bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells
Authors: Ailan He , Xiangwen Xiao , Daolong Ren , Lu Gan , Xiaofeng Ding , Xi Qiao , Xingwang Hu , Rushi Liu , Jian Zhang , Shuanglin Xiang 
Published: August 2009

Abstract

Background
Activator protein 2 gamma (AP-2γ) is a member of the transcription factor activator protein-2 (AP-2) family, which is developmentally regulated and plays a role in human neoplasia. AP-2γ has been found to be overexpressed in most breast cancers, and have a dual role to inhibit tumor initiation and promote tumor progression afterwards during mammary tumorigensis.

Methods
To identify the gene targets that mediate its effects, we performed chromatin immunoprecipitation (ChIP) to isolate AP-2γ binding sites on genomic DNA from human breast cancer cell line MDA-MB-453.

Results
20 novel DNA fragments proximal to potential AP-2γ targets were obtained. They are categorized into functional groups of carcinogenesis, metabolism and others. A combination of sequence analysis, reporter gene assays, quantitative real-time PCR, electrophoretic gel mobility shift assays and immunoblot analysis further confirmed the four AP-2γ target genes in carcinogenesis group: ErbB2, CDH2, HPSE and IGSF11. Our results were consistent with the previous reports that ErbB2 was the target gene of AP-2γ. Decreased expression and overexpression of AP-2γ in human breast cancer cells significantly altered the expression of these four genes, indicating that AP-2γ directly regulates them.

Conclusion
This suggested that AP-2γ can coordinate the expression of a network of genes, involving in carcinogenesis, especially in breast cancer. They could serve as therapeutic targets against breast cancers in the future.
Short-term effects of implemented high intensity shoulder elevation during computer work
Authors: Larsen Mette K , Samani Afshin , Madeleine Pascal , Olsen Henrik B , Søgaard Karen , Holtermann Andreas 
Published: August 2009

Abstract

Background
Work-site strength training sessions are shown effective to prevent and reduce neck-shoulder pain in computer workers, but difficult to integrate in normal working routines. A solution for avoiding neck-shoulder pain during computer work may be to implement high intensity voluntary contractions during the computer work. However, it is unknown how this may influence productivity, rate of perceived exertion (RPE) as well as activity and rest of neck-shoulder muscles during computer work. The aim of this study was to investigate short-term effects of a high intensity contraction on productivity, RPE and upper trapezius activity and rest during computer work and a subsequent pause from computer work.

Methods
18 female computer workers performed 2 sessions of 15 min standardized computer mouse work preceded by 1 min pause with and without prior high intensity contraction of shoulder elevation. RPE was reported, productivity (drawings per min) measured, and bipolar surface electromyography (EMG) recorded from the dominant upper trapezius during pauses and sessions of computer work. Repeated measure ANOVA with Bonferroni corrected post-hoc tests was applied for the statistical analyses.

Results
The main findings were that a high intensity shoulder elevation did not modify RPE, productivity or EMG activity of the upper trapezius during the subsequent pause and computer work. However, the high intensity contraction reduced the relative rest time of the uppermost (clavicular) trapezius part during the subsequent pause from computer work (p < 0.04).

Conclusion
Since a preceding high intensity shoulder elevation did not impose a negative impact on perceived effort, productivity or upper trapezius activity during computer work, implementation of high intensity contraction during computer work to prevent neck-shoulder pain may be possible without affecting the working routines. However, the unexpected reduction in clavicular trapezius rest during a pause with preceding high intensity contraction requires further investigation before high intensity shoulder elevations can be recommended as an integrated part of computer work.
Identifying the needs of penile cancer sufferers: A systematic review of the quality of life, psychosexual and psychosocial literature in penile cancer
Authors: Maddineni Satish B , Lau Maurice M , Sangar Vijay K 
Published: August 2009

Abstract

Background
Penile cancer is an uncommon malignancy with an incidence of 1 per 100,000. Conservative and radical treatments can be disfiguring and may have an impact on sexual function, quality of life (QOL), social interactions, self-image and self-esteem. Knowledge of how this disease affects patients is paramount to developing a global, multi-disciplinary approach to treatment.

Methods
A Medline/PubMed literature search was conducted using the terms "sexual function penis cancer"; "quality of life penis cancer" and "psychological effects penis cancer" from 1985 to 2008. Articles containing quantitative data on QOL, sexual function or psychological well-being were included.

Results
128 patients from 6 studies were included. 5 studies contained retrospective data whilst 1 study collected prospective data on erectile function. In the 6 studies 13 different quantitative tools were used to assess psychological well-being, QOL and sexual function. The General Health Questionnaire (GHQ) showed impaired well-being in up to 40% in 2 studies. Patients undergoing more mutilating treatments were more likely to have impaired well-being. The Hospital Anxiety and Depression Score (HADS) demonstrated pathological anxiety up to 31% in 2 studies. 1 study used the Diagnostic and Statistical Manual of Mental Disorders of psychiatric illness (DSM III-R) with 53% exhibiting mental illness, 25% avoidance behaviour and 40% impaired well-being. 12/30 suffered from post-traumatic stress disorder. The IIEF-15 was the commonest tool used to assess sexual function. The results varied from 36% in 1 study with no sexual function to 67% in another reporting reduced sexual satisfaction to 78% in another reporting high confidence with erections.

Conclusion
The treatment of penile cancer results in negative effects on well-being in up to 40% with psychiatric symptoms in approximately 50%. Up to two-thirds of patients report a reduction in sexual function. This study demonstrates that penile cancer sufferers can exhibit significant psychological dysfunction, yet no standardised tools or interventional pathways are available. Therefore, there is a need to identify and assess adequate tools to measure psychological and sexual dysfunction in this group of patients.
Use of placebo interventions among Swiss primary care providers
Authors: Fässler Margrit , Gnädinger Markus , Rosemann Thomas , Biller-Andorno Nikola 
Published: August 2009

Abstract

Background
Placebo interventions can have meaningful effects for patients. However, little is known about the circumstances of their use in clinical practice. We aimed to investigate to what extent and in which way Swiss primary care providers use placebo interventions. Furthermore we explored their ideas about the ethical and legal issues involved.

Methods
599 questionnaires were sent to general practitioners (GPs) and paediatricians in private practice in the Canton of Zurich in Switzerland. To allow for subgroup analysis GPs in urban, suburban, and rural areas as well as paediatricians were selected in an even ratio.

Results
233 questionnaires were completed (response rate 47%). 28% of participants reported that they never used placebo interventions. More participants used impure placebos therapeutically than pure placebos (57% versus 17%, McNemar's χ2 = 78, p < 0.001). There is not one clear main reason for placebo prescription. Placebo use was communicated to patients mostly as being "a drug or a therapy" (64%). The most frequently chosen ethical premise was that they "can be used as long as the physician and the patient work together in partnership" (60% for pure and 75% for impure placebos, McNemar's χ2 = 12, p < 0.001). A considerable number of participants (11–38%) were indecisive about statements regarding the ethical and legal legitimacy of using placebos.

Conclusion
The data obtained from Swiss primary care providers reflect a broad variety of views about placebo interventions as well as a widespread uncertainty regarding their legitimacy. Primary care providers seem to preferentially use impure as compared to pure placebos in their daily practice. An intense debate is required on appropriate standards regarding the clinical use of placebo interventions among medical professionals.
NUCKS overexpression in breast cancer
Authors: Drosos Yiannis , Kouloukoussa Mirsini , Østvold Anne Carine , Grundt Kirsten , Goutas Nikos , Vlachodimitropoulos Dimitrios , Havaki Sophia , Kollia Panagoula , Kittas Christos , Marinos Evangelos , Aleporou-Marinou Vassiliki 
Published: August 2009

Abstract

Background
NUCKS (Nuclear, Casein Kinase and Cyclin-dependent Kinase Substrate) is a nuclear, DNA-binding and highly phosphorylated protein. A number of reports show that NUCKS is highly expressed on the level of mRNA in several human cancers, including breast cancer. In this work, NUCKS expression on both RNA and protein levels was studied in breast tissue biopsies consisted of invasive carcinomas, intraductal proliferative lesions, benign epithelial proliferations and fibroadenomas, as well as in primary cultures derived from the above biopsies. Specifically, in order to evaluate the level of NUCKS protein in correlation with the histopathological features of breast disease, immunohistochemistry was employed on paraffin sections of breast biopsies of the above types. In addition, NUCKS expression was studied by means of Reverse Transcription PCR (RT-PCR), real-time PCR (qRT-PCR) and Western immunoblot analyses in the primary cell cultures developed from the same biopsies.

Results
The immunohistochemical Results showed intense NUCKS staining mostly in grade I and II breast carcinomas compared to normal tissues. Furthermore, NUCKS was moderate expressed in benign epithelial proliferations, such as adenosis and sclerosing adenosis, and highly expressed in intraductal lesions, specifically in ductal carcinomas in situ (DCIS). It is worth noting that all the fibroadenoma tissues examined were negative for NUCKS staining. RT-PCR and qRT-PCR showed an increase of NUCKS expression in cells derived from primary cultures of proliferative lesions and cancerous tissues compared to the ones derived from normal breast tissues and fibroadenomas. This increase was also confirmed by Western immunoblot analysis. Although NUCKS is a cell cycle related protein, its expression does not correlate with Ki67 expression, neither in tissue sections nor in primary cell cultures.

Conclusion
The results show overexpression of the NUCKS protein in a number of non malignant breast lesions and cancerous tissues. In particular, the NUCKS overexpression in ADH and DCIS indicates a significant role of this protein in neoplastic progression.
Community response to intermittent preventive treatment of malaria in infants (IPTi) delivered through the expanded programme of immunization in five African settings
Authors: Gysels Marjolein , Pell Christopher , Mathanga Don P , Adongo Philip , Odhiambo Frank , Gosling Roly , Akweongo Patricia , Mwangi Rose , Okello George , Mangesho Peter , Slutsker Lawrence , Kremsner Peter G , Grobusch Martin P , Hamel Mary J , Newman Robert D , Pool Robert 
Published: August 2009

Abstract

Background
IPTi delivered through EPI has been shown to reduce the incidence of clinical malaria by 20–59%. However, new health interventions can only be effective if they are also socially and culturally acceptable. It is also crucial to ensure that attitudes to IPTi do not negatively influence attitudes to and uptake of immunization, or that people do not misunderstand IPTi as immunization against malaria and neglect other preventive measures or delay treatment seeking.

Methods
These issues were studied in five African countries in the context of clinical trials and implementation studies of IPTi. Mixed methods were used, including structured questionnaires (1,296), semi-structured interviews (168), in-depth interviews (748) and focus group discussions (95) with mothers, fathers, health workers, community members, opinion leaders, and traditional healers. Participant observation was also carried out in the clinics.

Results
IPTi was widely acceptable because it resonated with existing traditional preventive practices and a general concern about infant health and good motherhood. It also fit neatly within already widely accepted routine vaccination. Acceptance and adherence were further facilitated by the hierarchical relationship between health staff and mothers and by the fact that clinic attendance had a social function for women beyond acquiring health care. Type of drug and regimen were important, with newer drugs being seen as more effective, but potentially also more dangerous. Single dose infant formulations delivered in the clinic seem to be the most likely to be both acceptable and adhered to. There was little evidence that IPTi per se had a negative impact on attitudes to EPI or that it had any affect on EPI adherence. There was also little evidence of IPTi having a negative impact on health seeking for infants with febrile illness or existing preventive practices.

Conclusion
IPTi is generally acceptable across a wide range of settings in Africa and involving different drugs and regimens, though there is a strong preference for a single dose infant formulation. IPTi does not appear to have any negative effect on attitudes to EPI, and it is not interpreted as immunization against malaria.
Incidental thyroid lesions detected by FDG-PET/CT: prevalence and risk of thyroid cancer
Authors: Bae Ja Seong , Chae Byung Joo , Park Woo Chan , Kim Jeong Soo , Kim Sung Hoon , Jung Sang Seol , Song Byung Joo 
Published: August 2009

Abstract

Background
Incidentally found thyroid lesions are frequently detected in patients undergoing FDG-PET/CT. The aim of this study was to investigate the prevalence of incidentally found thyroid lesions in patients undergoing FDG-PET/CT and determine the risk for thyroid cancer.

Methods
FDG-PET/CT was performed on 3,379 patients for evaluation of suspected or known cancer or cancer screening without any history of thyroid cancer between November 2003 and December 2005. Medical records related to the FDG-PET/CT findings including maximum SUV(SUVmax) and pattern of FDG uptake, US findings, FNA, histopathology received by operation were reviewed retrospectively.

Results
Two hundred eighty five patients (8.4%) were identified to have FDG uptake on FDG-PET/CT. 99 patients with focal or diffuse FDG uptake underwent further evaluation. The cancer risk of incidentally found thyroid lesions on FDG-PET/CT was 23.2% (22/99) and the cancer risks associated with focal and diffuse FDG uptake were 30.9% and 6.4%. There was a significant difference in the SUVmax between the benign and malignant nodules (3.35 ± 1.69 vs. 6.64 ± 4.12; P < 0.001). There was a significant correlation between the SUVmax and the size of the cancer.

Conclusion
The results of this study suggest that incidentally found thyroid lesions by FDG-PET/CT, especially a focal FDG uptake and a high SUV, have a high risk of thyroid malignancy. Further diagnostic work-up is needed in these cases.
Computerized surveillance of opioid-related adverse drug events in perioperative care: a cross-sectional study
Authors: Eckstrand Julie A , Habib Ashraf S , Williamson Abbie , Horvath Monica M , Gattis Katherine G , Cozart Heidi , Ferranti Jeffrey 
Published: August 2009

Abstract

Background
Given the complexity of surgical care, perioperative patients are at high risk of opioid-related adverse drug events. Existing methods of detection, such as trigger tools and manual chart review, are time-intensive which makes sustainability challenging. Using strategic rule design, computerized surveillance may be an efficient, pharmacist-driven model for event detection that leverages existing staff resources.

Methods
Computerized adverse drug event surveillance uses a logic-based rules engine to identify potential adverse drug events or evolving unsafe clinical conditions. We extended an inpatient rule (administration of naloxone) to detect opioid-related oversedation and respiratory depression to perioperative care at a large academic medical center. Our primary endpoint was the adverse drug event rate. For all patients with a naloxone alert, manual chart review was performed by a perioperative clinical pharmacist to assess patient harm. In patients with confirmed oversedation, other patient safety event databases were queried to determine if they could detect duplicate, prior, or subsequent opioid-related events.

Results
We identified 419 cases of perioperative naloxone administration. Of these, 101 were given postoperatively and 69 were confirmed as adverse drug events after chart review yielding a rate of 1.89 adverse drug events/1000 surgical encounters across both the inpatient and ambulatory settings. Our ability to detect inpatient opioid adverse drug events increased 22.7% by expanding surveillance into perioperative care. Analysis of historical surveillance data as well as a voluntary reporting database revealed that 11 of our perioperative patients had prior or subsequent harmful oversedation. Nine of these cases received intraoperative naloxone, and 2 had received naloxone in the post-anesthesia care unit. Pharmacist effort was approximately 3 hours per week to evaluate naloxone alerts and confirm adverse drug events.

Conclusion
A small investment of resources into a pharmacist-driven surveillance model gave great gains in organizational adverse drug event detection. The patients who experienced multiple events are particularly relevant to future studies seeking risk factors for opioid induced respiratory depression. Computerized surveillance is an efficient, impactful, and sustainable model for ongoing capture and analysis of these rare, but potentially serious events.
Dysregulated expression of Fau and MELK is associated with poor prognosis in breast cancer
Authors: Pickard Mark R , Green Andrew R , Ellis Ian O , Caldas Carlos , Hedge Vanessa L , Mourtada-Maarabouni Mirna , Williams Gwyn T 
Published: August 2009

Abstract
Introduction
Programmed cell death through apoptosis plays an essential role in the hormone-regulated physiological turnover of mammary tissue. Failure of this active gene-dependent process is central both to the development of breast cancer and to the appearance of the therapy-resistant cancer cells that produce clinical relapse. Functional expression cloning in two independent laboratories has identified Finkel–Biskis–Reilly murine sarcoma virus-associated ubiquitously expressed gene (Fau) as a novel apoptosis regulator and candidate tumour suppressor. Fau modifies apoptosis-controller Bcl-G, which is also a key target for candidate oncoprotein maternal embryonic leucine zipper kinase (MELK).

Methods
We have used RNA interference to downregulate Fau and Bcl-G expression, both simultaneously and independently, in breast cancer cells in vitro to determine the importance of their roles in apoptosis. Expression of Fau, Bcl-G and MELK was measured by quantitative RT-PCR in breast cancer tissue and in matched breast epithelial tissue from the same patients. Expression data of these genes obtained using microarrays from a separate group of patients were related to patient survival in Kaplan–Meier analyses.

Results
siRNA-mediated downregulation of either Fau or Bcl-G expression inhibited apoptosis, and the inhibition produced by combining the two siRNAs was consistent with control of Bcl-G by Fau. Fau expression is significantly reduced in breast cancer tissue and this reduction is associated with poor patient survival, as predicted for a candidate breast cancer tumour suppressor. In addition, MELK expression is increased in breast cancer tissue and this increase is also associated with poor patient survival, as predicted for a candidate oncogene. Bcl-G expression is reduced in breast cancer tissue but decreased Bcl-G expression showed no correlation with survival, indicating that the most important factors controlling Bcl-G activity are post-translational modification (by Fau and MELK) rather than the rate of transcription of Bcl-G itself.

Conclusions
The combination of in vitro functional studies with the analysis of gene expression in clinical breast cancer samples indicates that three functionally interconnected genes, Fau, Bcl-G and MELK, are crucially important in breast cancer and identifies them as attractive targets for improvements in breast cancer risk prediction, prognosis and therapy.
Continuous terlipressin versus vasopressin infusion in septic shock (TERLIVAP): a randomized, controlled pilot study
Authors: Morelli Andrea , Ertmer Christian , Rehberg Sebastian , Lange Matthias , Orecchioni Alessandra , Cecchini Valeria , Bachetoni Alessandra , D'Alessandro Mariadomenica , Van Aken Hugo , Pietropaoli Paolo , Westphal Martin 
Published: August 2009

AbstractIntroductionRecent clinical data suggest that early administration of vasopressin analogues may be advantageous compared to a last resort therapy. However, it is still unknown whether vasopressin and terlipressin are equally effective for hemodynamic support in septic shock. The aim of the present prospective, randomized, controlled pilot trial study was, therefore, to compare the impact of continuous infusions of either vasopressin or terlipressin, when given as first-line therapy in septic shock patients, on open-label norepinephrine requirements.MethodsWe enrolled septic shock patients (n = 45) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomized to receive continuous infusions of either terlipressin (1.3 μg·kg-1·h-1), vasopressin (.03 U·min-1) or norepinephrine (15 μg·min-1; n = 15 per group). In all groups, open-label norepinephrine was added to achieve a mean arterial pressure between 65 and 75 mmHg, if necessary. Data from right heart and thermo-dye dilution catheterization, gastric tonometry, as well as laboratory variables of organ function were obtained at baseline, 12, 24, 36 and 48 hours after randomization. Differences within and between groups were analyzed using a two-way ANOVA for repeated measurements with group and time as factors. Time-independent variables were compared with one-way ANOVA.ResultsThere were no differences among groups in terms of systemic and regional hemodynamics. Compared with infusion of .03 U of vasopressin or 15 μg·min-1of norepinephrine, 1.3 μg·kg-1·h-1of terlipressin allowed a marked reduction in catecholamine requirements (0.8 ± 1.3 and 1.2 ± 1.4 vs. 0.2 ± 0.4 μg·kg-1·min-1at 48 hours; eachP< 0.05) and was associated with less rebound hypotension (P< 0.05). At the end of the 48-hour intervention period, bilirubin concentrations were higher in the vasopressin and norepinephrine groups as compared with the terlipressin group (2.3 ± 2.8 and 2.8 ± 2.5 vs. 0.9 ± 0.3 mg·dL-1; eachP< 0.05). A time-dependent decrease in platelet count was only observed in the terlipressin group (P< 0.001 48 hours vs. BL).ConclusionsThe present study provides evidence that continuous infusion of low-dose terlipressin – when given as first-line vasopressor agent in septic shock – is effective in reversing sepsis-induced arterial hypotension and in reducing norepinephrine requirements.Trial registrationClinicalTrial.gov NCT00481572.