bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Crosslinking for Agonistic CD40 Monoclonal Antibodies as Immune Therapy of Cancer
Authors: Richman Lee P. , Vonderheide Robert H. 
Published: November 2013

Abstract
Agonists of the TNF superfamily of receptors hold promise as novel therapy for cancer. Recent data on agonistic antimurine TNF receptors (TNFR) such as CD40 suggest that the specific engagement of Fc receptor (FcR) is required for optimal antitumor effects, prompting calls to engineer antihuman CD40 and other TNFR monoclonal antibodies (mAb) accordingly. CP-870,893 is a fully human anti-CD40 mAb, selected in part because it is an immunoglobulin G2 (IgG2), which is presumed to have poor reactivity with FcR; however, CP-870,893 has been evaluated in multiple clinical trials with beneficial activity in patients with melanoma, pancreatic, and other cancers. Here, we confirmed that the activity of antimurine CD40 mAb was dependent on FcγRIIB engagement, was decreased significantly in FcγRIIB−/− mice, and upon Fc-crosslinking antimouse CD40 mAb enhanced the activation of antigen-presenting cells. In contrast, the CP-870,893-mediated activation of human B cells was not enhanced with anti-IgG crosslinking nor abrogated when used as an F(ab)′2 reagent. Crosslinking of CP-870,893 using the CD32-expressing K562 cells yielded an Fc-dependent modest increase in the expression of some activation markers relative to that of the soluble CP-870,893 mAb. Classic Fc-dependent functions such as antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CMC) were minimal for CP-870,893 as compared with the IgG1 anti-CD20 mAb rituximab, which mediated both ADCC and CMC in parallel assays. Antimouse CD40 mAb competed for the CD40 ligand binding site, but CP-870,893 did not. Thus, Fc crosslinking is not an essential requirement for agonistic antihuman CD40 mAbs, in which potency is more dependent on the CD40 epitope recognized and the strength of the signal achieved. Cancer Immunol Res; 2(1); 19–26. ©2013 AACR.
Sample Size and Cost Analysis for Pulmonary Arterial Hypertension Drug Trials Using Various Imaging Modalities to Assess Right Ventricular Size and Function End Points
Authors: Addetia Karima , Bhave Nicole M. , Tabit Corey E. , Gomberg-Maitland Mardi , Freed Benjamin H. , Dill Karin E. , Lang Roberto M. , Mor-Avi Victor , Patel Amit R. 
Published: November 2013

Background—
Placebo-controlled trials for pulmonary arterial hypertension are no longer acceptable because new therapies must show clinically significant effects on top of standard treatment. The purpose of this study was to estimate sample sizes and imaging costs for the planning of a hypothetical pulmonary arterial hypertension drug trial using imaging to detect changes in right ventricular size and function in response to combined therapy.

Methods and Results—

Same-day cardiovascular MR (CMR) and 2-dimensional (2D) and 3D transthoracic echocardiography (2DTTE and 3DTTE) were performed in 22 patients with pulmonary arterial hypertension (54±13 years of age) twice, 6 months apart. Short-axis CMR cines and full-volume 3DTTE data sets of the right ventricle were used to measure end-diastolic volume and ejection fraction. Fractional area change was obtained from 2DTTE. Sample size calculations used a 2-sample
t
test model incorporating differences between baseline and 6-month measurements. Cost estimates were made using the Medicare fee schedule. No significant differences were noted between baseline and follow-up measurements. Large SDs reflected variable progression of disease in individual patients on standard therapy and measurement variability. These sources of variability resulted in intertechnique differences in sample sizes: to detect a change of 5% to 15% in 3DTTE-derived right ventricular ejection fraction and fractional area change or change of 15 to 30 mL in 3DTTE right ventricular end-diastolic volume; sample sizes were 2× to 2.5× those required by CMR. As a result, the total cost of a trial using complete TTE was greater than CMR, which was greater than limited TTE.

Conclusions—
Because of lower measurement variability, CMR is more cost saving in pulmonary arterial hypertension drug trials than echocardiography, unless limited TTE is used.
Variation in Use of Left Ventriculography in the Veterans Affairs Health Care System
Authors: Heidenreich Paul A. , Lin Shoutzu , Knowles Joshua W. , Perez Marco , Maddox Thomas M. , Ho Michael P. , Rumsfeld John S. , Sahay Anju , Massie Barry M. , Tsai Thomas T. , Witteles Ronald M. 
Published: November 2013

Background—
Contrast left ventriculography is a method of measuring left ventricular function usually performed at the discretion of the invasive cardiologist during cardiac catheterization. We sought to determine variation in the use of left ventriculography in the Veterans Affairs (VA) Health Care System.

Methods and Results—
We identified adult patients who underwent cardiac catheterization including coronary angiography between 2000 and 2009 in the VA Health Care System. We determined patient and hospital predictors of the use of left ventriculography as well as the variation in use across VA facilities. Results were validated using data from the VA’s Clinical Assessment, Reporting, and Tracking (CART) program. Of 457 170 cardiac catheterization procedures among 336 853 patients, left ventriculography was performed on 263 695 (58%) patients. Use of left ventriculography decreased over time (64% in 2000 to 50% in 2009) and varied markedly across facilities (<1–>95% of cardiac catheterizations). Patient factors explained little of the large variation in use between facilities. When the cohort was restricted to those with an echocardiogram in the prior 30 days and no intervening event, left ventriculography was still performed in 50% of cases.

Conclusions—
There is large variation in the use of left ventriculography across VA facilities that is not explained by patient characteristics.
Temporal Trends in Quality of Care Among Recipients of Implantable Cardioverter-Defibrillators
Authors: Dodson John A. , Lampert Rachel , Wang Yongfei , Hammill Stephen C. , Varosy Paul , Curtis Jeptha P. 
Published: November 2013

Background—
The ICD Registry was established in 2006 in part to measure quality of care in patients undergoing implantation of implantable cardioverter-defibrillators (ICDs); however, whether outcomes have improved since initiation of the registry is unknown. Our objective was to examine changes over time in 3 quality metrics available from the registry.

Methods and Results—

We performed an observational study of 367 153 patients who received new ICD implants from April 2006 to March 2010. Three quality metrics were selected: Adverse events (in-hospital complications or mortality), optimal medical therapy (OMT), and cardiac resynchronization therapy (CRT). OMT was defined as prescription of β-blocker and either angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in eligible patients. CRT eligibility was determined by QRS ≥120 ms, left ventricular ejection fraction ≤35%, and New York Heart Association class III/IV. Observation periods were divided into four 12-month intervals. We analyzed changes over time and used hierarchical logistic regression to adjust for potential confounders. Adverse events decreased over time (3.7% to 2.8%,
P
<0.001). Among eligible patients, rates of OMT and CRT increased over time (OMT: 69.0% to 74.3%,
P
<0.001; CRT: 80.5% to 84.2%,
P
<0.001). After adjustment for potential confounders, patients were significantly less likely to experience adverse events in year 4 than in year 1 (odds ratio, 0.75; 95% confidence interval, 0.71–0.79) and significantly more likely to receive OMT (odds ratio, 1.29; 95% confidence interval, 1.26–1.32) and CRT (odds ratio, 1.42; 95% confidence interval, 1.35–1.49).

Conclusions—
Since initiation of the ICD Registry, adverse events have been decreasing, and rates of OMT and CRT among eligible patients have been increasing, although there is still significant room for improvement.
Racial/Ethnic Differences in Dyslipidemia Patterns
Authors: Frank Ariel T.H. , Zhao Beinan , Jose Powell O. , Azar Kristen M.J. , Fortmann Stephen P. , Palaniappan Latha P. 
Published: November 2013

Background—
No studies have comprehensively examined the prevalence of dyslipidemia, a major risk factor for cardiovascular disease, among diverse racial/ethnic minority groups. The primary aim of this study was to identify racial/ethnic differences in dyslipidemia among minorities including Asian Americans (Asian Indian, Chinese, Filipino, Japanese, Korean, or Vietnamese), Mexican Americans, and blacks compared with non-Hispanic whites.

Methods and Results—
Using a 3-year cross section (2008–2011), we identified 169 430 active primary care patients (35 years or older) from an outpatient healthcare organization in northern California. Age-standardized prevalence rates were calculated for 3 dyslipidemia subtypes: high triglycerides (fasting laboratory value ≥150 mg/dL), low levels of high-density lipoprotein cholesterol (fasting laboratory value <40 mg/dL [men] and <50 mg/dL [women]), and high levels of low-density lipoprotein cholesterol (fasting laboratory value ≥130 mg/dL or taking low-density lipoprotein–lowering agents). Odds ratios were calculated by multivariable logistic regression, with adjustment for patient characteristics (age, measured body mass index, smoking). Compared with non-Hispanic whites, every minority subgroup had an increased prevalence of high triglycerides except blacks. Most minority groups had an increased prevalence of low high-density lipoprotein cholesterol, except for Japanese and blacks. The prevalence of high low-density lipoprotein cholesterol was increased among Asian Indians, Filipinos, Japanese, and Vietnamese compared with non-Hispanic whites.

Conclusions—
Minority groups, except for blacks, were more likely to have high triglyceride/low high-density lipoprotein cholesterol dyslipidemia. Further research is needed to determine how racial/ethnic differences in dyslipidemia affect racial/ethnic differences in cardiovascular disease rates.
Pattern Not Volume of Bleeding Predicts Angiographic Vasospasm in Nonaneurysmal Subarachnoid Hemorrhage
Authors: Raya Amanda , Zipfel Gregory J. , Diringer Michael N. , Dacey Ralph G. , Derdeyn Colin P. , Rich Keith M. , Chicoine Michael R. , Dhar Rajat 
Published: November 2013

Background and Purpose—
Spontaneous idiopathic subarachnoid hemorrhage (SAH) with a perimesencephalic bleeding pattern is usually associated with a benign course, whereas a diffuse bleeding pattern has been associated with a higher risk of vasospasm and disability. We evaluated whether volume of bleeding explains this disparity.

Methods—
Pattern and amount of bleeding (by Hijdra and intraventricular hemorrhage scores) were assessed in 89 patients with nonaneurysmal SAH. Outcomes included angiographic vasospasm, delayed cerebral ischemia, and functional outcome at 1 year.

Results—

Diffuse bleeding was associated with significantly higher Hijdra and intraventricular hemorrhage scores than perimesencephalic SAH,
P
≤0.003. Angiographic vasospasm was more likely in diffuse versus perimesencephalic SAH (45% versus 27%; odds ratio, 2.9;
P
=0.08), but adjustment for greater blood burden only partially attenuated this trend (adjusted odds ratio, 2.2; 95% confidence interval, 0.69–7.2;
P
=0.18); delayed cerebral ischemia was only seen in those with diffuse bleeding. Patients with diffuse bleeding were less likely to be discharged home (68% versus 90%;
P
=0.01) and tended to have more residual disability (modified Rankin scale, 3–6; 20% versus 6%;
P
=0.18).

Conclusions—
Nonaneurysmal SAH can still result in vasospasm and residual disability, especially in those with diffuse bleeding. This disparity is only partially accounted for by greater cisternal or intraventricular blood, suggesting that the mechanism and distribution of bleeding may be as important as the amount of hemorrhage in patients with idiopathic SAH.
Improvements in LICOM2. Part II: Arctic Circulation
Authors: Huang Wen-Yu , Wang Bin , Li Li-Juan , Yu Yong-Qiang 
Published: November 2013

Abstract
A known issue of the National Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics/Institute of Atmospheric Physics Climate Ocean Model, version 2 (LICOM2, the standard version) is the use of an artificial island in the Arctic Ocean. The computational instability in the polar region seriously influences the model performance in terms of the Arctic circulation. The above-mentioned instability was originally attributed to the converging zonal grids in the polar region. However, this study finds that better computational stability could be achieved in an improved version of LICOM2 (i.e., LICOM2_imp) after four improvements on implementations of the vertical mixing, mesoscale eddy parameterization, and bottom drag schemes. LICOM2_imp is then able to reduce the aforesaid artificial island to a point (i.e., the North Pole).
Two experiments of 650-yr integration by LICOM2_imp are carried out using different bathymetries: Exp IMPV0 with the artificial island (88°–90°N) and IMPV1 with only the single pole. The focus of this paper is on the Arctic circulation. Exp IMPV1 gives a more reasonable distribution of salinity and temperature in the Arctic Ocean, a more accurate location of the center of the Beaufort Gyre, and a better net volume flux of the transpolar drift. With more realistic bathymetry in the Arctic Ocean, the biases of net volume fluxes across the Fram Strait, Barents Sea Opening, and Barents Sea Exit are reduced from 1.71 to 1.56, from 0.23 to 0.10, and from 0.71 to 0.45 Sv (1 Sv ≡ 106 m3 s−1), respectively, closer to the observations. The large biases of the net volume fluxes at the Fram Strait in both experiments may be attributed to the closed Nares Strait and other straits/channels in the Canadian Arctic Archipelago.
Patent ductus arteriosus in preterm infants: Benefits of early surgical closure
Authors: Fonseca Elizabeth , Georgiev Stanimir G , Gorenflo Matthias , Loukanov Tsvetomir S 
Published: November 2013

Background Patent ductus arteriosus in preterm neonates leads to significant morbidity. Surgery is indicated when pharmacological treatment fails or is contraindicated, but the optimal timing remains unclear. Methods We retrospectively studied all 41 preterm neonates with symptomatic ductus arteriosus who underwent ligation between 1988 and 2009. We compared early complications rates and late neurological outcomes of patients operated on before 21 days of age with these operated on later. Results The median gestational age at birth was 26 weeks (range 23–31 weeks) and median weight at birth was 930 g (range 510–1500 g); 34 (82.9%) received pharmacological treatment before surgery. Fourteen (34.1%) patients underwent surgical closure before 21 days of age and 27 (65.9%) after 21 days. The 2 groups did not differ significantly in gestational age and weight at birth, but those operated on after 21 days received significantly more pharmacological treatment cycles. Patients in the early closure group had shorter intubation times: median 23 days (range 13–35 days) vs. 43 days (range 27–84 days; p < 0.001) and shorter neonatal intensive care unit stay: median 44 days (range 31–66 days) vs. 76 days (range 41–97 days; p < 0.001), with significantly lower rates of bronchopulmonary dysplasia, intraventricular hemorrhage, and acute renal failure, and significantly better neurological outcomes. Discussion Performing early ligation of symptomatic ductus arteriosus after unsuccessful pharmacological therapy in preterm neonates might lower complication rates and improve neurological outcome. Prospective randomized studies are needed to determine the optimal treatment.
Surgical outcome of Fontan conversion and arrhythmia surgery: Need a pacemaker?
Authors: Terada Takafumi , Sakurai Hajime , Nonaka Toshimichi , Sakurai Takahisa , Sugiura Junya , Taneichi Tetsuyoshi , Ohtsuka Ryohei 
Published: November 2013

Background Atrial tachyarrhythmias are frequent complications in the late period after the Fontan procedure, and important risk factors for a poor prognosis. The impact of Fontan conversion and arrhythmia surgery in failed Fontan patients has been described in many reports. Objective We evaluated our experience with Fontan conversion procedures, concomitant arrhythmia surgery, and pacemaker implantation. Methods We reviewed the hospital records of 25 consecutive patients who underwent a Fontan conversion procedure from January 2004 to March 2012. Twenty-four patients had arrhythmia surgery using cryoablation and radiofrequency ablation at the time of conversion. A bilateral atrial maze procedure was performed in 6 patients, right-side maze in 15, and isthmus block in 3. Three patients with a diagnosis of corrected transposition of the great arteries underwent simultaneous pacemaker implantation electively. Results There was no early death and one late death during a mean follow-up period of 21.2 months. Three tachyarrhythmia recurrences developed, and there were 4 occurrences of sinus bradycardia. Five of these patients required postoperative pacemaker implantation. Conclusion The mid-term results of Fontan conversion and arrhythmia surgery in our institute were satisfactory. The occurrence of unexpected postoperative pacemaker requirement was high in the patients who underwent a right atrial or bilateral atrial maze procedure. Pacemaker or lead implantation is recommended for patients planned to undergo a right-side or full maze procedure.
Protective effects of onion (Allium cepa) extract against doxorubicin-induced hepatotoxicity in rats
Authors: Mete Rafet , Oran Mustafa , Topcu Birol , Oznur Meltem , Seber Erdogan Selcuk , Gedikbasi Asuman , Yetisyigit Tarkan 
Published: November 2013

Background/aim: Doxorubicin (DOX) is a widely used and potent chemotherapeutic agent. However, serious dose-limiting toxicity through generation of free oxygen radicals is a commonly encountered clinical problem. The aim of the current study was to assess the protective role of onion ( Allium cepa) extract (ACE) against DOX-induced hepatotoxicity in rats. Method: A total of 24 rats were randomly divided into 3 equal experimental groups: (1) DOX; (2) ACE + DOX; and (3) control groups. ACE was given orally as 1 mL of fresh ACE juice for 14 consecutive days followed by DOX injection. DOX was injected intraperitoneally in a single dose of 30 mg/kg body weight to induce hepatotoxicity, and the rats were killed after 48 h from injection. Control group was given saline only. Results: In the ACE pretreated group (ACE + DOX), serum aspartate transaminase, alanine transaminase, and tissue malondialdehyde and glutathione levels were significantly lower, while superoxide dismutase and glutathione peroxidase were higher compared with the DOX group. The histopathological examination of liver specimens revealed parenchymal necrosis, proliferation of biliary duct in DOX group; while ACE pretreatment provided marked reduction in these changes. Conclusion: Our study indicates that pretreatment with ACE protects against DOX-induced hepatotoxicity due to the antioxidant properties of ACE. Further studies on efficacy of antioxidant treatment by ACE in DOX-mediated toxicity and underlying mechanisms would provide a better explanation.
Adolescents’ Needs for Nurses’ Support When Initiating Breastfeeding
Authors: Pentecost Ryoko , Grassley Jane S. 
Published: November 2013

Background: Increasing the number of infants who are breastfed has become a worldwide health priority because of the extensively documented health and economic benefits of breastfeeding for mothers and their children. It is unfortunate that adolescents initiate and continue breastfeeding at rates lower than adult women. Health care providers can improve these breastfeeding rates through the social support they offer adolescent mothers as they initiate breastfeeding. Objective: The purpose of this study was to explore the needs of adolescents for social support from nurses when initiating breastfeeding. Methods: Secondary qualitative content analysis of 90 adolescents’ responses to 2 open-ended questions was conducted using social support theory as a framework. The 2 researchers independently categorized each response as informational, instrumental, emotional, and/or appraisal social support. Results: Adolescent mothers wanted nurses to take the time to explain breastfeeding, answer their questions, and provide consistent information that supported their informational needs. Emotional needs were met as the nurse provided for the adolescents’ privacy, treated them with respect, and stayed calm. Nurses met adolescents’ appraisal support needs through praise and encouragement. Participants valued instrumental support that included being given opportunities to work out breastfeeding under a nurse’s guidance. Conclusion: Adolescents needed a combination of informational, instrumental, emotional, and appraisal support. Adolescent mothers appreciate and value nurses who take the time to dialogue with them about breastfeeding.
In vivo evaluation of brain damage in the course of systemic lupus erythematosus using magnetic resonance spectroscopy, perfusion-weighted and diffusion-tensor imaging
Authors: Zimny A , Szmyrka-Kaczmarek M , Szewczyk P , Bladowska J , Pokryszko-Dragan A , Gruszka E , Wiland P , Sasiadek M 
Published: November 2013

Twenty-two neuropsychiatric (NPSLE) and 13 systemic lupus erythematosus (SLE) patients with a normal appearing brain on plain magnetic resonance (MR) as well as 20 age-matched healthy controls underwent MR spectroscopy (MRS), perfusion-weighted (PWI) and diffusion-tensor imaging (DTI). In MRS NAA/Cr, Cho/Cr and mI/Cr ratios were calculated from the posterior cingulate cortex and left parietal white matter. In PWI, values of cerebral blood volume (CBV) were assessed from 14 regions, including gray and white matter. In DTI fractional anisotropy (FA) values were obtained from 14 white matter tracts including projection, commissural and association fibers. All MR measurements were correlated with clinical data. SLE and NPSLE patients showed significantly ( p < 0.05) lower NAA/Cr ratios within both evaluated regions and FA values within the cingulum, as well as a tendency to cortical hypoperfusion. Compared to SLE, NPSLE subjects revealed lower FA values within a wide range of association fibers and corpus callosum. Advanced MR techniques are capable of in vivo detection of complex microstructural brain damage in SLE and NPSLE subjects regarding neuronal loss, mild hypoperfusion and white matter disintegrity. MRS and DTI seem to show the highest usefulness in depicting early changes in normal appearing gray and white matter in SLE patients.