tbuckley/cabot-search huggingface dataset:
Evaluation of 30-Day Hospital Readmission After Surgery for Advanced-Stage Ovarian Cancer in a Medicare Population
Authors: Ramez N. Eskander, Jenny Chang, Argyrios Ziogas, Hoda Anton-Culver, Robert E. Bristow
Journal: Journal of Clinical Oncology (2014)

To analyze rate, risk factors, and costs associated with 30-day readmission after ovarian cancer surgery.The SEER-Medicare linked database (1992 to 2010) was used to evaluate readmission rates within 30 days of index surgery in patients with stage IIIC/IV ovarian, primary peritoneal, or fallopian tube cancer. Multivariable logistic regression was used to identify factors associated with readmission.Of 5,152 eligible patients, 1,003 (19.5%) were readmitted within 30 days of discharge. Mean patient age was 75 years. Diagnoses associated with readmission included infection (34.7%), dehydration (34.3%), ileus/obstruction (26.2%), metabolic/electrolyte derangements (23.1%), and anemia (12.3%). In multivariable analysis, year of discharge was significantly associated with 30-day readmission (1996 to 2000: odds ratio [OR], 1.32; 95% CI, 1.01 to 1.71; 2001 to 2005: OR, 1.58; 95% CI, 1.24 to 2.0; 2006 to 2010: OR, 1.73; 95% CI, 1.35 to 2.21; referent years 1992 to 1995), as were length of index hospital stay more than 8 days (OR, 1.39; 95% CI, 1.18 to 1.64) and discharge to a skilled nursing facility (OR, 1.3; 95% CI, 1.04 to 1.63). Patients readmitted within 30 days had a significantly greater 1-year mortality rate compared with patients not readmitted (41.1% v 25.1%, respectively; P < .001). The median cost of readmission hospital stay was $9,220 in year 2010 dollars, with a total cost of $9.3 million over the study period.Early readmission after surgery for ovarian cancer is common. There is a significant association between 30-day readmission and 1-year mortality. These findings may catalyze development of targeted interventions to decrease early readmission, improve patient outcomes, and control health care costs.
Clinical and Pathologic Features of Familial Interstitial Pneumonia
Authors: Mark P. Steele, Marcy C. Speer, James E. Loyd, Kevin K. Brown, Aretha Herron, Susan H. Slifer, Lauranell H. Burch, Momen M. Wahidi, John A. Phillips, Thomas A. Sporn, H. Page McAdams, Marvin I. Schwarz, David A. Schwartz
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Several lines of evidence suggest that genetic factors and environmental exposures play a role in the development of pulmonary fibrosis.We evaluated families with 2 or more cases of idiopathic interstitial pneumonia among first-degree family members (familial interstitial pneumonia, or FIP), and identified 111 families with FIP having 309 affected and 360 unaffected individuals.The presence of probable or definite FIP was based on medical record review in 28 cases (9.1%); clinical history, diffusing capacity of carbon monoxide (DL(CO)), and chest X-ray in 16 cases (5.2%); clinical history, DL(CO), and high-resolution computed tomography chest scan in 191 cases (61.8%); clinical history and surgical lung biopsy in 56 cases (18.1%); and clinical history and autopsy in 18 cases (5.8%).Older age (68.3 vs. 53.1; p < 0.0001), male sex (55.7 vs. 37.2%; p < 0.0001), and having ever smoked cigarettes (67.3 vs. 34.1%; p < 0.0001) were associated with the development of FIP. After controlling for age and sex, having ever smoked cigarettes remained strongly associated with the development of FIP (odds ratio(adj), 3.6; 95% confidence interval, 1.3-9.8). Evidence of aggregation of disease was highly significant (p < 0.001) among sibling pairs, and 20 pedigrees demonstrated vertical transmission, consistent with autosomal dominant inheritance. Forty-five percent of pedigrees demonstrated phenotypic heterogeneity, with some pedigrees demonstrating several subtypes of idiopathic interstitial pneumonia occurring within the same families.These findings suggest that FIP may be caused by an interaction between a specific environmental exposure and a gene (or genes) that predisposes to the development of several subtypes of idiopathic interstitial pneumonia.
Exercise training increases glycogen synthase activity and GLUT4 expression but not insulin signaling in overweight nondiabetic and type 2 diabetic subjects
Authors: Christine Y. Christ-Roberts, Thongchai Pratipanawatr, Wilailak Pratipanawatr, Rachele Berria, Renata Belfort, Sangeeta Kashyap, Lawrence J. Mandarino
Journal: Metabolism (2004)
Extrafollicular B cell activation by marginal zone dendritic cells drives T cell–dependent antibody responses
Authors: Craig P. Chappell, Kevin E. Draves, Natalia V. Giltiay, Edward A. Clark
Journal: The Journal of Experimental Medicine (2012)

Dendritic cells (DCs) are best known for their ability to activate naive T cells, and emerging evidence suggests that distinct DC subsets induce specialized T cell responses. However, little is known concerning the role of DC subsets in the initiation of B cell responses. We report that antigen (Ag) delivery to DC-inhibitory receptor 2 (DCIR2) found on marginal zone (MZ)–associated CD8α− DCs in mice leads to robust class-switched antibody (Ab) responses to a T cell–dependent (TD) Ag. DCIR2+ DCs induced rapid up-regulation of multiple B cell activation markers and changes in chemokine receptor expression, resulting in accumulation of Ag-specific B cells within extrafollicular splenic bridging channels as early as 24 h after immunization. Ag-specific B cells primed by DCIR2+ DCs were remarkably efficient at driving naive CD4 T cell proliferation, yet DCIR2-induced responses failed to form germinal centers or undergo affinity maturation of serum Ab unless toll-like receptor (TLR) 7 or TLR9 agonists were included at the time of immunization. These results demonstrate DCIR2+ DCs have a unique capacity to initiate extrafollicular B cell responses to TD Ag, and thus define a novel division of labor among splenic DC subsets for B cell activation during humoral immune responses.
Retrovirally mediated correction of bone marrow–derived mesenchymal stem cells from patients with mucopolysaccharidosis type I
Authors: Melissa A. Baxter, Robert F. Wynn, Jonathan A. Deakin, Ilaria Bellantuono, Kirsten G. Edington, Alan Cooper, Guy T. N. Besley, Heather J. Church, J. Ed Wraith, Trevor F. Carr, Leslie J. Fairbairn
Journal: Blood (2002)
Protein kinase G dysfunction is an important factor in induced pulmonary hypertension in mice
Authors: En-Ting Chang
Journal: Thorax (2012)

Protein kinase G dysfunction is an important factor in induced pulmonary hypertension in miceIn this preclinical study, the authors hypothesised that deficiency of protein kinase G-1 (PKG-1), a serine/threonine kinase, would induce pulmonary hypertension (PH) in mice through Rho A/Rho kinase activation.Protein kinase G-1-knockout (Prkg1 -/-) mice had decreased PKG-1 and increased pulmonary artery systolic pressure compared to wild type mice.Prkg1 -/-mice had marked microvascular remodelling and precapillary occlusion in the lung, suggesting the two mechanisms cause PH in Prkg1 -/-mice.The increased pulmonary artery pressure was independent of left-sided heart disease and systemic hypertension at day 45 in Prkg1 -/-mice.Furthermore, the western blot of Prkg1 -/-mice showed decreased phosphorylation of Rho A Ser188 and increased activation of Rho A. After fasudil (a Rho kinase inhibitor) treatment, a significant decrease in pulmonary artery pressure was noted in Prkg1 -/-mice.In this study, the authors showed that PKG-1 deficiency results in activation of Rho A-Rho kinase signalling, which causes vascular remodelling and vasoconstriction, leading to PH.Short term inhibition of Rho kinase by fasudil decreased pulmonary pressure in Prkg1 -/-mice.Thus, based on the mouse model, PKG-1 deficiency should be one of the important key mechanisms inducing pulmonary artery pressure in Prkg1 -/-mice.However, extrapolating this evidence from Prkg1 -/-mice to PH human population will require further study.
Multiple molecular forms of human lactoferrin. Identification of a class of lactoferrins that possess ribonuclease activity and lack iron-binding capacity.
Authors: P Furmanski, Z P Li, M B Fortuna, C V Swamy, M R Das
Journal: The Journal of Experimental Medicine (1989)

Lactoferrin (Lf), the major iron-binding component of milk, also a major constituent of the specific granules of neutrophils involved in antimicrobial activity and a glycoprotein thought to play a role in regulatory functions in the hematopoietic system as well as other physiologic activities, is shown to occur in three isoforms. One, Lf-alpha, binds iron; the other two, Lf-beta and Lf-gamma, express potent RNase activity, but do not bind iron. The three isoforms are very similar or identical in Mr, pI, partial proteolytic peptide patterns, NH2-terminal amino acid sequence, and reactivity with mAbs and polyclonal antisera against the RNase and Lf, respectively. The finding of structurally similar but enzymatically distinct forms of Lf may be related to the diverse functions of the molecule.
PULMONARY VENOUS FLOW AS ASSESSED BY TRANSESOPHAGEAL ECHOCARDIOGRAPHY INDEPENDENTLY PREDICTS MORTALITY IN PATIENTS WITH DILATED CARDIOMYOPATHY. A THIRTEEN YEAR FOLLOW-UP STUDY
Authors: Carlo Caiati, Mario Lepera, Daniela Santoro, Alessandro De Santis, Assunta Piscopo, Caterina Rizzo, Delia De Santis, Rocco Lagioia
Journal: Journal of the American College of Cardiology (2012)
Methylated <i>NEUROD1</i> Promoter is a Marker for Chemosensitivity in Breast Cancer
Authors: Heidi Fiegl, Allison Jones, Cornelia Hauser-Kronberger, Georg Hutarew, Roland Reitsamer, Robin L. Jones, Mitch Dowsett, Elisabeth Mueller-Holzner, Gudrun Windbichler, Günter Daxenbichler, Georg Goebel, Christian Ensinger, Ian Jacobs, Martin Widschwendter
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Chemotherapy can be an integral component of the adjuvant management strategy for women with early stage breast cancer. To date, no tool is available to predict or monitor the efficacy of these therapies. The aim of this proof-of-principle study was to assess whether NEUROD1 DNA methylation is able to predict the response to neoadjuvant and adjuvant chemotherapy. Experimental Design: Recently, we showed that NEUROD1 DNA is differentially methylated in neoplastic versus nonneoplastic breast tissue samples. In this study, we used MethyLight and analyzed NEUROD1 methylation in (a) 74 breast cancer tissue samples, (b) two independent sets of pretreatment core biopsies of 23 (training set) and 21 (test set) neoadjuvantly treated breast cancer patients, and (c) pretherapeutic and posttherapeutic serum samples from 107 breast cancer patients treated with adjuvant chemotherapy. Results: High-grade tumors showed higher NEUROD1 methylation levels. Estrogen receptor–negative breast cancers with high NEUROD1 methylation were 10.8-fold more likely to respond with a complete pathologic response following neoadjuvant chemotherapy. Patients with positive serum pretreatment NEUROD1 methylation, which persisted after chemotherapy, indicated poor relapse-free and overall survival in univariate and multivariate analyses (relative risk for relapse, 6.2; 95% confidence interval, 1.6-24; P = 0.008, and relative risk for death, 14; 95% confidence interval, 1.6-120; P = 0.02). Conclusions: These data support the view that NEUROD1 methylation is a chemosensitivity marker in estrogen receptor–negative breast cancer.
LSD Research: The Impact of Lay Publicity
Authors: CHARLES C. DAHLBERG, RUTH MECHANECK, STANLEY FELDSTEIN
Journal: American Journal of Psychiatry (1968)

An inquiry was sent to 29 investigators conducting research involving the use of LSD or other hallucinogens, in an effort to determine what effects publicity about LSD may have had upon their research. Nineteen of the investigators reported that the publicity had negatively affected the recruitment of "appropriate" subjects, the attitudes of already participating subjects, the behavior of research personnel, and the continuation of several research projects.
Carvedilol reverses cardiac insufficiency in AKAP5 knockout mice by normalizing the activities of calcineurin and CaMKII
Authors: X. Li, S. M. Matta, R. D. Sullivan, S. W. Bahouth
Journal: Cardiovascular Research (2014)

AimsCardiac β-adrenergic receptors (β-AR) are key regulators of cardiac haemodynamics and size. The scaffolding protein A-kinase anchoring protein 79/150 (AKAP5) is a key regulator of myocardial signalling by β-ARs. We examined the function of AKAP5 in regulating cardiac haemodynamics and size, and the role of β-ARs and Ca2+-regulated intracellular signalling pathways in this phenomenon.
Molecular Pathology Shows p16 Methylation in Nonadenomatous Pituitaries from Patients with Cushing’s Disease
Authors: David J. Simpson, Anne M. McNicol, David C. Murray, Adil Bahar, Helen E. Turner, John A. H. Wass, Margaret M. Esiri, Richard N. Clayton, William E. Farrell
Journal: Clinical Cancer Research (2004)

The majority of cases of Cushing's disease are due to the presence of a corticotroph microadenoma. Less frequently no adenoma is found and histology shows either corticotroph hyperplasia, or apparently normal pituitary. In this study we have used molecular pathology to determine whether the tissue labeled histologically as "normal" is indeed abnormal.Tissue from 31 corticotroph adenomas and 16 nonadenomatous pituitaries were subject to methylation-sensitive PCR to determine the methylation status of the p16 gene CpG island. The proportion of methylated versus unmethylated CpG island was determined using combined bisulphite restriction analysis. Methylation status was correlated with immunohistochemical detection of p16.Seventeen of 31 adenomas (54.8%), 4 of 6 cases of corticotroph hyperplasia, and 7 of 10 apparently normal pituitaries showed p16 methylation. Ten of 14 (71%; P = 0.01) adenomas and 2 of 3 cases of corticotroph hyperplasia, which were methylated, failed to express p16 protein. However, only 2 of 7 apparently normal pituitaries that were methylated failed to express p16 protein. Quantitative analysis of methylation using combined bisulphite restriction analysis showed only unmethylated CpG islands in postmortem normal pituitaries; however, in adenomas 80-90% of the cells within a specimen were methylated. The reverse was true for corticotroph hyperplasia and apparently normal pituitaries where only 10-20% of the cells were methylated. Thus, the decreased proportion of cells that were methylated, particularly in those cases of apparently normal pituitary, is the most likely explanation for the lack of association between this change and loss of cognate protein in these cases.To our knowledge this is the first report that describes an intrinsic molecular change, namely methylation of the p16 gene CpG island, common to all three histological patterns associated with Cushing's disease. Thus, the use of molecular pathology reveals abnormalities undetected by routine pathological investigation. In cases of "apparently" normal pituitaries it is not possible to determine whether the change is associated with adenoma cells "scattered" throughout the gland, albeit few in number, or with the ancestor-clonal origin of these tumor cells.
Tumor Cells Transduced with the MHC Class II Transactivator and CD80 Activate Tumor-Specific CD4+ T Cells Whether or Not They Are Silenced for Invariant Chain
Authors: James A. Thompson, Samudra K. Dissanayake, Bruce R. Ksander, Keith L. Knutson, Mary L. Disis, Suzanne Ostrand-Rosenberg
Journal: Cancer Research (2006)

Abstract The specificity and potency of the immune system make immunotherapy a potential strategy for the treatment of cancer. To exploit this potential, we have developed cell-based cancer vaccines consisting of tumor cells expressing syngeneic MHC class II and costimulatory molecules. The vaccines mediate tumor regression in mice and activate human CD4+ T cells in vitro. Previous vaccines were generated by transducing MHC II negative tumor cells with a single HLA-DR allele. Because expression of multiple MHC II alleles would facilitate presentation of a broader repertoire of tumor antigens, we have now transduced tumor cells with the MHC class II transactivator (CIITA), a regulatory gene that coordinately increases expression of all MHC II alleles. Previous studies in mice indicated that coexpression of the MHC II accessory molecule invariant chain (Ii) inhibited presentation of endogenously synthesized tumor antigens and reduced vaccine efficacy. To determine if Ii expression affects presentation of MHC class II–restricted endogenously synthesized tumor antigens in human tumor cells, HLA-DR-MCF10 breast cancer cells were transduced with the CIITA, CD80 costimulatory molecule gene, and with or without small interfering RNAs (siRNA) specific for Ii. Ii expression is silenced &amp;gt;95% in CIITA/CD80/siRNA transductants; down-regulation of Ii does not affect HLA-DR expression or stability; and Ii+ and Ii− transductants activate human CD4+ T cells to DRB1*0701-restricted HER-2/neu epitopes. Therefore, tumor cells transduced with the CIITA, CD80, and with or without Ii siRNA present endogenously synthesized tumor antigens and are potential vaccines for activating tumor-specific CD4+ T cells. (Cancer Res 2006; 66(2): 1147-54)
Cyclophilin D Modulates Mitochondrial Acetylome
Authors: Tiffany Tuyen M. Nguyen, Renee Wong, Sara Menazza, Junhui Sun, Yong Chen, Guanghui Wang, Marjan Gucek, Charles Steenbergen, Michael N. Sack, Elizabeth Murphy
Journal: Circulation Research (2013)

Rationale: Mice lacking cyclophilin D (CypD −/− ), a mitochondrial chaperone protein, have altered cardiac metabolism. As acetylation has been shown to regulate metabolism, we tested whether changes in protein acetylation might play a role in these metabolic changes in CypD −/− hearts. Objective: Our aim was to test the hypothesis that loss of CypD alters the cardiac mitochondrial acetylome. Methods and Results: To identify changes in lysine-acetylated proteins and to map acetylation sites after ablation of CypD, we subjected tryptic digests of isolated cardiac mitochondria from wild-type and CypD −/− mice to immunoprecipitation using agarose beads coupled to antiacetyl lysine antibodies followed by mass spectrometry. We used label-free analysis for the relative quantification of the 875 common peptides that were acetylated in wild-type and CypD −/− samples and found 11 peptides (10 proteins) decreased and 96 peptides (48 proteins) increased in CypD −/− samples. We found increased acetylation of proteins in fatty acid oxidation and branched-chain amino acid metabolism. To evaluate whether this increase in acetylation might play a role in the inhibition of fatty acid oxidation that was previously reported in CypD −/− hearts, we measured the activity of l -3-hydroxyacyl-CoA dehydrogenase, which was acetylated in the CypD −/− hearts. Consistent with the hypothesis, l -3-hydroxyacyl-CoA dehydrogenase activity was inhibited by ≈50% compared with the wild-type mitochondria. Conclusions: These results implicate a role for CypD in modulating protein acetylation. Taken together, these results suggest that ablation of CypD leads to changes in the mitochondrial acetylome, which may contribute to altered mitochondrial metabolism in CypD −/− mice.
Self‐Assembled Proteins and Peptides as Scaffolds for Tissue Regeneration
Authors: Yihua Loo, Melis Goktas, Ayse B. Tekinay, Mustafa O. Guler, Charlotte A. E. Hauser, Anna Mitraki
Journal: Advanced Healthcare Materials (2015)

Self‐assembling proteins and peptides are increasingly gaining interest for potential use as scaffolds in tissue engineering applications. They self‐organize from basic building blocks under mild conditions into supramolecular structures, mimicking the native extracellular matrix. Their properties can be easily tuned through changes at the sequence level. Moreover, they can be produced in sufficient quantities with chemical synthesis or recombinant technologies to allow them to address homogeneity and standardization issues required for applications. Here. recent advances in self‐assembling proteins, peptides, and peptide amphiphiles that form scaffolds suitable for tissue engineering are reviewed. The focus is on a variety of motifs, ranging from minimalistic dipeptides, simplistic ultrashort aliphatic peptides, and peptide amphiphiles to large “recombinamer” proteins. Special emphasis is placed on the rational design of self‐assembling motifs and biofunctionalization strategies to influence cell behavior and modulate scaffold stability. Perspectives for combination of these “bottom‐up” designer strategies with traditional “top‐down” biofabrication techniques for new generations of tissue engineering scaffolds are highlighted.
A phase 1 dose escalation study of idarubicin combined with methotrexate, vindesine, and prednisolone for untreated elderly patients with primary central nervous system lymphoma: The GOELAMS LCP 99 trial
Authors: Gaelle Olivier, Aline Clavert, Laurence Lacotte‐Thierry, Martine Gardembas, Martine Escoffre‐Barbe, Annie Brion, Isabelle Cumin, Eric Legouffe, Philippe Solal‐Celigny, Michèle Chabin, Pierre Ingrand, Philippe Colombat, Vincent Delwail
Journal: American Journal of Hematology (2014)

Treatment of primary central nervous system lymphoma (PCNSL) in elderly patients remains unsatisfactory. To develop a new high-dose methotrexate (HD-MTX)-based regimen including idarubicin, a phase 1 multicenter dose escalation study was conducted to determine the maximum-tolerated dose (MTD) of idarubicin. Thirty-five immunocompetent patients with PCNSL were enrolled. The median age was 65 years (range, 60-70 years). MTX and vindesine (VDS) were given at the fixed dose of 3 g/m(2) (6-hr intravenous [IV]) and 3 mg/m(2) IV on day 1, respectively. Prednisolone (PRED) was given at the fixed dose of 60 mg/m(2) (IV or orally) on days 1-5. Idarubicin was escalated in increments of 2 mg/m(2) with doses ranging from 12-18 mg/m(2) IV on day 1. Treatment was repeated three times every 3 weeks. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia for more than 7 days, thrombocytopenia grade 4 or nonhaematological toxicity more than grade 2. The MTD of idarubicin was reached at 16 mg/m(2) . At this level, the main haematological toxicities were thrombocytopenia grade 4: 5% and neutropenia grade 3 or 4 (52%); the main nonhaematological toxicities were grade 3 or 4 infectious disease (5%) and grade 2 renal failure (9%). For the study population, median overall and progression-free survival were 19 and 13 months, respectively. Our study suggests that the MTD of idarubicin in combination with HD-MTX, VDS, and PRED, should be 16 mg/m(2) . Further studies will be necessary to challenge a standard treatment in elderly patients with PCNSL.
THREE CASES OF VOLVULUS OF THE SIGMOID FLEXURE OF THE COLON
Authors: W. G. Nash
Journal: BMJ (1929)

the case which had had no morphine prioir to the operatioii had hail the heroin administered much sooller tlhain in tlhe first case.Since this episode, whiclh nearly ended in.a catastrophe, my practice has been (1) to be quite sure that the lpatient is fully round from the anaesthetic before any hypodermic injection is administered, and (2) to giv- only 1/12 grain of heroin, and to repeat it if necessary.My preference for heroin over moirphine is still very stronlg; buit the above two cases show that its effect o'n the resp)itatory centre may be exceedingly dangerous unless it is given in small doses.It is to draw attention to this fact that I have tlhought it advisable to publish these two cases.