bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract C65: Drug-tolerant cancer cells show reduced tumor-initiating capacity: Depletion of CD44+ cells and evidence for epigenetic mechanisms
Authors: Chen Xin , Fokt Izabela , Skora Stanislaw , Priebe Waldemar , Bi Yongyi , Tang Dean G. , Yan Hong , Zhang Qiuping , Qin Jichao , Li Hangwen , Liu Can , Davis Tammy , Coletta Luis D. , Klostergaard Jim 
Published: May 2013

Abstract
Cancer stem cells (CSCs) possess high tumor-initiating capacity and have been reported to be resistant to therapeutics. Vice versa, therapy-resistant cancer cells seem to manifest CSC phenotypes and properties. It has been generally assumed that drug-resistant cancer cells may all be CSCs although the generality of this assumption is unknown. Here, we chronically treated Du145 prostate cancer cells with etoposide, paclitaxel and some experimental drugs (i.e., staurosporine and 2 paclitaxel analogs), which led to populations of drug-tolerant cells (DTCs). Surprisingly, these DTCs, when implanted either subcutaneously or orthotopically into NOD/SCID mice, exhibited much reduced tumorigenicity or were even nontumorigenic. Drug-tolerant DLD1 colon cancer cells selected by a similar chronic selection protocol also displayed reduced tumorigenicity whereas drug-tolerant UC14 bladder cancer cells demonstrated either increased or decreased tumor-regenerating capacity. Drug-tolerant Du145 cells demonstrated low proliferative and clonogenic potential and were virtually devoid of CD44+ cells. Prospective knockdown of CD44 in Du145 cells inhibited cell proliferation and tumor regeneration whereas restoration of CD44 expression in drug-tolerant Du145 cells increased cell proliferation and partially increased tumorigenicity. Interestingly, drug-tolerant Du145 cells showed both increases and decreases in many ‘stemness’ genes. Finally, evidence was provided that chronic drug exposure generated DTCs via epigenetic mechanisms involving molecules such as CD44 and KDM5A. Our results thus reveal that 1) not all DTCs are necessarily CSCs; 2) conventional chemotherapeutic drugs such as taxol and etoposide may directly target CD44+ tumor-initiating cells; and 3) DTCs generated via chronic drug selection involve epigenetic mechanisms.
Citation Format: Xin Chen, Izabela Fokt, Stanislaw Skora, Waldemar Priebe, Yongyi Bi, Dean G. Tang, Hong Yan, Qiuping Zhang, Jichao Qin, Hangwen Li, Can Liu, Tammy Davis, Luis D. Coletta, Jim Klostergaard. Drug-tolerant cancer cells show reduced tumor-initiating capacity: Depletion of CD44+ cells and evidence for epigenetic mechanisms [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C65.
Abstract PR2: Optimization and applications of a tissue slice culture model of the normal and malignant human prostate
Authors: Maund Sophia Lisette , Nolley Rosalie , Peehl Donna 
Published: May 2013

Abstract
Current in vitro and in vivo models for prostate cancer do not accurately recapitulate many critical aspects of prostate cancer biology. In vitro cell culture systems lack tissue architecture, complex cellular interactions, and the prostate microenvironment. Neither xenograft nor transgenic models generate authentic prostate pathobiology, and genetic and molecular fidelity is often a concern both in vitro and in vivo. Ex vivo organotypic culture systems have been used as valuable research models for several tissue types. Our lab has recently established a tissue slice graft model for prostate cancer in vivo using precision-cut 300 micron slices of radical prostatectomy tissue implanted under the mouse renal capsule. We have also developed a complimentary in vitro tissue slice culture (TSC) model that we have used for a variety of studies, including evaluation of the DNA damage response in normal cell types of the prostate. The main challenges for normal prostate TSC are maintaining luminal cell integrity beyond 48 hours and preventing hyperproliferation of basal cells. Less is known about the maintenance of cancer in TSCs. We have compared several culture conditions and can maintain normal prostate structure and function up to 4 days using PFMR-4A media supplemented with cholera toxin, epidermal growth factor, bovine pituitary extract, phosphoethanolamine, hydrocortisone, selenium, gentamycin, retinoic acid, insulin, vitamin E, and androgen R1881. Dose-response and time-course experiments revealed that the optimal concentration of R1881 for luminal cell integrity is 50nM. We verified expression of luminal and basal cell-specific markers by immunofluorescence of frozen sections, and we observed secretion of PSA by ELISA.
In addition, confocal microscopy is a useful technology for visualizing the 3-dimensional architecture of TSCs. With robust survival of TSCs up to 4 days in vitro, we have a wide range of ongoing and future experimental directions including drug delivery and cell targeting, invasion and migration studies, and metabolic and molecular profiling. Furthermore, we are poised for collaboration with those who want to test their experimental methods in an intact prostate cancer model in vitro. The prostate TSC model is undoubtedly more authentic than current in vitro models, and we are optimizing its utility with the goal of executing more realistic pre-clinical studies.
This abstract is also presented as Poster A69.
Citation Format: Sophia Lisette Maund, Rosalie Nolley, Donna Peehl. Optimization and applications of a tissue slice culture model of the normal and malignant human prostate [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr PR2.
Female Mystics in Mediaeval Islam: The Quiet Legacy
Authors: Azad Arezou 
Published: May 2013

Abstract
Historians and analysts of current affairs alike are interested in the role that women have played in Islam, including the extent to which women were the agents and creators of Islamic mysticism. We still know surprisingly little about premodern learned women, particularly from the eastern Iranian world. This article describes one female mystic, Umm ʿAlī, who flourished in ninth-century Balkh and has so far eluded modern scholarship. A historiographical study of her provides insight into how the representations of mystical women changed over time. From the earlier sources, we learn that Umm ʿAlī applied creative and interesting strategies that provided her access to the highest sources of learning. Umm ʿAlī’s case also allows for some tentative conclusions on the importance of pedigree, and the practice of strategic marriages that connect local power-holders with the ʿulamāʾ.
Climate Change from 1850 to 2005 Simulated in CESM1(WACCM)
Authors: Marsh Daniel R. , Mills Michael J. , Kinnison Douglas E. , Lamarque Jean-Francois , Calvo Natalia , Polvani Lorenzo M. 
Published: May 2013

Abstract
The NCAR Community Earth System Model (CESM) now includes an atmospheric component that extends in altitude to the lower thermosphere. This atmospheric model, known as the Whole Atmosphere Community Climate Model (WACCM), includes fully interactive chemistry, allowing, for example, a self-consistent representation of the development and recovery of the stratospheric ozone hole and its effect on the troposphere. This paper focuses on analysis of an ensemble of transient simulations using CESM1(WACCM), covering the period from the preindustrial era to present day, conducted as part of phase 5 of the Coupled Model Intercomparison Project. Variability in the stratosphere, such as that associated with stratospheric sudden warmings and the development of the ozone hole, is in good agreement with observations. The signals of these phenomena propagate into the troposphere, influencing near-surface winds, precipitation rates, and the extent of sea ice. In comparison of tropospheric climate change predictions with those from a version of CESM that does not fully resolve the stratosphere, the global-mean temperature trends are indistinguishable. However, systematic differences do exist in other climate variables, particularly in the extratropics. The magnitude of the difference can be as large as the climate change response itself. This indicates that the representation of stratosphere–troposphere coupling could be a major source of uncertainty in climate change projections in CESM.
Estuary Classification Revisited
Authors: Guha Anirban , Lawrence Gregory A. 
Published: May 2013

AbstractStudies over a period of several decades have resulted in a relatively simple set of equations describing the tidally and width-averaged balances of momentum and salt in a rectangular estuary. The authors rewrite these equations in a fully nondimensional form that yields two nondimensional variables: (i) the estuarine Froude number and (ii) a modified tidal Froude number. The latter is the product of the tidal Froude number and the square root of the estuarine aspect ratio. These two variables are used to define a prognostic estuary classification scheme, which compares favorably with published estuarine data.
Tripod Index
Authors: Arunakul Marut , Amendola Annunziato , Gao Yubo , Goetz Jessica E. , Femino John E. , Phisitkul Phinit 
Published: May 2013

Background: No single radiographic measurement takes into account complete foot alignment. We have created the Tripod Index (TI) to allow assessment of complex foot deformities using a standing anteroposterior (AP) radiograph of the foot. We hypothesized that TI would demonstrate good intraobserver and interobserver reliability and correlate with currently accepted radiographic parameters, in both flatfoot and cavovarus foot deformities. Methods: Three groups of patients were studied: 26 patients (30 feet) with flatfoot, 29 patients (30 feet) with cavovarus foot, and 51 patients (60 feet) without foot deformity as controls. Weight-bearing radiographs were obtained: foot AP with a hemispherical marker around the heel plus standard lateral and hindfoot alignment views. Radiographic measurements were made by 2 blinded investigators. Statistical analysis included intraclass correlation coefficients (ICCs), correlation of the TI with existing radiographic measurements using Pearson coefficients, and comparison between patient groups using analysis of variance. Results: Intraobserver and interobserver ICCs of TI (0.99 and 0.98, respectively) were excellent. In the flatfoot group, TI significantly correlated with AP talonavicular coverage angle ( r = 0.43), medial cuneiform–fifth metatarsal height ( r = -0.59), coronal plane hindfoot alignment ( r = 0.53), and clinical hindfoot alignment ( r = 0.39). In the cavovarus foot group, TI correlated significantly with AP talonavicular coverage angle ( r = 0.77), calcaneal pitch angle ( r = 0.39), medial cuneiform–fifth metatarsal height ( r = -0.65), coronal plane hindfoot alignment ( r = 0.55), and clinical hindfoot alignment ( r = 0.61). Statistically significant differences between flatfoot-control and cavovarus foot–control were found in TI, AP talonavicular coverage angle, lateral talo–first metatarsal angle, calcaneal pitch angle, medial cuneiform–fifth metatarsal height, coronal plane hindfoot alignment, and clinical assessment of hindfoot alignment (all with P < .001). Conclusion: The TI was demonstrated to be a valid and reliable radiographic measurement to quantify the magnitude of complex foot deformities when evaluating flatfoot and cavovarus foot. Clinical Relevance: The TI may be helpful as an integrated assessment of complex foot deformities. Further clinical studies are recommended. Level of Evidence: Level III, retrospective comparative study.
Nobody was dirty: Intervening in inconspicuous consumption of laundry routines
Authors: Jack Tullia 
Published: May 2013

Collective conventions play a significant role in resource consumption, in particular habitual, inconspicuous consumption ingrained in daily practices. To embed pro-environmental default practices in everyday life, an understanding of materiality, habits and cultural context is useful. Household rituals consume environmentally critical resources; laundry provides an example of this phenomenon, cleanliness collective conventions leading to inconspicuous routinised consumption of laundry resources (water, energy). Intervening into cleanliness conventions, 31 people in Melbourne were engaged to wear the same pair of jeans for three months without washing them. Transcripts from interviews about their experience were used to draw insights on how individual courses of actions are shaped by collective conventions. Participants’ experience of materiality, habits and cultural context indicate that to save environmental resources shifting collective conventions may be more effectual than challenging individual routines. This paper explores some of the opportunities in intervening into the inconspicuous consumption of laundry routines and shifting collective conventions towards low wash acceptance, with implications for other mundane resource-consuming lifestyle practices.
Anterior Cruciate Ligament Reconstruction and Osteoarthritis
Authors: Magnussen Robert A. , Duthon Victoria , Servien Elvire , Neyret Philippe 
Published: May 2013

Objective: The goals of this study are to address several questions, the answers to which are key to the understanding and eventually to the prevention of this frequent source of morbidity. These questions include the following: (1) What is the natural history of anterior cruciate ligament (ACL) deficiency? (2) How important is the status of the meniscus at the time of reconstruction? (3) Does ACL reconstruction prevent the development of osteoarthritis in the long term? (4) Can we predict which patients will develop osteoarthritis? (5) What can be done? Design: This study addresses the key questions above through the long-term follow-up of a cohort of patients treated with ACL reconstruction by Professor Henri Dejour in Lyon, France, supplemented with a review of the relevant literature. Results: The prevalence of osteoarthritis in ACL-deficient knees is about 40% after 15 years and close to 90% after 25 to 35 years. It remains unclear whether reconstruction of the ACL significantly reduces this risk. The status of the meniscus at the time of ACL reconstruction is a strong predictor of the risk of osteoarthritis: Patients who undergo total meniscectomy are at 2- to 10-fold increased risk of developing osteoarthritis relative to those with intact menisci. Patients showing early evidence of arthritis at short- to medium-term follow-up are at high risk for progression over subsequent years. Numerous emerging techniques may provide tools to more effectively prevent and treat osteoarthritis following ACL injury in the future. Conclusion: Osteoarthritis following ACL injury continues to be a major problem requiring further research.
The level of residual disease based on mutant NPM1 is an independent prognostic factor for relapse and survival in AML
Authors: Shayegi Nona , Kramer Michael , Bornhäuser Martin , Schaich Markus , Schetelig Johannes , Platzbecker Uwe , Röllig Christoph , Heiderich Caroline , Landt Olfert , Ehninger Gerhard , Thiede Christian 
Published: May 2013

Key PointsNPM1 RT-PCR levels >1% are associated with poor overall and disease-free survival in AML patients treated with chemotherapy. NPM1 MRD levels >10% are associated with poor overall and disease-free survival in AML patients after allogeneic transplantation.
Distinct position-specific sequence features of hexa-peptides that form amyloid-fibrils: application to discriminate between amyloid fibril and amorphous β-aggregate forming peptide sequences
Authors: Thangakani A Mary , Kumar Sandeep , Velmurugan D , Gromiha M Michael 
Published: May 2013

Abstract

Background
Comparison of short peptides which form amyloid-fibrils with their homologues that may form amorphous β-aggregates but not fibrils, can aid development of novel amyloid-containing nanomaterials with well defined morphologies and characteristics. The knowledge gained from the comparative analysis could also be applied towards identifying potential aggregation prone regions in proteins, which are important for biotechnology applications or have been implicated in neurodegenerative diseases. In this work we have systematically analyzed a set of 139 amyloid-fibril hexa-peptides along with a highly homologous set of 168 hexa-peptides that do not form amyloid fibrils for their position-wise as well as overall amino acid compositions and averages of 49 selected amino acid properties.

Results
Amyloid-fibril forming peptides show distinct preferences and avoidances for amino acid residues to occur at each of the six positions. As expected, the amyloid fibril peptides are also more hydrophobic than non-amyloid peptides. We have used the results of this analysis to develop statistical potential energy values for the 20 amino acid residues to occur at each of the six different positions in the hexa-peptides. The distribution of the potential energy values in 139 amyloid and 168 non-amyloid fibrils are distinct and the amyloid-fibril peptides tend to be more stable (lower total potential energy values) than non-amyloid peptides. The average frequency of occurrence of these peptides with lower than specific cutoff energies at different positions is 72% and 50%, respectively. The potential energy values were used to devise a statistical discriminator to distinguish between amyloid-fibril and non-amyloid peptides. Our method could identify the amyloid-fibril forming hexa-peptides to an accuracy of 89%. On the other hand, the accuracy of identifying non-amyloid peptides was only 54%. Further attempts were made to improve the prediction accuracy via machine learning. This resulted in an overall accuracy of 82.7% with the sensitivity and specificity of 81.3% and 83.9%, respectively, in 10-fold cross-validation method.

Conclusions
Amyloid-fibril forming hexa-peptides show position specific sequence features that are different from those which may form amorphous β-aggregates. These positional preferences are found to be important features for discriminating amyloid-fibril forming peptides from their homologues that don't form amyloid-fibrils.
Antibacterial activities of almond skins on cagA-positive and-negative clinical isolates of Helicobacter pylori
Authors: Bisignano Carlo , Filocamo Angela , La Camera Erminia , Zummo Sebastiana , Fera Maria Teresa , Mandalari Giuseppina 
Published: May 2013

Abstract

Background

Helicobacter pylori is known to be a gastric pathogen of humans. Eradication regimens for H. pylori infection have some side effects, compliance problems, relapses, and antibiotic resistance. Therefore, the need for alternative therapies for H. pylori infections is of special interest. We have previously shown that polyphenols from almond skins are active against a range of food-borne pathogens. The aim of this study was to evaluate the antibacterial effects of natural almond skins before and after simulated human digestion and the pure flavonoid compounds epicatechin, naringenin and protocatechuic acid against H. pylori.

Results

H. pylori strains were isolated from gastric biopsy samples following standard microbiology procedures. Also, cagA and vacA genes were identified using PCR. Susceptibility studies on 34 strains of H. pylori, including two reference strains (ATCC 43504, ATCC 49503), were performed by the standard agar dilution method.
Natural almond skin was the most effective compound against H. pylori (MIC range, 64 to 128 μg/ml), followed by natural skin post gastric digestion (MIC range, 128 to 512 μg/ml), and natural almond skin post gastric plus duodenal digestion (MIC range, 256 to 512 μg/ml). Amongst the pure flavonoid compounds, protocatechuic acid showed the greatest activity (MIC range, 128 to 512 μg/ml) against H. pylori strains.

Conclusions
Polyphenols from almond skins were effective in vitro against H. pylori, irrespective of genotype status and could therefore be used in combination with antibiotics as a novel strategy for antibiotic resistance.
Age dependence of tumor genetics in unfavorable neuroblastoma: arrayCGH profiles of 34 consecutive cases, using a Swedish 25-year neuroblastoma cohort for validation
Authors: Cetinkaya Cihan , Martinsson Tommy , Sandgren Johanna , Träger Catarina , Kogner Per , Dumanski Jan , Díaz de Ståhl Teresita , Hedborg Fredrik 
Published: May 2013

Abstract

Background
Aggressive neuroblastoma remains a significant cause of childhood cancer death despite current intensive multimodal treatment protocols. The purpose of the present work was to characterize the genetic and clinical diversity of such tumors by high resolution arrayCGH profiling.

Methods
Based on a 32K BAC whole-genome tiling path array and using 50-250K Affymetrix SNP array platforms for verification, DNA copy number profiles were generated for 34 consecutive high-risk or lethal outcome neuroblastomas. In addition, age and MYCN amplification (MNA) status were retrieved for 112 unfavorable neuroblastomas of the Swedish Childhood Cancer Registry, representing a 25-year neuroblastoma cohort of Sweden, here used for validation of the findings. Statistical tests used were: Fisher’s exact test, Bayes moderated t-test, independent samples t-test, and correlation analysis.

Results
MNA or segmental 11q loss (11q-) was found in 28/34 tumors. With two exceptions, these aberrations were mutually exclusive. Children with MNA tumors were diagnosed at significantly younger ages than those with 11q- tumors (mean: 27.4 vs. 69.5 months; p=0.008; n=14/12), and MNA tumors had significantly fewer segmental chromosomal aberrations (mean: 5.5 vs. 12.0; p<0.001). Furthermore, in the 11q- tumor group a positive correlation was seen between the number of segmental aberrations and the age at diagnosis (Pearson Correlation 0.606; p=0.037). Among nonMNA/non11q- tumors (n=6), one tumor displayed amplicons on 11q and 12q and three others bore evidence of progression from low-risk tumors due to retrospective evidence of disease six years before diagnosis, or due to tumor profiles with high proportions of numerical chromosomal aberrations. An early age at diagnosis of MNA neuroblastomas was verified by registry data, with an average of 29.2 months for 43 cases that were not included in the present study.

Conclusion
MNA and segmental 11q loss define two major genetic variants of unfavorable neuroblastoma with apparent differences in their pace of tumor evolution and in genomic integrity. Other possible, but less common, routes in the development of aggressive tumors are progression of low-risk infant-type lesions, and gene amplifications other than MYCN. Knowledge on such nosological diversity of aggressive neuroblastoma might influence future strategies for therapy.