bluuebunny/crossref_metadata_2025_split huggingface dataset:
IPH2101, a novel anti-inhibitory KIR antibody, and lenalidomide combine to enhance the natural killer cell versus multiple myeloma effect
Authors: Benson Don M. , Bakan Courtney E. , Zhang Shuhong , Collins Shauna M. , Liang Jing , Srivastava Shivani , Hofmeister Craig C. , Efebera Yvonne , Andre Pascale , Romagne Francois , Bléry Mathieu , Bonnafous Cécile , Zhang Jianying , Clever David , Caligiuri Michael A. , Farag Sherif S. 
Published: October 2011

Abstract
Multiple myeloma (MM) patients who receive killer cell Ig–like receptor (KIR) ligand–mismatched, T cell–depleted, allogeneic transplantation may have a reduced risk of relapse compared with patients who receive KIR ligand–matched grafts, suggesting the importance of this signaling axis in the natural killer (NK) cell-versus-MM effect. Expanding on this concept, IPH2101 (1-7F9), an anti-inhibitory KIR mAb, enhances NK-cell function against autologous MM cells by blocking the engagement of inhibitory KIR with cognate ligands, promoting immune complex formation and NK-cell cytotoxicity specifically against MM cell targets but not normal cells. IPH2101 prevents negative regulatory signals by inhibitory KIR, whereas lenalidomide augments NK-cell function and also appears to up-regulate ligands for activating NK-cell receptors on MM cells. Lenalidomide and a murine anti-inhibitory NK-cell receptor Ab mediate in vivo rejection of a lenalidomide-resistant tumor. These mechanistic, preclinical data support the use of a combination of IPH2101 and lenalidomide in a phase 2 trial for MM.
The transhepatic endotoxin gradient is present despite liver cirrhosis and is attenuated after transjugular portosystemic shunt (TIPS).
Authors: Benten Daniel , Wiesch Julian Schulze zur , Sydow Karsten , Koops Andreas , Buggisch Peter , Böger Rainer H , Gaydos Charlotte A , Won Helen , Franco Veronica , Lohse Ansgar W , Ray Stuart C , Balagopal Ashwin 
Published: October 2011

AbstractBackgroundTranslocation of gut-derived bacterial products such as endotoxin is a major problem in liver cirrhosis.MethodsTo assess the hepatic clearance of bacterial products in individuals with cirrhosis, we tested concentrations of Gram-negative bacterial lipopolysaccharide (LPS), LPS-binding protein (LBP), and the precursor of nitric oxide (NO), L-arginine, in a cohort of 8 stable patients with liver cirrhosis before and after elective transjugular portosystemic shunt (TIPS) implantation, including central venous, hepatic venous, and portal venous measurements.ResultsUsing an adapted LPS assay, we detected high portal venous LPS concentrations (mean 1743 ± 819 pg/mL). High concentrations of LPS were detectable in the central venous blood (931 ± 551 pg/mL), as expected in persons with cirrhosis. The transhepatic LPS gradient was found to be 438 ± 287 pg/mL, and 25 ± 12% of portal LPS was cleared by the cirrhotic liver. After TIPS, central venous LPS concentrations increased in the hepatic and central veins, indicating shunting of LPS with the portal blood through the stent. This paralleled a systemic increase of L-arginine, whereas the NO synthase inhibitor asymmetric dimethylarginine (ADMA) remained unchanged, suggesting that bacterial translocation may contribute to the pathogenesis of circulatory dysfunction post-TIPS.ConclusionsThis study provides quantitative estimates of the role of the liver in the pathophysiology of bacterial translocation. The data indicate that the cirrhotic liver retains the capacity for clearance of bacterial endotoxin from the portal venous blood and that TIPS implantation attenuates this clearance. Thus, increased endotoxin concentrations in the systemic circulation provide a possible link to the increased encephalopathy in TIPS patients.
INSPIRE: A phase III study of the BLP25 liposome vaccine (L-BLP25) in Asian patients with unresectable stage III non-small cell lung cancer
Authors: Wu Yi-Long , Park Keunchil , Soo Ross A , Sun Yan , Tyroller Karin , Wages David , Ely Guy , Yang James Chih-Hsin , Mok Tony 
Published: October 2011

Abstract

Background
Previous research suggests the therapeutic cancer vaccine L-BLP25 potentially provides a survival benefit in patients with locally advanced unresectable stage III non-small cell lung carcinoma (NSCLC). These promising findings prompted the phase III study, INSPIRE, in patients of East-Asian ethnicity. East-Asian ethnicity is an independent favourable prognostic factor for survival in NSCLC. The favourable prognosis is most likely due to a higher incidence of EGFR mutations among this patient population.

Methods/design
The primary objective of the INSPIRE study is to assess the treatment effect of L-BLP25 plus best supportive care (BSC), as compared to placebo plus BSC, on overall survival time in East-Asian patients with unresectable stage III NSCLC and either documented stable disease or an objective response according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria following primary chemoradiotherapy. Those in the L-BLP25 arm will receive a single intravenous infusion of cyclophosphamide (300 mg/m2) 3 days before the first L-BLP25 vaccination, with a corresponding intravenous infusion of saline to be given in the control arm. A primary treatment phase of 8 subcutaneous vaccinations of L-BLP25 930 μg or placebo at weekly intervals will be followed by a maintenance treatment phase of 6-weekly vaccinations continued until disease progression or discontinuation from the study.

Discussion
The ongoing INSPIRE study is the first large study of a therapeutic cancer vaccine specifically in an East-Asian population. It evaluates the potential of maintenance therapy with L-BLP25 to prolong survival in East-Asian patients with stage III NSCLC where there are limited treatment options currently available.

Study number
EMR 63325-012

Trial Registration
Clinicaltrials.gov reference: NCT01015443
Multiple etiologies of axonal sensory motor polyneuropathy in a renal transplant recipient: a case report
Authors: Etemadi Jalal , Shoja Mohammadali M , Ghabili Kamyar , Talebi Mahnaz , Namdar Hossein , Mirnour Reshad 
Published: October 2011

AbstractIntroductionNeurological complications leading to morbidity and mortality are not frequent in renal transplant recipients. Here, we report a renal transplant recipient who presented with diminished strength in his limbs probably due to multiple etiologies of axonal sensorimotor polyneuropathy, which resolved with intravenous immunoglobulin.Case presentationA 49-year-old Iranian male renal transplant recipient with previous history of autosomal dominant polycystic kidney disease presented with diminished strength in his limbs one month after surgery. Our patient was on cyclosporine A, mycophenolate mofetil and prednisone. Although a detected hypophosphatemia was corrected with supplemental phosphate, the loss of strength was still slowly progressive and diffuse muscular atrophy was remarkable in his trunk, upper limb and pelvic girdle. Meanwhile, his cranial nerves were intact. Post-transplant diabetes mellitus was diagnosed and insulin therapy was initiated. In addition, as a high serum cyclosporine level was detected, the dose of cyclosporine was reduced. Our patient was also put on intravenous ganciclovir due to positive serum cytomegalovirus immunoglobulin M antibody. Despite the reduction of oral cyclosporine dose along with medical therapy for the cytomegalovirus infection and diabetes mellitus, his muscular weakness and atrophy did not improve. One week after administration of intravenous immunoglobulin, a significant improvement was noted in his muscular weakness.ConclusionA remarkable response to intravenous immunoglobulin is compatible with an immunological basis for the present condition (post-transplant polyneuropathy). In cases of post-transplant polyneuropathy with a high clinical suspicion of immunological origin, administration of intravenous immunoglobulin may be recommended.
Mid-Gestational Maternal Free Thyroxine Concentration and Offspring Neurocognitive Development at Age Two Years
Authors: Craig Wendy Y. , Allan Walter C. , Kloza Edward M. , Pulkkinen Andrea J. , Waisbren Susan , Spratt Daniel I. , Palomaki Glenn E. , Neveux Louis M. , Haddow James E. 
Published: October 2011

Context:
Lower neurocognitive development scores at age 2 yr have been reported in association with euthyroid hypothyroxinemia during early pregnancy.

Objective:
The objective of this study was to further explore this association with euthyroid hypothyroxinemia during early pregnancy.

Design:
This was an observational, nested case-control study.

Setting:
The study was conducted at physician offices and prenatal clinics throughout Maine.

Study Subjects:
Between May 2004 and March 2006, TSH was measured in 5734 women in conjunction with second-trimester Down syndrome screening. After completion of pregnancy, free T4 was measured in stored second-trimester sera from euthyroid women (TSH 0.1–3.5 mIU/ml; n = 5560). Women with free T4 at the third centile or less (n = 99) were matched with women whose free T4 was at the 10th to the 90th centile (n = 99).

Interventions:
There were no interventions.

Main Outcome Measure:
Bayley Scales of Infant Development (BSID III) were administered to the 198 offspring at age 2 yr. Scores for cognitive, language, and motor development were compared between matched pairs of offspring from the two groups before and after correcting for relevant variables.

Results:
Unadjusted BSID-III scores (cognitive, language, and motor) were lower by about 3% at age 2 yr among offspring of 98 hypothyroxinemic women (cases), reaching borderline significance for cognitive and motor scores. After adjustment for gestational age, the child's age at testing, maternal weight, and education, all differences diminished and became nonsignificant. Scores less than 85 were more frequent among case children but did not reach statistical significance (P = 0.14).

Conclusions:
Isolated hypothyroxinemia during the second trimester is not associated with significantly lower BSID-III scores at age 2 yr, compared with scores for offspring of matched euthyroxinemic women.
Long- and Medium-Chain Fatty Acids Induce Insulin Resistance to a Similar Extent in Humans Despite Marked Differences in Muscle Fat Accumulation
Authors: Hoeks Joris , Mensink Marco , Hesselink Matthijs K. C. , Ekroos Kim , Schrauwen Patrick 
Published: October 2011

Context:
Animal studies revealed that medium-chain fatty acids (MCFA), due to their metabolic characteristics, are not stored in skeletal muscle and may therefore not give rise to potentially hazardous lipid species impeding insulin signaling.

Objective:
We here hypothesized that infusion of medium-chain triacylglycerols (MCT) in healthy lean subjects does not lead to ectopic fat accumulation and hence does not result in lipid-induced insulin resistance.

Design and Methods:
Nine healthy lean male subjects underwent a 6-h hyperinsulinemic-euglycemic clamp with simultaneous infusion of 1) a 100% long-chain triacylglycerols (LCT) emulsion, 2) a 50/50% MCT/LCT emulsion, or 3) glycerol in a randomized crossover design. Muscle biopsies were taken before and after each clamp.

Results:
MCT/LCT infusion raised plasma free fatty acid levels to a similar level compared with LCT infusion alone. Despite elevated free fatty acid levels, intramyocellular triacylglycerol (IMTG) levels were not affected by the MCT/LCT emulsion, whereas LCT infusion resulted in an approximately 1.6-fold increase in IMTG. These differences in muscle fat accumulation did not result in significant differences in lipid-induced insulin resistance between LCT (−28%, P = 0.003) and MCT/LCT (−20%, P &lt; 0.001). Total skeletal muscle ceramide content as well as lactosyl- and glucosylceramide levels were not affected by any of the interventions. In addition, the distribution pattern of all ceramide species remained unaltered.

Conclusions:
Although we confirm that MCFA do not lead to ceramide and IMTG accumulation in skeletal muscle tissue in humans, they do induce insulin resistance. These results indicate that, in humans, MCFA may not be beneficial in preventing peripheral insulin resistance.
Craniopharyngiomas Express Embryonic Stem Cell Markers (SOX2, OCT4, KLF4, and SOX9) as Pituitary Stem Cells but Do Not Coexpress RET/GFRA3 Receptors
Authors: Garcia-Lavandeira Montserrat , Saez Carmen , Diaz-Rodriguez Esther , Perez-Romero Sihara , Senra Ana , Dieguez Carlos , Japon Miguel A. , Alvarez Clara V. 
Published: October 2011

Context:
Adult stem cells maintain some markers expressed by embryonic stem cells and express other specific markers depending on the organ where they reside. Recently, stem/progenitor cells in the rodent and human pituitary have been characterized as expressing GFRA2/RET, PROP1, and stem cell markers such as SOX2 and OCT4 (GPS cells).

Objective:
Our objective was to detect other specific markers of the pituitary stem cells and to investigate whether craniopharyngiomas (CRF), a tumor potentially derived from Rathke's pouch remnants, express similar markers as normal pituitary stem cells.

Design:
We conducted mRNA and Western blot studies in pituitary extracts, and immunohistochemistry and immunofluorescence on sections from normal rat and human pituitaries and 20 CRF (18 adamantinomatous and two papillary).

Results:
Normal pituitary GPS stem cells localized in the marginal zone (MZ) express three key embryonic stem cell markers, SOX2, OCT4, and KLF4, in addition to SOX9 and PROP1 and β-catenin overexpression. They express the RET receptor and its GFRA2 coreceptor but also express the coreceptor GFRA3 that could be detected in the MZ of paraffin pituitary sections. CRF maintain the expression of SOX2, OCT4, KLF4, SOX9, and β-catenin. However, RET and GFRA3 expression was altered in CRF. In 25% (five of 20), both RET and GFRA3 were detected but not colocalized in the same cells. The other 75% (15 of 20) lose the expression of RET, GFRA3, or both proteins simultaneously.

Conclusions:
Human pituitary adult stem/progenitor cells (GPS) located in the MZ are characterized by expression of embryonic stem cell markers SOX2, OCT4, and KLF4 plus the specific pituitary embryonic factor PROP1 and the RET system. Redundancy in RET coreceptor expression (GFRA2 and GFRA3) suggest an important systematic function in their physiological behavior. CRF share the stem cell markers suggesting a common origin with GPS. However, the lack of expression of the RET/GFRA system could be related to the cell mislocation and deregulated growth of CRF.
A Study of Image Reconstruction for Complex Targets Buried in a Slab Medium Using the Unrelated Illumination Method
Authors: Chiu Chien-Ching , Li Ching-Lieh , Wu Chih-Yuan , Jen Lin Chun 
Published: October 2011

Abstract
This paper investigates the image reconstruction for inhomogeneous dielectric cylinders coated on a conductor with a known cross section buried in a stratified dielectric medium. The buried dielectric cylinder scatters a group of unrelated incident waves illuminated from outside. The scattered field is recorded outside the stratified dielectric medium. By the proper arrangement of a group of unrelated incident fields, the difficulties of ill-posedness and nonlinearity are circumvented, and the permittivity distribution can be reconstructed through simple matrix operations. In the direct scattering part, a set of nonlinear integral equations is deduced mainly based on the boundary conditions. The method of moments is applied to numerically calculate the scattered E field. For the inverse scattering part, the unrelated illumination method is employed to determine the electrical properties of the dielectric cylinder from the measured scattered E fields. The numerical results show that good reconstruction can be obtained both with and without Gaussian noise in measured data.
Study of density of interface states in MOS structure with ultrathin NAOS oxide
Authors: Jurečka Stanislav , Kobayashi Hikaru , Kim Woo-Byoung , Takahashi Masao , Pinčík Emil 
Published: October 2011

Abstract
The quality of the interface region in a semiconductor device and the density of interface states (DOS) play important roles and become critical for the quality of the whole device containing ultrathin oxide films. In the present study the metal-oxide-semiconductor (MOS) structures with ultrathin SiO2 layer were prepared on Si(100) substrates by using a low temperature nitric acid oxidation of silicon (NAOS) method. Carrier confinement in the structure produces the space quantization effect important for localization of carriers in the structure and determination of the capacitance. We determined the DOS by using the theoretical capacitance of the MOS structure computed by the quantum mechanical approach. The development of the density of SiO2/Si interface states was analyzed by theoretical modeling of the C-V curves, based on the superposition of theoretical capacitance without interface states and additional capacitance corresponding to the charges trapped by the interface states. The development of the DOS distribution with the passivation procedures can be determined by this method.
Clinical trials in the era of personalized oncology
Authors: Maitland Michael L. , Schilsky Richard L. 
Published: October 2011

AbstractThe rapid pace of discoveries in tumor biology, imaging technology, and human genetics hold promise for an era of personalized oncology care. The successful development of a handful of new targeted agents has generated much hope and hype about the delivery of safer and more effective new treatments for cancer. The design and conduct of clinical trials has not yet adjusted to a new era of personalized oncology and so we are more in transition to that era than in it. With the development of treatments for breast cancer as a model, we review the approaches to clinical trials and the development of novel therapeutics in the prior era of population oncology, the current transitional era, and the future era of personalized oncology. CA Cancer J Clin 2011. © 2011 American Cancer Society.
Mapping the Transcriptional Machinery of the IL-8 Gene in Human Bronchial Epithelial Cells
Authors: Bezzerri Valentino , Borgatti Monica , Finotti Alessia , Tamanini Anna , Gambari Roberto , Cabrini Giulio 
Published: October 2011

Abstract
IL-8 released from bronchial epithelial cells infected with Pseudomonas aeruginosa plays a crucial role in the chronic lung pathology of patients affected by cystic fibrosis. Novel anti-inflammatory approaches will benefit from a thorough understanding of the regulatory mechanisms involved in the transcription of this chemokine to identify potential pharmacological targets. We addressed this issue by investigating the role of phosphoproteins and transcription factors (TFs) on transcription of IL-8 gene in the human bronchial epithelial IB3-1, CuFi-1, and Calu-3 cells. P. aeruginosa increased the basal phosphorylation of the ERK1/2 pathway components 90-kDa ribosomal S6 kinase (RSK)1/2 and mitogen- and stress-activated kinase-2 and of the p38 MAPK pathway components p38α/δ/γ and heat shock protein 27 (HSP27). The involvement of these kinases in the expression of IL-8 gene was confirmed with pharmacological inhibitors of ERK1/2, RSK, p38, and HSP27 both at transcription and secretion levels. Transfection of TF decoy oligodeoxynucleotides, designed to interfere with the interaction of the TFs NF-κB, NF-IL6, AP-1, CREB, and CHOP with the corresponding consensus sequences identified in the IL-8 promoter, reduced the P. aeruginosa-dependent transcription of IL-8, suggesting their participation in the transcriptional machinery. Stimulation of IB3-1 cells with IL-1β led to a similar pattern of activation, whereas the pattern of phosphoproteins and of TFs modulated by TNF-α differentiated sharply. In conclusion, the results highlight a novel role for RSK1/2 and HSP27 phosphoproteins and of the cooperative role of the TFs NF-κB, NF-IL6, AP-1, CHOP, and CREB in P. aeruginosa-dependent induction of transcription of the IL-8 gene in human bronchial epithelial cells.
Cutting Edge: Calcium/Calmodulin-Dependent Protein Kinase Type IV Is Essential for Mesangial Cell Proliferation and Lupus Nephritis
Authors: Ichinose Kunihiro , Rauen Thomas , Juang Yuang-Taung , Kis-Toth Katalin , Mizui Masayuki , Koga Tomohiro , Tsokos George C. 
Published: October 2011

Abstract
Renal involvement in systemic lupus erythematosus remains a major cause of morbidity and mortality. Although immune parameters that instigate renal damage have been characterized, their link to local processes, which execute tissue damage, is poorly understood. Using genetic-deletion and pharmacological-inhibition approaches, we demonstrated that calcium/calmodulin-dependent protein kinase type IV, which contributes to altered cytokine production in systemic lupus erythematosus patients, controls spontaneous and platelet-derived growth factor-stimulated mesangial cell proliferation and promotes IL-6 production through AP-1. Our studies identified calcium/calmodulin-dependent protein kinase type IV as a valuable treatment target for lupus nephritis and point out the importance of local kidney factors in the expression of tissue damage that, if properly targeted, should enhance clinical benefit and limit toxicity.
Clinicopathologic Correlation of Epidemiologic and Histopathologic Features of Pediatric Bacterial Lymphadenitis
Authors: Nunes Rosado Flavia G. , Stratton Charles W. , Mosse Claudio A. 
Published: October 2011

Context.—Infection is a common cause of lymphadenopathy in children and has numerous microbial etiologies. Lymph node biopsy is considered a keystone in arriving at a definite diagnosis. An accurate differential diagnosis from a lymph node biopsy can expedite diagnosis and minimize ancillary testing.
Objective.—To assess and compare the histopathologic and epidemiologic features of common and uncommon pediatric bacterial lymphadenitis.
Design.—We searched our database for surgical specimens that had a positive identification of bacteria during an 8-year period. The chart was reviewed to assess the pathogen identified and epidemiologic data. The archival tissue sections were reviewed and the histopathologic findings described for each pathogen.
Results.—The review of 368 pediatric lymph node biopsies identified 33 cases with a bacterial infection. These comprised 21 cases of Mycobacterium avium complex (60%), 1 of Mycobacterium fortuitum (3%), 7 of Bartonella henselae (20%), 2 of Yersinia enterocolitica (7%), 1 of Francisella tularensis (3%) and 1 of Streptococcus pyogenes (3%).
Conclusions.—Each of these infectious lymphadenitides had distinct epidemiologic and histopathologic features that are discussed in this report.
Quality and Safety in Medical Care: What Does the Future Hold?
Authors: Liang Bryan A. , Mackey Tim 
Published: October 2011

Context.—The rapid changes in health care policy, embracing quality and safety mandates, have culminated in programs and initiatives under the Patient Protection and Affordable Care Act.Objective.—To review the context of, and anticipated quality and patient safety mandates for, delivery systems, incentives under health care reform, and models for future accountability for outcomes of care.Design.—Assessment of the provisions of Patient Protection and Affordable Care Act, other reform efforts, and reform initiatives focusing on future quality and safety provisions for health care providers.Results.—Health care reform and other efforts focus on consumerism in the context of price. Quality and safety efforts will be structured using financial incentives, best-practices research, and new delivery models that focus on reaching benchmarks while reducing costs. In addition, patient experience will be a key component of reimbursement, and a move toward “retail” approaches directed at the individual patient may supplant traditional “wholesale” efforts at attracting employers.Conclusions.—Quality and safety have always been of prime importance in medicine. However, in the future, under health care reform and associated initiatives, a shift in the paradigm of medicine will integrate quality and safety measurement with financial incentives and a new emphasis on consumerism.