bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes after major or bidirectional ABO‐mismatched allogeneic hematopoietic progenitor cell transplantation after pretransplant isoagglutinin reduction with donor‐type secretor plasma with or without plasma exchange
Authors: Curley Cameron , Pillai Elango , Mudie Kari , Western Robyn , Hutchins Cheryl , Durrant Simon , Kennedy Glen A. 
Published: August 2011

BACKGROUND: Major ABO mismatch in hematopoietic progenitor cell transplantation (HPCT) is associated with a range of immunohematologic consequences including progenitor cell infusion (PCI)‐related hemolysis, delayed red blood cell engraftment, and pure red cell aplasia (PRCA). Although pretransplant (recipient) isoagglutinin reduction may be associated with decreased immunohematologic complications in this setting, there is no consensus with respect to strategies for isoagglutinin reduction.STUDY DESIGN AND METHODS: This observational study assessed the efficacy of a standardized pretransplant isoagglutinin reduction strategy incorporating donor‐type secretor plasma infusions with or without plasma exchange to prevent PCI‐associated hemolysis and PRCA in major or bidirectional ABO‐mismatched peripheral blood HPCT. All major or bidirectional ABO‐mismatched HPCTs performed between 1999 and 2010 were identified from an institutional database. Immunohematologic outcomes were determined retrospectively by review of individual medical records.RESULTS: In total 110 major or bidirectional ABO‐mismatched HPCTs had been performed. No patient developed hemolysis after PCI. With respect to PRCA incidence, 16 patients (15%) were excluded due to early mortality and three (3%) due to incomplete data; of the remaining 91 patients, five (5%) developed PRCA. Patients with PRCA had significantly higher pretransplant isoagglutinin titers (p = 0.0001) compared to those who did not develop PRCA.CONCLUSIONS: Use of a standardized pretransplant isoagglutinin reduction strategy including donor‐type secretor plasma infusions is both safe and efficient in preventing PCI‐associated hemolysis and is associated with low rates of posttransplant PRCA.
Phase Transitions, Magnetic and Piezoelectric Properties of Rare‐Earth‐Substituted BiFeO3 Ceramics
Authors: Troyanchuk Igor O. , Karpinsky Dmitry V. , Bushinsky Maxim V. , Mantytskaya Olga S. , Tereshko Nina V. , Shut Victor N. 
Published: August 2011

The concentration range of the stability of polar (R3c) and antipolar phases in the Bi1−xRExFeO3 (RE–La ‐ Dy) solid solutions has been determined by X‐ray study of the polycrystalline samples. Both polar and antipolar phases become less stable with a decrease of the rare earth ionic radii. It is stimulated by a reduction of the rare‐earth ions polarizability with a decrease in ionic radii. The antipolar phase is characterized by a weak ferromagnetic state, whereas the polar one exhibits dominantly antiferromagnetic behavior near the polar‐antipolar morphotropic boundary. The local piezoelectric response decreases with increase in antipolar phase content in the mixed polar‐antipolar structural state. It is suggested that the piezoelectric activity is associated with polar (R3c) phase.
Temporal changes in salivary glands of non‐obese diabetic mice as a model for Sjögren’s syndrome
Authors: Roescher N , Lodde BM , Vosters JL , Tak PP , Catalan MA , Illei GG , Chiorini JA 
Published: August 2011

Oral Diseases (2011) 18, 96–106Objective:  Non‐obese diabetic (NOD) mice develop an autoimmune exocrinopathy that shows similarities with Sjögren’s syndrome. They provide an experimental model to study the pathoetiogenesis of this disease.Materials and Methods:  Salivary gland (SG) function and salivary sodium content were measured in 8‐, 12‐, 16‐ and 20‐week‐old NOD and age‐matched CB6 mice. In NOD mice, SG expression of phenotypic cell markers, B cell‐stimulating and costimulatory molecules were evaluated. Cytokine levels were measured in serum and SG homogenates.Results:  Microscopically evident SG inflammation in NOD mice was preceded by expression of intercellular adhesion molecule 1 on epithelial cells in the presence of macrophages and relatively high levels of cytokines. Next, an influx consisting of mainly T, B, natural killer, plasma and dendritic cells was seen. Most cytokines, except for interleukin (IL)12/IL23p40 and B cell‐activating factor, decreased or remained stable over time, while glandular function deteriorated from 16 weeks of age onward compared with CB6 mice.Conclusion:  Sjögren’s syndrome‐like disease in NOD mice occurs in multiple stages; immunological and physiological abnormalities can be detected before focal inflammation appears and salivary output declines. Extrapolating this knowledge to human subjects could help in understanding the pathogenesis and aid the identification of potential therapeutic targets.
Genetic evaluation of the longevity of the Holstein population in Japan using a Weibull proportional hazard model
Authors: SASAKI Osamu , AIHARA Mitsuo , HAGIYA Koichi , NISHIURA Akiko , ISHII Kazuo , SATOH Masahiro 
Published: August 2011

ABSTRACTThe objective of this study was to confirm the stability of the genetic estimation of longevity of the Holstein population in Japan. Data on the first 10 lactation periods were obtained from the Livestock Improvement Association of Japan. Longevity was defined as the number of days from first calving until culling or censoring. DATA1 and DATA2 included the survival records for the periods 1991–2003 and 1991–2005, respectively. The proportional hazard model included the effects of the region‐parity‐lactation stage‐milk yield class, age at first calving, the herd–year–season, and sire. The heritabilities on an original scale of DATA1 and DATA2 were 0.119 and 0.123, respectively. The estimated transmitting abilities (ETAs) of young sires in DATA1 may have been underestimated, but coefficient δ, which indicated the bias of genetic trend between DATA1 and DATA2, was not significant. The regression coefficient of ETAs between DATA1 and DATA2 was very close to 1. The proportional hazard model could steadily estimate the ETA for longevity of the sires in Japan.
Assessment of Global and Regional Left Ventricular Volume and Shape by Real‐Time 3‐Dimensional Echocardiography in Dogs with Myxomatous Mitral Valve Disease
Authors: Ljungvall I. , Höglund K. , Carnabuci C. , Tidholm A. , Häggström J. 
Published: August 2011

Background:Left ventricular (LV) remodeling occurs in response to chronic volume overload. Real‐time 3‐dimensional (RT3D) echocardiography offers new modalities for LV assessment.Objective:To investigate LV changes in shape and volume in response to different severities of naturally acquired myxomatous mitral valve disease (MMVD) in dogs by RT3D echocardiography.Animals:Sixty‐five client‐owned dogs.Methods:Prospectively recruited dogs were classified by standard echocardiography into healthy, mild, moderate, and severe MMVD groups. Endocardial border tracking of LV RT3D dataset was performed, from which global and regional (automatically acquired basal, mid, and apical segments based on LV long‐axis length) end‐diastolic (EDV) and end‐systolic volumes (ESV), LV long‐axis length, and sphericity index were obtained.Results:Global and regional EDV and ESV (indexed to body weight) were most prominently increased in dogs with severe MMVD. All 3 regional LV segments contributed to increased global EDV and ESV with increasing MMVD severity, but mid‐EDV contributed the most to the global EDV increase. Furthermore, LV long‐axis length and LV sphericity index increased with increasing MMVD severity. Basal and apical EDV segments displayed the strongest association with sphericity index (P< .0001).Conclusions and Clinical Importance:The most prominent LV volume expansion was found in dogs with severe MMVD. Increased EDV, primarily in the mid‐segment, leads to rounding of LV apical and basal segments in response to increasing MMVD severity. Assessment of LV volume and shape potentially could allow early detection of dogs at risk for rapid progression into congestive heart failure.
Regional Industrial Structure Concentration in the United States: Trends and Implications
Authors: Drucker Joshua 
Published: August 2011

abstractIn a seminal article, Chinitz (1961) considered the effects of industry size, structure, and economic diversification on the performance of firms and regional economies. His inquiry suggested a related but conceptually distinct issue: how does the extent to which a regional industry or industrial sector is concentrated in a small number of firms affect the local performance of that industry? The question has not been addressed systematically in empirical research other than case studies, principally because accurately measuring regional concentration requires firm‐level information. This exploratory study uses confidential plant‐level data to gauge concentration in manufacturing industries at the regional scale across the continental United States, to explore changes over time in geographic patterns of concentration, and to investigate associations between regional industrial structure concentration and changes in employment. The implications for understanding the impacts of regional industrial structure on economic development processes are discussed.
Identification of Protein-Protein Interaction Inhibitors Targeting Vaccinia Virus Processivity Factor for Development of Antiviral Agents
Authors: Schormann Norbert , Sommers Charnell Inglis , Prichard Mark N. , Keith Kathy A. , Noah James W. , Nuth Manunya , Ricciardi Robert P. , Chattopadhyay Debasish 
Published: August 2011

ABSTRACTPoxvirus uracil DNA glycosylase D4 in association with A20 and the catalytic subunit of DNA polymerase forms the processive polymerase complex. The binding of D4 and A20 is essential for processive polymerase activity. Using an AlphaScreen assay, we identified compounds that inhibit protein-protein interactions between D4 and A20. Effective interaction inhibitors exhibited both antiviral activity and binding to D4. These results suggest that novel antiviral agents that target the protein-protein interactions between D4 and A20 can be developed for the treatment of infections with poxviruses, including smallpox.
Clofazimine Analogs with Efficacy against Experimental Tuberculosis and Reduced Potential for Accumulation
Authors: Lu Yu , Zheng Meiqin , Wang Bin , Fu Lei , Zhao Weijie , Li Peng , Xu Jian , Zhu Hui , Jin Haixia , Yin Dali , Huang Haihong , Upton Anna M. , Ma Zhenkun 
Published: August 2011

ABSTRACT

The global tuberculosis crisis urgently demands new, efficacious, orally available drugs with the potential to shorten and simplify the long and complex treatments for drug-sensitive and drug-resistant disease. Clofazimine, a riminophenazine used for many years to treat leprosy, demonstrates efficacy in animal models of tuberculosis via a novel mode of action. However, clofazimine's physicochemical and pharmacokinetic properties contribute to side effects that limit its use; in particular, an extremely long half-life and propensity for tissue accumulation together with clofazimine's dye properties leads to unwelcome skin discoloration. We recently conducted a systematic structure-activity study of more than 500 riminophenazine analogs for anti-
Mycobacterium tuberculosis
activity. We describe here the characteristics of 12 prioritized compounds in more detail. The new riminophenazine analogs demonstrated enhanced
in vitro
activity compared to clofazimine against replicating
M. tuberculosis
H37Rv, as well as panels of drug-sensitive and drug-resistant clinical isolates. The new compounds demonstrate at least equivalent activity compared to clofazimine against intracellular
M. tuberculosis
and, in addition, most of them were active against nonreplicating
M. tuberculosis
. Eleven of these more water-soluble riminophenazine analogs possess shorter half-lives than clofazimine when dosed orally to mice, suggesting that they may accumulate less. Most importantly, the nine compounds that progressed to efficacy testing demonstrated inhibition of bacterial growth in the lungs that is superior to the activity of an equivalent dose of clofazimine when administered orally for 20 days in a murine model of acute tuberculosis. The efficacy of these compounds, along with their decreased potential for accumulation and therefore perhaps also for tissue discoloration, warrants further study.
Enhancement of Carboplatin-Mediated Lung Cancer Cell Killing by Simultaneous Disruption of Glutathione and Thioredoxin Metabolism
Authors: Fath Melissa A. , Ahmad Iman M. , Smith Carmen J. , Spence Jacquelyn , Spitz Douglas R. 
Published: August 2011

Abstract
Purpose: Cancer cells (relative to normal cells) show increased steady-state levels of hydroperoxides that are compensated by increased glucose and hydroperoxide metabolism. The current study determined whether inhibitors of glucose and hydroperoxide metabolism could induce chemoradiosensitization by enhancing oxidative stress in lung cancer cells.
Experimental Design: A549 and NCI-H292 human lung carcinoma cells were treated with 2-deoxy-d-glucose (2DG) combined with carboplatin + ionizing radiation (IR). Lung cancer cells were further sensitized with inhibitors of glutathione (GSH)- and thioredoxin (Trx)-dependent metabolism [buthionine sulfoximine (BSO) and auranofin, respectively] in vitro and in vivo.
Results: When 2DG was combined with carboplatin + IR, clonogenic cell killing was enhanced in A549 and NCI-H292 cells, and this combination was more effective than paclitaxel + carboplatin + IR. The thiol antioxidant (N-acetylcysteine, NAC) was capable of protecting cancer cells from 2DG + carboplatin -induced cell killing. Simultaneous treatment of cancer cells with BSO and auranofin, at doses that were not toxic as single agents, also enhanced lung cancer cell killing and sensitivity to 2DG + carboplatin. This treatment combination also increased oxidation of both GSH and Trx, which were inhibited by NAC. Mice treated with auranofin + BSO showed no alterations in circulating leukocytes or red blood cells. Xenograft lung tumor growth in mice was more effectively inhibited by treatment with auranofin + BSO + carboplatin than animals treated with carboplatin or auranofin + BSO alone.
Conclusions: These results show in vitro and in vivo that simultaneous inhibition of GSH and Trx metabolism can effectively inhibit lung cancer cell growth and induce chemosensitization by a mechanism that involves thiol-mediated oxidative stress. Clin Cancer Res; 17(19); 6206–17. ©2011 AACR.
mTOR Inhibition, the Second Generation: ATP-Competitive mTOR Inhibitor Initiates Unexpected Receptor Tyrosine Kinase–Driven Feedback Loop
Authors: Keniry Megan , Parsons Ramon 
Published: August 2011

Abstract
mTOR inhibition with the ATP-competitive kinase inhibitor AZD8055 induces receptor tyrosine kinase–dependent feedback activation of AKT. Cancer Discovery; 1(3); 203–4. © 2011 AACR.
Commentary on Rodrik-Outmezguine et al., p. 248.
Recurrent Postural Vasovagal Syncope
Authors: Vaddadi Gautam , Guo Ling , Esler Murray , Socratous Florentia , Schlaich Markus , Chopra Reena , Eikelis Nina , Lambert Gavin , Trauer Thomas , Lambert Elisabeth 
Published: August 2011

Background—
The pathophysiology of vasovagal syncope is poorly understood, and the treatment usually ineffective. Our clinical experience is that patients with vasovagal syncope fall into 2 groups, based on their supine systolic blood pressure, which is either normal (>100 mm Hg) or low (70–100 mm Hg). We investigated neural circulatory control in these 2 phenotypes.

Methods and Results—

Sympathetic nervous testing was at 3 levels: electric, measuring sympathetic nerve firing (microneurography); neurochemical, quantifying norepinephrine spillover to plasma; and cellular, with Western blot analysis of sympathetic nerve proteins. Testing was done during head-up tilt (HUT), simulating the gravitational stress of standing, in 18 healthy control subjects and 36 patients with vasovagal syncope, 15 with the low blood pressure phenotype and 21 with normal blood pressure. Microneurography and norepinephrine spillover increased significantly during HUT in healthy subjects. The microneurography response during HUT was normal in normal blood pressure and accentuated in low blood pressure phenotype (
P
=0.05). Norepinephrine spillover response was paradoxically subnormal during HUT in both patient groups (
P
=0.001), who thus exhibited disjunction between nerve firing and neurotransmitter release; this lowered norepinephrine availability, impairing the neural circulatory response. Subnormal norepinephrine spillover in low blood pressure phenotype was linked to low tyrosine hydroxylase (43.7% normal,
P
=0.001), rate-limiting in norepinephrine synthesis, and in normal blood pressure to increased levels of the norepinephrine transporter (135% normal,
P
=0.019), augmenting transmitter reuptake.

Conclusions—
Patients with recurrent vasovagal syncope, when phenotyped into 2 clinical groups based on their supine blood pressure, show unique sympathetic nervous system abnormalities. It is predicted that future therapy targeting the specific mechanisms identified in the present report should translate into more effective treatment.
n-3 Polyunsaturated Fatty Acids in the Prevention of Atrial Fibrillation Recurrences After Electrical Cardioversion
Authors: Nodari Savina , Triggiani Marco , Campia Umberto , Manerba Alessandra , Milesi Giuseppe , Cesana Bruno M. , Gheorghiade Mihai , Dei Cas Livio 
Published: August 2011

Background—
n-3 polyunsaturated fatty acids (n-3 PUFAs) exert antiarrhythmic effects and reduce sudden cardiac death. However, their role in the prevention of atrial fibrillation remains controversial. We aimed to determine the effect of n-3 PUFAs in addition to amiodarone and a renin-angiotensin-aldosterone system inhibitor on the maintenance of sinus rhythm after direct current cardioversion in patients with persistent atrial fibrillation.

Methods and Results—

We conducted a randomized, double-blind, placebo-controlled, parallel-arm trial in patients with persistent atrial fibrillation, with at least 1 relapse after cardioversion, and treated with amiodarone and a renin-angiotensin-aldosterone system inhibitor. Participants were assigned to placebo or n-3 PUFAs 2 g/d and then underwent direct current cardioversion 4 weeks later. The primary end point was the probability of maintenance of sinus rhythm at 1 year after cardioversion. Of 254 screened patients, 199 were found to be eligible and randomized. At the 1-year follow up, the probability of maintenance of sinus rhythm was significantly higher in the n-3 PUFAs–treated patients compared with the placebo group (hazard ratio, 0.62 [95% confidence interval, 0.52 to 0.72] and 0.36 [95% confidence interval, 0.26 to 0.46], respectively;
P
=0.0001).

Conclusions—
In patients with persistent atrial fibrillation on amiodarone and a renin-angiotensin-aldosterone system inhibitor, the addition of n-3 PUFAs 2 g/d improves the probability of the maintenance of sinus rhythm after direct current cardioversion. Our data suggest that n-3 PUFAs may exert beneficial effects in the prevention of atrial fibrillation recurrence. Further studies are needed to confirm and expand our findings.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01198275.
Diabetes Mellitus Worsens Diastolic Left Ventricular Dysfunction in Aortic Stenosis Through Altered Myocardial Structure and Cardiomyocyte Stiffness
Authors: Falcão-Pires Inês , Hamdani Nazha , Borbély Attila , Gavina Cristina , Schalkwijk Casper G. , van der Velden Jolanda , van Heerebeek Loek , Stienen Ger J.M. , Niessen Hans W.M. , Leite-Moreira Adelino F. , Paulus Walter J. 
Published: August 2011

Background—
Aortic stenosis (AS) and diabetes mellitus (DM) are frequent comorbidities in aging populations. In heart failure, DM worsens diastolic left ventricular (LV) dysfunction, thereby adversely affecting symptoms and prognosis. Effects of DM on diastolic LV function were therefore assessed in aortic stenosis, and underlying myocardial mechanisms were identified.

Methods and Results—

Patients referred for aortic valve replacement were subdivided into patients with AS and no DM (AS; n=46) and patients with AS and DM (AS-DM; n=16). Preoperative Doppler echocardiography and hemodynamics were implemented with perioperative LV biopsies. Histomorphometry and immunohistochemistry quantified myocardial collagen volume fraction and myocardial advanced glycation end product deposition. Isolated cardiomyocytes were stretched to 2.2-μm sarcomere length to measure resting tension (F
passive
). Expression and phosphorylation of titin isoforms were analyzed with gel electrophoresis with ProQ Diamond and SYPRO Ruby stains. Reduced LV end-diastolic distensibility in AS-DM was evident from higher LV end-diastolic pressure (21±1 mm Hg for AS versus 28±4 mm Hg for AS-DM;
P
=0.04) at comparable LV end-diastolic volume index and attributed to higher myocardial collagen volume fraction (AS, 12.9±1.1% versus AS-DM, 18.2±2.6%;
P
<0.001), more advanced glycation end product deposition in arterioles, venules, and capillaries (AS, 14.4±2.1 score per 1 mm
2
versus AS-DM, 31.4±6.1 score per 1 mm
2
;
P
=0.03), and higher F
passive
(AS, 3.5±1.7 kN/m
2
versus AS-DM, 5.1±0.7 kN/m
2
;
P
=0.04). Significant hypophosphorylation of the stiff N2B titin isoform in AS-DM explained the higher F
passive
and normalization of F
passive
after in vitro treatment with protein kinase A.

Conclusions—

Worse diastolic LV dysfunction in AS-DM predisposes to heart failure and results from more myocardial fibrosis, more intramyocardial vascular advanced glycation end product deposition, and higher cardiomyocyte F
passive
, which was related to hypophosphorylation of the N2B titin isoform.
Quality of life assessment as a predictor of survival in non-small cell lung cancer
Authors: Braun Donald P , Gupta Digant , Staren Edgar D 
Published: August 2011

Abstract

Background
There are conflicting and inconsistent results in the literature on the prognostic role of quality of life (QoL) in cancer. We investigated whether QoL at admission could predict survival in lung cancer patients.

Methods
The study population consisted of 1194 non-small cell lung cancer patients treated at our institution between Jan 2001 and Dec 2008. QoL was evaluated using EORTC-QLQ-C30 prior to initiation of treatment. Patient survival was defined as the time interval between the date of first patient visit and the date of death from any cause/date of last contact. Univariate and multivariate Cox regression evaluated the prognostic significance of QoL.

Results
Mean age at presentation was 58.3 years. There were 605 newly diagnosed and 589 previously treated patients; 601 males and 593 females. Stage of disease at diagnosis was I, 100; II, 63; III, 348; IV, 656; and 27 indeterminate. Upon multivariate analyses, global QoL as well as physical function predicted patient survival in the entire study population. Every 10-point increase in physical function was associated with a 10% increase in survival (95% CI = 6% to 14%, p < 0.001). Similarly, every 10-point increase in global QoL was associated with a 9% increase in survival (95% CI = 6% to 11%, p < 0.001). Furthermore, physical function, nausea/vomiting, insomnia, and diarrhea (p < 0.05 for all) in newly diagnosed patients, but only physical function (p < 0.001) in previously treated patients were predictive of survival.

Conclusions
Baseline global QoL and physical function provide useful prognostic information in non-small cell lung cancer patients.