bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a prototype gantry system for preclinical x‐ray phase‐contrast computed tomography
Authors: Tapfer Arne , Bech Martin , Pauwels Bart , Liu Xuan , Bruyndonckx Peter , Sasov Alexander , Kenntner Johannes , Mohr Jürgen , Walter Marco , Schulz Joachim , Pfeiffer Franz 
Published: October 2011

Purpose:To explore the potential of grating‐based x‐ray phase‐contrast imaging for clinical applications, a first compact gantry system was developed. It is designed such that it can be implemented into anin‐vivo small‐animal phase‐contrast computed tomography (PC‐CT) scanner. The purpose of the present study is to assess the accuracy and quantitativeness of the described gantry in both absorption and phase‐contrast.Methods:A phantom, containing six chemically well‐defined liquids, was constructed. A tomography scan with cone‐beam reconstruction of this phantom was performed yielding the spatial distribution of the linear attenuation coefficient μ and decrement δ of the complex refractive index. Theoretical values of μ and δ were calculated for each liquid from tabulated data and compared with the experimentally measured values. Additionally, a color‐fused image representation is proposed to display the complementary absorption and phase‐contrast information in a single image.Results:Experimental and calculated data of the phantom agree well confirming the quantitativeness and accuracy of the reconstructed spatial distributions of μ and δ. The proposed color‐fused image representation, which combines the complementary absorption and phase information, considerably helps in distinguishing the individual substances.Conclusions:The concept of grating‐based phase‐contrast computed tomography (CT) can be implemented into a compact, cone‐beam geometry gantry setup. The authors believe that this work represents an important milestone in translating phase‐contrast x‐ray imaging from previous proof‐of‐principle experiments to first preclinical biomedical imaging applications on small‐animal models.
A3 Those in peril on the sea: the maritime work of the UK military SAR
Authors: Dykes L , Thomas M , Hird J 
Published: October 2011

At any time, thousands of people are at sea around the UK. We wished to ascertain the nature of maritime emergencies attended by UK military (Royal Air Force/Royal Navy) SAR helicopters.MethodAll UK military SAR “medrescues” 1 January 2009–13 March 2010 were entered onto a database. Clinical scenarios were extracted from winchmen's reports. Acuity was estimated using the Manchester Triage Score.ResultsOf 907 SAR medrescues during the 15.5-month audit period, 172 (19%) were maritime.Mean age of casualty 44 years (range 16–87); 90% male.Of 130 reports with vessel type noted, 28% of casualties were from fishing boats, 20% military ships; 12% dive boats, 11% passenger ferries/cruise ships and 10% oil rigs. The remainder were on boats ranging from small pleasure craft to oil tankers, plus one surfer.The aircraft was able to land on the vessel in 13% of the 168 jobs where this information was recorded, mainly oil-rigs and military ships. The remaining 87% were winched aboard the aircraft.7% of cases were diving-related emergencies; 53% medical/surgical and 40% trauma (including drowning/near-drowning).151/172 cases had sufficient information to enable estimation of Manchester Triage category: 66/151 (44%) were category 1 or 2 and 77/151 (51%) category 3. Only 8/151 (5%) were category 4. None were category 5.ConclusionMedical emergencies at sea are surprisingly diverse, with a wide variety of major and minor injuries & illnesses. This series ranges from diving emergencies, major trauma, an elderly cruise ship passenger with a ruptured AAA, and obstetric emergencies. Our data are retrospective and the MTS is not designed for prehospital use, but most maritime cases attended by RAF/RN SAR helicopters appear to be genuinely urgent. Lives would be at risk without the service, which features both winching capability & a technician or HPC-registered paramedic on board.
Water level thresholds of benthic macroinvertebrate richness, structure, and function of boreal lake stony littoral habitats
Authors: White Michael S. , Xenopoulos Marguerite A. , Metcalfe Robert A. , Somers Keith M. 
Published: October 2011

We investigated the role of water level fluctuation on benthic macroinvertebrate communities of stony littoral habitats located in the Boreal Shield Ecozone. Using the reference condition approach (RCA), regression analysis, nonmetric multidimensional scaling (NMDS), and analysis of variance (ANOVA), we analyzed the benthic macroinvertebrate community structure of 20 natural lakes and 28 hydroelectric reservoirs to determine if they are structured by change in water level (amplitude). Along a gradient of amplitude intensity, we found that taxa richness decreases with increasing amplitude (r2 = 0.47–0.60). Littoral benthic macroinvertebrate community structure is significantly different in reservoirs that experience amplitudes > 2.0 m. Out of 28 reservoirs, 13 fell outside the 95.5% confidence ellipse determined by 20 reference lakes. Functional mobility group and functional feeding group composition are also altered with increasing amplitude (nonparametric ANOVA, P < 0.05). Further, a change in benthic macroinvertebrate functional composition occurs after a change in taxa richness. Interestingly, reservoirs that experienced amplitudes < 2.0 m had benthic macroinvertebrate communities whose structural and functional composition is similar to lakes experiencing natural water level fluctuations.
Chlorogenic acid differentially affects postprandial glucose and glucose-dependent insulinotropic polypeptide response in rats
Authors: Tunnicliffe Jasmine M. , Eller Lindsay K. , Reimer Raylene A. , Hittel Dustin S. , Shearer Jane 
Published: October 2011

Regular coffee consumption significantly lowers the risk of type 2 diabetes (T2D). Coffee contains thousands of compounds; however, the specific component(s) responsible for this reduced risk is unknown. Chlorogenic acids (CGA) found in brewed coffee inhibit intestinal glucose uptake in vitro. The objective of this study was to elucidate the mechanisms by which CGA acts to mediate blood glucose response in vivo. Conscious, unrestrained, male Sprague–Dawley rats were chronically catheterized and gavage-fed a standardized meal (59% carbohydrate, 25% fat, 12% protein), administered with or without CGA (120 mg·kg–1), in a randomized crossover design separated by a 3-day washout period. Acetaminophen was co-administered to assess the effects of CGA on gastric emptying. The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were measured. GLP-1 response in the presence of glucose and CGA was further examined, using the human colon cell line NCI-H716. Total area under the curve (AUC) for blood glucose was significantly attenuated in rats fed CGA (p < 0.05). Despite this, no differences in plasma insulin or nonesterified fatty acids were observed, and gastric emptying was not altered. Plasma GIP response was blunted in rats fed CGA, with a lower peak concentration and AUC up to 180 min postprandially (p < 0.05). There were no changes in GLP-1 secretion in either the in vivo or in vitro study. In conclusion, CGA treatment resulted in beneficial effects on blood glucose response, with alterations seen in GIP concentrations. Given the widespread consumption and availability of coffee, CGA may be a viable prevention tool for T2D.
Endurance and resistance training lowers C-reactive protein in young, healthy females
Authors: Daray Laura A. , Henagan Tara M. , Zanovec Michael , Earnest Conrad P. , Johnson Lisa G. , Winchester Jason , Tuuri Georgianna , Stewart Laura K. 
Published: October 2011

The purpose of this study was to determine whether endurance (E) or endurance + resistance (ER) training affects C-reactive protein (CRP) and if these changes are related to alterations in fitness and (or) body composition in young females. Thirty-eight females (aged 18–24 years) were assigned to 1 of 3 groups: (1) E, (2) ER or (3) active control (AC). The E and ER groups completed 15 weeks of marathon training. The ER group performed additional resistance training and the AC group maintained their usual exercise routine. Primary outcomes were measured pre- and post-training and included anthropometric indices, dual-energy x-ray absorptiometry, plasma CRP, time to complete 1.5 miles (in minutes), and upper and lower body strength tests (i.e., 8 repetition max on bench and leg press (ER group only)). There were no differences in any variable among the groups at baseline. After training, the E group decreased time to complete 1.5 miles (p < 0.05). The AC group decreased percent and absolute body fat while the E group decreased percent body fat, absolute body fat, and android and gynoid body fat (p < 0.05). The ER group significantly improved strength (p < 0.001) and reduced plasma CRP from 2.0 ± 1.1 to 0.8 ± 0.3 mg·L–1 (p = 0.03). No significant associations were observed between CRP and measures of body composition or aerobic capacity. Combined endurance and resistance training may be an effective modality for reducing plasma CRP in young adult females independent of changes in aerobic capacity or body composition.
A prospective evaluation of non-interval- and interval-based exercise training progressions in rodents
Authors: Jendzjowsky Nicholas G. , DeLorey Darren S. 
Published: October 2011

Non-interval and interval training progressions were used to determine (i) the mean rate at which treadmill speed could be incremented daily using a non-interval training progression to train rats to run continuously at different intensities and (ii) the number of training days required for rats to run continuously at different exercise intensities with non-interval- and interval-based training progressions to establish methods of progressive overload for rodent exercise training studies. Rats were randomly assigned to mild-intensity (n = 5, 20 m·min–1, 5% grade), moderate-intensity (n = 5, 30 m·min–1, 5% grade), and heavy-intensity non-interval groups (n = 5, 40 m·min–1, 5% grade) or a heavy-intensity interval (n = 5, 40 m·min–1, 5% grade) group and ran 5 days·week–1 for 6 weeks. Non-interval training involved a daily increase of treadmill speed, whereas interval training involved a daily increase of interval time, until the animal could run continuously at a prescribed intensity. In mild-, moderate-, and heavy-intensity non-interval-trained rats, treadmill speed was increased by 0.6 ± 0.7 m·min–1·day–1, 0.6 ± 0.2 m·min–1·day–1, and 0.8 ± 0.1 m·min–1·day–1, respectively. Target training intensity and duration were obtained following 0.4 ± 0.5 days, 17 ± 3 days, and 23 ± 3 training days (p < 0.05) in mild-, moderate-, and heavy-intensity groups, respectively. In contrast, interval-trained rodents required 11 ± 1 training days. These data demonstrate that rodents will tolerate an increase in treadmill speed of ∼0.7 ± 0.1 m·min–1·day–1 and that this progression enables rats to run continuously at moderate and heavy intensities with 3–4 weeks of progressive overload. Interval training significantly reduces the number of training days required to attain a target intensity.
Evidence that the association between exercise intensity and insulin sensitivity is sex dependent
Authors: Hougham Kaitlyn A. , Ross Robert 
Published: October 2011

The purpose of this study was to determine if, after adjusting for the contribution of exercise dose, exercise intensity was associated with the improvement of insulin sensitivity. Abdominally obese, sedentary men (n = 16, (mean ± SD) age 45.0 ± 7.5 years, waist circumference 108.6 ± 5.3 cm) and women (n = 18, (mean ± SD) age 42.3 ± 6.2 years, waist circumference 100.1 ± 8.2 cm) performed daily, supervised exercise for 3 and 4 months, respectively. Exercising at a self-selected exercise intensity, men were required to expend 700 kcal per session and women 500 kcal per session. Exercise intensity and dose were determined using heart rate and oxygen consumption data obtained from repeated graded exercise tests. Insulin sensitivity was determined by hyperinsulinemic euglycemic clamp. Insulin sensitivity improved in both men and women (change scores: men 7.2 ± 5.4 mg·(kg skeletal muscle (skm))–1·min–1; women 5.8 ± 7.1 mg·(kg skm)–1·min–1; p < 0.05). Exercise intensity was associated with the improvement of insulin sensitivity in men (unstandardized regression coefficient (β) = 0.43, p = 0.02). Adjusting for exercise dose, total abdominal adipose tissue (AT), or visceral AT did not alter this association (p < 0.05). Exercise intensity was not associated with the improvement of insulin sensitivity in women (β = –0.11, p = 0.7). Adjusting for exercise dose, total abdominal AT, or visceral AT did not change this association in women (p > 0.05). Our findings suggest that exercise intensity is independently associated with the improvement of insulin sensitivity in abdominally obese men but not women.
A Novel Aldehyde Dehydrogenase-3 Activator Leads to Adult Salivary Stem Cell EnrichmentIn Vivo
Authors: Banh Alice , Xiao Nan , Cao Hongbin , Chen Che-Hong , Kuo Peiwen , Krakow Trevor , Bavan Brindha , Khong Brian , Yao Mike , Ha Chi , Kaplan Michael J. , Sirjani Davud , Jensen Kristin , Kong Christina S. , Mochly-Rosen Daria , Koong Albert C. , Le Quynh-Thu 
Published: October 2011

AbstractPurpose: To assess aldehyde dehydrogenase (ALDH) expression in adult human and murine submandibular gland (SMG) stem cells and to determine the effect of ALDH3 activation in SMG stem cell enrichment.Experimental Design: Adult human and murine SMG stem cells were selected by cell surface markers (CD34 for human and c-Kit for mouse) and characterized for various other stem cell surface markers by flow cytometry and ALDH isozymes expression by quantitative reverse transcriptase PCR. Sphere formation and bromodeoxyuridine (BrdUrd) incorporation assays were used on selected cells to confirm their renewal capacity and three-dimensional (3D) collagen matrix culture was applied to observe differentiation. To determine whether ALDH3 activation would increase stem cell yield, adult mice were infused with a novel ALDH3 activator (Alda-89) or with vehicle followed by quantification of c-Kit+/CD90+ SMG stem cells and BrdUrd+ salispheres.Results: More than 99% of CD34+ huSMG stem cells stained positive for c-Kit, CD90 and 70% colocalized with CD44, Nestin. Similarly, 73.8% c-Kit+ mSMG stem cells colocalized with Sca-1, whereas 80.7% with CD90. Functionally, these cells formed BrdUrd+ salispheres, which differentiated into acinar- and ductal-like structures when cultured in 3D collagen. Both adult human and murine SMG stem cells showed higher expression of ALDH3 than in their non–stem cells and 84% of these cells have measurable ALDH1 activity. Alda-89 infusion in adult mice significantly increased c-Kit+/CD90+ SMG population and BrdUrd+ sphere formation compared with control.Conclusion: This is the first study to characterize expression of different ALDH isozymes in SMG stem cells. In vivo activation of ALDH3 can increase SMG stem cell yield, thus providing a novel means for SMG stem cell enrichment for future stem cell therapy. Clin Cancer Res; 17(23); 7265–72. ©2011 AACR.
SAR3419: An Anti-CD19-Maytansinoid Immunoconjugate for the Treatment of B-Cell Malignancies
Authors: Blanc Veronique , Bousseau Anne , Caron Anne , Carrez Chantal , Lutz Robert J. , Lambert John M. 
Published: October 2011

AbstractSAR3419 is a novel anti-CD19 humanized monoclonal antibody conjugated to a maytansine derivate through a cleavable linker for the treatment of B-cell malignancies. SAR3419 combines the strengths of a high-potency tubulin inhibitor and the exquisite B-cell selectivity of an anti-CD19 antibody. The internalization and processing of SAR3419, following its binding at the surface of CD19-positive human lymphoma cell lines and xenograft models, release active metabolites that trigger cell-cycle arrest and apoptosis, leading to cell death and tumor regression. SAR3419 has also been shown to be active in different lymphoma xenograft models, including aggressive diffuse large B-cell lymphoma, resulting in complete regressions and tumor-free survival. In these models, the activity of SAR3419 compared favorably with rituximab and lymphoma standard of care chemotherapy. Two phase I trials with 2 different schedules of SAR3419 as a single agent were conducted in refractory/relapsed B-cell non-Hodgkin lymphoma. Activity was reported in both schedules, in heavily pretreated patients of both follicular and diffuse large B-cell lymphoma subtypes, with a notable lack of significant hematological toxicity, validating SAR3419 as an effective antibody-drug conjugate and opening opportunities in the future. Numerous B-cell–specific anti-CD19 biologics are available to treat B-cell non-Hodgkin lymphoma, and early phase I results obtained with SAR3419 suggest that it is a promising candidate for further development in this disease. In addition, thanks to the broad expression of CD19, SAR3419 may provide treatment options for B-cell leukemias that are often CD20-negative. Clin Cancer Res; 17(20); 6448–58. ©2011 AACR.
Antibody-Drug Conjugates of Calicheamicin Derivative: Gemtuzumab Ozogamicin and Inotuzumab Ozogamicin
Authors: Ricart Alejandro D. 
Published: October 2011

Abstract
Antibody-drug conjugates (ADC) are an attractive approach for the treatment of acute myeloid leukemia and non-Hodgkin lymphomas, which in most cases, are inherently sensitive to cytotoxic agents. CD33 and CD22 are specific markers of myeloid leukemias and B-cell malignancies, respectively. These endocytic receptors are ideal for an ADC strategy because they can effectively carry the cytotoxic payload into the cell. Gemtuzumab ozogamicin (GO, Mylotarg) and inotuzumab ozogamicin consist of a derivative of calicheamicin (a potent DNA-binding cytotoxic antibiotic) linked to a humanized monoclonal IgG4 antibody directed against CD33 or CD22, respectively. Both of these ADCs have a target-mediated pharmacokinetic disposition. GO was the first drug to prove the ADC concept in the clinic, specifically in phase II studies that included substantial proportions of older patients with relapsed acute myeloid leukemia. In contrast, in phase III studies, it has thus far failed to show clinical benefit in first-line treatment in combination with standard chemotherapy. Inotuzumab ozogamicin has shown remarkable clinical activity in relapsed/refractory B-cell non-Hodgkin lymphoma, and it has started phase III evaluation. The safety profile of these ADCs includes reversible myelosuppression (especially neutropenia and thrombocytopenia), elevated hepatic transaminases, and hyperbilirubinemia. There have been postmarketing reports of hepatotoxicity, especially veno-occlusive disease, associated with GO. The incidence is ∼2%, but patients who undergo hematopoietic stem cell transplantation have an increased risk. As we steadily move toward the goal of personalized medicine, these kinds of agents will provide a unique opportunity to treat selected patient subpopulations based on the expression of their specific tumor targets. Clin Cancer Res; 17(20); 6417–27. ©2011 AACR.
Antibody Fusion Proteins: Anti-CD22 Recombinant Immunotoxin Moxetumomab Pasudotox
Authors: Kreitman Robert J. , Pastan Ira 
Published: October 2011

Abstract
Recombinant immunotoxins are fusion proteins that contain the cytotoxic portion of a protein toxin fused to the Fv portion of an antibody. The Fv binds to an antigen on a target cell and brings the toxin into the cell interior, where it arrests protein synthesis and initiates the apoptotic cascade. Moxetumomab pasudotox, previously called HA22 or CAT-8015, is a recombinant immunotoxin composed of the Fv fragment of an anti-CD22 monoclonal antibody fused to a 38-kDa fragment of Pseudomonas exotoxin A, called PE38. Moxetumomab pasudotox is an improved, more active form of a predecessor recombinant immunotoxin, BL22 (also called CAT-3888), which produced complete remission in relapsed/refractory hairy cell leukemia (HCL), but it had a &lt;20% response rate in chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL), diseases in which the leukemic cells contain much lower numbers of CD22 target sites. Compared with BL22, moxetumomab pasudotox is up to 50-fold more active on lymphoma cell lines and leukemic cells from patients with CLL and HCL. A phase I trial was recently completed in HCL patients, who achieved response rates similar to those obtained with BL22 but without dose-limiting toxicity. In addition to further testing in HCL, moxetumomab pasudotox is being evaluated in phase I trials in patients with CLL, B-cell lymphomas, and childhood ALL. Moreover, protein engineering is being used to increase its activity, decrease nonspecific side effects, and remove B-cell epitopes. Clin Cancer Res; 17(20); 6398–405. ©2011 AACR.
Defective Mismatch Repair Status as a Prognostic Biomarker of Disease-Free Survival in Stage III Colon Cancer Patients Treated with Adjuvant FOLFOX Chemotherapy
Authors: Zaanan Aziz , Fléjou Jean-François , Emile Jean-François , Des Guetz Gaëtan , Cuilliere-Dartigues Peggy , Malka David , Lecaille Cédric , Validire Pierre , Louvet Christophe , Rougier Philippe , de Gramont Aimery , Bonnetain Franck , Praz Françoise , Taïeb Julien 
Published: October 2011

Abstract
Purpose: Adding oxaliplatin to adjuvant 5-fluorouracil (5-FU) chemotherapy improves 3-year disease-free survival (DFS) after resection of stage III colon cancer. Several studies suggest that patients with tumors exhibiting defective mismatch repair (MMR) do not benefit from adjuvant 5-FU chemotherapy, but there are few data on 5-FU–oxaliplatin (FOLFOX) adjuvant chemotherapy in this setting. The aim of this study was to evaluate the prognostic value of MMR status for DFS in patients with stage III colon cancer receiving adjuvant FOLFOX chemotherapy.
Experimental Design: MMR status was determined by microsatellite instability testing or immunohistochemistry in 303 unselected patients with stage III colon cancer receiving adjuvant FOLFOX chemotherapy in 9 centers. Cox proportional hazards models were used to examine the association between MMR status and 3-year DFS.
Results: The 3-year DFS rate was significantly higher in the 34 patients (11.2% of the study population) with defective MMR tumors (90.5%) than in patients with proficient MMR tumors (73.8%; log-rank test; HR = 2.16; 95% CI, 1.09–4.27; P = 0.027). In multivariate analysis, MMR status remained an independent significant prognostic factor for DFS (HR = 4.48; 95% CI, 1.34–14.99; P = 0.015).
Conclusion: MMR status is an independent prognostic biomarker for DFS in patients with stage III colon cancer receiving adjuvant FOLFOX chemotherapy. Clin Cancer Res; 17(23); 7470–8. ©2011 AACR.