bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized study of washing 40‐ to 42‐day‐stored red blood cells
Authors: Bennett‐Guerrero Elliott , Kirby Brett S. , Zhu Hongmei , Herman Annadele E. , Bandarenko Nicholas , McMahon Timothy J. 
Published: April 2014

BackgroundPretransfusion washing of red blood cells (RBCs) stored for a longer duration may have theoretical advantages but few data exist to support this practice. In many hospital settings, use of a point‐of‐care cell washer could conceivably be used to quickly wash allogeneic RBCs before transfusion. The purpose of this preliminary study was to compare a point‐of‐care device with a common blood bank device for washing longer‐stored RBCs.Study Design and MethodsForty RBC units stored for 40 to 42 days were randomized to washing with the COBE 2991 device (Terumo BCT; FDA‐cleared for washing stored RBCs) or the Cell Saver Elite (Haemonetics; FDA‐cleared point‐of‐care device for processing and washing fresh autologous shed whole blood). Supernatant and unit RBCs from unwashed (baseline) and washed blood were assayed for potassium, lactate, intracellular ATP, percentage of RBC recovery, cell‐free hemoglobin, RBC microparticles, and RBCs were examined for susceptibility to hemolysis by physical stress.ResultsBoth devices recovered a high percentage of RBCs and efficiently removed extracelluar potassium. Washing with the Elite resulted in significant increases in cell‐free Hb, percent hemolysis, and RBC microparticle production, whereas washing with the COBE 2991 did not (fold Δ = 2.1 vs. 1.0, 4.6 vs. 1.2, 2.0 vs. 1.1, respectively; p < 0.05). Hemolysis induced by physical stress was not altered by washing.ConclusionAlthough point‐of‐care washing of longer‐stored RBCs is appealing, these preliminary data suggest that transfusion of washed, longer‐stored units could result in potentially greater exposure to plasma free Hb. More data are needed before this practice can be routinely recommended.
Safety evaluation of combination CCNU and continuous toceranib phosphate (Palladia®) in tumour‐bearing dogs: a phase I dose‐finding study
Authors: Pan X. , Tsimbas K. , Kurzman I. D. , Vail D. M. 
Published: April 2014

AbstractWhile maintaining a standard toceranib dosage [2.75 mg kg−1, PO, every other day (EOD)], three dose‐escalating CCNU cohorts up to and including 60 mg m−2, PO, q3wk, were completed. The dose‐limiting toxicities (DLT) for the combination were neutropenia and the maximum tolerated dose (MTD) for CCNU when given with continuous toceranib was determined to be 50 mg m−2, q3wk. While activity is not a primary objective of phase I trials, we observed one complete (lymphoma) and four partial responses (lymphoma, sarcoma, undifferentiated carcinoma and prostatic carcinoma) and two dogs experienced stable disease for >6 weeks [gastric adenocarcinoma and metastatic multilobulated osteochondrosarcoma (MLO)] for an objective response rate of 38.4% and a biological response rate of 53.8%. Concurrent continuous toceranib (2.75 mg kg−1, EOD) and pulse dose CCNU (50 mg m−2, q3wk) was well tolerated. Phase II effectiveness and phase III prospective randomized trials should further interrogate the potential activity of this combination.
Thromboelastographic evaluation of hemostatic function in dogs treated for crotalid snake envenomation
Authors: Armentano Robert A. , Bandt Carsten , Schaer Michael , Pritchett John , Shih Andre 
Published: April 2014

AbstractObjectiveTo characterize the overall hemostatic changes in dogs envenomated by crotaline snakes via kaolin‐activated thromboelastography (TEG), and to determine any prognostic/monitoring value from a TEG tracing on presentation, as well as during treatment with antivenom therapy.DesignProspective observational, cohort study.SettingUniversity teaching hospital and primary emergency hospital.AnimalsThirty‐eight dogs envenomated by crotaline snakes.InterventionsTEG tracings were evaluated on presentation to the hospital (pre) as well as immediately following (post) and 12 hours (12 h post) after antivenom treatment, if administered.Measurements and Main ResultsAt presentation, data were available for 38 dogs envenomated by crotaline snakes. Twenty dogs were in Group 1 (Antivenin [Crotalidae] Polyvalent antivenom), 12 dogs were in Group 2 (Antivipmyn antivenom), and 6 dogs in Group 3 that were not treated with antivenom. The average number of vials administered to group 1 and 2 were equal at 2.2. On presentation, based on a G value < TEG reference range, 15/38 (39%) of the dogs had hypocoagulable TEG tracings. There was a significant increase in G and MA value from the pre and 12 hour post measurement (P = 0.0001 and 0.0003, respectively), as well as from the post to 12 hour post measurement (P = 0.003 and, 0.014, respectively). During the study, 5 of 38 dogs died (13%) and of the dogs that died, 4/5 (80%) had angle and MA equal to zero on presentation. A decreased G and MA were significantly associated with mortality (P = 0.02 and 0.04, respectively).ConclusionsA hypocoagulable TEG tracing, particularly a decreased G value and MA, is associated with an increased mortality in crotaline snake envenomation. G and MA also demonstrate a significant increase over treatment time.
Decreased central venous oxygen saturation despite normalization of heart rate and blood pressure post shock resuscitation in sick dogs
Authors: Young Brian C. , Prittie Jennifer E. , Fox Philip , Barton Linda J. 
Published: April 2014

AbstractObjectiveTo evaluate traditional and global perfusion parameters in clinical canine shock patients, and to evaluate for occult hypoperfusion as evidenced by low central venous oxygen saturation or high plasma lactate concentrations in clinical patients resuscitated to traditional endpoints.DesignClinical observational trial designed with a 1‐year data entry period and patient follow‐up of 28 days posthospital presentation.SettingLarge, private urban teaching hospital, and emergency and critical care center.AnimalsAdult canine patients presenting to the emergency department with untreated shock.InterventionsNone.Measurements and Main ResultsPatients received fluid resuscitation to normalize perfusion parameters based on physical examination and arterial blood pressure (BP). Monitoring of central venous pressure (CVP) and central venous oxygen saturation (ScvO2) was feasible with current standard of care interventions in critically ill, client‐owned dogs. Decreased ScvO2was observed in 37.8% of patients resuscitated to normal traditional perfusion parameters. Hyperlactatemia was commonly recorded.ConclusionsDecreased ScvO2exists in a significant proportion of critically ill dogs following standard fluid resuscitation for shock, providing a relevant target population for implementation of a more standardized early goal‐directed therapy bundle in veterinary patients. Normalization of heart rate, blood pressure, mentation, and perfusion parameters directed by physical examination may be attained despite the persistence of significant tissue hypoperfusion and oxygen debt.
Diagnostic accuracy of the SNAP and Spec canine pancreatic lipase tests for pancreatitis in dogs presenting with clinical signs of acute abdominal disease
Authors: Haworth Mark D. , Hosgood Giselle , Swindells Katrin L. , Mansfield Caroline S. 
Published: April 2014

AbstractObjectivesTo (i) assess the clinical diagnostic accuracy of SNAP canine pancreatic lipase (cPL) and specific canine pancreatic lipase (Spec cPL) and (ii) assess the agreement of an abnormal test result between SNAP cPL and Spec cPL in dogs presenting with acute abdominal disease.DesignProspective observational cohort study.SettingUniversity teaching hospital emergency center.AnimalsThirty‐eight client‐owned dogs that presented with acute abdominal disease, with a known final diagnosis between March 2009 and April 2010. Dogs were retrospectively assigned into 2 groups, dogs with acute pancreatitis (AP) (Group 1) and dogs without AP (Group 2).InterventionsPaired serum samples obtained within 24 hours of presentation were analyzed using the SNAP cPL test and Spec cPL assay.Measurements and ResultsSNAP cPL clinical sensitivity and specificity was 82% (9/11 dogs of group 1) and 59% (16/27 dogs of group 2), respectively. Spec cPL clinical sensitivity and specificity was 70% (7/10 dogs of group 1) and 77% (20/26 dogs of group 2), respectively. Accuracy of the SNAP and Spec cPL for a clinical diagnosis of pancreatitis was found to be 66% and 75%, respectively. Agreement between a positive SNAP (cPL ≥ 200 μg/L) and a clinical diagnosis pancreatitis resulted in κ = 0.33. Agreement between an increased Spec (cPL ≥ 400 μg/L) and a clinical diagnosis of pancreatitis resulted in a κ = 0.43. The agreement between SNAP and Spec cPL (cPL ≥ 200 μg/L) for the entire cohort resulted in κ = 0.78.ConclusionSNAP cPL and Spec cPL results may provide a "false positive" diagnosis of pancreatitis in up to 40% of dogs presenting with acute abdominal disease. There is good overall agreement between SNAP cPL and Spec cPL; however, there were 4/38 dogs with positive SNAP cPL and "normal" Spec cPL.
Bounds for zeros of Meixner and Kravchuk polynomials
Authors: Jooste A. , Jordaan K. 
Published: April 2014

AbstractThe zeros of certain different sequences of orthogonal polynomials interlace in a well-defined way. The study of this phenomenon and the conditions under which it holds lead to a set of points that can be applied as bounds for the extreme zeros of the polynomials. We consider different sequences of the discrete orthogonal Meixner and Kravchuk polynomials and use mixed three-term recurrence relations, satisfied by the polynomials under consideration, to identify bounds for the extreme zeros of Meixner and Kravchuk polynomials.
Vaccine-Induced Measles Virus-Specific T Cells Do Not Prevent Infection or Disease but Facilitate Subsequent Clearance of Viral RNA
Authors: Lin Wen-Hsuan W. , Pan Chien-Hsiung , Adams Robert J. , Laube Beth L. , Griffin Diane E. 
Published: April 2014

ABSTRACTInfection with wild-type measles virus (MeV) induces lifelong protection from reinfection, and parenteral delivery of the live attenuated measles vaccine (LAV) also provides protection from measles. The level of neutralizing antibody is a good indicator of protection, but the independent roles of MeV-specific antibody and T cells have not been identified. In this study, macaques immunized with LAV through a nebulizer and a mouthpiece developed MeV-specific T-cell responses but not neutralizing antibodies. Upon challenge with wild-type MeV, these animals developed rashes and viremias similar to those in naive animals but cleared viral RNA from blood 25 to 40 days faster. The nebulizer-immunized animals also had more robust MeV-specific CD4+and CD8+T-cell responses than the naive animals after challenge, characterized by a higher number and better durability of gamma interferon (IFN-γ)-producing cells. Induction of MeV-specific circulating CD4+and CD8+T cells capable of producing multiple cytokines correlated with clearance of viral RNA in the nebulizer-immunized macaques. These studies demonstrated that MeV-specific T-cell immunity alone did not prevent measles, but T-cell priming enhanced the magnitude, durability, and polyfunctionality of MeV-specific T cells after challenge infection and correlated with more rapid clearance of MeV RNA.IMPORTANCEThe components of vaccine-induced immunity necessary for protection from infection and disease have not been clearly identified for most vaccines. Vaccine development usually focuses on induction of antibody, but T-cell-based vaccines are also under development. The live attenuated measles vaccine (LAV) given subcutaneously induces both T cells and neutralizing antibody and provides solid protection from infection. LAV delivered to the upper respiratory tract through a nebulizer and mouthpiece induced a T-cell response but no neutralizing antibody. These T-cell-primed macaques demonstrated no protection from rash or viremia when challenged with wild-type MeV, but viral RNA was cleared more rapidly than in unimmunized animals. Thus, T-cell immunity did not protect from infection or acute disease but facilitated virus clearance during recovery. These studies demonstrate the importance and independent roles of T cells and antibody in protection and recovery from measles.
Predicting sleep disordered breathing in outpatients with suspected OSA
Authors: Cowan Douglas C , Allardice Gwen , MacFarlane Duncan , Ramsay Darren , Ambler Heather , Banham Stephen , Livingston Eric , Carlin Christopher 
Published: April 2014

ObjectiveTo validate the utilities of Berlin, STOP and STOP-BANG Questionnaires, other patient characteristics, comorbidities, Epworth Sleepiness Scale (ESS), fractional exhaled nitric oxide (FENO) and blood markers for the prediction of sleep disordered breathing (SDB) on limited polygraphy.SettingNorth Glasgow Sleep Service (a tertiary referral centre).Participants129 consecutive patients, aged ≥16 years, referred to the sleep clinic for assessment of possible obstructive sleep apnoea.InterventionsWe selected cut-points of apnoea hypopnoea index (AHI) of ≥5 and ≥15/h from their home polygraphy and determined associations of these with individual symptoms, questionnaire scores and other results. Receiver operating characteristic analysis and univariate and multivariate logistic regression were used to explore these.Primary and secondary outcomes measuresPrimary: The utility of STOP, STOP-BANG and Berlin Questionnaires for prediction of SDB.Secondary: The utility of other measures for prediction of SDB.ResultsAHI was ≥5 in 97 patients and ≥15 in 56 patients. STOP and STOP-BANG scores were associated with both AHI cut-points but results with ESS and Berlin Questionnaire scores were negative. STOP-BANG had a negative predictive value 1.00 (0.77–1.00) for an AHI ≥15 with a score ≥3 predicting AHI ≥5 with sensitivity 0.93 (95% CI 0.84 to 0.98) and accuracy 79%, while a score ≥6 predicted AHI ≥15 with specificity 0.78 (0.65 to 0.88) and accuracy 72%. Neck circumference ≥17 inch and presence of witnessed apnoeas were independent predictors of SDB.ConclusionsSTOP and STOP-BANG Questionnaires have utility for the prediction of SDB in the sleep clinic population. Modification of the STOP-BANG Questionnaire merits further study in this and other patient groups.
The quality of police data on RTC fatalities in India
Authors: Raban Magdalena Z , Dandona Lalit , Dandona Rakhi 
Published: April 2014

BackgroundPolice records are the major source of data on road traffic collision (RTC) deaths in India.ObjectiveTo examine the utility and quality of police data on RTC deaths available from two sources.MethodsPolice data on RTC deaths available from National Crime Records Bureau (NCRB) and Ministry of Road Transport and Highways (MoRTH) were accessed. The utility of these data for surveillance and consistency of data reported by the two organisations was examined. Data completeness was assessed for India, its six geographic regions and for the mode of travel using cause of death estimates from the Sample Registration System (SRS) and Global Burden of Disease (GBD) as a reference.ResultsData imperative for surveillance including deaths by age and sex for each state, the counterpart vehicle or object and use of safety equipment were not available. The total number of deaths reported by NCRB and MoRTH was similar across states but showed large differences by mode of travel categories. Compared with GBD, completeness of the number of fatalities reported by both sources in 2010 was approximately 50%. Completeness for the geographic regions ranged from 26.4% to 76.4%, using SRS data, in 2001–2003.ConclusionsThis detailed examination of police data on RTC fatalities from two sources has raised several questions about the validity of these data and has highlighted a number of gaps that limit the usefulness of these data for surveillance and informing road safety policies. Unless these are addressed, significant reductions in RTC fatalities cannot be achieved in India.
Genetically predicted 17β-estradiol and systemic inflammation in women: a separate-sample Mendelian randomisation analysis in the Guangzhou Biobank Cohort Study
Authors: Zhao J , Jiang C Q , Lam T H , Liu B , Cheng K K , Kavikondala S , Zhang W S , Leung G M , Schooling C M 
Published: April 2014

BackgroundMany chronic diseases are characterised by low-grade systemic inflammation. Oestrogens may promote immune response consistent with sex-specific patterns of diseases. In vitro culture and animal experiments suggest oestrogens are anti-inflammatory and might thereby protect against low-grade systemic inflammation. Evidence from epidemiological studies is limited. Using a Mendelian randomisation analysis with a separate-sample instrumental variable (SSIV) estimator, we examined the association of genetically predicted 17β-estradiol with well-established systemic inflammatory markers (total white cell count, granulocyte and lymphocyte count).MethodsA genetic score predicting 17β-estradiol was developed in 237 young Chinese women (university students) from Hong Kong based on a parsimonious set of genetic polymorphisms (ESR1(rs2175898) andCYP19A1(rs1008805)). Multivariable linear regression was used to examine the association of genetically predicted 17β-estradiol with systemic inflammatory markers among 3096 older (50+ years) Chinese women from the Guangzhou Biobank Cohort Study.ResultsPredicted 17β-estradiol was negatively associated with white blood cell count (−6.3 103/mL, 95% CI −11.4 to −1.3) and granulocyte count (−4.5 103/mL, 95% CI −8.5 to −0.4) but not lymphocyte count (−1.5 103/mL, 95% CI −3.4 to 0.4) adjusted for age only. Results were similar further adjusted for education, smoking, use of alcohol, physical activity, Body Mass Index, waist-hip ratio, age of menarche, age at menopause, use of hormonal contraceptives and hormone replacement therapy.ConclusionsEndogenous genetically predicted 17β-estradiol reduced low-grade systemic inflammatory markers (white blood cell count and granulocyte count), consistent with experimental and ecological evidence of 17β-estradiol promoting immune response. Replication in a larger sample is required.
Concomitant Intake of Quercetin with a Grain-Based Diet Acutely Lowers Postprandial Plasma Glucose and Lipid Concentrations in Pigs
Authors: Wein Silvia , Wolffram Siegfried 
Published: April 2014

Treatment goals of diabetes mellitus type 2 (DMT2) include glycemic control and reduction of nonglycemic risk factors, for example, dyslipidemia. Quercetin, a plant-derived polyphenol, often discussed for possible antidiabetic effects, was investigated for acute postprandial glucose- and lipid-lowering effects in healthy growing pigs. Male pigs (n = 16, body weight = BW 25–30 kg) were fed flavonoid-poor grain-based meals without (GBM) or with quercetin (GBMQ). In a first experiment, postprandial plasma concentrations of glucose, nonesterified fatty acids (NEFA), and triacylglycerols were analyzed in 8 pigs receiving 500 g of either GBM or GBMQ (10 mg/kg BW) in a cross-over design. Blood samples were collected before, and up to 5 h every 30 min, as well as 6 and 8 h after the feeding. In the second experiment, 2 h after ingestions of 1000 g of either GBM or GBMQ (50 mg/kg BW) animals were sacrificed; gastric content was collected and analyzed for dry matter content. Quercetin ingestion reduced postprandial glucose, NEFA, and TG concentration, but two hours after ingestion of the meal no effect on gastric emptying was observed. Our results point to inhibitory effects of quercetin on nutrient absorption, which appear not to be attributable to delayed gastric emptying.
Immune-Based Antitumor Effects of BRAF Inhibitors Rely on Signaling by CD40L and IFNγ
Authors: Ho Ping-Chih , Meeth Katrina M. , Tsui Yao-Chen , Srivastava Bhaskar , Bosenberg Marcus W. , Kaech Susan M. 
Published: April 2014

Abstract
B-RafV600E inhibitors have been suggested to promote tumor regression with the help of host immunity, but this hypothesis has not been examined directly in detail. In this study, we profiled immunologic changes in the tumor microenvironment and tumor-infiltrating lymphocytes (TIL) in a B-RafV600E/Pten-driven murine model of melanoma after administration of the B-RafV600E small molecule inhibitor PLX4720. In this model, we found that as tumors developed, they gradually acquired immunosuppressive features, including accumulation of regulatory T cells (Treg) and CD11b+/Gr-1+ myeloid cells and loss of Th1 effector functions on CD4+ TILs, such as CD40L and IFNγ expression. PLX4720 administration promoted development of a more immune stimulatory microenvironment associated with a relative increase in CD40L and IFNγ expression on intratumoral CD4+ TILs and a reduced accumulation of Tregs and CD11b+/Gr-1+ myeloid cells. Strikingly, CD40L or IFNγ blockade compromised the ability of PLX4720 to inhibit melanoma growth. Supporting this result, agonistic CD40 antibody was sufficient to evoke antitumor immunity and suppress tumor growth in tumor-bearing mice. Taken together, our results establish the critical role of immune-related changes, with key contributions for CD40L and IFNγ signaling in the antitumor responses triggered in vivo by B-RafV600E inhibitors. Cancer Res; 74(12); 3205–17. ©2014 AACR.
Noninvasive Urinary Metabolomic Profiling Identifies Diagnostic and Prognostic Markers in Lung Cancer
Authors: Mathé Ewy A. , Patterson Andrew D. , Haznadar Majda , Manna Soumen K. , Krausz Kristopher W. , Bowman Elise D. , Shields Peter G. , Idle Jeffrey R. , Smith Philip B. , Anami Katsuhiro , Kazandjian Dickran G. , Hatzakis Emmanuel , Gonzalez Frank J. , Harris Curtis C. 
Published: April 2014

Abstract
Lung cancer remains the most common cause of cancer deaths worldwide, yet there is currently a lack of diagnostic noninvasive biomarkers that could guide treatment decisions. Small molecules (&lt;1,500 Da) were measured in urine collected from 469 patients with lung cancer and 536 population controls using unbiased liquid chromatography/mass spectrometry. Clinical putative diagnostic and prognostic biomarkers were validated by quantitation and normalized to creatinine levels at two different time points and further confirmed in an independent sample set, which comprises 80 cases and 78 population controls, with similar demographic and clinical characteristics when compared with the training set. Creatine riboside (IUPAC name: 2-{2-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-oxolan-2-yl]-1-methylcarbamimidamido}acetic acid), a novel molecule identified in this study, and N-acetylneuraminic acid (NANA) were each significantly (P &lt; 0.00001) elevated in non–small cell lung cancer and associated with worse prognosis [HR = 1.81 (P = 0.0002), and 1.54 (P = 0.025), respectively]. Creatine riboside was the strongest classifier of lung cancer status in all and stage I-II cases, important for early detection, and also associated with worse prognosis in stage I-II lung cancer (HR = 1.71, P = 0.048). All measurements were highly reproducible with intraclass correlation coefficients ranging from 0.82 to 0.99. Both metabolites were significantly (P &lt; 0.03) enriched in tumor tissue compared with adjacent nontumor tissue (N = 48), thus revealing their direct association with tumor metabolism. Creatine riboside and NANA may be robust urinary clinical metabolomic markers that are elevated in tumor tissue and associated with early lung cancer diagnosis and worse prognosis. Cancer Res; 74(12); 3259–70. ©2014 AACR.