bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a video‐guided real‐time patient motion monitoring system
Authors: Ju Sang Gyu , Huh Woong , Hong Chae‐Seon , Kim Jin Sung , Shin Jung Suk , Shin Eunhyuk , Han Youngyih , Ahn Yong Chan , Park Hee Chul , Choi Doo Ho 
Published: April 2012

Purpose:The authors developed a video image‐guided real‐time patient motion monitoring (VGRPM) system using PC‐cams, and its clinical utility was evaluated using a motion phantom.Methods:The VGRPM system has three components: (1) an image acquisition device consisting of two PC‐cams, (2) a main control computer with a radiation signal controller and warning system, and (3) patient motion analysis software developed in‐house. The intelligent patient motion monitoring system was designed for synchronization with a beam on/off trigger signal in order to limit operation to during treatment time only and to enable system automation. During each treatment session, an initial image of the patient is acquired as soon as radiation starts and is compared with subsequent live images, which can be acquired at up to 30 fps by the real‐time frame difference‐based analysis software. When the error range exceeds the set criteria (δmovement) due to patient movement, a warning message is generated in the form of light and sound. The described procedure repeats automatically for each patient. A motion phantom, which operates by moving a distance of 0.1, 0.2, 0.3, 0.5, and 1.0 cm for 1 and 2 s, respectively, was used to evaluate the system performance. The authors measured optimal δmovement for clinical use, the minimum distance that can be detected with this system, and the response time of the whole system using a video analysis technique. The stability of the system in a linear accelerator unit was evaluated for a period of 6 months.Results:As a result of the moving phantom test, the δmovement for detection of all simulated phantom motion except the 0.1 cm movement was determined to be 0.2% of total number of pixels in the initial image. The system can detect phantom motion as small as 0.2 cm. The measured response time from the detection of phantom movement to generation of the warning signal was 0.1 s. No significant functional disorder of the system was observed during the testing period.Conclusions:The VGRPM system has a convenient design, which synchronizes initiation of the analysis with a beam on/off signal from the treatment machine and may contribute to a reduction in treatment error due to patient motion and increase the accuracy of treatment dose delivery.
Prospective Screening of Novel Antibacterial Inhibitors of Dihydrofolate Reductase for Mutational Resistance
Authors: Frey Kathleen M. , Viswanathan Kishore , Wright Dennis L. , Anderson Amy C. 
Published: April 2012

ABSTRACT

Resistance to trimethoprim (TMP) resulting from point mutations in the enzyme drug target dihydrofolate reductase (DHFR) drives the development of new antifolate inhibitors effective against methicillin-resistant
Staphlococcus aureus
(MRSA). For the past several years we have used structure-based design to create propargyl-linked antifolates that are highly potent antibacterial agents. In order to focus priority on the development of lead compounds with a low propensity to induce resistance, we prospectively evaluated resistance profiles for two of these inhibitors in an MRSA strain. By selection with the lead inhibitors, we generated resistant strains that contain single point mutations F98Y and H30N associated with TMP resistance and one novel mutation, F98I, in DHFR. Encouragingly, the pyridyl propargyl-linked inhibitor selects mutants at low frequency (6.85 × 10
−10
to 1.65 × 10
−9
) and maintains a low MIC (2.5 μg/ml) and a low mutant prevention concentration (1.25 μg/ml), strongly supporting its position as a lead compound. Results from this prospective screening method inform the continued design of antifolates effective against mutations at the Phe 98 position. Furthermore, the method can be used broadly to incorporate ideas for overcoming resistance early in the development process.
Smac Mimetic LBW242 Sensitizes XIAP-Overexpressing Neuroblastoma Cells for TNF-α–Independent Apoptosis
Authors: Eschenburg Georg , Eggert Angelika , Schramm Alexander , Lode Holger N. , Hundsdoerfer Patrick 
Published: April 2012

Abstract
Despite intensive treatment regimens, high-risk and late-stage neuroblastoma tends to have a poor survival outcome. Overexpression of the apoptotic regulator, X-linked inhibitor of apoptosis protein (XIAP), has been associated with chemotherapy resistance in several cancers including neuroblastoma. Here, we report preclinical evidence that XIAP offers an effective therapeutic target in neuroblastoma. Human and murine neuroblastoma cells were treated with the Smac mimetic LBW242 alone or in combination with cytotoxic drugs used clinically to treat neuroblastoma. Expression of XIAP protein, but not mRNA, was highly increased in neuroblastoma cells compared to healthy adrenal gland tissue, consistent with a posttranscriptional regulation of XIAP expression. Treatment with LBW242 sensitized human and murine neuroblastoma cells to chemotherapy-induced apoptosis, which was mediated by activation of both the intrinsic and extrinsic apoptosis pathways. Although Smac mimetics have been reported to stimulate TNF-α–induced apoptosis by degradation of cellular IAP (cIAP)-1/2, we found that LBW242-mediated sensitization in neuroblastoma cells occurred in a TNF-α–independent manner, despite induction of cIAP-1/2 degradation and TNF-α expression. Together, our findings show that XIAP targeting sensitizes neuroblastoma to chemotherapy-induced apoptosis, suggesting a novel therapeutic approach to treat this childhood malignancy. Cancer Res; 72(10); 2645–56. ©2012 AACR.
Predominance of mTORC1 over mTORC2 in the Regulation of Proliferation of Ovarian Cancer Cells: Therapeutic Implications
Authors: Montero Juan Carlos , Chen Xi , Ocaña Alberto , Pandiella Atanasio 
Published: April 2012

Abstract
mTOR is a serine/threonine kinase that acts by binding different sets of proteins forming two complexes, termed mTORC1 and mTORC2. mTOR is deregulated in a substantial proportion of ovarian tumors. Despite the use of drugs directed to mTOR in ongoing clinical trials, the functional relevance of the individual mTORC branches in ovarian cancer is not known. Here, we show that mTORC1 and mTORC2 were constitutively active in ovarian cancer cell lines. Knockdown of raptor or rictor, proteins required for the function of mTORC1 or mTORC2, respectively, resulted in profound inhibition of ovarian cancer cell proliferation. The knockdown of raptor had a more important inhibitory effect than the knockdown of rictor, indicating mTORC1 had a predominant role over mTORC2 in the control of ovarian cancer cell proliferation. Rapamycin decreased the proliferation of ovarian cancer cells, and this was accompanied by inhibition of the phosphorylation of S6, a protein used as readout of mTORC1 function. However, rapamycin had only a marginal effect on the phosphorylation status of 4E-BP1, another mTORC1 substrate. Therefore, mTORC1 probably controls p4E-BP1 along two distinct pathways, one of them sensitive to rapamycin and another insensitive. The dual PI3K/mTOR inhibitor BEZ235 was more efficient than rapamycin in its inhibitory action on ovarian cancer cell proliferation. Biochemically, BEZ235 completely inhibited pS6, p4E-BP1, and pAkt. Our results suggest that broad-spectrum mTOR inhibitors that block mTORC1 and mTORC2 are more desirable for their clinical development in ovarian cancer than agents exclusively targeting one of the mTOR branches. Mol Cancer Ther; 11(6); 1342–52. ©2012 AACR.
The Role of the PGE2–Aromatase Pathway in Obesity-Associated Breast Inflammation
Authors: Wang Dingzhi , DuBois Raymond N. 
Published: April 2012

Abstract
Subbaramaiah and colleagues present the first evidence indicating that a cyclooxygenase-2–prostaglandin E2–aromatase pathway promotes obesity-associated inflammation in women's breast tissues. Their findings shed new light on obesity-associated inflammation in general and provide a rationale for developing effective chemopreventive and therapeutic strategies targeting this pathway for obese women with breast inflammation and patients with hormone-dependent breast cancer. Cancer Discov; 2(4); 308–10. ©2012 AACR.
Commentary on Subbaramaiah et al., p. 356.
Radial Artery Versus Femoral Artery Access Options in Coronary Angiogram Procedures
Authors: Schwalm Jon-David , Stacey Dawn , Pericak Dan , Natarajan Madhu K. 
Published: April 2012

Background—
Vascular access options in coronary angiography can be considered a preference-sensitive decision, where the benefits/risks have different levels of significance, depending on the individual patient. For preference-sensitive healthcare options, patient decision aids (PtDA) significantly improve the process of decision-making. The purpose of this trial was to evaluate the effectiveness of an evidence-based PtDA compared with usual care in patients eligible for radial and femoral artery access.

Methods and Results—

We conducted a single-center, nonblinded, randomized controlled trial with patients eligible for both femoral and radial access as per their treating physician. The PtDA was designed to guide patients to make an informed choice, consistent with their preferences and values. The primary outcome, decisional conflict, was assessed using the validated decisional conflict scale. One hundred fifty patients were randomized (vascular access PtDA=76 versus usual care=74). The intervention group had a significantly reduced decisional conflict scale compared with control (unadjusted 14.8 versus 19.5,
P
=0.04) and were significantly more knowledgeable regarding risks/benefits associated with each vascular access (mean knowledge score 3/5 (95% confidence interval, 2.6 to 3.3) versus 2/5 (95% confidence interval, 1.7 to 2.3,
P
<0.01). PtDA patients had better informed value congruence with their vascular access received (47.3% versus 25.7%,
P
<0.01). There were no significant differences in procedural success or safety between the 2 groups.

Conclusions—
A vascular access PtDA for eligible patients undergoing coronary angiogram procedures reduces decisional conflict and improves value congruence and the patients' knowledge of their healthcare options; however, a multicenter study, powered to confirm these benefits and evaluate differences in procedural success or complications, is required.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01032551.
Cardiac G-Protein–Coupled Receptor Kinase 2 Ablation Induces a Novel Ca
2+
Handling Phenotype Resistant to Adverse Alterations and Remodeling After Myocardial Infarction
Authors: Raake Philip W. , Zhang Xiaoying , Vinge Leif E. , Brinks Henriette , Gao Erhe , Jaleel Naser , Li Yingxin , Tang Mingxin , Most Patrick , Dorn Gerald W. , Houser Steven R. , Katus Hugo A. , Chen Xiongwen , Koch Walter J. 
Published: April 2012

Background—
G-protein–coupled receptor kinase 2 (GRK2) is a primary regulator of β-adrenergic signaling in the heart. G-protein–coupled receptor kinase 2 ablation impedes heart failure development, but elucidation of the cellular mechanisms has not been achieved, and such elucidation is the aim of this study.

Methods and Results—

Myocyte contractility, Ca
2+
handling and excitation-contraction coupling were studied in isolated cardiomyocytes from wild-type and GRK2 knockout (GRK2KO) mice without (sham) or with myocardial infarction (MI). In cardiac myocytes isolated from unstressed wild-type and GRK2KO hearts, myocyte contractions and Ca
2+
transients were similar, but GRK2KO myocytes had lower sarcoplasmic reticulum (SR) Ca
2+
content because of increased sodium-Ca
2+
exchanger activity and inhibited SR Ca
2+
ATPase by local protein kinase A–mediated activation of phosphodiesterase 4 resulting in hypophosphorylated phospholamban. This Ca
2+
handling phenotype is explained by a higher fractional SR Ca
2+
release induced by increased L-type Ca
2+
channel currents. After β-adrenergic stimulation, GRK2KO myocytes revealed significant increases in contractility and Ca
2+
transients, which were not mediated through cardiac L-type Ca
2+
channels but through an increased SR Ca
2+
. Interestingly, post-MI GRK2KO mice showed better cardiac function than post-MI control mice, which is explained by an improved Ca
2+
handling phenotype. The SR Ca
2+
content was better maintained in post-MI GRK2KO myocytes than in post-MI control myocytes because of better-maintained L-type Ca
2+
channel current density and no increase in sodium-Ca
2+
exchanger in GRK2KO myocytes. An L-type Ca
2+
channel blocker, verapamil, reversed some beneficial effects of GRK2KO.

Conclusions—

These data argue for novel differential regulation of L-type Ca
2+
channel currents and SR load by GRK2. G-protein–coupled receptor kinase 2 ablation represents a novel beneficial Ca
2+
handling phenotype resisting adverse remodeling after MI.
Praetorian Prefects’ Power and Senatorial Status in the Third Century: Re-evaluating Historia Augusta, Vita Alexandri 21.5
Authors: Mennen Inge 
Published: April 2012

Abstract
In Vita Alexandri 21.5 the author of the Historia Augusta claims that praetorian prefects were elevated to the rank of senator by Severus Alexander to make sure that no Roman senator would be judged by someone who was not a senator. Most scholars agree that the writer of the Historia Augusta makes a muddle of truth, half truth and falsehood concerning the grant of senatorial dignity to praetorian prefects. Yet they pay little attention to the statement concerning the motive of the prefects’ status upgrade. Re-interpretations based on recent discoveries suggest that information from the Historia Augusta may contain elements of truth, which makes it worthwhile to re-evaluate cases for which alternative sources are available. In this article, the case of L. Petronius Taurus Volusianus, praetorian prefect under Gallienus and consul in AD 261, is discussed against the background of changing power and status relations in the third century, showing that Historia Augusta, Vita Alexandri 21.5 may contain more truth than is usually agreed upon.
Jumping to Conclusions? Media Coverage of Jumps Racing Debates in Australia
Authors: Montoya Daniel , McManus Phil , Albrecht Glenn 
Published: April 2012

AbstractShould jumps racing be banned? This paper examines print media coverage of the future of “jumps racing” in 21 Australian newspapers between February 2008 and December 2009, a period of intense debate over its future due to high-profile incidents of horse deaths, campaigning by animal activists, and increased media coverage. In November 2009, Racing Victoria Limited banned jumps racing following the 2010 season but later opened the possibility of jumps racing in 2011 and beyond. The research finds that there is significant variation in support for, and opposition to, jumps racing in different newspapers; that there is sometimes a discrepancy between the perspectives of articles and letters on this issue; and the importance of jumps racing to particular small cities is reflected in the media coverage. While recent events and mounting public pressure may eventually contribute to the demise of steeplechasing and hurdling in Victoria, the termination of horse racing is not a foregone conclusion.
Marker analysis for detection of the Mi-1.2 resistance gene in tomato hybrid rootstocks and cultivars
Authors: Cortada Laura , Mantelin Sophie , Verdejo-Lucas Soledad , Kaloshian Isgouhi 
Published: April 2012

In tomato, the REX-1 marker is typically used to detect the root-knot nematode resistance gene Mi-1.2 in Solanum lycopersicum cultivars with introgression from S. peruvianum (Sp). However, using this marker, false positives have been reported in hybrid tomato rootstocks with introgressions from other Solanum species. We evaluated the reliability of available PCR-based markers Mi23, PMi and PM3 for detection of root-knot nematode resistance in a set of tomato hybrid rootstocks, cultivars and in several accessions of different Solanum species. Results showed that none of the tested markers was able to identify unequivocally lines with resistant phenotype. The Mi23 marker amplified from the susceptible tomato cvs Ailsa Craig and Chatham was Sp-like, while the PMi marker was highly polymorphic in several accessions of Solanum species and did not distinguish between a susceptible accession of S. peruvianum (LA1336) and two resistant accessions/clones (PI270435-2R2 and PI270435-3MH). In addition, the PM3 marker generated amplification products from the susceptible tomato cv. Tyrmes and susceptible accessions of S. chilense (LA1969 and LA2746) that were also Sp-like. Fingerprinting Mi-1.2 gene homologues (MiGHs) using primers flanking intron-1 in the tomato hybrid rootstocks and nematode-resistant and susceptible cvs indicated a great variation in the number and nature of the MiGHs. In silico analysis with the existing Mi-1.2 gene-specific primers C1/2, IMO-F1/R1 and VIGS-F indicated that they were not specific for the Mi-1.2 gene as they could amplify a fragment with a similar size from MiGHs from S. lycopersicum as well as other MiGHs from S. peruvianum. A newly designed Mi-1.2 gene-specific primer, Pau-do, used with an existing primer, C2S4, amplified an identical fragment of 1494 bp from cDNA of nematode-resistant tomato cv. Motelle and rootstocks Beaufort and Maxifort. Overall, this paper provides information to breeders, scientists and growers on the limited reliability of the available molecular tools to characterise root-knot nematode resistance in hybrid tomato rootstocks. The results show that, as most of the current markers are not universal and can lead to the appearance of false positives for root-knot nematode resistance, the resistance response of hybrid tomato rootstocks will still need to be evaluated through infection tests.
Fasting and postprandial conditions affect both fatty acids and lipid compositions in the hypothalamus and fat-soluble vitamins in the serum of male rats
Authors: Dayangac Alpaslan , Gosselink Kristin Leigh , Yilmaz Okkes 
Published: April 2012

The purpose of this study was to examine the effects of fasting and re-feeding on lipid derivative patterns in the hypothalamus, and on vitamin, cholesterol and malondialdehyde (MDA) levels in serum. Adult male Wistar albino rats were assigned (n = 6/group) as follows: normally-fed controls (CON), fasted for 24 h (24F), fasted for 48 h (48F), and fed normally for 2 d after fasting for 48 h (FAF). Biochemical measures were analyzed by gas chromatography (GC) and high performance liquid chromatography (HPLC). Our results demonstrate that hypothalamic saturated fatty acid (C16:0, C18:0) levels were lower, and unsaturated fatty acid (C22:6 n-3, C22:4 n-6, C20:4 n-6) levels were higher, in the 48F and FAF groups than in CON (). In addition, hypothalamic monounsaturated fatty acid (MUFA) levels were lower, and polyunsaturated fatty acids (PUFA) levels were higher, in 24F than in CON. Total hypothalamic lipids in both 24F and 48F were higher than CON, and cholesterol was elevated in the hypothalami of all experimental groups as compared to CON. Serum malondialdehyde was higher in fasted and FAF groups; 24F and 48F also had higher serum cholesterol levels, than CON (, ). Serum α-tocoferol, retinol and vitamin C values were lower in 48F than CON (). In conclusion, we demonstrate that feeding state can significantly alter brain fatty acid and lipid derivative levels, and serum concentrations of cholesterol and vitamins. These changes may consequently influence lipid peroxidation, fatty acid synthase or desaturase system in hypothalamic fields.
The Bachelet Effect on Gender-Equity Policies
Authors: Stevenson Linda S. 
Published: April 2012

From 2006 to 2010, Michelle Bachelet carried out her role as president with a high degree of success in many ways, to the point that she left office with an unprecedented 80 percent popularity rating among all Chileans. Among women, she was an important symbolic figure, and she was supportive of and quite successful at proposing and implementing policy to support liberal and more traditional forms of maternal women’s rights. However, an assessment of policy impacts in terms of their practical results and their political valences reveals that she was less supportive and consequently less successful in the areas of socialist and radical women’s rights. Entre 2006 y 2010, Michelle Bachelet asumió su cargo como presidente con alto grado de éxito en varias formas, de modo de que al momento de dejar la oficina gozaba una popularidad sin precedente del ochenta porciento de los chilenos. Entre las mujeres fue un símbolo importante ya que apoyaba tanto como promovía de manera exitosa la implementación de una política liberal y tradicional en los derechos maternos. Sin embargo una evaluación de las consecuencias de su política en resultados prácticos y sus valencias políticas pone en relieve que su apoyo fue menos y por consiguiente menos eficaz en el área de los derechos de la mujer socialista y radical.
Early Adoption of Transoral Robotic Surgical Program
Authors: Cognetti David M. , Luginbuhl Adam J. , Nguyen Anthony L. , Curry Joseph M. 
Published: April 2012

ObjectiveThe objective of this study is to demonstrate the feasibility and safety of establishing a transoral robotic surgical (TORS) program in the post–Food and Drug Administration (FDA) approval setting. Early outcomes are compared with the previously reported results of pioneering centers.Study DesignClinical data from a prospective TORS study.SettingAcademic university institution.Subjects and MethodsSixty‐one patients treated with 63 TORS procedures. Main outcome measures: intraoperative times, margin status, complications, time to diet, and percutaneous endoscopic gastrostomy (PEG) tube retention rate. The authors also report oncologic outcomes on their first 30 patients.ResultsThe spectrum of subsites included tongue base, tonsil, parapharyngeal space, retromolar trigone, supraglottis, and posterior pharyngeal wall. Surgical console time averaged 79 ± 53 minutes. After re‐resection of 4 patients, final negative margin status was 94% (50/53). A subset of 30 patients with squamous cell carcinoma reaching an average of 18 months of follow‐up had a local regional control rate of 97% with a disease‐free survival rate of 90%. The PEG tube retention rate was 7%. Complications included 2 readmissions with dehydration, 1 aspiration pneumonia, and 2 with minor oropharyngeal bleeding. Ninety‐one percent of patients resumed an oral diet by the first postoperative visit.ConclusionThe initiation of a TORS program in the post‐FDA setting can be achieved in a safe and efficient manner. Early results of pioneering TORS centers are reproducible. Continued investigation of TORS as a treatment option for oropharygneal carcinoma is warranted.