VCZ trough concentrations at two sequential time points was calculated at 0.71 (CI, 0.51 to 0.92). The inflammatory response appears to play a significant role in the largely unpredictable pharmacokinetics of VCZ, especially in patients with high inflammatory response, as reflected by high CRP concentrations.
Network Analysis of Sequence-Function Relationships and Exploration of Sequence Space of TEM β-Lactamases
Authors: Zeil Catharina , Widmann Michael , Fademrecht Silvia , Vogel Constantin , Pleiss Jürgen 
Published: February 2016

ABSTRACT

The Lactamase Engineering Database (
www.LacED.uni-stuttgart.de
) was developed to facilitate the classification and analysis of TEM β-lactamases. The current version contains 474 TEM variants. Two hundred fifty-nine variants form a large scale-free network of highly connected point mutants. The network was divided into three subnetworks which were enriched by single phenotypes: one network with predominantly 2be and two networks with 2br phenotypes. Fifteen positions were found to be highly variable, contributing to the majority of the observed variants. Since it is expected that a considerable fraction of the theoretical sequence space is functional, the currently sequenced 474 variants represent only the tip of the iceberg of functional TEM β-lactamase variants which form a huge natural reservoir of highly interconnected variants. Almost 50% of the variants are part of a quartet. Thus, two single mutations that result in functional enzymes can be combined into a functional protein. Most of these quartets consist of the same phenotype, or the mutations are additive with respect to the phenotype. By predicting quartets from triplets, 3,916 unknown variants were constructed. Eighty-seven variants complement multiple quartets and therefore have a high probability of being functional. The construction of a TEM β-lactamase network and subsequent analyses by clustering and quartet prediction are valuable tools to gain new insights into the viable sequence space of TEM β-lactamases and to predict their phenotype. The highly connected sequence space of TEM β-lactamases is ideally suited to network analysis and demonstrates the strengths of network analysis over tree reconstruction methods.
Serological Conservation of Parasite-Infected Erythrocytes Predicts Plasmodium falciparum Erythrocyte Membrane Protein 1 Gene Expression but Not Severity of Childhood Malaria
Authors: Warimwe George M. , Abdi Abdirahman I. , Muthui Michelle , Fegan Gregory , Musyoki Jennifer N. , Marsh Kevin , Bull Peter C. 
Published: February 2016

ABSTRACT

Plasmodium falciparum
erythrocyte membrane protein 1 (PfEMP1), expressed on
P. falciparum-
infected erythrocytes, is a major family of clonally variant targets of naturally acquired immunity to malaria. Previous studies have demonstrated that in areas where malaria is endemic, antibodies to infected erythrocytes from children with severe malaria tend to be more seroprevalent than antibodies to infected erythrocytes from children with nonsevere malaria. These data have led to a working hypothesis that PfEMP1 variants associated with parasite virulence are relatively conserved in structure. However, the longevity of such serologically conserved variants in the parasite population is unknown. Here, using infected erythrocytes from recently sampled clinical
P. falciparum
samples, we measured serological conservation using pools of antibodies in sera that had been sampled 10 to 12 years earlier. The serological conservation of infected erythrocytes strongly correlated with the expression of specific PfEMP1 subsets previously found to be associated with severe malaria. However, we found no association between serological conservation
per se
and disease severity within these data. This contrasts with the simple hypothesis that
P. falciparum
isolates with a serologically conserved group of PfEMP1 variants cause severe malaria. The data are instead consistent with periodic turnover of the immunodominant epitopes of PfEMP1 associated with severe malaria.
The Yersiniabactin-Associated ATP Binding Cassette Proteins YbtP and YbtQ Enhance Escherichia coli Fitness during High-Titer Cystitis
Authors: Koh Eun-Ik , Hung Chia S. , Henderson Jeffrey P. 
Published: February 2016

ABSTRACT

The
Yersinia
high-pathogenicity island (HPI) is common to multiple virulence strategies used by
Escherichia coli
strains associated with urinary tract infection (UTI). Among the genes in this island are
ybtP
and
ybtQ
, encoding distinctive ATP binding cassette (ABC) proteins associated with iron(III)-yersiniabactin import in
Yersinia pestis
. In this study, we compared the impact of
ybtPQ
on a model
E. coli
cystitis strain during
in vitro
culture and experimental murine infections. A
ybtPQ
-null mutant exhibited no growth defect under standard culture conditions, consistent with nonessentiality in this background. A growth defect phenotype was observed and genetically complemented
in vitro
during iron(III)-yersiniabactin-dependent growth. Following inoculation into the bladders of C3H/HEN and C3H/HeOuJ mice, this strain exhibited a profound, 10
6
-fold competitive infection defect in the subgroup of mice that progressed to high-titer bladder infections. These results identify a virulence role for YbtPQ in the highly inflammatory microenvironment characteristic of high-titer cystitis. The profound competitive defect may relate to the apparent selection of
Yersinia
HPI-positive
E. coli
in uncomplicated clinical UTIs.
Susceptibility to Ticks and Lyme Disease Spirochetes Is Not Affected in Mice Coinfected with Nematodes
Authors: Maaz Denny , Rausch Sebastian , Richter Dania , Krücken Jürgen , Kühl Anja A. , Demeler Janina , Blümke Julia , Matuschka Franz-Rainer , von Samson-Himmelstjerna Georg , Hartmann Susanne 
Published: February 2016

ABSTRACTSmall rodents serve as reservoir hosts for tick-borne pathogens, such as the spirochetes causing Lyme disease. Whether natural coinfections with other macroparasites alter the success of tick feeding, antitick immunity, and the host's reservoir competence for tick-borne pathogens remains to be determined. In a parasitological survey of wild mice in Berlin, Germany, approximately 40% ofIxodes ricinus-infested animals simultaneously harbored a nematode of the genusHeligmosomoides. We therefore aimed to analyze the immunological impact of the nematode/tick coinfection as well as its effect on the tick-borne pathogenBorrelia afzelii. Hosts experimentally coinfected withHeligmosomoides polygyrusand larval/nymphalI. ricinusticks developed substantially stronger systemic type 2 T helper cell (Th2) responses, on the basis of the levels of GATA-3 and interleukin-13 expression, than mice infected with a single pathogen. During repeated larval infestations, however, anti-tick Th2 reactivity and an observed partial immunity to tick feeding were unaffected by concurrent nematode infections. Importantly, the strong systemic Th2 immune response in coinfected mice did not affect susceptibility to tick-borneB. afzelii. An observed trend for decreased local and systemic Th1 reactivity againstB. afzeliiin coinfected mice did not result in a higher spirochete burden, nor did it facilitate bacterial dissemination or induce signs of immunopathology. Hence, this study indicates that strong systemic Th2 responses in nematode/tick-coinfected house mice do not affect the success of tick feeding and the control of the causative agent of Lyme disease.