bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial DNA Mutation in Normal Margins and Tumors of Recurrent Head and Neck Squamous Cell Carcinoma Patients
Authors: Dasgupta Santanu , Koch Rachel , Westra William H. , Califano Joseph A. , Ha Patrick K. , Sidransky David , Koch Wayne M. 
Published: July 2010

Abstract
Mitochondrial DNA (mtDNA) mutations were reported in primary head and neck squamous cell carcinoma (HNSCC) patients. However, very little information is available on the mtDNA mutation pattern in the histologically negative surgical margins and tumors of HNSCC patients who experienced tumor recurrence. The present study aimed at understanding the nature and timing of mtDNA mutation in histologically negative margins, and tumors in HNSCC patients who developed local recurrence during the follow-ups. The entire 16.5-kb mitochondrial genome was sequenced in matched normal lymphocytes, histologically normal margins, and tumors of 50 recurrent HNSCC patients. The mtDNA mutations were then compared with clinical parameters. Forty-eight percent (24 of 50) of patients harbored at least one somatic mtDNA mutation in the tumor, and a total of 37 somatic mtDNA mutations were detected. The mtDNA mutations were mostly heteroplasmic in nature and nucleotide transitions (A↔G; T↔C). Forty-six percent of the mutations (17 of 37) were detected in the tumors and were also detectable in the corresponding histologically normal margin of the patients. The mtDNA mutations involved both coding and noncoding regions of the mtDNA. The majority (9 of 17, 53%) of the noncoding mutations involved tRNAs. Seventy-five percent (15 of 20) of the coding mtDNA mutations were nonsynonymous in nature and mainly affected cytochrome c oxidase (Complex IV), frequently altered in different human mitochondrial diseases including cancer. Analysis of mtDNA mutation could be an invaluable tool for molecular assessment of histologically negative margins and as well for monitoring HNSCC patients with locoregional recurrences. Cancer Prev Res; 3(9); 1205–11. ©2010 AACR.
Multiple Potential Molecular Contributors to Atrial Hypocontractility Caused by Atrial Tachycardia Remodeling in Dogs
Authors: Wakili Reza , Yeh Yung-Hsin , Yan Qi Xiao , Greiser Maura , Chartier Denis , Nishida Kunihiro , Maguy Ange , Villeneuve Louis-Robert , Boknik Peter , Voigt Niels , Krysiak Judith , Kääb Stefan , Ravens Ursula , Linke Wolfgang A. , Stienen Gerrit J.M. , Shi Yanfen , Tardif Jean-Claude , Schotten Ulrich , Dobrev Dobromir , Nattel Stanley 
Published: July 2010

Background—
Atrial fibrillation impairs atrial contractility, inducing atrial stunning that promotes thromboembolic stroke. Action potential (AP)-prolonging drugs are reported to normalize atrial hypocontractility caused by atrial tachycardia remodeling (ATR). Here, we addressed the role of AP duration (APD) changes in ATR-induced hypocontractility.

Methods and Results—

ATR (7-day tachypacing) decreased APD (perforated patch recording) by ≈50%, atrial contractility (echocardiography, cardiomyocyte video edge detection), and [Ca
2+
]
i
transients. ATR AP waveforms suppressed [Ca
2+
]
i
transients and cell shortening of control cardiomyocytes; whereas control AP waveforms improved [Ca
2+
]
i
transients and cell shortening in ATR cells. However, ATR cardiomyocytes clamped with the same control AP waveform had ≈60% smaller [Ca
2+
]
i
transients and cell shortening than control cells. We therefore sought additional mechanisms of contractile impairment. Whole-cell voltage clamp revealed reduced I
CaL
; I
CaL
inhibition superimposed on ATR APs further suppressed [Ca
2+
]
i
transients in control cells. Confocal microscopy indicated ATR-impaired propagation of the Ca
2+
release signal to the cell center in association with loss of t-tubular structures. Myofilament function studies in skinned permeabilized cardiomyocytes showed altered Ca
2+
sensitivity and force redevelopment in ATR, possibly due to hypophosphorylation of myosin-binding protein C and myosin light-chain protein 2a (immunoblot). Hypophosphorylation was related to multiple phosphorylation system abnormalities where protein kinase A regulatory subunits were downregulated, whereas autophosphorylation and expression of Ca
2+
-calmodulin-dependent protein kinase IIδ and protein phosphatase 1 activity were enhanced. Recovery of [Ca
2+
]
i
transients and cell shortening occurred in parallel after ATR cessation.

Conclusions—

Shortening of APD contributes to hypocontractility induced by 1-week ATR but accounts for it only partially. Additional contractility-suppressing mechanisms include I
CaL
current reduction, impaired subcellular Ca
2+
signal transmission, and altered myofilament function associated with abnormal myosin and myosin-associated protein phosphorylation. The complex mechanistic basis of the atrial hypocontractility associated with AF argues for upstream therapeutic targeting rather than interventions directed toward specific downstream pathophysiological derangements.
Religion and the Crisis of Historicism: Protestant and Catholic Perspectives
Authors: Paul Herman 
Published: July 2010

AbstractThis paper raises the question to what extent the crisis of historicism is to be seen as a religious problem. There is, of course, no need to argue that religion in a broad sense of the word ‐ ultimate concerns and fundamental values ‐ played major roles in the debates over historicism. However, virtually no studies have been conducted on how the crisis of historicism can be “mapped” on the religious landscape in a more specific sense. Which theological schools and which church denominations, for example, were most affected by or concerned over the crisis of historicism? I address this question by presenting three case-studies of Protestant and Roman-Catholic thinkers in the Netherlands. These examples show that especially those Christian intellectuals whose theological or philosophical traditions were indebted to historicist premises participated in debates over historicism. In practical terms, this implies that Protestants of various persuasions were more heavily involved than Roman-Catholics. In a final section, the paper suggests some implications of this finding for how the crisis of historicism is best understood.
Class Conflict and Industrial Location
Authors: Olsen Erik K. 
Published: July 2010

This paper examines the effect of class conflict on industrial location both theoretically and empirically. It demonstrates that there is a sound theoretical basis and empirical support for the conclusion that U.S. industries have chosen to abandon agglomeration and scale economies in order to secure a distribution of income that favors capital at the expense of labor. The decline of the U.S. manufacturing belt is examined with reference to union density, bargaining power, and the effects that large-scale production plants have on these factors. The meat packing industry in the postwar United States serves as a case study to establish the specific ways that class conflict has shaped the scale profile and geographic distribution of production plants. The paper builds upon the class conflict approach to urban and regional economics pioneered by Matthew Edel and David Gordon and aims to demonstrate its explanatory power. JEL classification: R30, J51, B51.
Distributional Consequences of Financial Crises: Evidence from Recent Crises
Authors: Gezici Armağan 
Published: July 2010

The paper examines the distributional consequences of financial crises based on the lessons of the past crises experiences of Argentina, Brazil, Korea, Mexico, and Turkey. It identifies the possible channels through which crises may affect functional and personal distribution of income. It concludes that the crises of the last two decades have both pro-capital and pro-finance distributional outcomes. JEL classification: D31, E25, O15, G01
The physical health challenges in patients with severe mental illness: cardiovascular and metabolic risks
Authors: Deakin Bill , Ferrier Nicol , Holt Richard IG , Millar Helen , Nutt David J , Reynolds Gavin , Samani Nilesh , Taylor David 
Published: July 2010

This supplement is the output of a roundtable discussion, attended by a multidisciplinary panel with a broad range of expertise, which includes the treatment of severe mental illness, cardiovascular disease, diabetes and pharmaceutical prescribing. The roundtable and writing of the supplement were organised and paid for by MSD, including the payment of Steve Titmarsh, a medical writer who was involved in the preparation and editing of this document
Diagnostic delay and clinical modifiers in alpha-1 antitrypsin deficiency
Authors: Köhnlein Thomas , Janciauskiene Sabina , Welte Tobias 
Published: July 2010

Background: Alpha-1 antitrypsin deficiency (AATD) is one of the most prevalent inherited diseases in Whites, but identification of affected patients and establishment of the diagnosis is still unsatisfactory. This study assessed the latencies and numbers of physicians involved in identifying AATD patients, and the importance of smoking, vaccination status, and specific augmentation therapy on the course of the disease. Method: Patients from Germany and Austria underwent a single written interview with 28 items. Five hundred and ninety-six patients were addressed and 44.9% replied. Results: The age at symptom onset was 39.1±10.1 years, and the diagnosis was established at the age of 45.1±10.9 years. From the 6-year delay in establishing the diagnosis, 1.4±1.7 (range 0.5—10.5) years were due to patients’ reluctance to seek medical attention. There were 3.2±2.4 (range 1—13) physicians involved in establishing the diagnosis. Smoking was associated with an earlier onset of respiratory symptoms and lower exercise capacity. Vaccination against pneumococci and/or influenza, and augmentation therapy resulted in significantly fewer exacerbations and fewer emergency room visits. Airway infections and passive smoking during childhood were not found to influence the onset of respiratory symptoms. Conclusions: In conclusion, there is still a large delay between symptom onset and AATD diagnosis. Smoking history, vaccination status, and augmentation therapy have an important impact on the course of the disease.
Determinants of participation in colonoscopic screening by siblings of colorectal cancer patients in France
Authors: Taouqi Myriam , Ingrand Isabelle , Beauchant Michel , Migeot Virginie , Ingrand Pierre 
Published: July 2010

AbstractBackgroundTargeted colonosocopic screening is recommended for first-degree relatives of colorectal cancer patients diagnosed before the age of 60 and offers the possibility of reducing morbidity and mortality, but participation remains too low. The objective of this study was to determine in a French population the factors that affect siblings' participation in screening, notably those relating to the individuals, their medical care, their family and their social network.MethodsA cross sectional survey was conducted in siblings of index patients having undergone surgery for colorectal cancer between 1999 and 2002 in two French counties. Siblings were contacted during 2007 and 2008 through the index patient. The factors affecting participation in colonoscopic screening were studied by logistic regression taking into account family cluster effect.Results172 siblings of 74 index cases were included. The declared rate of undergoing at least one colonoscopy among siblings was 66%; 95%CI 59-73%. Five variables were independently associated with colonoscopic screening: perceiving fewer barriers to screening (OR = 3.2; 95%CI 1.2-8.5), having received the recommendation to undergo screening from a physician (OR = 4.9; 1.7-13.7), perceiving centres practising colonoscopy as more accessible (OR = 3.2, 1.3-7.8), having discussed screening with all siblings (OR = 3.9; 1.6-9.6) and being a member of an association (OR = 2.6; 1.0-6.6).ConclusionsThe factors independently associated with participation in CRC screening by an individual at increased risk belonged to each of four dimensions relating to his individual psychosocial characteristics, to his relationship with a physician, within the family and social environment. The relevance of these results to clinical practice may help to improve compliance to recommendations in a global preventive strategy including all stages of the information pathway from the physician to the index patient and his relatives.
Protocol for a national audit on self-reported confidence levels, training requirements and current practice among trainee doctors in the UK: The Trainees Own Perception of Delivery of Care in Diabetes (TOPDOC) Study
Authors: George Jyothis T , McGrane David J , Warriner David , Rozario Kavitha S , Price Hermione C , Wilmot Emma G , Kar Partha , Jude Edward B , McKay Gerard A ,   the TOPDOC Study Team
Published: July 2010

Abstract

Background
As the incidence and prevalence of diabetes increases across the world, resource pressures require doctors without specialist training to provide care for people with diabetes. In the UK, national standards have been set to ensure quality diabetes care from diagnosis to the management of complications. In a multi-centre pilot study, we have demonstrated a lack of confidence among UK trainee doctors in managing diabetes. Suboptimal confidence was identified in a number of areas, including the management of diabetes emergencies. A national survey would clarify whether the results of our pilot study are representative and reproducible.

Methods/Design

Target cohort: All postgraduate trainee doctors in the UK.
Domains Studied: The self reported online survey questionnaire has 5 domains: (1) confidence levels in the diagnosis and management of diabetes, (2) working with diabetes specialists, (3) perceived adequacy of training in diabetes (4) current practice in optimising glycaemic control and (5) perceived barriers to seeking euglycaemia.

Assessment tools: Self-reported confidence is assessed using the 'Confidence Rating' (CR) scale for trainee doctors developed by the Royal College of Physicians. This scale has four points - ('not confident' (CR1), 'satisfactory but lacking confidence' (CR2), 'confident in some cases (CR3) and 'fully confident in most cases' (CR4).
Frequency of aspects of day-to-day practice is assessed using a six-point scale. Respondents have a choice of 'always' (100%), 'almost always' (80-99%), 'often' (50-79%), 'not very often' (20-49%) and 'rarely' (5-19%) or never (less than 5%).

Discussion
It is anticipated that the results of this national study will clarify confidence levels and current practice among trainee doctors in the provision of care for people with diabetes. The responses will inform efforts to enhance postgraduate training in diabetes, potentially improving the quality of care for people with diabetes.
The effect of starting point placement technique on thoracic transverse process strength: an ex vivo biomechanical study
Authors: Brown Barrett S , McIff Terence E , Glattes Rudolph C , Burton Douglas C , Asher Marc A 
Published: July 2010

Abstract

Background
The use of thoracic pedicle screws in spinal deformity, trauma, and tumor reconstruction is becoming more common. Unsuccessful screw placement may require salvage techniques utilizing transverse process hooks. The effect of different starting point placement techniques on the strength of the transverse process has not previously been reported. The purpose of this paper is to determine the biomechanical properties of the thoracic transverse process following various pedicle screw starting point placement techniques.

Methods
Forty-seven fresh-frozen human cadaveric thoracic vertebrae from T2 to T9 were disarticulated and matched by bone mineral density (BMD) and transverse process (TP) cross-sectional area. Specimens were randomized to one of four groups: A, control, and three others based on thoracic pedicle screw placement technique; B, straightforward; C, funnel; and D, in-out-in. Initial cortical bone removal for pedicle screw placement was made using a burr at the location on the transverse process or transverse process-laminar junction as published in the original description of each technique. The transverse process was tested measuring load-to-failure simulating a hook in compression mode. Analysis of covariance and Pearson correlation coefficients were used to examine the data.

Results
Technique was a significant predictor of load-to-failure (P = 0.0007). The least squares mean (LS mean) load-to-failure of group A (control) was 377 N, group B (straightforward) 355 N, group C (funnel) 229 N, and group D (in-out-in) 301 N. Significant differences were noted between groups A and C, A and D, B and C, and C and D. BMD (0.925 g/cm2 [range, 0.624-1.301 g/cm2]) was also a significant predictor of load-to-failure, for all specimens grouped together (P < 0.0001) and for each technique (P < 0.05). Level and side tested were not found to significantly correlate with load-to-failure.

Conclusions
The residual coronal plane compressive strength of the thoracic transverse process is dependent upon the screw starting point placement technique. The funnel technique significantly weakens transverse processes as compared to the straightforward technique, which does not significantly weaken the transverse process. It is also dependent upon bone mineral density, and low failure loads even in some control specimens suggest limited usefulness of the transverse process for axial compression loading in the osteoporotic thoracic spine.
MYBsuppresses differentiation and apoptosis of human breast cancer cells
Authors: Drabsch Yvette , Ramsay Robert G , Gonda Thomas J 
Published: July 2010

Abstract
Introduction
MYB is highly expressed in estrogen receptor positive (ER + ve) breast tumours and tumour cell lines. We recently demonstrated that MYB is essential for the proliferation of ER + ve breast cancer cells, and have now investigated its role in mammary epithelial differentiation.

Methods
MCF-7 breast cancer cells were treated with sodium butyrate, vitamin E succinate or 12-O-tetradecanoylphorbol-13-acetate to induce differentiation as measured by Nile Red staining of lipid droplets and β-casein expression. The non-tumorigenic murine mammary epithelial cell (MEC) line, HC11, was induced to differentiate with lactogenic hormones. MYB levels were manipulated by inducible lentiviral shRNA-mediated knockdown and retroviral overexpression.

Results
We found that MYB expression decreases following chemically-induced differentiation of the human breast cancer cell line MCF-7, and hormonally-induced differentiation of a non-tumorigenic murine mammary epithelial cell (MEC) line, HC11. We also found that shRNA-mediated MYB knockdown initiated differentiation of breast cancer cells, and greatly sensitised them to the differentiative and pro-apoptotic effects of differentiation-inducing agents (DIAs). Sensitisation to the pro-apoptotic effects DIAs is mediated by decreased expression of BCL2, which we show here is a direct MYB target in breast cancer cells. Conversely, enforced expression of MYB resulted in the cells remaining in an undifferentiated state, with concomitant suppression of apoptosis, in the presence of DIAs.

Conclusions
Taken together, these data imply that MYB function is critical in regulating the balance between proliferation, differentiation, and apoptosis in MECs. Moreover, our findings suggest MYB may be a viable therapeutic target in breast cancer and suggest specific approaches for exploiting this possibility.
Efficient, high-throughput transfection of human embryonic stem cells
Authors: Moore Jennifer C , Atze Kristin , Yeung Percy L , Toro-Ramos Alana J , Camarillo Cynthia , Thompson Kevin , Ricupero Christopher L , Brenneman Mark A , Cohen Rick I , Hart Ronald P 
Published: July 2010

Abstract
Introduction
Genetic manipulation of human embryonic stem cells (hESC) has been limited by their general resistance to common methods used to introduce exogenous DNA or RNA. Efficient and high throughput transfection of nucleic acids into hESC would be a valuable experimental tool to manipulate these cells for research and clinical applications.

Methods
We investigated the ability of two commercially available electroporation systems, the Nucleofection® 96-well Shuttle® System from Lonza and the Neon™ Transfection System from Invitrogen to efficiently transfect hESC. Transfection efficiency was measured by flow cytometry for the expression of the green fluorescent protein and the viability of the transfected cells was determined by an ATP catalyzed luciferase reaction. The transfected cells were also analyzed by flow cytometry for common markers of pluripotency.

Results
Both systems are capable of transfecting hESC at high efficiencies with little loss of cell viability. However, the reproducibility and the ease of scaling for high throughput applications led us to perform more comprehensive tests on the Nucleofection® 96-well Shuttle® System. We demonstrate that this method yields a large fraction of transiently transfected cells with minimal loss of cell viability and pluripotency, producing protein expression from plasmid vectors in several different hESC lines. The method scales to a 96-well plate with similar transfection efficiencies at the start and end of the plate. We also investigated the efficiency with which stable transfectants can be generated and recovered under antibiotic selection. Finally, we found that this method is effective in the delivery of short synthetic RNA oligonucleotides (siRNA) into hESC for knockdown of translation activity via RNA interference.

Conclusions
Our results indicate that these electroporation methods provide a reliable, efficient, and high-throughput approach to the genetic manipulation of hESC.