bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review and meta‐analysis of adjuvant interferon therapy after curative treatment for patients with viral hepatitis‐related hepatocellular carcinoma
Authors: Huang T.‐S. , Shyu Y.‐C. , Chen H.‐Y. , Yuan S.‐S. , Shih J.‐N. , Chen P.‐J. 
Published: April 2013

SummaryThe efficacy of adjuvant interferon treatment for the management of patients with viral hepatitis‐related hepatocellular carcinoma (HCC) following curative treatment is controversial. We have conducted a systematic review with meta‐analysis to assess the effects of adjuvant interferon therapy on survival outcomes. Randomized and nonrandomized studies (NRSs) comparing adjuvant interferon treatment with the standard of care for viral hepatitis‐related HCC after curative treatment were included. CENTRAL, Medline, EMBASE and the Science Citation Index were searched with complementary manual searches. The primary outcomes were recurrence‐free survival (RFS) and overall survival (OS). Nine randomized trials and 13 NRSs were included in the meta‐analysis. These nine randomized trials included 942 participants, of whom, 490 were randomized to the adjuvant interferon treatment group and 452 to the control group. The results of meta‐analysis showed unexplained heterogeneity for both RFS and OS. The 13 NRSs included 2214 participants, of whom, 493 were assigned to the adjuvant interferon treatment group and 1721 to the control group. The results of meta‐analysis showed that, compared with controls, adjuvant interferon treatment significantly improved the RFS [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.52–0.84, I2 = 29%] and OS (HR 0.43, 95% CI 0.34–0.56, I2 = 0%) of patients with hepatitis C virus‐related HCC following curative treatment. There was little evidence for beneficial effects on patients with hepatitis B virus‐related HCC. Future research should be aimed at clarifying whether the effects of adjuvant interferon therapy are more prominent in hepatitis C patients with sustained virological responses.
The Arabidopsis embryo as a miniature morphogenesis model
Authors: Wendrich Jos R. , Weijers Dolf 
Published: April 2013

SummaryFour basic ingredients of morphogenesis, oriented cell division and expansion, cell–cell communication and cell fate specification allow plant cells to develop into a wide variety of organismal architectures. A central question in plant biology is how these cellular processes are regulated and orchestrated. Here, we present the advantages of the early Arabidopsis embryo as a model for studying the control of morphogenesis. All ingredients of morphogenesis converge during embryogenesis, and the highly predictable nature of embryo development offers unprecedented opportunities for understanding their regulation in time and space. In this review we describe the morphogenetic principles underlying embryo patterning and discuss recent advances in their regulation. Morphogenesis is under tight transcriptional control and most genes that were identified as important regulators of embryo patterning encode transcription factors or components of signaling pathways. There exists, therefore, a large gap between the transcriptional control of embryo morphogenesis and the cellular execution. We describe the first such connections, and propose future directions that should help bridge this gap and generate comprehensive understanding of the control of morphogenesis.

Contents

Summary
14

I.
Ingredients of plant morphogenesis
14

II.
Arabidopsis embryo development: an amalgamation of morphogenetic processes
15

III.
Regulation of morphogenetic processes during embryogenesis
16

IV.
Genes to shape – cellular execution of transcriptional instructions
22

V.
Concluding remarks
22

Acknowledgements
23

References
23
The Role of Pain Catastrophizing Score in the Prediction of Venipuncture Pain Severity
Authors: Suren Mustafa , Kaya Ziya , Gokbakan Mehmet , Okan Ismail , Arici Semih , Karaman Serkan , Comlekci Mevlut , Balta Mehtap G. , Dogru Serkan 
Published: April 2013

AbstractBackgroundIn addition to the influence of tissue damage, the intensity of pain is also related to individual cognitive factors. The Pain Catastrophizing Scale (PCS) is used to measure individual tendency toward pain by inquiring about a subject's cognitive characteristics. Building on the knowledge that the venipuncture process causes severe pain and anxiety in some patients, the objective of this study was to investigate the relationship between the PCS score and venipuncture pain.MethodsPatients were asked to complete the PCS questionnaire. Patients' demographic features, presence of chronic pain and American Society of Anesthesiologists (ASA) scores were recorded. Clinical and demographic characteristics of the patients were used for correlation with the PCS scores. Using an 11‐point numeric rating scale (NRS), the patients then scored the amount of pain on cannulation.ResultsThis prospective study was conducted with 196 patients; 31 patients were excluded for various reasons. One hundred sixty‐five patients, 74 women and 91 men, were included in the evaluation. The study found that the venipuncture pain score had a significant positive correlation with the PCS score (r = 0.197, P < 0.05). With respect to age, no statistically significant differences in the PCS scores were found (P > 0.05). Female patients had a significantly higher PCS score than the males (P < 0.05). The PCS score of patients with chronic pain was found to be significantly higher in comparison with those without pain complaints (P < 0.05).ConclusionThere was a positive correlation between venipuncture pain and PCS score. Consequently, the venipuncture pain score could be useful in informing practitioners about a patient's pain considerations.
Peribacteroid space acidification: a marker of mature bacteroid functioning in Medicago truncatula nodules
Authors: PIERRE OLIVIER , ENGLER GILBERT , HOPKINS JULIE , BRAU FRÉDÉRIC , BONCOMPAGNI ERIC , HÉROUART DIDIER 
Published: April 2013

AbstractLegumes form a symbiotic interaction with Rhizobiaceae bacteria, which differentiate into nitrogen‐fixing bacteroids within nodules. Here, we investigated in vivo the pH of the peribacteroid space (PBS) surrounding the bacteroid and pH variation throughout symbiosis. In vivo confocal microscopy investigations, using acidotropic probes, demonstrated the acidic state of the PBS. In planta analysis of nodule senescence induced by distinct biological processes drastically increased PBS pH in the N2‐fixing zone (zone III). Therefore, the PBS acidification observed in mature bacteroids can be considered as a marker of bacteroid N2 fixation. Using a pH‐sensitive ratiometric probe, PBS pH was measured in vivo during the whole symbiotic process. We showed a progressive acidification of the PBS from the bacteroid release up to the onset of N2 fixation. Genetic and pharmacological approaches were conducted and led to disruption of the PBS acidification. Altogether, our findings shed light on the role of PBS pH of mature bacteroids in nodule functioning, providing new tools to monitor in vivo bacteroid physiology.
Experiences of parents' with children receiving long‐term home parenteral nutrition
Authors: Kawakami Chika , Fujiwara Chieko 
Published: April 2013

AbstractBackgroundHome parenteral nutrition (HPN) was introduced in the early 1970s. Parents with children receiving HPN are involved in their children's treatment and strive to resolve difficult problems in adapting to their new lifestyles. This study investigates the positive views acquired by parents' regarding their experiences with their children who are receiving long‐term HPN.MethodsParticipants were parents of preschool‐aged children who had been receiving total parenteral nutrition for 1–6 years. In‐depth interviews were conducted during which parents were questioned about their experiences during the process of providing HPN for their children. Qualitative content analysis was applied to the data.ResultsIt seemed useful to apply the concept of resilience; therefore, we classified the categories according to factors named in previous research studies on resilience. All parents showed increased resilience in the face of HPN‐related demands.ConclusionsThe planning and provision of care could be aided by the conceptualization of subjects' experiences as a process during which they have needs for support and information exchange. To approach this problem appropriately, health‐care professionals need to assess both children and parents on a continuous basis. Medical professionals should plan the care of ill children in advance so that appropriate help and support for their families can be provided. Better care for ill children needs to be accompanied by lasting relationships between parents and health‐care professionals.
Photochemistry of Tetraphenyldiboroxane and its Use as Photopolymerization Coinitiator,
Authors: Santos Willy G. , Schmitt Carla C. , Neumann Miguel G. 
Published: April 2013

Abstract2‐Hydroxyethyl methacrylate (HEMA) was photopolymerized in the presence of Safranine (SfH+) and tetraphenyldiboroxane (TPhB). Polymerization results are correlated with the photochemistry of TPhB and its ability to aggregate forming hydrophobic domains (critical aggregation concentration, cac, 1.2 × 10−4 M). Polymerization was not observed when the TPhB concentration was below the cac, indicating that the polymerization is initiated in the hydrophobic environment. The quenching of the triplet state of SfH+ by TPhB and the generation of the semireduced species of SfH+ suggests an electron transfer from the boron compound to the excited dye, and that the resulting boron‐centered radical initiates the polymerization process.
Cancer stem cells in lung cancer: Evidence and controversies
Authors: Alamgeer Muhammad , Peacock Craig D. , Matsui William , Ganju Vinod , Watkins D. Neil 
Published: April 2013

AbstractThe cancer stem cell (CSC) model is based on a myriad of experimental and clinical observations suggesting that the malignant phenotype is sustained by a subset of cells characterized by the capacity for self‐renewal, differentiation and innate resistance to chemotherapy and radiation. CSC may be responsible for disease recurrence after definitive therapy and may therefore be functionally synonymous with minimal residual disease. Similar to other solid tumours, several putative surface markers for lung CSC have been identified, including CD133 and CD44. In addition, expression and/or activity of the cytoplasmic enzyme aldehyde dehydrogenase ALDH and capacity of cells to exclude membrane permeable dyes (known as the ‘side population’) correlate with stem‐like function in vitro and in vivo. Embryonic stem cell pathways such as Hedgehog, Notch and WNT may also be active in lung cancers stem cells and therefore may be therapeutically targetable for maintenance therapy in patients achieving a complete response to surgery, radiotherapy or chemotherapy. This paper will review the evidence regarding the existence and function of lung CSC in the context of the experimental and clinical evidence and discuss some ongoing controversies regarding this model.
Vagal afferent fibres determine the oxytocin‐induced modulation of gastric tone
Authors: Holmes Gregory M. , Browning Kirsteen N. , Babic Tanja , Fortna Samuel R. , Coleman F. Holly , Travagli R. Alberto 
Published: April 2013

Key points
Oxytocin (OXT) inputs to the brainstem modulate cardiorespiratory, feeding and gastric functions.
Vagal afferent (sensory) inputs are known to modulate brainstem synapses involved in visceral reflexes; however, the neurocircuits through which OXT exerts its actions are still unknown.
In this study we elucidate these mechanisms of actions and report that vagal sensory fibres control these neurocircuits in a conditionally controlled manner such that brainstem synapses can prepare the neurocircuits to allow appropriate modulation of digestive processes.
The results presented here improve our understanding of the central regulation of gastrointestinal functions and have the potential of being extended to the understanding of cardiorespiratory and feeding functions controlled by adjacent brainstem centres.
Abstract  Oxytocin (OXT) inputs to the dorsal vagal complex (DVC; nucleus of the tractus solitarius (NTS) dorsal motor nucleus of the vagus (DMV) and area postrema) decrease gastric tone and motility. Our first aim was to investigate the mechanism(s) of OXT‐induced gastric relaxation. We demonstrated recently that vagal afferent inputs modulate NTS–DMV synapses involved in gastric and pancreatic reflexes via group II metabotropic glutamate receptors (mGluRs). Our second aim was to investigate whether group II mGluRs similarly influence the response of vagal motoneurons to OXT. Microinjection of OXT in the DVC decreased gastric tone in a dose‐dependent manner. The OXT‐induced gastric relaxation was enhanced following bethanechol and reduced by l‐NAME administration, suggesting a nitrergic mechanism of gastroinhibition. DVC application of the group II mGluR antagonist EGLU induced a gastroinhibition that was not dose dependent and shifted the gastric effects of OXT to a cholinergic‐mediated mechanism. Evoked and miniature GABAergic synaptic currents between NTS and identified gastric‐projecting DMV neurones were not affected by OXT in any neurones tested, unless the brainstem slice was (a) pretreated with EGLU or (b) derived from rats that had earlier received a surgical vagal deafferentation. Conversely, OXT inhibited glutamatergic currents even in naive slices, but their responses were unaffected by EGLU pretreatment. These results suggest that the OXT‐induced gastroinhibition is mediated by activation of the NANC pathway. Inhibition of brainstem group II mGluRs, however, uncovers the ability of OXT to modulate GABAergic transmission between the NTS and DMV, resulting in the engagement of an otherwise silent cholinergic vagal neurocircuit.
BLIP-II Is a Highly Potent Inhibitor of Klebsiella pneumoniae Carbapenemase (KPC-2)
Authors: Brown Nicholas G. , Chow Dar-Chone , Palzkill Timothy 
Published: April 2013

ABSTRACT

β-Lactamase inhibitory protein II (BLIP-II) is a potent inhibitor of class A β-lactamases. KPC-2 is a class A β-lactamase that is capable of hydrolyzing carbapenems and has become a widespread source of resistance to these drugs for Gram-negative bacteria. Determination of association and dissociation rate constants for binding between BLIP-II and KPC-2 reveals a very tight interaction with a calculated (
k
off
/
k
on
) equilibrium dissociation constant of 76 fM (76 × 10
−15
M).
Pharmacokinetics and Pharmacodynamics of Nemonoxacin against Streptococcus pneumoniae in an
In Vitro
Infection Model
Authors: Liang Wang , Chen Yuan-cheng , Cao Yu-ran , Liu Xiao-fang , Huang Jun , Hu Jia-li , Zhao Miao , Guo Qing-lan , Zhang Shu-jing , Wu Xiao-jie , Zhu De-mei , Zhang Ying-yuan , Zhang Jing 
Published: April 2013

ABSTRACT

The aim of this paper was to investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of nemonoxacin, a novel nonfluorinated quinolone, against
Streptococcus pneumoniae
in vitro
. A modified infection model was used to simulate the pharmacokinetics of nemonoxacin following scaling of single oral doses and multiple oral dosing. Four
S. pneumoniae
strains with different penicillin sensitivities were selected, and the drug efficacy was quantified by the change in log colony counts within 24 h. A sigmoid maximum-effect (
E
max
) model was used to analyze the relationship between PK/PD parameters and drug effect. Analysis indicated that the killing pattern of nemonoxacin shows a dualism which is mainly concentration dependent when the MIC is low and that the better PK/PD index should be the area under the concentration-time curve for the free, unbound fraction of the drug divided by the MIC (
f
AUC
0–24
/MIC), which means that giving the total daily amount of drug as one dose is appropriate under those conditions. When the MIC is high, the time (
T
) dependency is important and the valid PK/PD index should be the cumulative percentage of a 24-h period in which the drug concentration exceeds the MIC under steady-state pharmacokinetic conditions (
f
%
T
>MIC), which means that to split the maximum daily dose into several separate doses will benefit the eradication of the bacteria. To obtain a 3-log
10
-unit decrease, the target values of
f
AUC
0–24
/MIC and
f
%
T
>MIC are 47.05 and 53.4%, respectively.
A Novel Leishmania major Amastigote Assay in 96-Well Format for Rapid Drug Screening and Its Use for Discovery and Evaluation of a New Class of Leishmanicidal Quinolinium Salts
Authors: Bringmann Gerhard , Thomale Katja , Bischof Sebastian , Schneider Christoph , Schultheis Martina , Schwarz Tobias , Moll Heidrun , Schurigt Uta 
Published: April 2013

ABSTRACT

In most laboratories, the screening for leishmanicidal compounds is carried out with
Leishmania
promastigotes or axenic amastigotes. However, the best approach to identify leishmanicidal compounds is the use of amastigotes residing in macrophages. Reporter gene-based assays are relatively new tools in the search for drugs against eucaryotic protozoa, permitting the development of faster, more automated assays. In this paper, we report on the establishment of a rapid screening assay in a 96-well format. A luciferase-transgenic (Luc-tg)
Leishmania major
strain was generated and used to infect bone marrow-derived macrophages (BMDM). Amastigote-infected BMDM were treated with different compound concentrations. Cells were lysed with a luciferin-containing buffer, and the resulting luminescence was measured to determine the half-maximal inhibitory concentration (IC
50
). To validate this new amastigote screening assay, a library of a new class of quinolinium salts was synthesized and tested for leishmanicidal activity. Some of the quinolinium salts showed very promising activities, with IC
50
s against intracellular amastigotes (IC
50
< 1 μg/ml) and selectivity indices (SI > 20) that match the criteria of World Health Organization (WHO) for hits. Compound 21c (IC
50
= 0.03 μg/ml; SI = 358) could become a new lead structure for the development of improved chemotherapeutic drugs against
L. major
. In summary, we describe the establishment of a new 96-well format assay with Luc-transgenic
L. major
for the rapid screening of compounds for leishmanicidal activity against intracellular amastigotes and its application to the identification of a new class of quinolinium salts with most promising leishmanicidal activity.
Hydramacin-1 in Action: Scrutinizing the Barnacle Model
Authors: Michalek Matthias , Vincent Bruno , Podschun Rainer , Grötzinger Joachim , Bechinger Burkhard , Jung Sascha 
Published: April 2013

ABSTRACT

Hydramacin-1 (HM1) from the metazoan
Hydra
exerts antimicrobial activity against a wide range of bacterial strains. Notably, HM1 induces the aggregation of bacterial cells, accompanied by precipitation. To date, the proposed mechanism of peptide-lipid interaction, termed the barnacle model, has not been described on the molecular level. Here, we show by biochemical and biophysical techniques that the lipid-peptide interactions of HM1 are initiated by electrostatic and hydrophobic effects, in particular, by tryptophan and neighboring polar amino acid residues that cause an interfacial localization of the peptide between two self-contained lipid bilayers. The high binding constants of HM1 upon lipid interaction are in the range of other potent antimicrobial peptides, e.g., magainin, and can be reasonably explained by two distinct epitopes on the surface of the peptide's global structure, which both contain SWT(K/R) motifs. The residues of this motif favor localization of the peptide in the head group region of phospholipid bilayers up to a penetration depth of 4 Å and a minor participation of the lipids' hydrocarbon regions. Our results expand the knowledge about the molecular modes of action antimicrobial peptides use to tackle their target cells. Furthermore, the aggregation of living bacteria by HM1 was observed for a broad range of Gram-positive and Gram-negative bacteria. Therefore, the detailed view of peptide-lipid interactions described by the barnacle model consolidates it among the established models.
Effect of Cardiopulmonary Bypass on Regional Antibiotic Penetration into Lung Tissue
Authors: Hutschala D. , Skhirtladze K. , Kinstner C. , Zeitlinger M. , Wisser W. , Jaeger W. , Hoeferl M. , Müller M. , Tschernko E. 
Published: April 2013

ABSTRACTThe use of cardiopulmonary bypass (CPB) during cardiac surgery causes regional ventilation-perfusion mismatch, contributing to regional disturbances in antibiotic penetration into lung tissue. Ventilation-perfusion mismatch is associated with postoperative pneumonia, a frequent and devastating complication after cardiac surgery. In this prospective clinical animal study, we performedin vivomicrodialysis to determine the effect of CPB on regional penetration of levofloxacin (LVX) into lung tissue. Six pigs underwent surgery with CPB (CPB group), and another six pigs underwent surgery without CPB (off-pump coronary artery bypass grafting; OPCAB group). LVX (750 mg) was administered intravenously to all pigs immediately after surgery. For regional measurements of LVX in pulmonary concentrations, microdialysis probes were inserted in both lungs of each pig. Pigs were placed in the right lateral position. Time versus concentration profiles of unbound LVX were measured in the upper and lower lung tissue and plasma in all pigs. In all pigs, maximum concentrations (Cmax) of LVX were significantly lower in the upper lung than in the lower lung (OPCAB,P= 0.035; CPB,P< 0.001). MedianCmaxof LVX showed a significant difference in the upper versus lower lung in the CPB group (P< 0.05). No significant difference was found in the medianCmaxof LVX in the upper and the lower lung in the OPCAB group (P= 0.32). Our data indicate that CPB affects perioperative regional antibiotic penetration into lung tissue. Common clinical antibiotic dosing schemes should be reevaluated in patients undergoing coronary artery bypass grafting with CPB.