bluuebunny/crossref_metadata_2025_split huggingface dataset:
Making Statistical Significance More Significant
Authors: Baker Leanne F. , Mudge Joseph F. 
Published: June 2012

Abstract
We routinely set significance levels at 0.05, giving us one chance in 20 of a false positive result if the null hypothesis were true. Why? Why not instead choose values that minimise the combined chances of both false positives and false negatives? It is easy, say Leanne F. Baker and Joseph F. Mudge, so why not do it?
Newman, Vatican II, and the Triple Office
Authors: Phillips Peter 
Published: June 2012

AbstractAlthough not directly quoted in the documents of Vatican II, Newman should be regarded as an ‘invisible Father’ of the Council. This is evident the Council Fathers’ recognition of the importance of the historical situation as the place for practicing theology, a recognition of ‘the signs of the times’. We encounter revelation as fact rather than a set of hand‐me‐down propositions. Both Newman and Vatican II appreciated the role that the whole community of the Church plays in the articulation of doctrine. Newman invoked the model of the priestly, prophetic and regal office conferred on the Church by her Lord to challenge the increasing polarization between teachers and taught in the church and the damaging centralism that ensued. In a similar way the Council wished to restore a fruitful interplay between periphery and centre by acknowledging the collegiality of the bishops, and calling for a full involvement of laity in the life of the Church.
THE SPECIAL ISSUE ON ATTACHMENT: OVERREACHING THEORY AND DATA
Authors: Ludolph Pamela S. 
Published: June 2012

The Family Court Review Special Issue edited by McIntosh focused on the views of traditional attachment theorists, neglecting to interview more progressive thinkers or put many thought‐provoking questions to the traditionalists. The advances in attachment research in the last half century were little acknowledged. Among the unexplored research findings were the discovery that early attachment status can change, often as a result of negative life events; that maternal deprivation and other early losses are recoverable; and that infants do not require one primary caregiver to thrive. The notion that young children should not have overnight stays with their fathers was presented as fact, when little convincing research exists on the question.Key Points for Family Court Community:
The Family Court Review Special Issue presented the views of traditional attachment theorists.
More contemporary views of attachment were not presented in a balanced way.
Among the ideas supported by current attachment research that were insufficiently addressed are:
Pulmonary arteriovenous malformation: a rare anterior mediastinal mass
Authors: Walklin Ryan Patrick , Entwisle James , Cheung Ying Kei , Dayal Viswas 
Published: June 2012

SUMMARYPulmonary arteriovenous malformations are rare pulmonary vascular lesions which are associated with Osler Weber Rendu syndrome (hereditary haemorrhagic telangectasia). They act as right‐to‐left shunts and have cardiovascular and embolic complications. We present a patient with an apparent anterior mediastinal mass secondary to a pulmonary arteriovenous malformations which was successfully treated percutaneously.
Turning Tides: Prospects for More Diversity in Cognitive Science
Authors: Bender Andrea , Beller Sieghard , Medin Douglas L. 
Published: June 2012

AbstractThis conclusion of the debate on anthropology’s role in cognitive science provides some clarifications and an overview of emergent themes. It also lists, as cases of good practice, some examples of productive cross‐disciplinary collaboration that evince a forward momentum in the relationship between anthropology and the other cognitive sciences.
Reversal of P-glycoprotein-mediated multidrug resistance of human hepatic cancer cells by Astragaloside II
Authors: Huang Can , Xu Dujuan , Xia Quan , Wang Peipei , Rong Chao , Su Yong 
Published: June 2012

Abstract

Objectives
Chemoresistance is the main obstacle encountered in cancer treatment and is frequently associated with multidrug resistance (MDR). Astragaloside is a saponin which is widely used in traditional Chinese medicine. It has been reported that Astragaloside has antitumour effects on hepatocellular carcinoma Bel-7402 cells in vitro and in vivo. The purpose of this study was to examine the effects of Astragaloside II on the reversal of MDR and its molecular mechanism in vitro.

Methods
In this study, Bel-7402 and Bel-7402/FU cell lines were used as the experimental model. Drug sensitivity was determined using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, accumulation and efflux of Rh123 were analyzed by flow cytometer, the mRNA level of mdr1 was determined by RT-PCR and the protein levels of P-glycoprotein (P-gp) and mitogen-activated protein kinase were determined by Western blot.

Key findings
Astragaloside II (0.08 mg/ml) showed strong potency to increase 5-fluorouracil cytotoxicity toward 5-fluorouracil-resistant human hepatic cancer cells Bel-7402/FU. The mechanism of Astragaloside II on P-gp-mediated MDR demonstrated that Astragaloside II significantly increased the intracellular accumulation of rhodamine 123 via inhibition of P-gp transport function. Based on the analysis of P-gp and mdr1 gene expression using Western blot and RT-PCR, the results revealed that Astragaloside II could downregulate the expression of the P-gp and mdr1 gene. In addition, Astragaloside II suppressed phosphorylation of extracellular signal regulated kinase 1/2, p38 and c-Jun N-terminal kinase.

Conclusions
The results suggested that Astragaloside II is a potent MDR reversal agent and may be a potential adjunctive agent for hepatic cancer chemotherapy.
In-vitro inhibitory effect of Tualang honey on cytochrome P450 2C8 activity
Authors: Muthiah Yasotha Devi , Ong Chin Eng , Sulaiman Siti Amrah , Tan Soo Choon , Ismail Rusli 
Published: June 2012

Abstract

Objectives
To investigate the effect of Tualang honey on cytochrome P450 2C8 (CYP2C8) activity in vitro using an amodiaquine N-desethylase assay.

Methods
CYP2C8 and NADPH cytochrome P450 reductase was cotransformed, expressed and harvested. The incubation assay contained expressed proteins, MgCl2, NADP, glucose 6-phosphate, glucose-6-phosphate dehydrogenase, potassium phosphate buffer, and amodiaquine. The rate of conversion of amodiaquine to desethylamodiaquine, the metabolite, was determined using a high performance liquid chromatography (HPLC) method. The inhibition parameters, IC50 (concentration of inhibitor causing 50% inhibition of original enzyme activity) and apparent inhibition constant (Ki) values were determined.

Key findings
The recombinant proteins were successfully expressed and used to investigate the effect of Tualang honey on CYP2C8 activity. The activity was measured by the rate of metabolism of amodiaquine to desethylamodiaquine determined using a successfully developed HPLC method. Kinetic parameters as determined by nonlinear least-squares regression and evaluated with Aikeike's goodness of fit criteria revealed that Tualang honey competitively inhibited CYP2C8 activity in a dose-dependent manner. Maximum inhibition of 80% occurred at 0.01% honey. The IC50 and Ki values were (10.0 ± 3.0) × 10−3% and (5.1 ± 0.5) × 10−3% w/v, respectively.

Conclusions
This study has provided evidence for the in vitro inhibition of CYP2C8-mediated amodiaquine N-desethylase activity by Tualang honey. It revealed that honey, through this inhibition, may have the potential to cause in-vivo drug–food interaction with drugs metabolized by CYP2C8.
Effect of hypoxia on the dynamic response of hyperaemia in the contracting human calf muscle
Authors: Donnelly J. , Green S. 
Published: June 2012

New Findings
What is the central question of this study?The effect of hypoxia on the dynamic response of muscle hyperaemia during exercise is not known.
What is the main finding and its importance?Demonstrates that the effect of hypoxia on muscle hyperaemia is very rapid, occurring within the first 2–3 contractions of exercise and before the conventional oxygen‐dependent processes would exert their effects.
Although systemic hypoxia increases the muscle hyperaemic response during ‘steady‐state’ exercise, its effect on the dynamic characteristics of this response is not clear. In the present study, we first established that hypoxia increases the steady‐state hyperaemic response at low workloads during calf exercise. To study dynamic aspects of this response, eight subjects performed eight exercise trials while breathing a normoxic (fractional inspired O2= 0.2094) or hypoxic gas mixture (fractional inspired O2= 0.105). Subjects performed intermittent contractions (1 s) of the calf muscle at 20% maximal voluntary contraction, and the leg blood flow (LBF), leg vascular conductance (LVC) and EMG activities of the triceps surae muscles were measured during each contraction–relaxation period (3 s). The LBF and LVC responses were averaged for each subject and fitted using a four‐phase, exponential growth and decay function. Hypoxia evoked significant increases in the change in LBF (15%) and LVC (23%) from the start to the end of exercise, as well as the amplitude of the rapid growth phase of LBF and LVC (21%). Similar, but non‐significant, effects on the amplitude of the slow growth phase of LBF (P= 0.08) and LVC (P= 0.10) were observed. By contrast, hypoxia had no effect on temporal parameters of these growth phases, parameters defining the decay phases or EMG activities. These results suggest that the effect of hypoxia on exercise hyperaemia is targeted at the rapid and perhaps the slow growth phase of the response, and is not mediated by a change in the level of muscle activation.
Experimental Central Nervous System Aspergillosis Therapy: Efficacy, Drug Levels and Localization, Immunohistopathology, and Toxicity
Authors: Clemons Karl V. , Schwartz Julie A. , Stevens David A. 
Published: June 2012

ABSTRACT

We have shown previously that high-dose lipid amphotericin preparations are not more efficacious than lower doses in aspergillosis. We studied toxicity, drug concentrations and localization, and quantitative infection concurrently, using a 4-day model of central nervous system (CNS) aspergillosis to assess early events. Mice given
Aspergillus fumigatus
conidia intracerebrally, under a cyclophosphamide immunosuppressive regimen, were treated for 3 days (AmBisome at 3 or 10 mg/kg of body weight, Abelcet at 10 mg/kg, amphotericin B deoxycholate at 1 mg/kg, caspofungin at 5 mg/kg, or voriconazole at 40 mg/kg). Sampling 24 h after the last treatment showed that AmBisome at 3 but not at 10 mg/kg, as well as Abelcet, caspofungin, and voriconazole, reduced brain CFU. All regimens reduced renal infection. Minor renal tubular changes occurred with AmBisome or Abelcet therapy, whereas heart, lung, and brain showed no drug toxicity. Amphotericin B tissue and serum concentrations did not correlate with efficacy. Endothelial cell activation (ICAM-1 and P-selectin in cerebral capillaries) occurred during infection. Amphotericin B derived from AmBisome and Abelcet localized in activated endothelium and from Abelcet in intravascular monocytes. In 10-day studies dosing uninfected mice, minor renal tubular changes occurred after AmBisome or Abelcet at 1, 5, or 10 mg/kg with or without cyclophosphamide treatment; nephrosis occurred only with Abelcet in cyclophosphamide-treated mice. Hepatotoxicity occurred with AmBisome and Abelcet but was reduced in cyclophosphamide-treated mice. Marked CFU reduction by AmBisome at 3 mg/kg occurred in association with relatively more intense inflammation. Abelcet renal localization appears to be a precursor to late nephrotoxicity. Hepatotoxicity may contribute to high-dose Abelcet and AmBisome failures. Our novel observation of endothelial amphotericin localization during infection may contribute to amphotericin mechanism of efficacy.
O-Polysaccharide Glycosylation Is Required for Stability and Function of the Collagen Adhesin EmaA of Aggregatibacter actinomycetemcomitans
Authors: Tang Gaoyan , Ruiz Teresa , Mintz Keith P. 
Published: June 2012

ABSTRACT

Aggregatibacter actinomycetemcomitans
is hypothesized to colonize through the interaction with collagen and establish a reservoir for further dissemination. The trimeric adhesin EmaA of
A. actinomycetemcomitans
binds to collagen and is modified with sugars mediated by an O-antigen polysaccharide ligase (WaaL) that is associated with lipopolysaccharide (LPS) biosynthesis (G. Tang and K. Mintz, J. Bacteriol.
192:
1395–1404, 2010). This investigation characterized the function and cellular localization of EmaA glycosylation. The interruption of LPS biogenesis by using genetic and pharmacological methods changed the amount and biophysical properties of EmaA molecules in the outer membrane. In
rmlC
and
waaL
mutant strains, the membrane-associated EmaA was reduced by 50% compared with the wild-type strain, without changes in mRNA levels. The membrane-associated EmaA protein levels were recovered by complementation with the corresponding O-polysaccharide (O-PS) biosynthetic genes. In contrast, another trimeric autotransporter, epithelial adhesin ApiA, was not affected in the same mutant background. The inhibition of undecaprenyl pyrophosphate recycling by bacitracin resulted in a similar decrease in the membrane-associated EmaA protein. This effect was reversed by removal of the compound. A significant decrease in collagen binding activity was observed in strains expressing the nonglycosylated form of EmaA. Furthermore, the electrophoretic mobility shifts of the EmaA monomers found in the O-PS mutant strains were associated only with the membrane-associated protein and not with the cytoplasmic pre-EmaA protein, suggesting that this modification does not occur in the cytoplasm. The glycan modification of EmaA appears to be required for collagen binding activity and protection of the protein against degradation by proteolytic enzymes.
BCL2 Suppresses PARP1 Function and Nonapoptotic Cell Death
Authors: Dutta Chaitali , Day Tovah , Kopp Nadja , van Bodegom Diederik , Davids Matthew S. , Ryan Jeremy , Bird Liat , Kommajosyula Naveen , Weigert Oliver , Yoda Akinori , Fung Hua , Brown Jennifer R. , Shapiro Geoffrey I. , Letai Anthony , Weinstock David M. 
Published: June 2012

Abstract
BCL2 suppresses apoptosis by binding the BH3 domain of proapoptotic factors and thereby regulating outer mitochondrial membrane permeabilization. Many tumor types, including B-cell lymphomas and chronic lymphocytic leukemia, are dependent on BCL2 for survival but become resistant to apoptosis after treatment. Here, we identified a direct interaction between the antiapoptotic protein BCL2 and the enzyme PARP1, which suppresses PARP1 enzymatic activity and inhibits PARP1-dependent DNA repair in diffuse large B-cell lymphoma cells. The BH3 mimetic ABT-737 displaced PARP1 from BCL2 in a dose-dependent manner, reestablishing PARP1 activity and DNA repair and promoting nonapoptotic cell death. This form of cell death was unaffected by resistance to single-agent ABT-737 that results from upregulation of antiapoptotic BCL2 family members. On the basis of the ability of BCL2 to suppress PARP1 function, we hypothesized that ectopic BCL2 expression would kill PARP inhibitor–sensitive cells. Strikingly, BCL2 expression reduced the survival of PARP inhibitor–sensitive breast cancer and lung cancer cells by 90% to 100%, and these effects were reversed by ABT-737. Taken together, our findings show that a novel interaction between BCL2 and PARP1 blocks PARP1 enzymatic activity and suppresses PARP1-dependent repair. Targeted disruption of the BCL2–PARP1 interaction therefore may represent a potential therapeutic approach for BCL2-expressing tumors resistant to apoptosis. Cancer Res; 72(16); 4193–203. ©2012 AACR.
The State of Molecular Biomarkers for the Early Detection of Lung Cancer
Authors: Hassanein Mohamed , Callison J. Clay , Callaway-Lane Carol , Aldrich Melinda C. , Grogan Eric L. , Massion Pierre P. 
Published: June 2012

AbstractUsing biomarkers to select the most at-risk population, to detect the disease while measurable and yet not clinically apparent has been the goal of many investigations. Recent advances in molecular strategies and analytic platforms, including genomics, epigenomics, proteomics, and metabolomics, have identified increasing numbers of potential biomarkers in the blood, urine, exhaled breath condensate, bronchial specimens, saliva, and sputum, but none have yet moved to the clinical setting. Therefore, there is a recognized gap between the promise and the product delivery in the cancer biomarker field. In this review, we define clinical contexts where risk and diagnostic biomarkers may have use in the management of lung cancer, identify the most relevant candidate biomarkers of early detection, provide their state of development, and finally discuss critical aspects of study design in molecular biomarkers for early detection of lung cancer. Cancer Prev Res; 5(8); 992–1006. ©2012 AACR.
Targeting FACT Complex Suppresses Mammary Tumorigenesis in Her2/neu Transgenic Mice
Authors: Koman Igor E. , Commane Mairead , Paszkiewicz Geraldine , Hoonjan Bhupinder , Pal Srabani , Safina Alfiya , Toshkov Ilya , Purmal Andrei A. , Wang Dan , Liu Song , Morrison Carl , Gudkov Andrei V. , Gurova Katerina V. 
Published: June 2012

Abstract
Development of safe and effective tumor-preventive treatments for high-risk patient populations and therapies for early-stage cancer remains a critical need in oncology. We have recently discovered compound with anticancer activity, Curaxin-137, which modulates several important signaling pathways involved in even the very early stages of cancer. In tumor cells, Curaxin-137 inhibits NF-κB- and HSF1-dependent transcription (prosurvival pathways) and activates p53 (a proapoptotic pathway) without inducing DNA damage. These effects result from chromatin trapping and inhibition of activity of the FACT (facilitates chromatin transcription) complex by Curaxin-137. FACT has not been previously implicated in cancer, but we found that its subunits are overexpressed in breast cancer. On the basis of this background, we tested whether Curaxin-137 could suppress tumorigenesis in MMTV-neu transgenic mice, which spontaneously develop mammary carcinoma due to steroid receptor–regulated expression of the Her2 proto-oncogene. We found that chronic administration of Curaxin-137 in a preventive regimen to MMTV-neu mice did not cause any detectable changes in normal organs and tissues, yet inhibited tumor onset, delayed tumor progression, and prolonged survival of mice in a dose-dependent manner. Curaxin-137 induced changes in FACT, altered NF-κB localization, and activated p53 in tumor cells as expected from its defined mechanism of action. These results support further investigation of Curaxin-137 as a potential preventive and/or early-stage therapeutic agent for breast cancer. Cancer Prev Res; 5(8); 1025–35. ©2012 AACR.
Transvascular intracardiac applications of a miniaturized phased-array ultrasonic endoscope. Initial experience with intracardiac imaging in piglets.
Authors: Valdes-Cruz L M , Sideris E , Sahn D J , Murillo-Olivas A , Knudson O , Omoto R , Kyo S , Gulde R 
Published: June 2012

BACKGROUND
Recent advances in miniaturization of phased-array and mechanical ultrasound devices have resulted in exploration of alternative approaches to cardiac and vascular imaging in the form of transesophageal or intravascular imaging. Preliminary efforts in adapting phased-array endoscopes designed for transesophageal use to a transvascular approach have used full-sized phased-array devices introduced directly into the right atrium in open-chested animals. The purpose of this study was to assess the feasibility of using a custom-made, very small phased-array endoscope for intracardiac imaging introduced intravascularly through a jugular venous approach in young piglets.

METHODS AND RESULTS
Experimental atrial septal defects created in four piglets (3-4 weeks old) had been closed with a buttoned atrial septal defect closure device consisting of an occluder in the left atrium and a counteroccluder in the right atrium. Five to 15 days after atrial septal defect closure, the piglets were returned to the experimental laboratory, where a 6.3-mm, 17-element, 5-MHz phased-array probe mounted on a 4-mm endoscope was introduced through a cutdown incision of the external jugular vein and advanced to the right atrium. From the right atrium all four cardiac chambers, their inflows and outflows, and all four valves were well imaged with minimal superior and inferior rotation. High-resolution imaging of the atrial septum defined with anatomical accuracy, later verified by autopsy, the exact placement of both the occluder and counteroccluder in the left and right sides of the atrial septal defects and the absence of any shunting across the atrial septum in any of the four animals.

CONCLUSIONS
Our efforts indicate that transvascular passage of small phased-array probes can be easily accomplished and is a promising technique for detailed visualization of cardiac structures. This approach may provide an alternative to transesophageal echocardiography, particularly for guiding interventional procedures such as placement of transcatheter closure devices in pediatric patients.
Catheter modification of the atrioventricular junction with radiofrequency energy for control of atrioventricular nodal reentry tachycardia.
Authors: Lee M A , Morady F , Kadish A , Schamp D J , Chin M C , Scheinman M M , Griffin J C , Lesh M D , Pederson D , Goldberger J 
Published: June 2012

BACKGROUND
The utility of transcatheter application of radiofrequency energy to eliminate atrioventricular nodal reentrant tachycardia (AVNRT) was investigated.

METHODS AND RESULTS
Thirty-nine patients (mean age, 53 +/- 20 years; range 14-86 years) with medically refractory AVNRT underwent perinodal ablation with radiofrequency energy. A custom-designed 6F catheter with a large (3-mm-long) distal electrode and interelectrode pacing of 2 mm was used in the majority of cases. The catheter used for ablation was initially positioned across the tricuspid anulus to obtain the largest His bundle electrogram, then withdrawn to obtain the largest atrial:ventricular electrogram ratio, with a small His bundle electrogram (less than or equal to 100 microV). Each application of radiofrequency energy (350-550 kHz, 16.2 +/- 5.2 W) was stopped after 60 seconds or if PR prolongation or an impedance rise was noted. The endpoints of the procedure were persistent modification of atrioventricular nodal conduction (either first-degree atrioventricular block or impairment of ventriculoatrial conduction) and noninducibility of AVNRT before and during isoproterenol administration. Radiofrequency energy was applied a mean of 6.8 +/- 3.5 times per session. After a mean follow-up of 8 +/- 3.0 months, 32 of the 39 patients (82%) have been free of AVNRT, and did not have high grade AV block. Three patients (8%) developed complete atrioventricular block and had pacemakers implanted. Two patients had unsuccessful initial procedures, and two patients had initially successful ablations but had recurrences of tachycardia 4-6 weeks later. Elimination of AVNRT appeared to be due to effects on the retrograde fast pathway in most patients.

CONCLUSIONS
Radiofrequency ablation of the perinodal right atrium appears to be safe and effective for treatment of typical AVNRT: