bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Prescribing Pattern of a New Antipsychotic: A Descriptive Study of Aripiprazole for Psychiatric In‐Patients*
Authors: Andersen Stig Ejdrup , Johansson Majka , Manniche Charlotte 
Published: March 2008

Abstract:  In June 2004, aripiprazole was marketed as a second‐generation antipsychotic with an entire new mechanism of action. The objective of this descriptive study is to examine the day‐to‐day prescriptions of aripiprazole to an unselected population of psychiatric in‐patients. From 1 February to 1 May 2006, present and former in‐patients treated with aripiprazole were identified. Prescriptions of aripiprazole and psychoactive comedication were collected retrospectively from the patient records. Seventy‐one patients, mainly schizophrenic, received aripiprazole 2.5 to 55 mg/day for median 350 days. The median average exposure was 18.9 mg/day (range 2.5–45 mg/day) and exceeded 15 and 30 mg/day in 63% and 4.2% of the patients, respectively. Generally, aripiprazole was either added to the existing antipsychotic treatment or replaced other antipsychotics; only 17% of the patients were treatment‐naïve. In 25% aripiprazole, monotherapy was commenced whereas aripiprazole‐antipsychotic combinations were initially prescribed in 75%. Overall, 85% of the patients received periods of antipsychotic polypharmacy and aripiprazole was combined with 17 different antipsychotics. Each patient received median three (range 0–8) psychoactive drugs parallel with aripiprazole. This study demonstrates reality in psychopharmacology and quote aripiprazole as example. In day‐to‐day practice, aripiprazole is used as part of highly individualized regimens comprising polypharmacy and excessive dosing. Although theoretically appropriate for some patients, this approach also implies conducting unblinded and uncontrolled mini‐experiments. Sparse evidence supports this practice and effectiveness studies of aripiprazole that takes into account the true complexity of clinical prescribing are urgently needed.
Reliability of electromyographic and force measures during prone isometric back extension in subjects with and without low back pain
Authors: Pitcher Mark J. , Behm David G. , MacKinnon Scott N. 
Published: March 2008

Maximal voluntary isometric activations (MVIA) are frequently used as inputs for models attempting to predict muscle force and as normalization values in studies assessing muscle function. However, pain may adversely affect maximal muscle activation. The purpose of this study was to assess reliability of MVIA force and electromyographic (EMG) activity during prone isometric back extension in subjects with and without low back pain (LBP). A novel sub-maximal method using the percentages of the estimated mass of the head–arms–trunk (HAT) segment was also investigated. Repeated measures on 20 male volunteers divided into an LBP (n = 10) and a control group (n = 10) were made on 4 occasions. Force and EMG activity were recorded bilaterally from upper lumbar erector spinae (ULES), lower lumbar erector spinae (LLES), and biceps femoris (BF). Subjects exerted a maximal extension effort against a harness assembly that was attached to a force transducer. Submaximal exertions were also performed with an additional resistance of 100%, 110%, 120%, 130%, 140%, 150%, 160%, and 170% of HAT. Mean MVIA forces were significantly (p ≤ 0.05) lower in LBP vs. control. Intraclass correlation coefficients (ICC) for MVIA force, right and left ULES, and LLES EMG indicated high reliability in controls (R > 0.90), but were significantly less in LBP (R = 0.36–0.80). EMG of BF demonstrated excellent reliability across both groups (R > 0.90). The resistance at 100% HAT demonstrated the highest reliability for LBP patients, whereas higher percentages of HAT showed either similar or higher reliability for controls. Force output and back EMG activity are less reliable with LBP individuals and should be taken into consideration when testing.
The potential benefits of creatine and conjugated linoleic acid as adjuncts to resistance training in older adults
Authors: Tarnopolsky Mark A. , Safdar Adeel 
Published: March 2008

Human aging is associated with a significant reduction in muscle mass (sarcopenia) resulting in muscle weakness and functional limitations in the elderly. Sarcopenia has been associated with mitochondrial dysfunction and the accumulation of mtDNA deletions. Resistance training increases muscle strength and size and can increase mitochondrial capacity and decrease oxidative stress in older adults. Creatine monohydrate (CrM) and conjugated linoleic acid (CLA) have biological effects that could enhance some of the beneficial effects of resistance training in older adults (i.e., ↑ fat-free mass, ↓ total body fat). We have completed two resistance-training studies with CrM alone and CrM + CLA supplementation in older adults to evaluate the independent effects of exercise and dietary supplements, as well as their interactive effects. Our studies, and several others, have found that CrM enhanced the resistance exercise mediated gains in fat-free mass and strength. More recently, we found that the addition of CLA also lead to a significant reduction of body fat after six months of resistance training in older adults. Older adults have fewer wild-type mtDNA copies and higher amounts of mtDNA deletions as compared with younger adults in mature skeletal muscle; however, these deletions are not seen in the satellite cell-derived myoblast cultures. These findings, and the fact that mtDNA deletions are lower and wild-type mtDNA copy number is higher after resistance training in older adults, suggests that activation of satellite cells secondary to resistance exercise-induced muscle damage can dilute or “shift” the proportion of mtDNA genotype towards that of a younger adult. Recent evidence suggests that CrM supplementation in combination with strength training can enhance satellite cell activation and total myonuclei number per muscle fiber in young men. Future studies are required to determine whether the mitochondrial adaptations to resistance exercise in older adults are further enhanced with CrM supplementation and whether this is due to increased recruitment of satellite cells. It will also be important to determine whether these changes are maintained over a longer time period.
A chronic increase in physical activity inhibits fed-state mTOR/S6K1 signaling and reduces IRS-1 serine phosphorylation in rat skeletal muscle
Authors: Glynn Erin L. , Lujan Heidi L. , Kramer Victoria J. , Drummond Micah J. , DiCarlo Stephen E. , Rasmussen Blake B. 
Published: March 2008

A chronic increase in physical activity and (or) endurance training can improve insulin sensitivity in insulin-resistant skeletal muscle. Cellular mechanisms responsible for the development of insulin resistance are unclear, though one proposed mechanism is that nutrient overload chronically increases available energy, over-activating the mammalian target of rapamycin (mTOR) and ribosomal S6 kinase 1 (S6K1) signaling pathway leading to increased phosphorylation of serine residues on insulin receptor substrate-1 (IRS-1). The objective of this study was to determine if increased physical activity would inhibit mTOR/S6K1 signaling and reduce IRS-1 serine phosphorylation in rat skeletal muscle. Soleus muscle was collected from fed male Sprague–Dawley sedentary rats (Inactive) and rats with free access to running wheels for 9 weeks (Active). Immunoblotting methods were used to measure phosphorylation status of mTOR, S6K1, IRS-1, and PKB/Akt (protein kinase B/AKT), and total abundance of proteins associated with the mTOR pathway. Muscle citrate synthase activity and plasma insulin and glucose concentrations were measured. Phosphorylation of mTOR (Ser2448), S6K1 (Thr389), and IRS-1 (Ser636–639) was reduced in Active rats (p < 0.05). Total protein abundance of mTOR, S6K1, IRS-1, 4E-BP1, eEF2, PKB/Akt and AMPKα, and phosphorylation of PKB/Akt were unaffected (p > 0.05). Total SKAR protein, a downstream target of S6K1, and citrate synthase activity increased in Active rats (p < 0.05), though plasma insulin and glucose levels were unchanged (p > 0.05). Reduced mTOR/S6K1 signaling during chronic increases in physical activity may play an important regulatory role in the serine phosphorylation of IRS-1, which should be examined as a potential mechanism for attenuation of insulin resistance associated with increased IRS-1 serine phosphorylation.
Subcellular Localization of Activated Leukocyte Cell Adhesion Molecule Is a Molecular Predictor of Survival in Ovarian Carcinoma Patients
Authors: Mezzanzanica Delia , Fabbi Marina , Bagnoli Marina , Staurengo Samantha , Losa Marco , Balladore Emanuela , Alberti Paola , Lusa Lara , Ditto Antonino , Ferrini Silvano , Pierotti Marco A. , Barbareschi Mattia , Pilotti Silvana , Canevari Silvana 
Published: March 2008

Abstract
Purpose: Currently available clinicopathologic prognostic factors are imperfect predictors of clinical course in advanced-stage epithelial ovarian cancer patients. New molecular predictors are needed to identify patients with higher risk of relapse or death from disease. In a retrospective study, we investigated the prognostic impact of activated leukocyte cell adhesion molecule (ALCAM) expression in epithelial ovarian cancer.
Experimental Design: We analyzed the effect of cell-anchorage loss on ALCAM cellular localization in vitro and assessed ALCAM expression by immunohistochemistry in a series of 109 well-characterized epithelial ovarian cancer patient samples. Chi-square test, Kaplan-Meier method, and Cox proportional hazard analyses were used to relate ALCAM cellular localization to clinical-pathologic parameters and to overall survival (OS) rate.
Results: Loss of epithelial ovarian cancer cell anchorage was associated both in vitro and in vivo with decreased ALCAM membrane expression. In vivo, ALCAM was localized to cell membrane in normal surface ovarian epithelium, whereas in 67% of the epithelial ovarian cancer samples, membrane localization was decreased or even lost, and the molecule was mainly expressed in cytoplasm. Median OS in this group of patients was 58 months, whereas a median OS was not yet reached in patients with ALCAM membrane localization (P = 0.036, hazard ratio [HR] = 2.0, 95% confidence interval [CI] 1.1 to 3.5). In a multivariate Cox regression model including all the available clinicopathologic variables, loss of ALCAM membrane expression was an independent factor of unfavorable prognosis (P = 0.042, HR = 2.15, 95% CI: 1.0 to 4.5).
Conclusions: Decreased/lost ALCAM membrane expression is a marker of poorer outcome in epithelial ovarian cancer patients and might help to identify patients who could benefit from more frequent follow-up or alternative therapeutic modalities.
Class I Histone Deacetylase Expression Has Independent Prognostic Impact in Human Colorectal Cancer: Specific Role of Class I Histone Deacetylases In vitro and In vivo
Authors: Weichert Wilko , Röske Annika , Niesporek Silvia , Noske Aurelia , Buckendahl Ann-Christin , Dietel Manfred , Gekeler Volker , Boehm Markus , Beckers Thomas , Denkert Carsten 
Published: March 2008

Abstract
Purpose: Recently, several studies reported a strong functional link between histone deacetylases (HDAC) and the development of tumors of the large intestine. However, despite the importance of these molecules, comparably little is known on expression patterns and functions of specific HDAC isoforms in colorectal cancer.
Experimental Design: We characterized class I HDAC isoform expression patterns in a cohort of 140 colorectal carcinomas by immunohistochemistry. In addition, effects of HDAC inhibition by valproic acid and suberoylanilide hydroxamic acid, and specific HDAC isoform knockdown by short interfering RNA, were investigated in a cell culture model.
Results: We found class I HDACs highly expressed in a subset of colorectal carcinomas with positivity for HDAC1 in 36.4%, HDAC2 in 57.9%, and HDAC3 in 72.9% of cases. Expression was significantly enhanced in strongly proliferating (P = 0.002), dedifferentiated (P = 0.022) tumors. High HDAC expression levels implicated significantly reduced patient survival (P = 0.001), with HDAC2 expression being an independent survival prognosticator (hazard ratio, 2.6; P = 0.03). Short interfering RNA–based inhibition of HDAC1 and HDAC2 but not HDAC3 suppressed growth of colon cancer cells in vitro, although to a lesser extent than chemical HDAC inhibitors did.
Conclusions: The strong prognostic impact of HDAC isoforms in colorectal cancer, the interactions of HDACs with tumor cell proliferation and differentiation in vivo, and our finding that HDACs are differentially expressed in colorectal tumors suggest that the evaluation of HDAC expression in clinical trials for HDAC inhibitors might help to identify a patient subgroup who will exceptionally profit from such a treatment.
Targeting Hyaluronan Interactions in Malignant Gliomas and Their Drug-Resistant Multipotent Progenitors
Authors: Gilg Anne G. , Tye Sandra L. , Tolliver Lauren B. , Wheeler William G. , Visconti Richard P. , Duncan James D. , Kostova Felina V. , Bolds Letitia N. , Toole Bryan P. , Maria Bernard L. 
Published: March 2008

Abstract
Purpose: To determine if hyaluronan oligomers (o-HA) antagonize the malignant properties of glioma cells and treatment-resistant glioma side population (SP) cells in vitro and in vivo.
Experimental Design: A single intratumoral injection of o-HA was given to rats bearing spinal cord gliomas 7 days after engraftment of C6 glioma cells. At 14 days, spinal cords were evaluated for tumor size, invasive patterns, proliferation, apoptosis, activation of Akt, and BCRP expression. C6SP were isolated by fluorescence-activated cell sorting and tested for the effects of o-HA on BCRP expression, activation of Akt and epidermal growth factor receptor, drug resistance, and glioma growth in vivo.
Results: o-HA treatment decreased tumor cell proliferation, increased apoptosis, and down-regulated activation of Akt and the expression of BCRP. o-HA treatment of C6SP inhibited activation of epidermal growth factor receptor and Akt, decreased BCRP expression, and increased methotrexate cytotoxicity. In vivo, o-HA also suppressed the growth of gliomas that formed after engraftment of C6 or BCRP+ C6SP cells, although most C6SP cells lost their expression of BCRP when grown in vivo. Interestingly, the spinal cord gliomas contained many BCRP+ cells that were not C6 or C6SP cells but that expressed nestin and/or CD45; o-HA treatment significantly decreased the recruitment of these BCRP+ progenitor cells into the engrafted gliomas.
Conclusions: o-HA suppress glioma growth in vivo by enhancing apoptosis, down-regulating key cell survival mechanisms, and possibly by decreasing recruitment of host-derived BCRP+ progenitor cells. Thus, o-HA hold promise as a new biological therapy to inhibit HA-mediated malignant mechanisms in glioma cells and treatment-resistant glioma stem cells.
Correlation of CDA, ERCC1, and XPD Polymorphisms with Response and Survival in Gemcitabine/Cisplatin–Treated Advanced Non–Small Cell Lung Cancer Patients
Authors: Tibaldi Carmelo , Giovannetti Elisa , Vasile Enrico , Mey Valentina , Laan Adrie C. , Nannizzi Sara , Di Marsico Roberta , Antonuzzo Andrea , Orlandini Cinzia , Ricciardi Simona , Del Tacca Mario , Peters Godefridus J. , Falcone Alfredo , Danesi Romano 
Published: March 2008

Abstract
Purpose: Selecting patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in non–small cell lung cancer (NSCLC). Polymorphisms at the xeroderma pigmentosum group D (XPD), excision repair cross-complementing 1 (ERCC1), and cytidine deaminase (CDA) genes have been associated with alterations in enzymatic activity and may change sensitivity to the widely used cisplatin-gemcitabine regimen.
Experimental Design: Analyses of CDA, XPD, and ERCC1 polymorphisms were done on blood samples of 65 chemotherapy-naïve, advanced NSCLC patients treated with cisplatin-gemcitabine. Furthermore, CDA enzymatic activity was evaluated by high-performance liquid chromatography analysis. Association between XPD Asp312Asn and Lys751Gln, ERCC1 C118T, and CDA Lys27Gln polymorphisms and response, clinical benefit, toxicity, time to progression (TTP), and overall survival (OS) was estimated using Pearson's χ2 tests, the Kaplan-Meier method, the log-rank test, and the Cox proportional hazards model.
Results: The CDA Lys27Lys polymorphism significantly correlated with better clinical benefit (P = 0.04) and grade ≥3 neutropenia and thrombocytopenia, as well as with longer TTP and OS (P = 0.006 and P = 0.002, respectively), whereas no significant associations were found among ERCC1 and XPD polymorphisms and both response and clinical outcome. Finally, the enzymatic activity assay showed a significant lower mean in subjects harboring the CDA Lys27Lys polymorphism.
Conclusions: Our data suggested the role of CDA Lys27Lys polymorphism as a possible predictive marker of activity, toxicity, TTP, and OS in advanced NSCLC patients treated with cisplatin and gemcitabine. These results may be explained by the lower enzymatic activity associated with the Lys27Lys CDA and offer a potential new tool for treatment optimization.
Identification of Prognostic Biomarkers for Prostate Cancer
Authors: Kosari Farhad , Munz Jan Marie A. , Savci-Heijink C. Dilara , Spiro Craig , Klee Eric W. , Kube Dagmar Marie , Tillmans Lori , Slezak Jeff , Karnes R. Jeffrey , Cheville John C. , Vasmatzis George 
Published: March 2008

Abstract
Purpose: This paper describes a process for the identification of genes that can report on the aggressiveness of prostate tumors and thereby add to the information provided by current pathologic analysis.
Materials and Methods: Expression profiling data from over 100 laser capture microdissection derived samples from nonneoplastic epithelium; Gleason patterns 3, 4, and 5 and node metastasis prostate cancer were used to identify genes at abnormally high levels in only some tumors. These variably overexpressed genes were stratified by their association with aggressive phenotypes and were subsequently filtered to exclude genes with redundant expression patterns. Selected genes were validated in a case-control study in which cases (systemic progression within 5 years) and controls (no systemic progression at 7 years of follow-up) were matched for all clinical and pathologic criteria from time of prostatectomy (n = 175). Both cases and controls, therefore, could have nodal invasion or seminal vesicle involvement at the time of initial treatment.
Results: A number of candidate variably overexpressed genes selected for their association with aggressive prostate cancer phenotype were evaluated in the case control study. The most prominent candidates were SSTR1 and genes related to proliferation, including TOP2A.
Conclusions: The process described here identified genes that add information not available from current clinical measures and can improve the prognosis of prostate cancer.
Prognostic Factors in Renal Cell Carcinoma: Association of Preoperative Sodium Concentration with Survival
Authors: Vasudev Naveen S. , Brown Janet E. , Brown Sarah R. , Rafiq Rumana , Morgan Ruth , Patel Poulam M. , O'Donnell Dearbhaile , Harnden Patricia , Rogers Mark , Cocks Kim , Anderson Kirsty , Paul Alan , Eardley Ian , Selby Peter J. , Banks Rosamonde E. 
Published: March 2008

Abstract
Purpose: Conventional renal cell carcinoma (RCC) has a variable natural history, and determining individual prognosis is important to guide management. We have examined the prognostic significance of a large number of hematologic and biochemical variables, as well as traditional tumor-related factors in patients with RCC.
Experimental Design: Patients undergoing nephrectomy for newly diagnosed RCC between September 1998 and March 2005 were invited to participate. Clinical, pathologic, and laboratory data were recorded in each case, and immunophenotyping was carried out on a subset of patients. A planned subset analysis of patients presenting with N0M0 disease was done.
Results: Two hundred twelve patients with RCC formed the study population. In addition to tumor-related factors, multivariate analyses revealed preoperative serum sodium concentration to be independently and significantly associated with overall survival and disease-free survival when considered as both a continuous variable and when dichotomized to above and below the median value [139 mmol/L; reference range 135-145 mmol/L, hazard ratio 0.44, 95% confidence interval (95% CI) 0.22-0.88, P = 0.014]. Five-year overall survival estimates for patients above and below the median serum sodium were 67.6% (95% CI 54.2-80.9) and 44.3% (95% CI 32.8-55.8), respectively. These findings persisted in the N0M0 subgroup analysis.
Conclusions: We have confirmed the prognostic value of traditional tumor-related factors but, to our knowledge, these are the first data to show that low preoperative sodium concentration may be an important factor associated with reduced survival in patients with RCC, suggesting that serum sodium should be considered with established prognostic variables in modeling survival in RCC.
Inhibition of the Tumor Necrosis Factor-α Pathway Is Radioprotective for the Lung
Authors: Zhang Ming , Qian Jun , Xing Xianying , Kong Feng-Ming , Zhao Lujun , Chen Ming , Lawrence Theodore S. 
Published: March 2008

Abstract
Purpose: Radiation-induced lung toxicity limits the delivery of high-dose radiation to thoracic tumors. Here, we investigated the potential of inhibiting the tumor necrosis factor-α (TNF-α) pathway as a novel radioprotection strategy.
Experimental Design: Mouse lungs were irradiated with various doses and assessed at varying times for TNF-α production. Lung toxicity was measured by apoptosis and pulmonary function testing. TNF receptor 1 (TNFR1) inhibition, achieved by genetic knockout or antisense oligonucleotide (ASO) silencing, was tested for selective lung protection in a mouse lung metastasis model of colon cancer.
Results: Lung radiation induced local production of TNF-α by macrophages in BALB/c mice 3 to 24 hours after radiation (15 Gy). A similar maximal induction was found 1 week after the start of radiation when 15 Gy was divided into five daily fractions. Cell apoptosis in the lung, measured by terminal deoxyribonucleotide transferase–mediated nick-end labeling staining (mostly epithelial cells) and Western blot for caspase-3, was induced by radiation in a dose- and time-dependent manner. Specific ASO inhibited lung TNFR1 expression and reduced radiation-induced apoptosis. Radiation decreased lung function in BALB/c and C57BL mice 4 to 8 weeks after completion of fractionated radiation (40 Gy). Inhibition of TNFR1 by genetic deficiency (C57BL mice) or therapeutic silencing with ASO (BALB/c mice) tended to preserve lung function without compromising lung tumor sensitivity to radiation.
Conclusion: Radiation-induced lung TNF-α production correlates with early cell apoptosis and latent lung function damage. Inhibition of lung TNFR1 is selectively radioprotective for the lung without compromising tumor response. These findings support the development of a novel radioprotection strategy using inhibition of the TNF-α pathway.