bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenomic diversity of colorectal cancer indicated by LINE-1 methylation in a database of 869 tumors
Authors: Baba Yoshifumi , Huttenhower Curtis , Nosho Katsuhiko , Tanaka Noriko , Shima Kaori , Hazra Aditi , Schernhammer Eva S , Hunter David J , Giovannucci Edward L , Fuchs Charles S , Ogino Shuji 
Published: June 2010

Abstract

Background
Genome-wide DNA hypomethylation plays a role in genomic instability and carcinogenesis. LINE-1 (L1 retrotransposon) constitutes a substantial portion of the human genome, and LINE-1 methylation correlates with global DNA methylation status. LINE-1 hypomethylation in colon cancer has been strongly associated with poor prognosis. However, whether LINE-1 hypomethylators constitute a distinct cancer subtype remains uncertain. Recent evidence for concordant LINE-1 hypomethylation within synchronous colorectal cancer pairs suggests the presence of a non-stochastic mechanism influencing tumor LINE-1 methylation level. Thus, it is of particular interest to examine whether its wide variation can be attributed to clinical, pathologic or molecular features.

Design
Utilizing a database of 869 colorectal cancers in two prospective cohort studies, we constructed multivariate linear and logistic regression models for LINE-1 methylation (quantified by Pyrosequencing). Variables included age, sex, body mass index, family history of colorectal cancer, smoking status, tumor location, stage, grade, mucinous component, signet ring cells, tumor infiltrating lymphocytes, CpG island methylator phenotype (CIMP), microsatellite instability, expression of TP53 (p53), CDKN1A (p21), CTNNB1 (β-catenin), PTGS2 (cyclooxygenase-2), and FASN, and mutations in KRAS, BRAF, and PIK3CA.

Results
Tumoral LINE-1 methylation ranged from 23.1 to 90.3 of 0-100 scale (mean 61.4; median 62.3; standard deviation 9.6), and distributed approximately normally except for extreme hypomethylators [LINE-1 methylation < 40; N = 22 (2.5%), which were far more than what could be expected by normal distribution]. LINE-1 extreme hypomethylators were significantly associated with younger patients (p = 0.0058). Residual plot by multivariate linear regression showed that LINE-1 extreme hypomethylators clustered as one distinct group, separate from the main tumor group. The multivariate linear regression model could explain 8.4% of the total variability of LINE-1 methylation (R-square = 0.084). Multivariate logistic regression models for binary LINE-1 hypomethylation outcomes (cutoffs of 40, 50 and 60) showed at most fair predictive ability (area under receiver operator characteristics curve < 0.63).

Conclusions
LINE-1 extreme hypomethylators appear to constitute a previously-unrecognized, distinct subtype of colorectal cancers, which needs to be confirmed by additional studies. Our tumor LINE-1 methylation data indicate enormous epigenomic diversity of individual colorectal cancers.
Tumor promoting effects of CD95 signaling in chemoresistant cells
Authors: Ametller Elisabet , García-Recio Susana , Costamagna Domizziana , Mayordomo Cristina , Fernández-Nogueira Patricia , Carbó Neus , Pastor-Arroyo Eva María , Gascón Pedro , Almendro Vanessa 
Published: June 2010

Abstract

Background
CD95 is a death receptor controlling not only apoptotic pathways but also activating mechanisms promoting tumor growth. During the acquisition of chemoresistance to oxaliplatin there is a progressive loss of CD95 expression in colon cancer cells and a decreased ability of this receptor to induce cell death. The aim of this study was to characterize some key cellular responses controlled by CD95 signaling in oxaliplatin-resistant colon cancer cells.

Results
We show that CD95 triggering results in an increased metastatic ability in resistant cells. Moreover, oxaliplatin treatment itself stimulates cell migration and decreases cell adhesion through CD95 activation, since CD95 expression inhibition by siRNA blocks the promigratory effects of oxaliplatin. These promigratory effects are related to the epithelia-to-mesenchymal transition (EMT) phenomenon, as evidenced by the up-regulation of some transcription factors and mesenchymal markers both in vitro and in vivo.

Conclusions
We conclude that oxaliplatin treatment in cells that have acquired resistance to oxaliplatin-induced apoptosis results in tumor-promoting effects through the activation of CD95 signaling and by inducing EMT, all these events jointly contributing to a metastatic phenotype.
Symptomatic treatment (ibuprofen) or antibiotics (ciprofloxacin) for uncomplicated urinary tract infection? - Results of a randomized controlled pilot trial
Authors: Bleidorn Jutta , Gágyor Ildikó , Kochen Michael M , Wegscheider Karl , Hummers-Pradier Eva 
Published: June 2010

Abstract

Background
Uncomplicated lower urinary tract infections (UTI) are usually treated with antibiotics. However, there is little evidence for alternative therapeutic options.
This pilot study was set out 1) to make a rough estimate of the equivalence of ibuprofen and ciprofloxacin for uncomplicated urinary tract infection with regard to symptom resolution, and 2) to demonstrate the feasibility of a double-blind, randomized controlled drug trial in German general practices.

Methods
We performed a double-blind, randomized controlled pilot trial in 29 German general practices. Eighty otherwise healthy women aged 18 to 85 years, presenting with at least one of the main UTI symptoms dysuria and frequency and without any complicating factors, were randomly assigned to receive either ibuprofen 3 × 400 mg oral or ciprofloxacin 2 × 250 mg (+1 placebo) oral, both for three days.
Intensity of main symptoms - dysuria, frequency, low abdominal pain - was recorded at inclusion and after 4, 7 and 28 days, scoring each symptom from 0 (none) to 4 (very strong). The primary endpoint was symptom resolution on Day 4. Secondary outcomes were the burden of symptoms on Days 4 and 7 (based on the sum score of all symptoms), symptom resolution on Day 7 and frequency of relapses. Equivalence margins for symptom burden on Day 4 were pre-specified as +/- 0.5 sum score points. Data analysis was done by intention to treat and per protocol. Randomization was carried out on patient level by computer programme in blocks of six.

Results
Seventy-nine patients were analyzed (ibuprofen n = 40, ciprofloxacin n = 39). On Day 4, 21/36 (58.3%) of patients in the ibuprofen-group were symptom-free versus 17/33 (51.5%) in the ciprofloxacin-group. On Day 4, ibuprofen patients reported fewer symptoms in terms of total sum score (1; SD 1,42) than ciprofloxacin patients (1,3; SD 1,9), difference -0,33 (95% CI (-1,13 to +0,47)), PP (per protocol) analysis. During Days 0 and 9, 12/36 (33%) of patients in the ibuprofen-group received secondary antibiotic treatment due to ongoing or worsening symptoms, compared to 6/33 (18%) in the ciprofloxacin-group (non significant). A total of 58 non-serious adverse events were reported, 32 in the ibuprofen group versus 26 in the ciprofloxacin group (non significant).

Conclusions
Our results support the assumption of non-inferiority of ibuprofen compared to ciprofloxacin for treatment of symptomatic uncomplicated UTI, but need confirmation by further trials.

Trial registration
Trial registration number: ISRCTN00470468
See Commentary http://www.biomedcentral.com/1471-2296/11/42
Characterization of monoclonal antibodies against Muscovy duck reovirus σB protein
Authors: Liu Ming , Chen Xiaodan , Wang Yue , Zhang Yun , Li Yongfeng , Wang Yunfeng , Shen Nan , Chen Hualan 
Published: June 2010

Abstract

Background
The σB protein of Muscovy duck reovirus (DRV), one of the major structural proteins, is able to induce neutralizing antibody in ducks, but the monoclonal antibody (MAb) against σB protein has never been characterized.

Results
Four hybridoma cell lines secreting anti-DRV σB MAbs were obtained, designated 1E5, 2F7, 4E3 and 5D8. Immunoglobulin subclass tests differentiated them as IgG2b (1E5 and 4E3) and IgM (2F7 and 5D8). Dot blot and western blotting assays showed that MAbs reacted with His-σB protein in a conformation-independent manner. Competitive binding assay indicated that the MAbs delineated two epitopes, A and B of σB. Immunofluorescence assay indicated that the four MAbs could specifically bind to Vero cells infected with DRV and σB was distributed diffusely in the cytoplasma of infected cells. MAbs had universal reactivity to all DRVs tested in an antigen-capture enzyme-linked immunosorbent assay.

Conclusion
Results of this research provide important information about the four monoclonal antibodies and therefore the MAbs may be useful candidate for the development of a MAb capture ELISA for rapid detection of DRVs. In addition, it showed that the σB protein was located in the cytoplasma of infected cells by immunofluorescence assay with MAbs. Virus isolation and RT-PCR are reliable way for detection of DRV infection, but these procedures are laborious, time consuming, and requiring instruments. These obvious diagnosis problems highlight the ongoing demand of rapid, reproducible, and automatic methods for the sensitive detection of DRV.
Design, assembly, and validation of a nose-only inhalation exposure system for studies of aerosolized viable influenza H5N1 virus in ferrets
Authors: Tuttle Richard S , Sosna William A , Daniels Deirdre E , Hamilton Sara B , Lednicky John A 
Published: June 2010

Abstract

Background
The routes by which humans acquire influenza H5N1 infections have not been fully elucidated. Based on the known biology of influenza viruses, four modes of transmission are most likely in humans: aerosol transmission, ingestion of undercooked contaminated infected poultry, transmission by large droplets and self-inoculation of the nasal mucosa by contaminated hands. In preparation of a study to resolve whether H5N1 viruses are transmissible by aerosol in an animal model that is a surrogate for humans, an inhalation exposure system for studies of aerosolized H5N1 viruses in ferrets was designed, assembled, and validated. Particular attention was paid towards system safety, efficacy of dissemination, the viability of aerosolized virus, and sampling methodology.

Results
An aerosol generation and delivery system, referred to as a Nose-Only Bioaerosol Exposure System (NBIES), was assembled and function tested. The NBIES passed all safety tests, met expected engineering parameters, required relatively small quantities of material to obtain the desired aerosol concentrations of influenza virus, and delivered doses with high-efficacy. Ferrets withstood a mock exposure trial without signs of stress.

Conclusions
The NBIES delivers doses of aerosolized influenza viruses with high efficacy, and uses less starting material than other similar designs. Influenza H5N1 and H3N2 viruses remain stable under the conditions used for aerosol generation and sample collection. The NBIES is qualified for studies of aerosolized H5N1 virus.
"If you don't believe it, it won't help you": use of bush medicine in treating cancer among Aboriginal people in Western Australia
Authors: Shahid Shaouli , Bleam Ryan , Bessarab Dawn , Thompson Sandra C 
Published: June 2010

Abstract
Background
Little is known about the use of bush medicine and traditional healing among Aboriginal Australians for their treatment of cancer and the meanings attached to it. A qualitative study that explored Aboriginal Australians' perspectives and experiences of cancer and cancer services in Western Australia provided an opportunity to analyse the contemporary meanings attached and use of bush medicine by Aboriginal people with cancer in Western Australia

Methods
Data collection occurred in Perth, both rural and remote areas and included individual in-depth interviews, observations and field notes. Of the thirty-seven interviews with Aboriginal cancer patients, family members of people who died from cancer and some Aboriginal health care providers, 11 participants whose responses included substantial mention on the issue of bush medicine and traditional healing were selected for the analysis for this paper.

Results
The study findings have shown that as part of their healing some Aboriginal Australians use traditional medicine for treating their cancer. Such healing processes and medicines were preferred by some because it helped reconnect them with their heritage, land, culture and the spirits of their ancestors, bringing peace of mind during their illness. Spiritual beliefs and holistic health approaches and practices play an important role in the treatment choices for some patients.

Conclusions
Service providers need to acknowledge and understand the existence of Aboriginal knowledge (epistemology) and accept that traditional healing can be an important addition to an Aboriginal person's healing complementing Western medical treatment regimes. Allowing and supporting traditional approaches to treatment reflects a commitment by modern medical services to adopting an Aboriginal-friendly approach that is not only culturally appropriate but assists with the cultural security of the service.
Inverse folding of RNA pseudoknot structures
Authors: Gao James ZM , Li Linda YM , Reidys Christian M 
Published: June 2010

Abstract

Background
RNA exhibits a variety of structural configurations. Here we consider a structure to be tantamount to the noncrossing Watson-Crick and G-U-base pairings (secondary structure) and additional cross-serial base pairs. These interactions are called pseudoknots and are observed across the whole spectrum of RNA functionalities. In the context of studying natural RNA structures, searching for new ribozymes and designing artificial RNA, it is of interest to find RNA sequences folding into a specific structure and to analyze their induced neutral networks. Since the established inverse folding algorithms, RNAinverse, RNA-SSD as well as INFO-RNA are limited to RNA secondary structures, we present in this paper the inverse folding algorithm Inv which can deal with 3-noncrossing, canonical pseudoknot structures.

Results
In this paper we present the inverse folding algorithm Inv. We give a detailed analysis of Inv, including pseudocodes. We show that Inv allows to design in particular 3-noncrossing nonplanar RNA pseudoknot 3-noncrossing RNA structures-a class which is difficult to construct via dynamic programming routines. Inv is freely available at http://www.combinatorics.cn/cbpc/inv.html.

Conclusions
The algorithm Inv extends inverse folding capabilities to RNA pseudoknot structures. In comparison with RNAinverse it uses new ideas, for instance by considering sets of competing structures. As a result, Inv is not only able to find novel sequences even for RNA secondary structures, it does so in the context of competing structures that potentially exhibit cross-serial interactions.
Reversible bone pain and symmetric bone scan uptake in a dialysis patient treated with cinacalcet: a case report
Authors: Lenz Oliver , Sancassani Rhea , Bottino Carla , Fornoni Alessia 
Published: June 2010

Abstract

Introduction
The medical management of secondary hyperparathyroidism in patients with end-stage renal disease involves a combination of dietary restrictions, phosphate binders, active vitamin D analogs, and calcimimetics.

Case presentation
We report the case of a 36-year-old Hispanic dialysis patient, originally from Cuba and now residing in the USA, who developed severe bone pain and muscle twitching after starting low dose cinacalcet, despite normal pre-dialysis ionized calcium and elevated parathyroid hormone. The clinical symptoms correlated with increased symmetrical uptake on bone scan that resolved rapidly upon discontinuation of cinacalcet.

Conclusion
Cinacalcet may induce severe bone pain and a unique bone scan uptake pattern in hemodialysis patients.
Antisense oligonucleotide targeting Livin induces apoptosis of human bladder cancer cell via a mechanism involving caspase 3
Authors: Chuan Liu , Xiaohou Wu , Chunli Luo , Zili Hu , Zhikang Yin , Yunfeng He , Hu Du , Weili Zhang , Qing Jiang , Yanjun Lin 
Published: June 2010

AbstractBackground and Aimin recent years, Livin, a new member of IAPs family, is found to be a key molecule in cancers. Researchers consider Livin may become a new target for tumor therapy; however, the role of it in bladder cancer is still unclear. The purpose of this article is to investigate Antisense Oligonucleotide (ASODN) of Livin on treating bladder cancer cell and underlying mechanisms.MethodsPhosphorathioate modifying was used to synthesize antisense oligonucleotides targeting Livin, followed by transfection into human bladder cancer cell 5637. After transfection, Livin mRNA and protein level, cell proliferation and apoptosis changes, caspase3 level and its effect on human bladder cancer transplantable tumor in nude mice were measured.Resultresults showed Livin ASODN effectively inhibited Livin expression and tumor cell proliferation, and these effects probably through enhanced caspase3 activity and apoptosis of tumor cells. In nude mice transplantable tumor model, Livin expressions were inhibited meanwhile caspase3 expression was increased. Tumor growth slowed down and apoptosis was enhanced.ConclusionOur data suggest that Livin plays an important role in inhibiting apoptosis of bladder cancer cells. Livin ASODN may promote cell apoptosis, inhibit bladder cancer growth, and become one of the methods of gene therapy for bladder cancer.
An introduction to family‐centred services for children affected by HIV and AIDS
Authors: Richter Linda 
Published: June 2010

Family‐centred services in the context of HIV/AIDS acknowledge a broad view of a “family system” and ideally include comprehensive treatment and care, community agencies and coordinated case management. The importance of family‐centred care for children affected by HIV/AIDS has been recognized for some time. There is a clear confluence of changing social realities and the needs of children in families affected by HIV and AIDS, but a change of paradigm in rendering services to children through families, in both high‐prevalence and concentrated epidemic settings, has been slow to emerge.Despite a wide variety of model approaches, interventions, whether medical or psychosocial, still tend to target individuals rather than families. It has become clear that an individualistic approach to children affected by HIV and AIDS leads to confusion and misdirection of the global, national and local response. The almost exclusive focus on orphans, defined initially as a child who had lost one or both parents to AIDS, has occluded appreciation of the broader impact on children exposed to risk in other ways and the impact of the epidemic on families, communities and services for children. In addition, it led to narrowly focused, small‐scale social welfare and case management approaches with little impact on government action, global and national policy, integration with health and education interventions, and increased funding.National social protection programmes that strengthen families are now established in several countries hard hit by AIDS, and large‐scale pilots are underway in others. These efforts are supported by international and national development agencies, increasingly by governments and, more recently, by UNAIDS and the global AIDS community.There is no doubt that this is the beginning of a road and that there is still a long way to go, including basic research on families, family interventions, and effectiveness and costs of family‐centred approaches. It is also clear that many of the institutions that are intended to serve families sometimes fail and frequently even combat non‐traditional families.
Family‐centred approaches to the prevention of mother to child transmission of HIV
Authors: Betancourt Theresa S , Abrams Elaine J , McBain Ryan , Fawzi Mary C Smith 
Published: June 2010

BackgroundPrevention of mother to child transmission (PMTCT) programmes have traditionally been narrow in scope, targeting biomedical interventions during the perinatal period, rather than considering HIV as a family disease. This limited focus restricts programmes' effectiveness, and the opportunity to broaden prevention measures has largely been overlooked.Although prevention of vertical transmission is crucial, consideration of the family environment can enhance PMTCT. Family‐centred approaches to HIV prevention and care present an important direction for preventing paediatric infections while improving overall family health. This paper reviews available literature on PMTCT programmatic models that have taken a broader or family‐centred approach. We describe findings and barriers to the delivery of family‐centred PMTCT and identify a number of promising new directions that may achieve more holistic services for children and families.MethodsLiterature on the effectiveness of family‐centred PMTCT interventions available via PubMed, EMBASE and PsycINFO were searched from 1990 to the present. Four hundred and three abstracts were generated. These were narrowed to those describing or evaluating PMTCT models that target broader aspects of the family system before, during and/or after delivery of an infant at risk of acquiring HIV infection (N = 14).ResultsThe most common aspects of family‐centred care incorporated by PMTCT studies and programme models included counselling, testing, and provision of antiretroviral treatment for infected pregnant women and their partners. Antiretroviral therapy was also commonly extended to other infected family members. Efforts to involve fathers in family‐based PMTCT counselling, infant feeding counselling, and general decision making were less common, though promising. Also promising, but rare, were PMTCT programmes that use interventions to enrich family capacity and functioning; these include risk assessments for intimate partner violence, attention to mental health issues, and the integration of early childhood development services.ConclusionsDespite barriers, numerous opportunities exist to expand PMTCT services to address the health needs of the entire family. Our review of models utilizing these approaches indicates that family‐centred prevention measures can be effectively integrated within programmes. However, additional research is needed in order to more thoroughly evaluate their impact on PMTCT, as well as on broader family health outcomes.