bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic identification and evolutionary features of rhesus monkey small nucleolar RNAs
Authors: Zhang Yong , Liu Jun , Jia Chunshi , Li Tingting , Wu Rimao , Wang Jie , Chen Ying , Zou Xiaoting , Chen Runsheng , Wang Xiu-Jie , Zhu Dahai 
Published: March 2010

Abstract

Background
Recent studies have demonstrated that non-protein-coding RNAs (npcRNAs/ncRNAs) play important roles during eukaryotic development, species evolution, and in the etiology of disease. Rhesus macaques are the most widely used primate model in both biomedical research and primate evolutionary studies. However, most reports on these animals focus on the functional roles of protein-coding sequences, whereas very little is known about macaque ncRNAs.

Results
In the present study, we performed the first systematic profiling of intermediate-size ncRNAs (50 to 500 nt) from the rhesus monkey by constructing a cDNA library. We identified 117 rhesus monkey ncRNAs, including 80 small nucleolar RNAs (snoRNAs), 29 other types of known RNAs (snRNAs, Y RNA, and others), and eight unclassified ncRNAs. Comparative genomic analysis and northern blot hybridizations demonstrated that some snoRNAs were lineage- or species-specific. Paralogous sequences were found for most rhesus monkey snoRNAs, the expression of which might be attributable to extensive duplication within the rhesus monkey genome. Further investigation of snoRNA flanking sequences showed that some rhesus monkey snoRNAs are retrogenes derived from L1-mediated integration. Finally, phylogenetic analysis demonstrated that birds and primates share some snoRNAs and host genes thereof, suggesting that both the relevant host genes and the snoRNAs contained therein may be inherited from a common ancestor. However, some rhesus monkey snoRNAs hosted by non-ribosome-related genes appeared after the evolutionary divergence between birds and mammals.

Conclusions
We provide the first experimentally-derived catalog of rhesus monkey ncRNAs and uncover some interesting genomic and evolutionary features. These findings provide important information for future functional characterization of snoRNAs during primate evolution.
Identification of 5 novel genes methylated in breast and other epithelial cancers
Authors: Hill Victoria K , Hesson Luke B , Dansranjavin Temuujin , Dallol Ashraf , Bieche Ivan , Vacher Sophie , Tommasi Stella , Dobbins Timothy , Gentle Dean , Euhus David , Lewis Cheryl , Dammann Reinhard , Ward Robyn L , Minna John , Maher Eammon R , Pfeifer Gerd P , Latif Farida 
Published: March 2010

Abstract

Background
There are several high throughput approaches to identify methylated genes in cancer. We utilized one such recently developed approach, MIRA (methylated-CpG island recovery assay) combined with CpG island arrays to identify novel genes that are epigenetically inactivated in breast cancer.

Results
Using this approach we identified numerous CpG islands that demonstrated aberrant DNA methylation in breast cancer cell lines. Using a combination of COBRA and sequencing of bisulphite modified DNA, we confirmed 5 novel genes frequently methylated in breast tumours; EMILIN2, SALL1, DBC1, FBLN2 and CIDE-A. Methylation frequencies ranged from between 25% and 63% in primary breast tumours, whilst matched normal breast tissue DNA was either unmethylated or demonstrated a much lower frequency of methylation compared to malignant breast tissue DNA. Furthermore expression of the above 5 genes was shown to be restored following treatment with a demethylating agent in methylated breast cancer cell lines. We have expanded this analysis across three other common epithelial cancers (lung, colorectal, prostate). We demonstrate that the above genes show varying levels of methylation in these cancers. Lastly and most importantly methylation of EMILIN2 was associated with poorer clinical outcome in breast cancer and was strongly associated with estrogen receptor as well as progesterone receptor positive breast cancers.

Conclusion
The combination of the MIRA assay with CpG island arrays is a very useful technique for identifying epigenetically inactivated genes in cancer genomes and can provide molecular markers for early cancer diagnosis, prognosis and epigenetic therapy.
Prediction of breast cancer sensitivity to neoadjuvant chemotherapy based on status of DNA damage repair proteins
Authors: Asakawa Hideki , Koizumi Hirotaka , Koike Ayaka , Takahashi Makiko , Wu Wenwen , Iwase Hirotaka , Fukuda Mamoru , Ohta Tomohiko 
Published: March 2010

Abstract
Introduction
Various agents used in breast cancer chemotherapy provoke DNA double-strand breaks (DSBs). DSB repair competence determines the sensitivity of cells to these agents whereby aberrations in the repair machinery leads to apoptosis. Proteins required for this pathway can be detected as nuclear foci at sites of DNA damage when the pathway is intact. Here we investigate whether focus formation of repair proteins can predict chemosensitivity of breast cancer.

Methods
Core needle biopsy specimens were obtained from sixty cases of primary breast cancer before and 18-24 hours after the first cycle of neoadjuvant epirubicin plus cyclophosphamide (EC) treatment. Nuclear focus formation of DNA damage repair proteins was immunohistochemically analyzed and compared with tumor response to chemotherapy.

Results
EC treatment induced nuclear foci of γH2AX, conjugated ubiquitin, and Rad51 in a substantial amount of cases. In contrast, BRCA1 foci were observed before treatment in the majority of the cases and only decreased after EC in thirteen cases. The presence of BRCA1-, γH2AX-, or Rad51-foci before treatment or the presence of Rad51-foci after treatment was inversely correlated with tumor response to chemotherapy. DNA damage response (DDR) competence was further evaluated by considering all four repair indicators together. A high DDR score significantly correlated with low tumor response to EC and EC + docetaxel whereas other clinicopathological factors analyzed did not.

Conclusions
High performing DDR focus formation resulted in tumor resistance to DNA damage-inducing chemotherapy. Our results suggested an importance of evaluation of DDR competence to predict breast cancer chemosensitivity, and merits further studying into its usefulness in exclusion of non-responder patients.
Androgens Induce Nongenomic Stimulation of Colonic Contractile Activity through Induction of Calcium Sensitization and Phosphorylation of LC20 and CPI-17
Authors: González-Montelongo María C. , Marín Raquel , Gómez Tomás , Marrero-Alonso Jorge , Díaz Mario 
Published: March 2010

AbstractWe show that androgens, testosterone and 5α-dihydrotestosterone (DHT), acutely (∼40 min) provoke the mechanical potentiation of spontaneous and agonist-induced contractile activity in mouse colonic longitudinal smooth muscle. The results using flutamide, finasteride, cycloheximide, and actinomycin D indicate that androgen-induced potentiation is dependent on androgen receptors, requires reduction of testosterone to DHT, and occurs independently of transcriptional and translational events. Using permeabilized colonic smooth muscle preparations, we could demonstrate that mechanical potentiation is entirely due to calcium sensitization of contractile machinery. In addition, DHT (10 nm) increased phosphorylation of both 20-kDa myosin light chain (LC20) [regulatory myosin light chain, (MLC)] and CPI-17 (an endogenous inhibitor of MLC phosphatase). Paralleling these findings, inhibition of Rho-associated Rho kinase (ROK) and/or protein kinase C (PKC) with, respectively, Y27632 and chelerythrine, prevented LC20 phosphorylation and abolished calcium sensitization. In addition, inhibition of ROK prevents CPI-17 phosphorylation, indicating that ROK is located upstream PKC-mediated CPI-17 modulation in the signalling cascade. Additionally, androgens induce a rapid activation of RhoA and its translocation to the plasma membrane to activate ROK. The results demonstrate that androgens induce sensitization of colonic smooth muscle to calcium through activation of ROK, which in turn, activates PKC to induce CPI-17 phosphorylation. Activation of this pathway induces a potent steady stimulation of LC20 by inhibiting MLC phosphatase and displacing the equilibrium of the regulatory subunit towards its phosphorylated state. This is the first demonstration that colonic smooth muscle is a physiological target for androgen hormones, and that androgens modulate force generation of smooth muscle contractile machinery through nongenomic calcium sensitization pathways.
Determinants of Self-Reported Medicine Underuse Due to Cost: A Comparison of Seven Countries
Authors: Kemp Anna , Roughead Elizabeth , Preen David , Glover John , Semmens James 
Published: March 2010

Objectives To compare the predictors of self-reported medicine underuse due to cost across countries with different pharmaceutical subsidy systems and co-payments. Methods We analysed data from a 2007 survey of adults in Australia, Canada, Germany, the Netherlands, New Zealand (NZ), the United Kingdom (UK) and the United States (US). The predictors of underuse were calculated separately for each country using multivariate poisson regression. Results Reports of underuse due to cost varied from 3% in the Netherlands to 20% in the US. In Australia, Canada, NZ, the UK and the US, cost-related underuse was predicted by high out-of-pocket costs (RR range 2.0-4.6), below average income (RR range 1.9-3.1), and younger age (RR range 3.9-16.4). In all countries except Australia and the UK, history of depression was associated with cost-related underuse (RR range 1.2- 4.1). In Australia, Canada, Germany, the UK and the US lack of patient involvement in treatment decisions was associated with cost-related underuse (RR range 1.2-1.4). In Australia, Canada and NZ, indigenous persons more commonly reported underuse due to cost (RR range 2.1-2.9). Conclusions Cost-related underuse of medicines was least commonly reported in countries with the lowest out-of-pocket costs, the Netherlands and the UK. Countries with reduced co-payments or cost ceilings for low income patients showed the least disparity in rates of underuse between income groups. Despite differences in health insurance systems in these countries, age, ethnicity, depression, and involvement with treatment decisions were consistently predictive of underuse. There are opportunities for policy makers and clinicians to support medicine use in vulnerable groups.
Location of Printed Labels; Benazepril Confused with Benadryl; Important Fer-in-Sol Concentration Change; Not Well Known; Pound/Kilogram Confusion
Authors: Cohen Michael R. 
Published: March 2010

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs. Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below. Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications.
A Survey of Current Perceptions of Drug Information Practice and Training
Authors: Gettig Jacob P. , Jordan Joseph K. , Sheehan Amy Heck 
Published: March 2010

Purpose The purpose of this study was to determine the current perceptions of drug information practice and training. Methods Electronic surveys were sent to 417 pharmacists who likely would have drug information responsibilities. The survey collected information regarding job responsibilities, perceived importance of each responsibility to drug information practice, type of postgraduate training received to prepare for responsibilities, and perceived adequacy of training. Results There were 206 survey respondents. The most frequently cited primary job responsibilities were providing instruction to students and staff, operating drug information centers, and responding to drug information queries. Most respondents felt that educational instruction, pharmacy and therapeutics (P&T) committee support, and responding to drug information questions were very important to drug information practice. On-the-job experience was cited as the most frequent source of training. Of the respondents, 46% reported completion of a pharmacy practice residency and 40% reported completion of a drug information specialty residency, with 14% completing both. Fifteen percent of respondents had no postgraduate training. Most respondents felt prepared for current job responsibilities after postgraduate training, with the exceptions of information systems support, pharmacoeconomic evaluations, and clinical outcomes research. Conclusion Despite earlier recommendations, drug information job responsibilities within the study sample have changed little over the past decade. Respondents felt that most of their job responsibilities are important to drug information practice and that postgraduate training adequately prepared them for most of these responsibilities. However, only 40% of respondents received specialized training in drug information practice.
Granisetron Transdermal System
Authors: Cada Dennis J. , Levien Terri L. , Baker Danial E. 
Published: March 2010

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing inservices. A comprehensive target drug utilization evaluation (DUE) is also provided each month. With a subscription, the monographs are sent in print and are also available online. Monographs can be customized to meet the needs of a facility. Subscribers to The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The April 2009 monograph topics are dexlansoprazole, milnacipran, oxybutynin chloride 10% gel, fibrinogen concentrate (human), and ecallantide injection. The DUE is on proton pump inhibitors.
Revatio = Sildenafil = Viagra Vital Initiative by the Institute for Safe Medication Practices Can Keep Patients Safe Lyrica-Lopressor Mix-up Cell Phones and E-mail Could Prevent Harm Reuse of Insulin Pen for Multiple Patients Risks Transmission of Blood-Borne Disease
Authors: Cohen Michael R. 
Published: March 2010

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs. Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below. Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications.
Revision of a Treatment Algorithm for Community-Associated Methicillin-Resistant Staphylococcus Aureus Skin Infections
Authors: Segarra-Newnham Marisel 
Published: March 2010

Purpose Describe the need for a revision to a treatment algorithm for community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin infections 3 years after implementation. Methods Medical records for patients seen in the emergency department (ED) for CA-MRSA skin infections from October 2005 through August 2007 were compared with records for patients seen from September 2002 through September 2004. Results Most patients with CA-MRSA initially were seen in the ED; however, by mid-2007 an increasing number of patients were coming to primary care clinics, particularly with recurrent episodes, and treatment for CA-MRSA was suboptimal in this setting. In addition, approximately 14% of CA-MRSA cases were not considered high risk based on the algorithm risk assessment. When the algorithm was implemented, the risk assessment classified less than 5% of CA-MRSA cases as low risk. Furthermore, newly published data suggested that incision and drainage (I&D) was sufficient for small abscesses. Therefore, a revised algorithm that provided for treatment in all ambulatory settings, encouraged I&D for small abscesses, and facilitated empiric treatment for CA-MRSA in all cases of suspected staphylococcal infection was developed. Initial feedback from providers has been positive, and a post implementation review has been planned. Conclusion A treatment algorithm that initially facilitated the care of patients with CA-MRSA skin infections in the ED only required revision because changes in the epidemiology of this disease had been observed. The new algorithm provides for empiric treatment for CA-MRSA in all cases of suspected staphylococcal skin infection, regardless of perceived risk or setting.
Safer Connectors in the United Kingdom; Value of the Independent Double-Check; Medication Errors Column in 35th Year
Authors: Cohen Michael R. , Smetzer Judy L. 
Published: March 2010

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs. Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below. Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications.
Improving Insulin Distribution and Administration Safety Using Lean Six Sigma Methodologies
Authors: Yamamoto Jay , Abraham Divya , Malatestinic Bill 
Published: March 2010

Purpose To utilize Lean Six Sigma in a hospital environment to improve insulin medication safety, improve the efficiency of insulin delivery, and reduce costs by analyzing the dispensing and administration process. Methods A Six Sigma team from a pharmaceutical manufacturer and a multidisciplinary hospital team collaborated to evaluate and modify the insulin dispensing and administration process utilizing the Lean Six Sigma improvement process (DMAIC process: Define, Measure, Analyze, Improve, and Control). Key factors, or root causes, leading to problems within the system were identified and addressed to improve the efficiency of the process while maintaining quality and improving patient safety. Results A number of key steps were identified to streamline the insulin dispensing and administration process including checking medications centrally instead of at satellite pharmacies, adding additional insulins and associated supplies to automated dispensing cabinets on each floor, and replacing shared bins for medications with separate storage bins for each patient. Additional changes made following the Lean Six Sigma project resulted in a system with less variability and increased efficiency. In addition to improved patient safety, annualized overall cost savings of $75,000 were estimated following implementation primarily due to the elimination of rework done in the pharmacy due to misplaced vials. Conclusion This collaborative effort between a hospital and a pharmaceutical manufacturer successfully utilized Lean Six Sigma methodologies to demonstrate positive, validated outcomes in improving insulin safety and patient care. Additional product insights were gained by the pharmaceutical manufacturer to further improve insulin safety.
Appropriateness of Ciprofloxacin Dosing Based on a Population Pharmacokinetic Model
Authors: Perreiter Alexandra , Nix David E. , Matthias Kathryn R. 
Published: March 2010

Purpose Over the past two decades, the minimum inhibitory concentrations (MICs) of ciprofloxacin have been steadily increasing for gram-negative bacteria. One major reason cited for this “MIC creep” is underdosing of ciprofloxacin due to a lack of understanding of its pharmacodynamic properties. The primary objective of this study was to evaluate the frequency of underdosing of ciprofloxacin in a tertiary acute care medical center based on a population pharmacokinetic model. Secondary objectives included evaluation of appropriateness of dosing based on renal function and approved product labeling. Methods Seventy-six patients were included in this single-center, retrospective study. Data collection included demographic, laboratory, and microbiology data along with details on antibiotic administration. Patient-specific predicted 24-hour area under the curve/MIC (AUC24/MIC) values were estimated using a population pharmacokinetic model with a goal predicted AUC24/MIC of at least 100 and a preferred target value of 250. Results Only 8% of the subjects obtained a predicted AUC24/MIC higher than 250, while 34% of the subjects achieved a predicted AUC24/MIC of 100 or less. The majority of patients (79%) received a total daily intravenous-equivalent dose of 800 mg, whereas only 8% of subjects received an initial total daily intravenous-equivalent dose of 1,200 mg, which is the recommended dose for most severe infections. Overall 26% of subjects were prescribed an appropriate initial dose for their estimated renal function based on infection type and severity. Conclusion Ciprofloxacin for acute infection treatment was frequently underdosed based on US Food and Drug Administration–approved labeling and estimated predicted AUC24/MIC at a tertiary acute care medical center.