bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current status of molecular markers for prognostication and outcome in invasive bladder cancer
Authors: Gakis Georgios , Schwentner Christian , Todenhöfer Tilman , Stenzl Arnulf 
Published: January 2012

What's known on the subject? and What does the study add?Currently, prognostication of patients with invasive BC is hampered owing to the inadequacy of standard clinicopathological risk factors to predict accurately individual treatment outcomes. This review provides a comprehensive albeit brief overview on current studies elucidating the potential role of different molecular markers to close this gap of evidence. It focusses on biostatistical considerations in the interpretation of study results which are essential to provide meaningful clinical conclusions for an individual patient.OBJECTIVE
To improve prognostication and the management of patients with invasive bladder cancer (BC).
METHODS
Standard clinicopathological risk factors are not reliably enough to accurately predict outcomes in patients after radical treatment and guide clinicians for recommending selectively the use of adjuvant therapies.
With detailed insights into the molecular pathology of BC, biomarkers have come to the fore of researchers as a potential tool to close this gap of evidence.
However, their definitive role in the diagnostic and therapeutic management of patients with invasive BC has not clearly been addressed so far.
RESULTS
Invasive BC are an extremely heterogenenous group of malignancies which are characterized by multiple genetic alterations involved in the carcinogenesis and development of metastatic spread. Thus, it is questionable whether any single marker will provide superior prognostication compared with a combination of markers.
Current studies evaluating the predictive value of a multitude of markers have used high‐throughput technologies and investigated the gain in predictive accuracy within new nomograms which encompass well‐established clinicopathological and novel putative molecular parameters. p53 overexpression was found to be associated with increased risk of recurrence in urothelial and non‐urothelial cancer. In pT1 disease, the combination of p53, p21 and p16 as well as epigenetic alterations of myopodin expression has been shown to provide improved prognostication, and this might help to advocate more selectively the use of early radical treatment.
After the bladder‐sparing approach, p53 and p21 overexpression indicate decreased probability of long‐term bladder preservation. Additionally, altered retinoblastoma expression is associated with improved survival after adjuvant chemotherapy.
To provide meaningful conclusions for individual prognosis and the need of adjuvant treatment, biostatistical pitfalls in the analysis and interpretation of results have to be taken into account.
CONCLUSIONS
Different molecular markers have the potential to improve prognostication of patients with invasive BC and provide improved evidence for targeted therapy in the neoadjuvant, adjuvant and metastatic setting.
However, in order to advocate their routine clinical use on a sound scientific basis prospective data are still necessary.
Diet and its role in interstitial cystitis/bladder pain syndrome (IC/BPS) and comorbid conditions
Authors: Friedlander Justin I. , Shorter Barbara , Moldwin Robert M. 
Published: January 2012

What's known on the subject? and What does the study add?Nearly 90% of patients with interstitial cystitis/bladder pain syndrome (IC/BPS) report sensitivities to a wide variety of dietary comestibles. Current questionnaire‐based literature suggests that citrus fruits, tomatoes, vitamin C, artificial sweeteners, coffee, tea, carbonated and alcoholic beverages, and spicy foods tend to exacerbate symptoms, while calcium glycerophosphate and sodium bicarbonate tend to improve symptoms. At present we recommend employing a controlled method to determine dietary sensitivities, such as an elimination diet, in order to identify sensitivities while at the same time maintain optimal nutritional intake.We review current literature with regard to diet's effect upon IC/BPS and common comorbidities (irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, neuropathic pain, vulvodynia, and headache) with a focus upon questionnaire‐based investigations. We discuss the pathologic mechanisms that may link diet and IC/BPS related‐pain, concentrating upon specific comestibles such as acidic foods, foods high in potassium, caffeine, and alcohol.
Up to 90% of patients with interstitial cystitis/bladder pain syndrome (IC/BPS) report sensitivities to a wide variety of comestibles.
Pathological mechanisms suggested to be responsible for the relationship between dietary intake and symptom exacerbation include peripheral and/or central neural upregulation, bladder epithelial dysfunction, and organ ‘cross‐talk’, amongst others.
Current questionnaire‐based data suggests that citrus fruits, tomatoes, vitamin C, artificial sweeteners, coffee, tea, carbonated and alcoholic beverages, and spicy foods tend to exacerbate symptoms, while calcium glycerophosphate and sodium bicarbonate tend to improve symptoms.
Specific comestible sensitivities varied between patients and may have been influenced by comorbid conditions.
This suggests that a controlled method to determine dietary sensitivities, such as an elimination diet, may play an important role in patient management.
Surgical simulators in urological training – views of UK Training Programme Directors
Authors: Forster James A. , Browning Anthony J. , Paul Alan B. , Biyani C. Shekhar 
Published: January 2012

What's known on the subject? and What does the study add?The role of surgical simulators is currently being debated in urological and other surgical specialties. Simulators are not presently implemented in the UK urology training curriculum. The availability of simulators and the opinions of Training Programme Directors' (TPD) on their role have not been described.In the present questionnaire‐based survey, the trainees of most, but not all, UK TPDs had access to laparoscopic simulators, and that all responding TPDs thought that simulators improved laparoscopic training. We hope that the present study will be a positive step towards making an agreement to formally introduce simulators into the UK urology training curriculum.To discuss the current situation on the use of simulators in surgical training. To determine the views of UK Urology Training Programme Directors (TPDs) on the availability and use of simulators in Urology at present, and to discuss the role that simulators may have in future training. An online‐questionnaire survey was distributed to all UK Urology TPDs. In all, 16 of 21 TPDs responded. All 16 thought that laparoscopic simulators improved the quality of laparoscopic training. The trainees of 13 TPDs had access to a laparoscopic simulator (either in their own hospital or another hospital in the deanery). Most TPDs thought that trainees should use simulators in their free time, in quiet time during work hours, or in teaching sessions (rather than incorporated into the weekly timetable). We feel that the current apprentice‐style method of training in urological surgery is out‐dated. We think that all TPDs and trainees should have access to a simulator, and that a formal competency based simulation training programme should be incorporated into the urology training curriculum, with trainees reaching a minimum proficiency on a simulator before undertaking surgical procedures.
MUTUAL LEARNING IN DUTCH‐MOROCCAN AND DUTCH‐TURKISH MUNICIPAL PARTNERSHIPS
Authors: VAN EWIJK EDITH 
Published: January 2012

ABSTRACTThis paper focuses on mutual learning (learning by both involved parties) in Dutch‐Moroccan and Dutch‐Turkish municipal partnerships. This is particularly relevant as strengthening local governance is high on the agenda of both migrant source and destination countries and the body of knowledge on mutual learning in municipal partnerships is limited. After describing the national and local policy context, the paper presents an analysis of knowledge exchanges and learning at the level of local government and other society actors in the Netherlands, Turkey and Morocco. The results show that involved actors in the three countries learned in different ways within these partnerships. The international exchanges also helped strengthening connections between local government and non‐governmental actors in the involved countries. The potential for mutual learning was however not fully utilised due to the absence of clear learning strategies, existing language barriers and the lack of strategic involvement of other actors.
Characterization of fibrillar collagen types using multi‐dimensional multiphoton laser scanning microscopy
Authors: Lutz V. , Sattler M. , Gallinat S. , Wenck H. , Poertner R. , Fischer F. 
Published: January 2012

SynopsisIn dermal photodamage the ratio of the collagen types III to I changes. This makes the investigation of the fibrillar collagen type characteristics interesting for skin research. In this study collagen types were characterized using 5‐dimensional multiphoton laser scanning microscopy (5D‐IVT) that can be applied in vivo. Second harmonic generation (SHG) signals and fluorescence lifetimes of the collagen autofluorescence were analysed. Collagen type I generates a higher SHG intensity and a longer fluorescence lifetime compared to collagen type III. Thus, the SHG intensity decrease found in photodamaged skin might be explained by the increase in collagen type III. Calculating the in vivo relevant increase of collagen type III gives a negligible difference in fluorescence lifetime not qualifying this method for the determination of collagen type changes in dermal photodamage in vivo in human skin. However, for pathologies that exhibit higher differences in collagen types 5D‐IVT analysis might be a suitable method.
Computational models of plant development and form
Authors: Prusinkiewicz Przemyslaw , Runions Adam 
Published: January 2012

SummaryThe use of computational techniques increasingly permeates developmental biology, from the acquisition, processing and analysis of experimental data to the construction of models of organisms. Specifically, models help to untangle the non‐intuitive relations between local morphogenetic processes and global patterns and forms. We survey the modeling techniques and selected models that are designed to elucidate plant development in mechanistic terms, with an emphasis on: the history of mathematical and computational approaches to developmental plant biology; the key objectives and methodological aspects of model construction; the diverse mathematical and computational methods related to plant modeling; and the essence of two classes of models, which approach plant morphogenesis from the geometric and molecular perspectives. In the geometric domain, we review models of cell division patterns, phyllotaxis, the form and vascular patterns of leaves, and branching patterns. In the molecular‐level domain, we focus on the currently most extensively developed theme: the role of auxin in plant morphogenesis. The review is addressed to both biologists and computational modelers.

Contents

Summary
549

I.
A brief history of plant models
549

II.
Modeling as a methodology
550

III.
Mathematics of developmental models
551

IV.
Geometric models of morphogenesis
555

V.
Molecular‐level models
560

VI.
Conclusions
564

Acknowledgements
564

References
565
Heritability of Level of Response and Association with Recent Drinking History in Nonalcohol‐Dependent Drinkers
Authors: Kalu Nnenna , Ramchandani Vijay A. , Marshall Vanessa , Scott Denise , Ferguson Clifford , Cain Gloria , Taylor Robert 
Published: January 2012

Background:Level of response (LR) to alcohol has been shown to be associated with the risk of developing alcohol dependence and can be measured using the self‐rating of the effects of alcohol (SRE) questionnaire. This study examined the heritability of the SRE‐measured LR and the relationship between LR and recent alcohol drinking history (RDH) in a predominantly African American nonalcohol‐dependent population.Methods:This was a sibling study of 101 social drinkers aged 21 to 35 years recruited from the Washington, DC metropolitan area. Participants were administered the SRE to assess LR and the timeline followback (TLFB) to assess RDH. The indices of SRE used were total SRE score (SRTT), early drinking SRE score (SRED), regular drinking SRE score (SRRD), and heavy drinking SRE score (SRHD). Pearson's product‐moment correlation and linear regression were used to analyze SRE indices and RDH variables (quantity and drinks per drinking occasion). Heritability analysis was conducted using Sequential Oligogenic Linkage Analysis Routines (SOLAR) software with SRE indices as traits of interest.Results:There was a significant relationship between SRE and RDH measures. Drinks per drinking day, maximum drinks, and quantity of drinks were significantly associated with SRTT, SRHD, and SRRD (all p < 0.05). SRTT showed significant heritability (h2 = 0.67, p = 0.025), however, the SRE subindices (SRED, SRRD, SRHD) were not significantly heritable. Analysis performed in the subset consisting of only African Americans (n = 86) showed similar trends.Conclusions:LR, as measured by the SRE, is associated with RDH. The high level of heritability of the SRE total score suggests that genetics accounts for a significant proportion of the variation in the LR to alcohol in social drinkers.
Responding in a Test of Decision‐Making Under Risk is Under Moderate Genetic Control in the Rat
Authors: Ashenhurst James R. , Seaman Mitchel , David Jentsch J. 
Published: January 2012

Background:Risk‐taking, measured with laboratory tasks such as the Balloon Analog Risk Task (BART), is associated with real‐life manifestations of risky behaviors, which may be an important component of inherited liability to alcohol use disorders. To identify genomic factors that influence these traits, the current study (i) characterized performance of a rodent version of the BART in multiple inbred rat strains, (ii) tested the degree to which performance was under genetic control, (iii) explored sex differences in performance, and (iv) evaluated the risk‐taking behavior of F1 progeny of high‐risk‐ and low‐risk‐taking strains to examine modes of inheritance.Methods:Male and female rats (N = 100) from 5 inbred strains (Wistar‐Furth, Fischer‐344, Lewis, Spontaneously Hypertensive, Brown Norway) and Wistar‐Furth × Fischer‐344 hybrids were tested in the rat‐BART, as well as in tests of locomotor activity, sucrose preference, and general motivation.Results:About 55% of the variance in risk‐taking behavior was attributable to heritable factors. The Fischer‐344 strain was the most risk‐taking and the most variable in responding. The mating of low‐risk‐taking Wistar‐Furth and Fischer‐344 rats produced progeny that behaved most like the Fischer‐344 strain. Consistent with prior research in this laboratory (Jentsch et al., 2010), all rats were sensitive to changes in both risk and reinforcement parameters in the rat‐BART; rats decreased voluntary risk‐taking in the face of increasing risk and increased lever pressing when reinforcement probabilities were reduced.Conclusions:Our results endorse a moderately heritable pattern of risk‐taking behavior in rats. The behavior of the hybrid progeny suggests a polygenic model with most gene effects transmitted by mode of dominant inheritance. The identification of high‐risk and low‐risk strains allows for isolation of quantitative trait loci associated with task performance and for probing the relationships between risk‐taking and dimensions of alcohol use disorders.
Roles of the Locus Coeruleus and Adrenergic Receptors in Brain‐Mediated Hypothalamic–Pituitary–Adrenal Axis Responses to Intracerebroventricular Alcohol
Authors: Selvage Dan 
Published: January 2012

Background:Alcohol activates the hypothalamic–pituitary–adrenal (HPA) axis through its actions in both the periphery and the central nervous system (CNS). The studies presented here were designed to test the CNS‐specific noradrenergic mechanisms by which alcohol stimulates HPA activity in the male rat.Methods:We used an experimental paradigm in which a small, nontoxic amount (5 μl) of alcohol was slowly microinfused intracerebroventricularly (icv). Alcohol was administered icv to animals with lesions of the locus coeruleus (LC) or in animals pretreated with α‐ or β‐adrenergic receptor antagonists. Hormonal HPA activation was determined by measuring secretion of the pituitary stress hormone adrenocorticotropin (ACTH). Neuronal activation was determined by quantification of the expression of the transcription factor c‐fos (Fos).Results:As expected, icv alcohol stimulated ACTH secretion from the pituitary and Fos expression in the paraventricular nucleus of the hypothalamus (PVN). Bilateral electrolytic LC lesions blocked the ability of icv alcohol to stimulate ACTH secretion. Pretreatment with icv propranolol increased basal ACTH secretion levels, but icv alcohol did not increase this effect. Propranolol also blunted icv alcohol‐induced PVN Fos expression. A low dose of phenoxybenzamine, an α‐adrenergic receptor antagonist, did not affect the ability of icv alcohol to stimulate ACTH release. However, a higher dose of the drug was able to block the ACTH response to icv alcohol. Despite this, phenoxybenzamine did not inhibit alcohol‐induced Fos expression. Icv pretreatment with corynanthine, a selective α‐1 adrenergic receptor antagonist, modestly raised basal ACTH levels and blocked the icv alcohol‐induced secretion of this hormone.Conclusions:These results indicate that the LC and norepinephrine play important roles in HPA activation caused by icv alcohol administration, but that the specific adrenergic receptor subtypes involved in this phenomenon still need to be identified.
Comment on the Paper by Suffoletto et al. Entitled: Text‐Message‐Based Assessments and Brief Intervention for Young Adults Discharged from the Emergency Department
Authors: Baird Janette , Ranney Megan L. , Mello Michael J. 
Published: January 2012

Background:This commentary discusses the importance of the recent article by Suffoletto and colleagues (in press), from the perspective of the developing role that technology such as text‐messaging is serving as a means of increasing the reach of brief interventions for harmful alcohol use.Results:This study is important as it offers evidence from a well‐designed study that text‐messaging can be used to survey young adults about their alcohol use shows promising results for the potential efficacy of this technology to reduce alcohol use, including risky heavy episodic use. There are ethical and clinical considerations around text‐messaging that need to be examined.Conclusions:Future adequately powered randomized studies are needed to show the comparative effect of new technologies, such as text‐messaging, in comparison with more traditional methods of providing interventions in reducing harmful alcohol use.
Anti‐AnWj causing acute hemolytic transfusion reactions in a patient with aplastic anemia
Authors: Xu Zhaodong , Duffett Lisa , Tokessy Melanie , Cote Jacqueline , Goldman Mindy , Saidenberg Elianna 
Published: January 2012

BACKGROUND: AnWj is a high‐prevalence red blood cell (RBC) antigen in the ISBT 901 series. Only nine reports of anti‐AnWj have been published since it was first documented in 1972; two of these cases involved transfusion reactions. We present a case of a patient with aplastic anemia who developed anti‐AnWj with clinically significant hemolysis after transfusion of AnWj‐positive RBCs.STUDY DESIGN AND METHODS: A 56‐year‐old woman with aplastic anemia developed a pan‐reactive antibody with clinically significant hemolysis after transfusion of RBCs. Investigations included antibody identification by serologic methods at the national immunohematology reference laboratory and the in vitro monocyte‐monolayer assay (MMA) to predict clinical significance.RESULTS: The antibody was identified as having specificity for the AnWj antigen. The posttransfusion MMA indicated that the antibody had complement‐fixing capability highly likely to cause clinically significant acute hemolytic transfusion reactions. The patient required long‐term transfusion support with AnWj‐negative RBCs and Lu(a−b−) RBCs of the In(Lu) type which have reduced AnWj expression. Cross‐Canada and international collaboration was required to obtain rare units for transfusion.CONCLUSION: A case of acute hemolytic transfusion reaction caused by anti‐AnWj is reported in a patient with aplastic anemia requiring allogeneic stem cell transplantation. This is the second documented case of anti‐AnWj to cause a hemolytic transfusion reaction. The case demonstrates the complexity of managing patients with rare antibodies and the importance of international collaboration in the management of these difficult cases.
Comparing the Hyper‐Variable V4 and V9 Regions of the Small Subunit rDNA for Assessment of Ciliate Environmental Diversity
Authors: Dunthorn Micah , Klier Julia , Bunge John , Stoeck Thorsten 
Published: January 2012

AbstractThe hyper‐variable V4 and V9 regions of the small subunit (SSU) rDNA have been targeted for assessing environmental diversity of microbial eukaryotes using next generation sequencing technologies. Here, we explore how the genetic distances among these short fragments compare with the distances obtained from near full‐length SSU‐rDNA sequences by comparing all pairwise estimates, as well as within and among species of ciliates. Results show that pairwise distances from V4 more closely match the near full‐length SSU‐rDNA and are more comparable with previous studies based on much longer SSU‐rDNA fragments, then pairwise distances from V9. Thus, studies that use the V4 will estimate similar values of phylotype richness and community structure as would have been estimated using the full‐length SSU‐rDNA.
Acute New World cutaneous leishmaniasis presenting as tuberculoid granulomatous dermatitis
Authors: Miller Daniel D. , Gilchrest Barbara A. , Garg Amit , Goldberg Lynne J. , Bhawan Jag 
Published: January 2012

Acute primary cutaneous leishmaniasis typically presents microscopically with a lymphohistiocytic infiltrate containing admixed plasma cells, parasitized macrophages and abundant organisms. Tuberculoid granulomatous changes may occur in the later phases of primary infection. A 23‐year‐old male presented 1 month after visiting Peru with classic clinical findings of acute primary cutaneous leishmaniasis, while histopathology showed a tuberculoid granulomatous process that lacked any organisms in hematoxylin–eosin and fungal stains. Polymerase chain reaction (PCR) analysis and tissue cultures confirmed the diagnosis of cutaneous leishmaniasis with Leishmania (Viannia) panamensis infection. A pauci‐organism tuberculoid granulomatous process may uncommonly be the presenting histopathology in the acute infectious phase of cutaneous leishmaniasis. Clinicians and dermatopathologists should be aware of this atypical presentation, which may cause diagnostic confusion and delay proper treatment. PCR testing should be employed in cases with high clinical suspicion when histopathology is not definitive.Miller DD, Gilchrest BA, Garg A, Goldberg LJ, Bhawan J. Acute New World cutaneous leishmaniasis presenting as tuberculoid granulomatous dermatitis.