bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myeloid-derived suppressor cells help protective immunity toLeishmania majorinfection despite suppressed T cell responses
Authors: Pereira Wânia F , Ribeiro-Gomes Flávia L , Guillermo Landi V Costilla , Vellozo Natália S , Montalvão Fabrício , DosReis George A , Lopes Marcela F 
Published: September 2011

ABSTRACTTh1/Th2 cytokines play a key role in immune responses to Leishmania major by controlling macrophage activation for NO production and parasite killing. MDSCs, including myeloid precursors and immature monocytes, produce NO and suppress T cell responses in tumor immunity. We hypothesized that NO-producing MDSCs could help immunity to L. major infection. Gr1hi(Ly6Chi) CD11bhi MDSCs elicited by L. major infection suppressed polyclonal and antigen-specific T cell proliferation. Moreover, L. major-induced MDSCs killed intracellular parasites in a NO-dependent manner and reduced parasite burden in vivo. By contrast, treatment with ATRA, which induces MDSCs to differentiate into macrophages, increased development of lesions, parasite load, and T cell proliferation in draining LNs. Altogether, these results indicate that NO-producing MDSCs help protective immunity to L. major infection, despite suppressed T cell proliferation.
The Effects of Focus on Performance: Evidence from California Hospitals
Authors: KC Diwas Singh , Terwiesch Christian 
Published: September 2011

We use hospital-level discharge data from cardiac patients in California to estimate the effects of focus on operational performance. We examine focus at three distinct levels of the organization—at the firm level, at the operating unit level, and at the process flow level. We find that focus at each of these levels is associated with improved outcomes, namely, faster services at higher levels of quality, as indicated by lower lengths of stay (LOS) and reduced mortality rates. We then analyze the extent to which the superior operational outcome is driven by focused hospitals truly excelling in their operations or by focused hospitals simply “cherry-picking” easy-to-treat patients. To do this, we use an instrumental variables estimation strategy that effectively randomizes the assignment of patients to hospitals. After controlling for selective patient admissions, the previously observed benefits of firm level focus disappear; focused hospitals no longer demonstrate a statistically significant reduction in LOS or mortality rate. However, at more granular measures of focus within the hospital (e.g., operating unit level), we find that more focus leads to a shorter LOS, even after controlling for selective admission effects. This paper was accepted by Yossi Aviv, operations management.
Apologies as Signals: With Evidence from a Trust Game
Authors: Ho Benjamin 
Published: September 2011

Apologies are part of a social institution designed to restore frayed relationships not only in daily life but also in the domains of corporate governance, medical malpractice litigation, political reputation, organizational culture, etc. The theory shows that in a general class of moral hazard games with imperfect information about agents with two-dimensional type, apologies exhibit regular properties—e.g., apologies are more frequent in long relationships, early in relationships, and between better-matched partners. A variant of the trust game demonstrates that communication matters in a manner consistent with economic theory; specifically, the words “I am sorry” appear to select equilibrium behavior consistent with the theory's main predictions. This paper was accepted by Brad Barber, Teck Ho, and Terrance Odean, special issue editors.
Clinical and Demographic Factors Associated with Antipyretic Use in Gram-Negative Severe Sepsis and Septic Shock
Authors: Mohr Nicholas M , Fuller Brian M , Skrupky Lee P , Moy Hawnwan , Alunday Robert , Micek Scott T , Fagley Richard E 
Published: September 2011

Background: Antipyretic therapy is commonly prescribed for patients with Infection, but studies of its impact on clinical outcomes have yielded mixed results. No data exist to characterize the use of antipyretic medications in patients with severe sepsis or septic shock. Objective: To identify clinical and demographic factors associated with antipyretic medication administration in severe sepsis and septic shock. Methods: This single-center, retrospective, cohort study assessed febrile patients [temperature ≥38.3°C) with gram-negative severe sepsis or septic shock at an 1111-bed academic medical center between January 2002 and February 2008, Patients were excluded if they had liver disease, acute brain injury, or allergy to acetaminophen. Generalized estimating equations were used to estimate the effect of clinical factors on treatment of patients with antipyretic medications, Results: Although 76% of patients in this febrile cohort (n = 241) were prescribed an antipyretic agent, only 42% received antipyretic therapy; 95% of the doses were acetaminophen. Variables associated with antipyretic treatment were maximum body temperature (OR 2.11, 95% CI 1.53 to 2.89), time after sepsis diagnosis (OR 0.88, 95% CI 0.82 to 0.95), surgery during hospitalization (OR 0.49, 95% CI 0.31 to 0.80), death within 36 hours (OR 0.35, 95% CI 0.15 to 0.85). and mechanical ventilation (OR 0.58, 95% CI 0.34 to 0.98). Severity of illness factors, demographic factors, and patient treatment location did not predict who would receive antipyretic therapy. Conclusions: Most febrile episodes in patients with gram-negative severe sepsis or septic shock were not treated with antipyretic medications. Further studies are needed to demonstrate the effect of antipyretics on clinically relevant outcomes in severe sepsis and septic shock.
Current Perceptions and Practices Surrounding the Recognition and Treatment of Delirium in the Intensive Care Unit: A Survey of 250 Critical Care Pharmacists from Eight States
Authors: Devlin John W , Bhat Shubha , Roberts Russel J , Skrobik Yoanna 
Published: September 2011

Background: Pharmacists are key members of the intensive care unit (ICU) team; however, few data exist regarding their clinical role, perceptions, and current practices in recognizing and managing delirium. Objective: To describe current practices and perceptions of ICU pharmacists regarding delirium recognition and treatment relative to current recommendations. Methods: A self-administered survey was distributed to 457 pharmacists in 8 states who are members of the Society of Critical Care Medicine or the American College of Clinical Pharmacy and who spend 25% or more of their time providing clinical ICU pharmacy services. Results: A total of 250 (55%) pharmacists responded. A delirium screening tool was routinely used by few (7%) pharmacists. Lack of time (34%) and the belief that screening is a nursing role (24%) were key barriers to pharmacist screenings. Most (85%) said that delirium should be pharmacologically managed; 66% responded that 2 or more medications should be used. The treatments of first choice included Haloperidol (76%), an atypical antipsychotic (14%), or a benzodiazepine (10%). Frequently used treatments were Haloperidol (87%), quetiapine (59%), and lorazepam (47%). Haloperidol was perceived by many (42%) to have 1 or more randomized trials supporting its use for delirium and Food and Drug Administration approval for this indication (34%). Haloperidol was most often administered on a scheduled basis (62%), intravenously (92%), and al a daily dose of 5–10 mg (58%). While the QTc interval was frequently measured at least once per shift using an electrocardiogram strip (64%), it was not routinely measured in 20% of ICUs, and 60% continued haloperidol when the QTc exceeded 500 msec. Conclusions: Current practices and perceptions surrounding recognition and treatment of delirium in patients in the ICU by the critical care pharmacists surveyed are heterogeneous. Antipsychotics are frequently recommended by pharmacists for delirium treatment, despite a lack of rigorous evidence to support their use. While pharmacists are ideally suited to lead delirium recognition efforts and provide treatment recommendations in this area, these roles need further elucidation. The optimal pedagogical strategy to support these efforts remains unclear, and the potential impact of pharmacists’ efforts on patients’ outcomes is unknown.
Comparison of Serum Human Epididymis Protein 4 with Cancer Antigen 125 as a Tumor Marker in Patients with Malignant and Nonmalignant Diseases
Authors: Escudero Jose M , Auge Jose M , Filella Xavier , Torne Aureli , Pahisa Jaume , Molina Rafael 
Published: September 2011

BACKGROUND
Human epididymis protein 4 (HE4), a precursor of human epididymis protein, has been proposed as a tumor marker for ovarian cancer. We evaluated HE4 in comparison with cancer antigen 125 (CA 125) in healthy individuals and in patients with benign and malignant diseases.

METHODS
CA 125 and HE4 serum concentrations were determined in 101 healthy individuals, 535 patients with benign pathologies (292 with benign gynecologic diseases) and 423 patients with malignant diseases (127 with ovarian cancers). CA 125 and HE4 cutoffs were 35 kU/L and 140 pmol/L, respectively.

RESULTS
HE4 and CA 125 results were abnormal in 1.1% and 9.9% of healthy individuals and in 12.3% and 37% of patients with benign diseases, respectively. Renal failure was the most common cause of increased HE4 in patients with benign disease, who had significantly higher HE4 concentrations (P = 0.001) than patients with other benign diseases. HE4 showed a higher specificity than CA 125 in patients with benign gynecologic diseases, with abnormal concentrations in 1.3% and 33.2% of the patients, respectively. HE-4 concentrations were abnormal primarily in gynecologic cancer and lung cancer. By contrast, CA 125 was increased in many different nonovarian malignancies, including nonepithelial tumors. A significantly higher area under the ROC curve was obtained with HE4 than with CA 125 for differentiating benign from malignant diseases (0.755 vs 0.643) and in the differential diagnosis of gynecologic diseases (0.874 vs 0.722).

CONCLUSIONS
HE4 has significantly higher diagnostic specificity than CA 125, and the combination of CA 125 and HE4 improved the detection of ovarian cancer in all stages and histological types.
Altered Profile of Seminal Plasma MicroRNAs in the Molecular Diagnosis of Male Infertility
Authors: Wang Cheng , Yang Cuihua , Chen Xi , Yao Bing , Yang Chen , Zhu Chen , Li Limin , Wang Junjun , Li Xiaojun , Shao Yong , Liu Yang , Ji Jiang , Zhang Junfeng , Zen Ke , Zhang Chen-Yu , Zhang Chunni 
Published: September 2011

BACKGROUNDAlthough microRNAs (miRNAs) play essential roles in spermatogenesis, little is known about seminal plasma miRNAs in infertile men. We investigated the profile of seminal plasma miRNAs in infertile men to identify miRNAs that are altered in infertility; we then evaluated their diagnostic value.METHODSSeminal plasma samples were obtained from 289 infertile men and 168 age-matched fertile control individuals. The stability of the miRNAs was first assessed by time-course and freeze–thaw cycle analyses. The Solexa sequencing technology was used for an initial screen of the miRNAs in samples pooled from 45 patients with nonobstructive azoospermia, 58 patients with asthenozoospermia, and 100 fertile controls. A stem–loop quantitative reverse-transcription PCR (RT-qPCR) assay was conducted in the training and verification sets to confirm the concentrations of the altered miRNAs in 73 patients with nonobstructive azoospermia, 79 patients with asthenozoospermia, 34 patients with oligospermia, and 68 fertile controls.RESULTSThe miRNAs in seminal plasma were stable. The Solexa sequencing analysis demonstrated 19 markedly altered miRNAs in the patient groups, compared with the control group. RT-qPCR analysis identified 7 miRNAs (miR-34c-5p, miR-122, miR-146b-5p, miR-181a, miR-374b, miR-509–5p, and miR-513a-5p) as markedly decreased in azoospermia but increased in asthenozoospermia. The area under the ROC curve for these miRNAs ranged from 0.733 to 0.921, markedly higher than for routine biochemical parameters (0.510–0.622). Moreover, the concentrations of some selected miRNAs were also increased in the semen sperm of the asthenozoospermia patients.CONCLUSIONSThe measurement of miRNAs in seminal plasma provides a novel, noninvasive approach for diagnosing male infertility.
The tree of irreducible numerical semigroups with fixed Frobenius number
Authors: Blanco Victor , Rosales José Carlos 
Published: September 2011

Abstract.
In this paper we present a procedure to build the set of irreducible numerical semigroups with a fixed Frobenius number. The construction gives us a rooted tree structure for this set. Furthermore, by using the notion of Kunz-coordinates vector we translate the problem of finding such a tree into the problem of manipulating vectors with as many component as the Frobenius number.
Bond-valence Based Computational Design of High Performance Lithium Ion Battery Cathode Materials
Authors: Adams Stefan 
Published: September 2011

ABSTRACTLinking the bond valence mismatch to the absolute energy scale, a generally applicable Morse-type force-field is developed and applied to study ion conduction in mixed conducting solids using both an energy landscape approach and molecular dynamics (MD) simulations. Exploring strategies to enhance the power performance of safe low cost lithium ion battery cathode materials, amblygonite-type “high voltage” cathode materials LiVPO4F and LiFeSO4F are used as examples. The amblygonite-type structure exhibits channels for low-energy migration in combination with moderate energy thresholds for "back-up" pathways in perpendicular directions mitigating the effects of channel blocking in mixed conductors with strictly one-dimensional Li+ motion.
Familial Pediatric Endocrine Tumors
Authors: Millar Sarinda , Bradley Lisa , Donnelly Deirdre E. , Carson Dennis , Morrison Patrick J. 
Published: September 2011

Abstract

Learning Objectives
After completing this course, the reader will be able to: Explain the contribution of genetics to heritable aspects of pediatric cancer.Describe the applications of presymptomatic gene testing in family members with familial pediatric cancers to the early detection, prevention, and management of tumors in patients and their family members.
CME This article is available for continuing medical education credit at CME.TheOncologist.com
Pediatric endocrine tumors are rare but have fairly characteristic presentations. We describe an approach to diagnosis and management of five of the most common presentations including gonadoblastoma, paraganglioma, medullary thyroid cancer, adrenal cancer, and pituitary adenoma. Genetic testing can aid in the early detection and prevention and management of tumors in patients and in other family members.
An Emerging Entity: Pancreatic Adenocarcinoma Associated with a Known BRCA Mutation: Clinical Descriptors, Treatment Implications, and Future Directions
Authors: Lowery Maeve A. , Kelsen David P. , Stadler Zsofia K. , Yu Kenneth H. , Janjigian Yelena Y. , Ludwig Emmy , D'Adamo David R. , Salo-Mullen Erin , Robson Mark E. , Allen Peter J. , Kurtz Robert C. , O'Reilly Eileen M. 
Published: September 2011

Abstract

Learning Objectives
After completing this course, the reader will be able to: Describe the genetic syndromes associated with pancreas adenocarcinoma.Explain the potential role of platinum-based therapy and PARP inhibitors in BRCA-mutated pancreas adenocarcinoma.
CME This article is available for continuing medical education credit at CME.TheOncologist.com

Background.
BRCA1 and BRCA2 germline mutations are associated with an elevated risk for pancreas adenocarcinoma (PAC). Other BRCA-associated cancers have been shown to have greater sensitivity to platinum and poly(ADP-ribose) polymerase (PARP) inhibitors with better clinical outcomes than in sporadic cases; however, outcomes in BRCA-associated PAC have not been reported.

Methods.
Patients with a known BRCA1 or BRCA2 mutation and a diagnosis of PAC were identified from the Gastrointestinal Oncology Service, Familial Pancreas Cancer Registry, and Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center.

Results.
Fifteen patients, five male, with a BRCA1 (n = 4) or BRCA2 (n = 11) mutation and PAC and one patient with a BRCA1 mutation and acinar cell carcinoma of the pancreas were identified. Seven female patients (70%) had a prior history of breast cancer. Four patients received a PARP inhibitor alone or in combination with chemotherapy; three demonstrated an initial radiographic partial response by Response Evaluation Criteria in Solid Tumors whereas one patient had stable disease for 6 months. Six patients received platinum-based chemotherapy first line for metastatic disease; five of those patients had a radiographic partial response.

Conclusion.
BRCA mutation–associated PAC represents an underidentified, but clinically important, subgroup of patients. This is of particular relevance given the ongoing development of therapeutic agents targeting DNA repair, which may potentially offer a significant benefit to a genetically selected population. We anticipate that further study and understanding of the clinical and biologic features of BRCA-mutant PAC will aid in the identification of tissue biomarkers indicating defective tumor DNA repair pathways in sporadic PAC.
Responses of Gut Microbiota and Glucose and Lipid Metabolism to Prebiotics in Genetic Obese and Diet-Induced Leptin-Resistant Mice
Authors: Everard Amandine , Lazarevic Vladimir , Derrien Muriel , Girard Myriam , Muccioli Giulio G. , Neyrinck Audrey M. , Possemiers Sam , Van Holle Ann , François Patrice , de Vos Willem M. , Delzenne Nathalie M. , Schrenzel Jacques , Cani Patrice D. 
Published: September 2011

OBJECTIVE
To investigate deep and comprehensive analysis of gut microbial communities and biological parameters after prebiotic administration in obese and diabetic mice.

RESEARCH DESIGN AND METHODS
Genetic (ob/ob) or diet-induced obese and diabetic mice were chronically fed with prebiotic-enriched diet or with a control diet. Extensive gut microbiota analyses, including quantitative PCR, pyrosequencing of the 16S rRNA, and phylogenetic microarrays, were performed in ob/ob mice. The impact of gut microbiota modulation on leptin sensitivity was investigated in diet-induced leptin-resistant mice. Metabolic parameters, gene expression, glucose homeostasis, and enteroendocrine-related L-cell function were documented in both models.

RESULTS
In ob/ob mice, prebiotic feeding decreased Firmicutes and increased Bacteroidetes phyla, but also changed 102 distinct taxa, 16 of which displayed a &gt;10-fold change in abundance. In addition, prebiotics improved glucose tolerance, increased L-cell number and associated parameters (intestinal proglucagon mRNA expression and plasma glucagon-like peptide-1 levels), and reduced fat-mass development, oxidative stress, and low-grade inflammation. In high fat–fed mice, prebiotic treatment improved leptin sensitivity as well as metabolic parameters.

CONCLUSIONS
We conclude that specific gut microbiota modulation improves glucose homeostasis, leptin sensitivity, and target enteroendocrine cell activity in obese and diabetic mice. By profiling the gut microbiota, we identified a catalog of putative bacterial targets that may affect host metabolism in obesity and diabetes.
FoxO Feedback Control of Basal IRS-2 Expression in Pancreatic β-Cells Is Distinct From That in Hepatocytes
Authors: Tsunekawa Shin , Demozay Damien , Briaud Isabelle , McCuaig Jill , Accili Domenico , Stein Roland , Rhodes Christopher J. 
Published: September 2011

OBJECTIVE
Appropriate regulation of insulin receptor substrate 2 (IRS-2) expression in pancreatic β-cells is essential to adequately compensate for insulin resistance. In liver, basal IRS-2 expression is controlled via a temporal negative feedback of sterol regulatory element–binding protein 1 (SREBP-1) to antagonize transcription factors forkhead box class O (FoxO)1/FoxO3a at an insulin response element (IRE) on the IRS-2 promoter. The purpose of the study was to examine if a similar mechanism controlled IRS-2 expression in β-cells.

RESEARCH DESIGN AND METHODS
IRS-2 mRNA and protein expression, as well as IRS-2 gene promoter activity, were examined in isolated rat islets. Specific transcription factor association with the IRE on the IRS-2 promoter was examined by chromatin immunoprecipitation (ChIP) assay, and their nuclear translocation was examined by immunofluorescence. A direct in vivo effect of insulin on control of IRS-2 expression in liver and pancreatic islets was also investigated.

RESULTS
In IRS-2 promoter-reporter assays conducted in isolated islets, removal of the IRE decreased basal IRS-2 promoter activity in β-cells up to 80%. Activation of IRS signaling in isolated rat islets by insulin/IGF-I (used as an experimental in vitro tool) or downstream constitutive activation of protein kinase B (PKB) significantly decreased IRS-2 expression. In contrast, inhibition of phosphatidylinositol 3-kinase (PI3K) or PKB significantly increased IRS-2 levels in β-cells. ChIP assays indicated that transcription factors FoxO1 and FoxO3a associated with the IRE on the IRS-2 promoter in β-cells in a PI3K/PKB–dependent manner, whereas others, such as SREBP-1, the transcription factor binding to immunoglobulin heavy chain enhancer 3′, and the aryl hydrocarbon receptor nuclear translocator (ARNT), did not. However, only FoxO3a, not FoxO1, was capable of driving IRS-2 promoter activity via the IRE in β-cells. In vivo studies showed insulin was able to suppress IRS-2 expression via activation of SREBP-1 in the liver, but this mechanism was not apparent in pancreatic islets from the same animal.

CONCLUSIONS
The molecular mechanism for feedback control of IRS signaling to decrease IRS-2 expression in liver and β-cells is quite distinct, with a predominant role played by FoxO3a in β-cells.
Influence of Familial Risk on Diabetes Risk–Reducing Behaviors Among U.S. Adults Without Diabetes
Authors: Chang Man-huei , Valdez Rodolfo , Ned Renée M. , Liu Tiebin , Yang Quanhe , Yesupriya Ajay , Dowling Nicole F. , Meigs James B. , Bowen Michael S. , Khoury Muin J. 
Published: September 2011

OBJECTIVE
To test the association of family history of diabetes with the adoption of diabetes risk–reducing behaviors and whether this association is strengthened by physician advice or commonly known factors associated with diabetes risk.

RESEARCH DESIGN AND METHODS
We used cross-sectional data from the 2005–2008 National Health and Nutrition Examination Survey (NHANES) to examine the effects of family history of diabetes on the adoption of selected risk-reducing behaviors in 8,598 adults (aged ≥20 years) without diabetes. We used multiple logistic regression to model three risk reduction behaviors (controlling or losing weight, increasing physical activity, and reducing the amount of dietary fat or calories) with family history of diabetes.

RESULTS
Overall, 36.2% of U.S. adults without diabetes had a family history of diabetes. Among them, ~39.8% reported receiving advice from a physician during the past year regarding any of the three selected behaviors compared with 29.2% of participants with no family history (P &lt; 0.01). In univariate analysis, adults with a family history of diabetes were more likely to perform these risk-reducing behaviors compared with adults without a family history. Physician advice was strongly associated with each of the behavioral changes (P &lt; 0.01), and this did not differ by family history of diabetes.

CONCLUSIONS
Familial risk for diabetes and physician advice both independently influence the adoption of diabetes risk–reducing behaviors. However, fewer than half of participants with familial risk reported receiving physician advice for adopting these behaviors.