bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pain in cancer. An outcome research project to evaluate the epidemiology, the quality and the effects of pain treatment in cancer patients
Authors: Apolone Giovanni , Bertetto Oscar , Caraceni Augusto , Corli Oscar , De Conno Franco , Labianca Roberto , Maltoni Marco , Nicora Mariaflavia , Torri Valter , Zucco Furio ,   the Cancer Pain Outcome Research Study Group
Published: February 2006

Abstract

Background
Management of pain related to advanced or metastatic cancer, although the availability of several pharmacological and non-pharmacological interventions and the existence of well-known guidelines and protocols, is often difficult and inadequate. Evidence of the relative effectiveness of current options for treating cancer pain from comparative randomized studies is scanty.

Methods
In the context of a wider project, a multicenter, open label, prospective Outcome Research study will be launched in Italy in 2006 to investigate the epidemiology of cancer pain and of its treatments, the quality of analgesic-drug therapy and the effectiveness of alternative analgesic strategies in a large, prospective, unselected cohort of cancer patients using the state-of-the art of patient-reported-outcomes. About 100 Italian centers will recruit 2500 patients with advanced/progressive/metastatic cancer with pain (related to the cancer disease) requiring analgesic treatments. Each center is expected to recruit 25 consecutive and eligible patients during the study inception period. Approximately two months will be allowed for subject recruitment and enrollment. Subject evaluation and follow-up will be for 3 months. The effect on outcomes of various therapeutic analgesic options administered by physicians, given the observational approach where patients are not assigned at random to different treatments, will be compared using the propensity score approach, allowing the adjustment for treatment selection bias. Later, after the launch of the observational study and on the basis of results, in specific subsamples of patients and in select centers of the network, a Randomized Controlled Trial will be carried out to formally compare the efficacy of alternative analgesic strategies, with particular emphasis on oral morphine (as comparator) and buprenorphine patch (as experimental arm). Results from the outcome (cohort) and experimental (Randomized Controlled Trial) studies will ensure both the external and internal validity.
Female urogenital dysfunction following total mesorectal excision for rectal cancer
Authors: Daniels Ian R , Woodward Sheena , Taylor Fiona GM , Raja Ashraf , Toomey Paul 
Published: February 2006

Abstract

Background
The effect of Total Mesorectal Excision (TME) on sexual function in the male is well documented. However, there is little literature in female patients. The aim of this study was to review the pelvic autonomic nervous anatomy in the female and to perform a retrospective audit of urinary and sexual function in women following surgery for rectal cancer where TME had been performed. Urogenital dysfunction was assessed through interview and questionnaire.

Method
Twenty-three questionnaires, eighteen returned, were sent to women with a mean age 65.5 yrs (range 34–86). All had undergone total mesorectal excision for rectal cancer between 1998–2001. Mean follow-up was 18.8 months (range 3–35).

Results
Preoperatively 5/18 (28%) were sexually active, 3/18 (17%) of patients described urinary frequency and nocturia and 7/18 (39%) described symptoms of stress incontinence prior to surgery. Postoperatively all sexually active patients remained active although all described some discomfort with penetration. Two of the patients sexually active described reduced libido secondary to the stoma. Postoperative urinary symptoms developed with 59% reporting the development of nocturia, 18% developed stress incontinence and one patient required a permanent catheter. Of those with symptoms, 80% persisted longer than three months from surgery. Symptoms were predominant in those patients with low rectal cancers, particularly those undergoing abdomino-perineal excision and in those who had previously undergone abdominal hysterectomy.

Conclusion
The treatment of rectal cancer involves surgery to the pelvic floor. Despite nerve preservation this is associated with the development of worsening nocturia and stress incontinence. This is most marked in those patients who had previously undergone a hysterectomy. Further studies are warranted to assess the interaction with previous gynaecological surgery.
Is there a relationship between sperm chromosome abnormalities and sperm morphology?
Authors: Sun Fei , Ko Evelyn , Martin Renée H 
Published: February 2006

AbstractThis review explores the relationship between sperm chromosomal constitution and morphology. With the advent of techniques for obtaining information on the chromosome complements of spermatozoa, this relationship has been studied in fertile men and in men with a high frequency of chromosomal abnormalities. Using human sperm karyotype analysis, no relationship between sperm chromosome abnormalities and morphology was found in fertile men, translocation carriers or post-radiotherapy cancer patients. Fluorescence in situ hybridization (FISH) analysis has not generally revealed a specific association between morphologically abnormal sperm and sperm chromosome abnormalities, but has indicated that teratozoospermia, like other forms of abnormal semen profiles (aesthenozoospermia, oligozoospermia) is associated with a modest increase in the frequency of sperm chromosome abnormalities. However, FISH studies on some infertile men and mouse strains have suggested that certain types of morphologically abnormal spermatozoa, such as macrocephalic multitailed spermatozoa, are associated with a very significantly increased frequency of aneuploidy. Thus, there may be an association between sperm morphology and aneuploidy in infertile men with specific abnormalities.
Intercellular adhesion molecule-1 expression in human endometrium: implications for long term progestin only contraception
Authors: Schatz Frederick , Krikun Graciela , Baergen Rebecca N , Critchley Hilary OD , Kuczynski Edward , Lockwood Charles J 
Published: February 2006

Abstract

Background
Neutrophils infiltrate the endometrium pre-menstrually and after long-term progestin only-contraceptive (LTPOC) treatment. Trafficking of neutrophils involves endothelial cell-expressed intercellular adhesion molecule (ICAM-1). Previous studies observed that ICAM-1 was immunolocalized to the endothelium of endometrial specimens across the menstrual cycle, but disagreed as to whether extra-endothelial cell types express ICAM-1 and whether ICAM-1 expression varies across the menstrual cycle.

Methods
Endometrial biopsies were obtained from women across the menstrual cycle and from those on LTPOC treatment (either Mirena or Norplant). The biopsies were formalin-fixed and paraffin-embedded with subsequent immunohistochemical staining for ICAM-1.

Results
The current study found prominent ICAM-1 staining in the endometrial endothelium that was of equivalent intensity in different blood vessel types irrespective of the steroidal or inflammatory endometrial milieu across the menstrual cycle and during LTPOC therapy. Unlike the endothelial cells, the glands were negative and the stromal cells were weakly positive for ICAM immunostaining.

Conclusion
The results of the current study suggest that altered expression of ICAM-1 by endothelial cells does not account for the influx of neutrophils into the premenstrual and LTPOC-derived endometrium. Such neutrophil infiltration may depend on altered expression of neutrophil chemoattractants.
Studies of the role of steroid hormone in the regulation of oocyte maturation in cattle
Authors: Wang Hai Feng , Isobe Naoki , Kumamoto Kanako , Yamashiro Hideaki , Yamashita Yasuhisa , Terada Takato 
Published: February 2006

Abstract

Background
The objective of this study was to investigate whether the steroid hormone(s) secreted from cumulus-oocyte complexes (COCs) is a prerequisite for bovine oocyte maturation and cumulus expansion using aminoglutethimide (AGT), a P450 cholesterol side-chain cleavage inhibitor.

Methods
In experiment 1, COCs were cultured in maturation medium with various concentrations of AGT for 22 h to determine the effective concentration of AGT to inhibit steroid hormone secretion, meiotic maturation and cumulus expansion. In experiment 2, COCs were cultured in conditioned medium (CM) and TCM-199 medium with or without 10 mM AGT to check whether steroid hormones secreted from COCs were responsible for oocyte maturation and cumulus expansion. Experiments 3 and 4 were carried out to determine whether exogenous progesterone or estradiol-17beta was able to overcome the inhibitory effects of AGT on oocytes maturation and cumulus expansion. COCs cultured in 10 mM AGT-containing medium supplemented with various concentrations of progesterone or estradiol-17beta for 22 h were examined for oocyte maturation and cumulus expansion.

Results
Experiment 1 showed that a concentration of 10 mM AGT in medium was sufficient to block steroid hormone secretion, oocyte maturation and cumulus expansion, and that these inhibitory effects were fully reversible. In experiment 2, the addition of 10 mM AGT to CM did not significantly prevent oocyte maturation and cumulus expansion, implying that CM contains the steroid hormone(s) secreted from COCs, which are closely associated with oocyte maturation and cumulus expansion. The results in experiments 3 and 4 demonstrated that the addition of any concentration of progesterone or estradiol-17beta in the medium did not reduce the inhibitory effects of AGT on oocyte maturation and cumulus expansion.

Conclusion
Our results indicate that bovine oocytes surrounded by cumulus cells are prevented from maturation and cumulus expansion through the inhibition of steroid secretion due to AGT, and that these inhibitory effects of AGT on oocyte maturation and cumulus expansions can not be overcome by the addition of either progesterone or estradiol-17beta in the medium. These observations suggest that some steroid hormone(s) other than P4 and E2 secreted from bovine COCs is essential for their meiotic maturation and cumulus expansion.
Detection and quantification of lupus anticoagulants in plasma from heparin treated patients, using addition of polybrene
Authors: Jacobsen Eva M , Trettenes Elin J , Wisløff Finn , Abildgaard Ulrich 
Published: February 2006

Abstract

Background
Lupus anticoagulants prolong clotting times in phospholipid-dependent coagulation tests. Lupus Ratio assays are integrated tests for lupus anticoagulants that may be based on APTT, RVVT or dPT clotting times. If a patient is being treated with unfractionated heparin, however, the heparin prolong clotting times and the diagnosis of lupus anticoagulant is invalidated. Commercial assays may have heparin neutralising agents added to their reagents. However, the type and efficacy of the heparin neutralisation is often not documented. We wanted to test the influence and efficacy of heparin neutralisers in the Lupus Ratio assay.

Methods
Several heparin neutralisers were tested, and polybrene was chosen for further testing. Unfractionated heparin and/or polybrene were added to normal plasma and to plasma from patients with or without lupus anticoagulant and clotting times compared before and after the additions. Lupus anticoagulant-positive patients were given 5000 IU i.v. of unfractionated heparin and plasma was collected just before and five minutes after the injection. Lupus Ratios were calculated after polybrene was added to the postinjection samples.

Results
The Lupus Ratio became slightly lower when polybrene was added to plasma without heparin. Plasma heparinised in vitro and plasma from patients that had received heparin, both had Lupus Ratios nearly identical to the Lupus Ratios calculated before any additions.

Conclusion
By addition of polybrene to a final concentration of 7.9 μg/ml in test plasma, Lupus Ratio may be determined in lupus anticoagulant-negative as well as positive plasmas irrespective of the presence of heparin 0.0 – 1.3 U/ml.
Estimating health workforce needs for antiretroviral therapy in resource-limited settings
Authors: Hirschhorn Lisa R , Oguda Lulu , Fullem Andrew , Dreesch Norbert , Wilson Paul 
Published: February 2006

Abstract

Background
Efforts to increase access to life-saving treatment, including antiretroviral therapy (ART), for people living with HIV/AIDS in resource-limited settings has been the growing focus of international efforts. One of the greatest challenges to scaling up will be the limited supply of adequately trained human resources for health, including doctors, nurses, pharmacists and other skilled providers. As national treatment programmes are planned, better estimates of human resource needs and improved approaches to assessing the impact of different staffing models are critically needed. However there have been few systematic assessments of staffing patterns in existing programmes or of the estimates being used in planning larger programmes.

Methods
We reviewed the published literature and selected plans and scaling-up proposals, interviewed experts and collected data on staffing patterns at existing treatment sites through a structured survey and site visits.

Results
We found a wide range of staffing patterns and patient-provider ratios in existing and planned treatment programmes. Many factors influenced health workforce needs, including task assignments, delivery models, other staff responsibilities and programme size. Overall, the number of health care workers required to provide ART to 1000 patients included 1–2 physicians, 2–7 nurses, <1 to 3 pharmacy staff, and a much wider range of counsellors and treatment supporters. We estimate from these data that the equivalent of 20 000 to 100 000 physicians, nurses, pharmacists and other core clinical staff will be needed to meet the WHO target of treating 3 million people by the end of 2005. The total number of staff, including counsellors, administrators and other cadres, could be substantially higher.

Discussion
These data are consistent with other estimates of human resource requirements for antiretroviral therapy, but highlight the considerable variability of current staffing models and the importance of a broad range of factors in determining personnel needs. Few outcome or cost data are currently available to assess the effectiveness and efficiency of different staffing models, and it will be important to develop improved methods for gathering this information as treatment programmes are scaled up.
Identification of mitogen-activated protein kinase docking sites in enzymes that metabolize phosphatidylinositols and inositol phosphates
Authors: Caldwell Kevin K , Sosa Marcos , Buckley Colin T 
Published: February 2006

Abstract

Background
Reversible interactions between the components of cellular signaling pathways allow for the formation and dissociation of multimolecular complexes with spatial and temporal resolution and, thus, are an important means of integrating multiple signals into a coordinated cellular response. Several mechanisms that underlie these interactions have been identified, including the recognition of specific docking sites, termed a D-domain and FXFP motif, on proteins that bind mitogen-activated protein kinases (MAPKs). We recently found that phosphatidylinositol-specific phospholipase C-γ1 (PLC-γ1) directly binds to extracellular signal-regulated kinase 2 (ERK2), a MAPK, via a D-domain-dependent mechanism. In addition, we identified D-domain sequences in several other PLC isozymes. In the present studies we sought to determine whether MAPK docking sequences could be recognized in other enzymes that metabolize phosphatidylinositols (PIs), as well as in enzymes that metabolize inositol phosphates (IPs).

Results
We found that several, but not all, of these enzymes contain identifiable D-domain sequences. Further, we found a high degree of conservation of these sequences and their location in human and mouse proteins; notable exceptions were PI 3-kinase C2-γ, PI 4-kinase type IIβ, and inositol polyphosphate 1-phosphatase.

Conclusion
The results indicate that there may be extensive crosstalk between MAPK signaling and signaling pathways that are regulated by cellular levels of PIs or IPs.
Are fast food restaurants an environmental risk factor for obesity?
Authors: Jeffery Robert W , Baxter Judy , McGuire Maureen , Linde Jennifer 
Published: February 2006

Abstract

Objective
Eating at "fast food" restaurants has increased and is linked to obesity. This study examined whether living or working near "fast food" restaurants is associated with body weight.

Methods
A telephone survey of 1033 Minnesota residents assessed body height and weight, frequency of eating at restaurants, and work and home addresses. Proximity of home and work to restaurants was assessed by Global Index System (GIS) methodology.

Results
Eating at "fast food" restaurants was positively associated with having children, a high fat diet and Body Mass Index (BMI). It was negatively associated with vegetable consumption and physical activity. Proximity of "fast food" restaurants to home or work was not associated with eating at "fast food" restaurants or with BMI. Proximity of "non-fast food" restaurants was not associated with BMI, but was associated with frequency of eating at those restaurants.

Conclusion
Failure to find relationships between proximity to "fast food" restaurants and obesity may be due to methodological weaknesses, e.g. the operational definition of "fast food" or "proximity", or homogeneity of restaurant proximity. Alternatively, the proliferation of "fast food" restaurants may not be a strong unique cause of obesity.
Long-term starvation and ageing induce AGE-1/PI 3-kinase-dependent translocation of DAF-16/FOXO to the cytoplasm
Authors: Weinkove David , Halstead Jonathan R , Gems David , Divecha Nullin 
Published: February 2006

Abstract

Background

The provision of stress resistance diverts resources from development and reproduction and must therefore be tightly regulated. In Caenorhabditis elegans, the switch to increased stress resistance to promote survival through periods of starvation is regulated by the DAF-16/FOXO transcription factor. Reduction-of-function mutations in AGE-1, the C. elegans Class IA phosphoinositide 3-kinase (PI3K), increase lifespan and stress resistance in a daf-16 dependent manner. Class IA PI3Ks downregulate FOXOs by inducing their translocation to the cytoplasm. However, the circumstances under which AGE-1 is normally activated are unclear. To address this question we used C. elegans first stage larvae (L1s), which when starved enter a developmentally-arrested diapause stage until food is encountered.

Results

We find that in L1s both starvation and daf-16 are necessary to confer resistance to oxidative stress in the form of hydrogen peroxide. Accordingly, DAF-16 is localised to cell nuclei after short-term starvation. However, after long-term starvation, DAF-16 unexpectedly translocates to the cytoplasm. This translocation requires functional age-1. H2O2 treatment can replicate the translocation and induce generation of the AGE-1 product PIP3. Because feeding reduces to zero in ageing adult C. elegans, these animals may also undergo long-term starvation. Consistent with our observation in L1s, DAF-16 also translocates to the cytoplasm in old adult worms in an age-1-dependent manner.

Conclusion

DAF-16 is activated in the starved L1 diapause. The translocation of DAF-16 to the cytoplasm after long-term starvation may be a feedback mechanism that prevents excessive expenditure on stress resistance. H2O2 is a candidate second messenger in this feedback mechanism. The lack of this response in age-1(hx546) mutants suggests a novel mechanism by which this mutation increases longevity.
Identification of metabolic system parameters using global optimization methods
Authors: Polisetty Pradeep K , Voit Eberhard O , Gatzke Edward P 
Published: February 2006

Abstract

Background
The problem of estimating the parameters of dynamic models of complex biological systems from time series data is becoming increasingly important.

Methods and results
Particular consideration is given to metabolic systems that are formulated as Generalized Mass Action (GMA) models. The estimation problem is posed as a global optimization task, for which novel techniques can be applied to determine the best set of parameter values given the measured responses of the biological system. The challenge is that this task is nonconvex. Nonetheless, deterministic optimization techniques can be used to find a global solution that best reconciles the model parameters and measurements. Specifically, the paper employs branch-and-bound principles to identify the best set of model parameters from observed time course data and illustrates this method with an existing model of the fermentation pathway in Saccharomyces cerevisiae. This is a relatively simple yet representative system with five dependent states and a total of 19 unknown parameters of which the values are to be determined.

Conclusion
The efficacy of the branch-and-reduce algorithm is illustrated by the S. cerevisiae example. The method described in this paper is likely to be widely applicable in the dynamic modeling of metabolic networks.
A stochastic model of oncogene expression and the relevance of this model to cancer therapy
Authors: Alfano Francis D 
Published: February 2006

Abstract

Background
Ablation of an oncogene or of the activity of the protein it encodes can result in apoptosis and/or inhibit tumor cell proliferation. Therefore, if the oncogene or set of oncogenes contributing maximally to a tumor cell's survival can be identified, such oncogene(s) are the most appropriate target(s) for maximizing tumor cell kill.

Methods and results
A mathematical model is presented that describes cellular phenotypic entropy as a function of cellular proliferation and/or survival, and states of transformation and differentiation. Oncogenes become part of the cellular machinery, block apoptosis and differentiation or promote proliferation and give rise to new states of cellular transformation. Our model gives a quantitative assessment of the amount of cellular death or growth inhibition that result from the ablation of an oncogene's protein product. We review data from studies of chronic myelogenous leukemia and K562 cells to illustrate these principles.

Conclusion
The model discussed in this paper has implications for oncogene-directed therapies and their use in combination with other therapeutic modalities.
An immune reaction may be necessary for cancer development
Authors: Prehn Richmond T 
Published: February 2006

Abstract

Background
The hypothesis of immunosurveillance suggests that new neoplasms arise very frequently, but most are destroyed almost at their inception by an immune response. Its correctness has been debated for many years.
In its support, it has been shown that the incidences of many tumor types, though apparently not all, tend to be increased in immunodeficient animals or humans, but this observation does not end the debate.

Alternative model
There is an alternative to the surveillance hypothesis; numerous studies have shown that the effect of an immune reaction on a tumor is biphasic. For each tumor, there is some quantitatively low level of immune reaction that, relative to no reaction, is facilitating, perhaps even necessary for the tumor's growth in vivo. The optimum level of this facilitating reaction may often be less than the level of immunity that the tumor might engender in a normal subject.

Conclusion
The failure of a tumor to grow as well in the normal as it does in the immunosuppressed host is probably not caused by a lack of tumor-cell killing in the suppressed host. Instead, the higher level of immune response in a normal animal, even if it does not rise to tumor-inhibitory levels, probably gives less positive support to tumor growth. This seems more than a semantic distinction.