bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioequivalance and pharmacokinetic study of febuxostat in human plasma by using LC-MS/MS with liquid liquid extraction method
Authors: Chandu Babu Rao , Kanala Kanchanamala , Hwisa Nagiat T , Katakam Prakash , Khagga Mukkanti 
Published: April 2013

Abstract
A bioequivalence study was proved of generic Febuxostat 80 mg tablets (T) in healthy volunteers.For this purpose, Authors developed a simple, sensitive, selective, rapid, rugged and reproducible liquid chromatography–tandem mass spectrometry method for the quantification of Febuxostat (FB) in human plasma using Febuxostat D7 (FBD7) as an internal standard (IS) was used. Chromatographic separation was performed on Ascentis Express C18 (50x4.6 mm, 3.5 μ) column. Mobile phase composed of 10 mM Ammonium formate: Acetonitrile (20:80 v/v), with 0.8 mL/min flow-rate. Drug and IS were extracted by Liquid- liquid extraction. FB and FBD7 were detected with proton adducts at m/z 317.1→261.1 and 324.2→262.1 in multiple reaction monitoring (MRM) positive mode respectively. The method was validated with the correlation coefficients of (r2) ≥ 0.9850 over a linear concentration range of 1.00-8000.00 ng/mL. This method demonstrated intra and inter-day precision within 2.64 to 3.88 and 2.76 to 8.44% and accuracy within 97.33 to 99.05 and 100.30 to 103.19% for FB. This method is successfully applied in the Bioequivalence study of 9 human volunteers.
Safety and efficacy of intravenous infusion of allogeneic cryopreserved mesenchymal stem cells for treatment of chronic kidney disease in cats: results of three sequential pilot studies
Authors: Quimby Jessica M , Webb Tracy L , Habenicht Lauren M , Dow Steven W 
Published: April 2013

Abstract
Introduction
Administration of mesenchymal stem cells (MSCs) has been shown to improve renal function in rodent models of chronic kidney disease (CKD), in part by reducing intrarenal inflammation and suppressing fibrosis. CKD in cats is characterized by tubulointerstitial inflammation and fibrosis, and thus treatment with MSCs might improve renal function and urinary markers of inflammation in this disease. Therefore, a series of pilot studies was conducted to assess the safety and efficacy of intravenous administration of allogeneic adipose-derived MSCs (aMSCs) in cats with naturally occurring CKD.

Methods
Cats enrolled in these studies received an intravenous infusion of allogeneic aMSCs every 2 weeks collected from healthy, young, specific pathogen-free cats. Cats in pilot study 1 (six cats) received 2 × 106 cryopreserved aMSCs per infusion, cats in pilot study 2 (five cats) received 4 × 106 cryopreserved aMSCs per infusion, and cats in pilot study 3 (five cats) received 4 × 106 aMSCs cultured from cryopreserved adipose. Serum biochemistry, complete blood count, urinalysis, urine protein, glomerular filtration rate, and urinary cytokine concentrations were monitored during the treatment period. Changes in clinical parameters were compared statistically by means of repeated measures analysis of variance (ANOVA) followed by Bonferroni’s correction.

Results
Cats in pilot study 1 had few adverse effects from the aMSC infusions and there was a statistically significant decrease in serum creatinine concentrations during the study period, however the degree of decrease seems unlikely to be clinically relevant. Adverse effects of the aMSC infusion in cats in pilot study 2 included vomiting (2/5 cats) during infusion and increased respiratory rate and effort (4/5 cats). Cats in pilot study 3 did not experience any adverse side effects. Serum creatinine concentrations and glomerular filtration rates did not change significantly in cats in pilot studies 2 and 3.

Conclusions
Administration of cryopreserved aMSCs was associated with significant adverse effects and no discernible clinically relevant improvement in renal functional parameters. Administration of aMSCs cultured from cryopreserved adipose was not associated with adverse effects, but was also not associated with improvement in renal functional parameters.
The characteristic expression pattern of BMI-1 and SALL4 genes in placenta tissue and cord blood
Authors: Chen Shaohua , Liu Sichu , Xu Ling , Yang Lijian , Jin Zhenyi , Ma Yu , Li Bo , Wu Xiuli , Yang Jianchang , Ma Yupo , Li Yangqiu 
Published: April 2013

Abstract
Introduction
SALL4 and BMI-1 are important factors in hematopoiesis. Placental tissue (PT) and umbilical cord blood (CB) are rich in hematopoietic stem/progenitor cells (HSCs/HPCs), but their SALL4 and BMI-1 expression levels remain unknown.

Methods
Real-time PCR was used to determine the expression level of these genes in PT and CB from ten cases, and ten healthy donors were used as controls.

Results
A significantly higher BMI-1 and SALL4 gene expression level was found in PT (median: 17.548 and 34.362, respectively) than in cord blood mononuclear cells (CBMCs) (median: 2.071 and 11.300, respectively) (P = 0.0001 and P = 0.007) and healthy peripheral blood mononuclear cells (PBMCs) (median: 0.259 and 0.384, respectively) (P = 0.001 and P <0.0001), and their expression level was lower in PBMCs than in CBMCs (P = 0.029 and P = 0.002). A positive correlation between the BMI-1 and SALL4 genes was found in the PT and CB groups, while there was no significant correlation between these genes in the healthy group. There was also no significant correlation between the expression level of each gene in PT and CB.

Conclusions
These results describe the characteristic features of the BMI-1 and SALL4 gene expression pattern in placental tissue and cord blood. Placental tissue with higher expression level of both genes may be considered as a potential resource for SALL4-related HPC expansion.
Harnessing Technology to Improve Clinical Trials: Study of Real-Time Informatics to Collect Data, Toxicities, Image Response Assessments, and Patient-Reported Outcomes in a Phase II Clinical Trial
Authors: Pietanza M. Catherine , Basch Ethan M. , Lash Alex , Schwartz Lawrence H. , Ginsberg Michelle S. , Zhao Binsheng , Shouery Marwan , Shaw Mary , Rogak Lauren J. , Wilson Manda , Gabow Aaron , Latif Marcia , Lin Kai-Hsiung , Wu Qinfei , Kass Samantha L. , Miller Claire P. , Tyson Leslie , Sumner Dyana K. , Berkowitz-Hergianto Alison , Sima Camelia S. , Kris Mark G. 
Published: April 2013

Purpose In clinical trials, traditional monitoring methods, paper documentation, and outdated collection systems lead to inaccuracies of study information and inefficiencies in the process. Integrated electronic systems offer an opportunity to collect data in real time. Patients and Methods We created a computer software system to collect 13 patient-reported symptomatic adverse events and patient-reported Karnofsky performance status, semi-automated RECIST measurements, and laboratory data, and we made this information available to investigators in real time at the point of care during a phase II lung cancer trial. We assessed data completeness within 48 hours of each visit. Clinician satisfaction was measured. Results Forty-four patients were enrolled, for 721 total visits. At each visit, patient-reported outcomes (PROs) reflecting toxicity and disease-related symptoms were completed using a dedicated wireless laptop. All PROs were distributed in batch throughout the system within 24 hours of the visit, and abnormal laboratory data were available for review within a median of 6 hours from the time of sample collection. Manual attribution of laboratory toxicities took a median of 1 day from the time they were accessible online. Semi-automated RECIST measurements were available to clinicians online within a median of 2 days from the time of imaging. All clinicians and 88% of data managers felt there was greater accuracy using this system. Conclusion Existing data management systems can be harnessed to enable real-time collection and review of clinical information during trials. This approach facilitates reporting of information closer to the time of events, and improves efficiency, and the ability to make earlier clinical decisions.
Cediranib for Metastatic Alveolar Soft Part Sarcoma
Authors: Kummar Shivaani , Allen Deborah , Monks Anne , Polley Eric C. , Hose Curtis D. , Ivy S. Percy , Turkbey Ismail B. , Lawrence Scott , Kinders Robert J. , Choyke Peter , Simon Richard , Steinberg Seth M. , Doroshow James H. , Helman Lee 
Published: April 2013

Purpose Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor, for which no effective standard systemic treatment exists for patients with unresectable disease. Cediranib is a potent, oral small-molecule inhibitor of all three vascular endothelial growth factor receptors (VEGFRs). Patients and Methods We conducted a phase II trial of once-daily cediranib (30 mg) given in 28-day cycles for patients with metastatic, unresectable ASPS to determine the objective response rate (ORR). We also compared gene expression profiles in pre- and post-treatment tumor biopsies and evaluated the effect of cediranib on tumor proliferation and angiogenesis using positron emission tomography and dynamic contrast-enhanced magnetic resonance imaging. Results Of 46 patients enrolled, 43 were evaluable for response at the time of analysis. The ORR was 35%, with 15 of 43 patients achieving a partial response. Twenty-six patients (60%) had stable disease as the best response, with a disease control rate (partial response + stable disease) at 24 weeks of 84%. Microarray analysis with validation by quantitative real-time polymerase chain reaction on paired tumor biopsies from eight patients demonstrated downregulation of genes related to vasculogenesis. Conclusion In this largest prospective trial to date of systemic therapy for metastatic ASPS, we observed that cediranib has substantial single-agent activity, producing an ORR of 35% and a disease control rate of 84% at 24 weeks. On the basis of these results, an open-label, multicenter, randomized phase II registration trial is currently being conducted for patients with metastatic ASPS comparing cediranib with another VEGFR inhibitor, sunitinib.
Development and prevalence of femoroacetabular impingement-associated morphology in a paediatric and adolescent population
Authors: Monazzam S. , Bomar J. D. , Dwek J. R. , Hosalkar H. S. , Pennock A. T. 
Published: April 2013

We investigated the development of CT-based bony radiological parameters associated with femoroacetabular impingement (FAI) in a paediatric and adolescent population with no known orthopaedic hip complaints. We retrospectively reformatted and reoriented 225 abdominal CTs into standardised CT pelvic images with neutral pelvic tilt and inclination (244 female and 206 male hips) in patients ranging from two to 19 years of age (mean 10.4 years). The Tönnis angle, acetabular depth ratio, lateral centre–edge angle, acetabular version and α-angle were assessed.Acetabular measurements demonstrated increased acetabular coverage with age and/or progressive ossification of the acetabulum. The α-angle decreased with age and/or progressive cortical bone development and resultant narrowing of the femoral neck. Cam and pincer morphology occurred as early as ten and 12 years of age, respectively, and their prevalence in the adolescent patient population is similar to that reported in the adult literature. Future aetiological studies of FAI will need to focus on the early adolescent population.Cite this article: Bone Joint J 2013;95-B:598–604.
Reduction of blood loss with the use of a new combined intra-operative and post-operative autologous blood transfusion system compared with no drainage in primary total hip replacement
Authors: Horstmann W. G. , Swierstra M. J. , Ohanis D. , Castelein R. M. , Kollen B. J. , Verheyen C. C. P. M. 
Published: April 2013

Autologous retransfusion and no-drainage are both blood-saving measures in total hip replacement (THR). A new combined intra- and post-operative autotransfusion filter system has been developed especially for primary THR, and we conducted a randomised controlled blinded study comparing this with no-drainage. A total of 204 THR patients were randomised to autologous blood transfusion (ABT) (n = 102) or no-drainage (n = 102). In the ABT group, a mean of 488 ml (sd 252) of blood was retransfused. The mean lowest post-operative haemoglobin level during the hospital stay was higher in the autotransfusion group (10.6 g/dl (7.8 to 13.9) vs 10.2 g/dl (7.5 to 13.3); p = 0.01). The mean haemoglobin levels for the ABT and no-drainage groups were not significantly different on the first day (11.3 g/dl (7.8 to 13.9) vs 11.0 g/dl (8.1 to 13.4); p = 0.07), the second day (11.1 g/dl (8.2 to 13.8) vs 10.8 g/dl (7.5 to 13.3); p = 0.09) or the third day (10.8 g/dl (8.0 to 13.0) vs 10.6 g/dl (7.5 to 14.1); p = 0.15). The mean total peri-operative net blood loss was 1464 ml (sd 505) in the ABT group and 1654 ml (sd 553) in the no-drainage group (p = 0.01). Homologous blood transfusions were needed in four patients (3.9%) in the ABT group and nine (8.8%) in the no-drainage group (p = 0.15). No statistically significant difference in adverse events was found between the groups. The use of a new intra- and post-operative autologous blood transfusion filter system results in less total blood loss and a smaller maximum decrease in haemoglobin levels than no-drainage following primary THR. Cite this article: Bone Joint J 2013;95-B:616–22.
The cost of outpatient venous thromboembolism prophylaxis following lower limb injuries
Authors: Menakaya C. U. , Pennington N. , Muthukumar N. , Joel J. , Ramirez Jimenez A. J. , Shaw C. J. , Mohsen A. 
Published: April 2013

This paper reports the cost of outpatient venous thromboembolism (VTE) prophylaxis following 388 injuries of the lower limb requiring immobilisation in our institution, from a total of 7408 new patients presenting between May and November 2011. Prophylaxis was by either self-administered subcutaneous dalteparin (n = 128) or oral dabigatran (n = 260). The mean duration of prophylaxis per patient was 46 days (6 to 168). The total cost (pay and non-pay) for prophylaxis with dalteparin was £107.54 and with dabigatran was £143.99. However, five patients in the dalteparin group required nurse administration (£23 per home visit), increasing the cost of dalteparin to £1142.54 per patient. The annual cost of VTE prophylaxis in a busy trauma clinic treating 12 700 new patients (2010/11), would be £92 526.33 in the context of an income for trauma of £1.82 million, which represents 5.3% of the outpatient tariff. Outpatient prophylaxis in a busy trauma clinic is achievable and affordable in the context of the clinical and financial risks involved. Cite this article: Bone Joint J 2013;95-B:673–7.
An Organelle Gatekeeper Function forCaenorhabditis elegansUNC-16 (JIP3) at the Axon Initial Segment
Authors: Edwards Stacey L , Yu Szi-chieh , Hoover Christopher M , Phillips Barret C , Richmond Janet E , Miller Kenneth G 
Published: April 2013

AbstractNeurons must cope with extreme membrane trafficking demands to produce axons with organelle compositions that differ dramatically from those of the cell soma and dendrites; however, the mechanism by which they accomplish this is not understood. Here we use electron microscopy and quantitative imaging of tagged organelles to show that Caenorhabditis elegans axons lacking UNC-16 (JIP3/Sunday Driver) accumulate Golgi, endosomes, and lysosomes at levels up to 10-fold higher than wild type, while ER membranes are largely unaffected. Time lapse microscopy of tagged lysosomes in living animals and an analysis of lysosome distributions in various regions of unc-16 mutant axons revealed that UNC-16 inhibits organelles from escaping the axon initial segment (AIS) and moving to the distal synaptic part of the axon. Immunostaining of native UNC-16 in C. elegans neurons revealed a localized concentration of UNC-16 at the initial segment, although UNC-16 is also sparsely distributed in distal regions of axons, including the synaptic region. Organelles that escape the AIS in unc-16 mutants show bidirectional active transport within the axon commissure that occasionally deposits them in the synaptic region, where their mobility decreases and they accumulate. These results argue against the long-standing, untested hypothesis that JIP3/Sunday Driver promotes anterograde organelle transport in axons and instead suggest an organelle gatekeeper model in which UNC-16 (JIP3/Sunday Driver) selectively inhibits the escape of Golgi and endosomal organelles from the AIS. This is the first evidence for an organelle gatekeeper function at the AIS, which could provide a regulatory node for controlling axon organelle composition.
New Roles for Old Characters: An Educational Primer for Use with “Vps Factors Are Required for Efficient Transcription Elongation in Budding Yeast”
Authors: Duina Andrea A 
Published: April 2013

Abstract
An article from Alan Hinnebusch’s laboratory in the March 2013 issue of GENETICS establishes an exciting new link between proteins with well-established roles in the endomembrane system and the process of transcription elongation. This Primer article provides tools needed for students to fully appreciate, analyze, and critically evaluate the experiments and interpretations of Gaur et al. (2013). The primer includes detailed descriptions of techniques used in the study, such as the chromatin immunoprecipitation assay and assays for transcription elongation, and it provides a framework to facilitate an understanding of how a combination of genetic, biochemical, and cell microscopy experimental approaches were used by the authors to converge on a single major conclusion. Suggestions for using this Primer article in an undergraduate or graduate-level course in conjunction with the original article to promote student learning are also presented.
Related article in GENETICS: Gaur, N. A., J. Hasek, D. G. Brickner, H. Qiu, F. Zhang et al., 2013 Vps factors are required for efficient transcription elongation in budding yeast. Genetics 193: 829–851.
Association of Procalcitonin With Acute Pyelonephritis and Renal Scars in Pediatric UTI
Authors: Leroy Sandrine , Fernandez-Lopez Anna , Nikfar Roya , Romanello Carla , Bouissou François , Gervaix Alain , Gurgoze Metin K. , Bressan Silvia , Smolkin Vladislav , Tuerlinckx David , Stefanidis Constantinos J. , Vaos Georgos , Leblond Pierre , Gungor Firat , Gendrel Dominique , Chalumeau Martin 
Published: April 2013

BACKGROUND AND OBJECTIVE:
Urinary tract infections (UTIs) are common childhood bacterial infections that may involve renal parenchymal infection (acute pyelonephritis [APN]) followed by late scarring. Prompt, high-quality diagnosis of APN and later identification of children with scarring are important for preventing future complications. Examination via dimercaptosuccinic acid scanning is the current clinical gold standard but is not routinely performed. A more accessible assay could therefore prove useful. Our goal was to study procalcitonin as a predictor for both APN and scarring in children with UTI.

METHODS:
A systematic review and meta-analysis of individual patient data were performed; all data were gathered from children with UTIs who had undergone both procalcitonin measurement and dimercaptosuccinic acid scanning.

RESULTS:
A total of 1011 patients (APN in 60.6%, late scarring in 25.7%) were included from 18 studies. Procalcitonin as a continuous, class, and binary variable was associated with APN and scarring (P &lt; .001) and demonstrated a significantly higher (P &lt; .05) area under the receiver operating characteristic curve than either C-reactive protein or white blood cell count for both pathologies. Procalcitonin ≥0.5 ng/mL yielded an adjusted odds ratio of 7.9 (95% confidence interval [CI]: 5.8–10.9) with 71% sensitivity (95% CI: 67–74) and 72% specificity (95% CI: 67–76) for APN. Procalcitonin ≥0.5 ng/mL was significantly associated with late scarring (adjusted odds ratio: 3.4 [95% CI: 2.1–5.7]) with 79% sensitivity (95% CI: 71–85) and 50% specificity (95% CI: 45–54).

CONCLUSIONS:
Procalcitonin was a more robust predictor compared with C-reactive protein or white blood cell count for selectively identifying children who had APN during the early stages of UTI, as well as those with late scarring.
No Win… Facing the Ethical Perils of Welfare Reform
Authors: Withorn Ann 
Published: April 2013

The Personal Responsibility and Work Opportunity Art of 1996, or “welfare reform,” is highly controversial public policy. In every state the ‘devolution’ of federal entitlements has created intense debate and new legislation, either presaging the national changes or in response to them. In addition to being a source of deep political conflict, welfare reform has also created immediate and continuing dilemmas for the people who try to work within the new rules and for those struggling to change them. The author reviews the context for understanding welfare reform as an ethical problem for the whole society, and uses examples drawn from her work as a teacher and welfare rights activist to illustrate the day-to-day problems that welfare reform forces upon women who use the system and workers whose job it is to help them. Finally, possibilities for responding at different levels are presented.
Efficacy and Safety of Busulfan-Based Conditioning Regimens for Multiple Myeloma
Authors: Reece Donna , Song Kevin , LeBlanc Richard , Mezzi Khalid , Olujohungbe Ade , White Darrell , Zaman Faraz , Belch Andrew 
Published: April 2013

Abstract
Multiple myeloma is a malignancy of B cells characterized by accumulation of abnormal plasma cells in the bone marrow. In the past 20 years, the use of high-dose therapies and novel agents has resulted in significant and meaningful improvements in survival. Autologous stem cell transplantation (auto-SCT) following a high-dose melphalan-conditioning regimen represents the standard of care for younger patients as well as older patients with a good performance status. A number of strategies have been proposed to improve the outcome of auto-SCTs, including the incorporation of new agents such as thalidomide, lenalidomide, and bortezomib into the induction regimen administered before auto-SCT; the administration of maintenance therapy after auto-SCT; the incorporation of novel agents into chemotherapeutic regimens after transplantation as consolidation therapy; and the use of reduced-intensity allogeneic transplantation after an initial autograft. Although these approaches have demonstrated some success in improving responses after auto-SCT, none of these strategies are curative. An additional strategy to improve outcomes after auto-SCT is to enhance the immediate pretransplant conditioning regimens by either increasing the dose of melphalan or by incorporating novel agents, such as busulfan. This literature review focuses on the efficacy and safety of busulfan-based conditioning regimens for auto-SCT in patients with multiple myeloma.