tbuckley/cabot-search huggingface dataset:
What Adoption Gave Me
Authors: Cathy C. Schubert
Journal: Annals of Internal Medicine (2015)

On Being a Doctor17 November 2015What Adoption Gave MeCathy C. Schubert, MDCathy C. Schubert, MDFrom Indiana University School of Medicine, Indianapolis, Indiana.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M15-1225 Audio Reading - "What Adoption Gave Me" Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "What Adoption Gave Me," by C.C. Schubert. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In our society, stories about childhood adoption run the gamut. They may be tales of tragedy involving loss, abuse, neglect, Child Protective Services, and foster care. In other instances, the stories are of salvation, warmth, adversity overcome, and love.A voice seldom heard from in adoption stories, however, is that of the birth mother. At best, a birth mother is sometimes lauded for giving a miraculous gift to a loving family in need of a child. At worst, she is viewed with suspicion and scorn for getting "knocked up" in the first place, for choosing to carry her child to ... Author, Article, and Disclosure InformationAuthors: Cathy C. Schubert, MDAffiliations: From Indiana University School of Medicine, Indianapolis, Indiana.Corresponding Author: Cathy C. Schubert, MD, 1481 West 10th Street, Mail Code 111, Indianapolis, IN 46202; e-mail, caschube@iu.edu. PreviousarticleNextarticle Advertisement Audio Reading - "What Adoption Gave Me" Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "What Adoption Gave Me," by C.C. Schubert. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 17 November 2015Volume 163, Issue 10Page: 803-804KeywordsBirthDementiaEmotionsFellowshipsHeartIntelligenceKneesPatient advocacyPregnancyResidency ePublished: 17 November 2015 Issue Published: 17 November 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Dasatinib blocks transcriptional and promigratory responses to transforming growth factor-beta in pancreatic adenocarcinoma cells through inhibition of Smad signalling: implications for in vivo mode of action
Authors: Tobias Bartscht, Benjamin Rosien, Dirk Rades, Roland Kaufmann, Harald Biersack, Hendrik Lehnert, Frank Gieseler, Hendrik Ungefroren
Journal: Molecular Cancer (2015)

We have previously shown in pancreatic ductal adenocarcinoma (PDAC) cells that the SRC inhibitors PP2 and PP1 effectively inhibited TGF-β1-mediated cellular responses by blocking the kinase function of the TGF-β type I receptor ALK5 rather than SRC. Here, we investigated the ability of the clinically utilised SRC/ABL inhibitor dasatinib to mimic the PP2/PP1 effect. The effect of dasatinib on TGF-β1-dependent Smad2/3 phosphorylation, general transcriptional activity, gene expression, cell motility, and the generation of tumour stem cells was measured in Panc-1 and Colo-357 cells using immunoblotting, reporter gene assays, RT-PCR, impedance-based real-time measurement of cell migration, and colony formation assays, respectively. In both PDAC cell lines, dasatinib effectively blocked TGF-β1-induced Smad phosphorylation, activity of 3TPlux and pCAGA(12)-luc reporter genes, cell migration, and expression of individual TGF-β1 target genes associated with epithelial-mesenchymal transition and invasion. Moreover, dasatinib strongly interfered with the TGF-β1-induced generation of tumour stem cells as demonstrated by gene expression analysis and single cell colony formation. Dasatinib also inhibited the high constitutive migratory activity conferred on Panc-1 cells by ectopic expression of kinase-active ALK5. Our data suggest that the clinical efficiency of dasatinib may in part be due to cross-inhibition of tumour-promoting TGF-β signalling. Dasatinib may be useful as a dual TGF-β/SRC inhibitor in experimental and clinical therapeutics to prevent metastatic spread in late-stage PDAC and other tumours.
Association Between Olfactory Dysfunction and Amnestic Mild Cognitive Impairment and Alzheimer Disease Dementia
Authors: Rosebud O. Roberts, Teresa J. H. Christianson, Walter K. Kremers, Michelle M. Mielke, Mary M. Machulda, Maria Vassilaki, Rabe E. Alhurani, Yonas E. Geda, David S. Knopman, Ronald C. Petersen
Journal: JAMA Neurology (2015)

To increase the opportunity to delay or prevent mild cognitive impairment (MCI) or Alzheimer disease (AD) dementia, markers of early detection are essential. Olfactory impairment may be an important clinical marker and predictor of these conditions and may help identify persons at increased risk.To examine associations of impaired olfaction with incident MCI subtypes and progression from MCI subtypes to AD dementia.Participants enrolled in the population-based, prospective Mayo Clinic Study of Aging between 2004 and 2010 were clinically evaluated at baseline and every 15 months through 2014. Participants (N = 1630) were classified as having normal cognition, MCI (amnestic MCI [aMCI] and nonamnestic MCI [naMCI]), and dementia. We administered the Brief Smell Identification Test (B-SIT) to assess olfactory function.Mild cognitive impairment, AD dementia, and longitudinal change in cognitive performance measures.Of the 1630 participants who were cognitively normal at the time of the smell test, 33 died before follow-up and 167 were lost to follow-up. Among the 1430 cognitively normal participants included, the mean (SD) age was 79.5 (5.3) years, 49.4% were men, the mean duration of education was 14.3 years, and 25.4% were APOE ε4 carriers. Over a mean 3.5 years of follow-up, there were 250 incident cases of MCI among 1430 cognitively normal participants. We observed an association between decreasing olfactory identification, as measured by a decrease in the number of correct responses in B-SIT score, and an increased risk of aMCI. Compared with the upper B-SIT quartile (quartile [Q] 4, best scores), hazard ratios (HRs) (95% CI) were 1.12 (0.65-1.92) for Q3 (P = .68); 1.95 (1.25-3.03) for Q2 (P = .003); and 2.18 (1.36-3.51) for Q1 (P = .001) (worst scores; P for trend <.001) after adjustment for sex and education, with age as the time scale. There was no association with naMCI. There were 64 incident dementia cases among 221 prevalent MCI cases. The B-SIT score also predicted progression from aMCI to AD dementia, with a significant dose-response with worsening B-SIT quartiles. Compared with Q4, HR (95% CI) estimates were 3.02 (1.06-8.57) for Q3 (P = .04); 3.63 (1.19-11.10) for Q2 (P = .02); and 5.20 (1.90-14.20) for Q1 (P = .001). After adjusting for key predictors of MCI risk, B-SIT (as a continuous measure) remained a significant predictor of MCI (HR, 1.10 [95% CI, 1.04-1.16]; P < .001) and improved the model concordance.Olfactory impairment is associated with incident aMCI and progression from aMCI to AD dementia. These findings are consistent with previous studies that have reported associations of olfactory impairment with cognitive impairment in late life and suggest that olfactory tests have potential utility for screening for MCI and MCI that is likely to progress.
A Case of Metastatic Paraganglioma with Good Response to Combination of Cyclophosphamide, Vincristine and Dacarbazine
Authors: Shinya Kobayashi, Akihiko Watanabe, Masahide Ota, Takefumi Ito, Kiyohiro Fujiwara, Hiroko Sugimura, Yuichi Takezawa
Journal: Annals of Oncology (2014)
Artificial Rearing of Rat Pups: Implications for Nutrition Research
Authors: M S Patel, S Vadlamudi, G L Johanning
Journal: Annual Review of Nutrition (1994)

INTRODUCTION . . . • • • • • . . . . . . . • • . • . . . . . . . • . • . • • • . . . . . . . . . • . . . . . . . . . . . . . 21 ARTIFICIAL REARING TECHNIQUES . . . . . . • . . . . . . . . . . • • . . . . . . . . . . . . . . . . . . 23 Hand Feeding. . . . . . . . . . . • . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 Surgical and NOIISurgicalImpiantation of Feeding Tubes. . . . . . . • . . . . . . . . . . . . . . 23 Automatic Feeder Procedure. • . • • • . • • • • • . • . • • . • . • . • . • • . . . • . . . . • . . • . • . . . . . 26 PREPARATION OF MILK-SUBSTITUTE FORMULAS . . . • . . . . . . . . . . . . . . . . . . . . 26 Milk-based Formulas. • • • • • . • . • • • . • • • . • • . • • • . • . • . • • • • • • . . • • • . • . • . . . . . . . . 26 Non-milk-based Formulas . . . . . . . • • . • . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 GROWTH AND METABOLIC ADAPTATIONS DURING TIlE PREWEANING PERIOD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 Carbohydrate-Metabolizing En<;ymes in the Intestine . . . .. ... ...... .. . ........ 29 Brain pev�lopmen�  31 HepatiC LipogenesIS . . . . . . • . . . . . . . . . • . . . . . . . . . • . . . . . . . . . • . . . . . . . . . . . . . . . 32 LONG-TERM CONSEQUENCES OF EARLY NUTRITIONAL INTERVENTION .. , 35 CONCLUDING REMARKS. . • • • . . . . . . . . . . . . . . . . . . • . . . . . . . . . . . . . . . . . . . . . . . . 37
Cancer Immunotherapy Using Interleukin-2 and Interleukin-2-Activated Lymphocytes
Authors: S A Rosenberg, M T Lotze
Journal: Annual Review of Immunology (1986)

The development of immunologic approaches to the treatment of cancer has progressed through major changes in the past five years. In the 1970s considerable enthusiasm existed for immunotherapeutic approaches to cancer based on attempts to provide nonspecific stimulation of the host immune system in the hope that this general increase in immune reactiv­ ity would lead to an increased reactivity to putative tumor antigens on growing cancers. This approach was based on minimal experimental data from animal tumor models. A large number of clinical trials in humans utilized attempts to stimulate the immune system nonspecifically. Using substances such as Bacillus Calmette-Guerin (BCG), methenol-extracted residue (MER), Corynebacterium parvum, levamisole, and other immune stimulators, researchers treated patients with extensive tumor, as well as with minimal tumor burdens. This experience was almost universally unsuccessful and, both in animal tumor model systems and in the human, has largely been abandoned (I). An alternate approach to cancer immunotherapy can be categorized as passive or adoptive immunotherapy, in which the tumor-bearing host receives the systemic transfer of immunologic reagents such as antibodies or reactive cells already possessing antitumor reactivity (2-5). Because the
First conference on cancer immunotherapy gets “explosion of interest”
Authors: Nigel Hawkes
Journal: BMJ (2015)

Registration for the first international conference on cancer immunotherapy, to be held in New York from 16 September, has sold out. The venue—the Sheraton in Times Square—is too small to accommodate the many who wanted to attend.

What the conference organisers call “an explosion of interest” in the subject has reached the National Institute for Health and Care Excellence, better known for rejecting many new cancer drugs as costly and marginally effective. This week it gave approval to pembrolizumab, a new immunological treatment for melanoma, in record time.1

The man credited with pioneering the field in the 1990s, James Allison of the University of Texas MD Anderson Cancer Research Center, has just won a Lasker award, a prestigious prize many of whose recipients have …
The Relation of Oncogenesis and Cytogenetics in Leukemia and Lymphoma
Authors: M Pearson, J D Rowley
Journal: Annual Review of Medicine (1985)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
A single scale for comparing dose-intensity of all chemotherapy regimens in breast cancer: summation dose-intensity.
Authors: W Hryniuk, E Frei, F A Wright
Journal: Journal of Clinical Oncology (1998)

To construct a single scale for comparing the dose-intensity of all chemotherapy regimens in breast cancer.First-line single-agent trials in metastatic disease were reviewed. The unit dose-intensity (UDI) that was required to produce a 30% complete response plus partial response (CR + PR) rate was determined for each drug. Randomized trials were then analyzed that prospectively tested dose-intensity. The dose-intensities of the drugs in each arm were expressed as fractions of their UDIs and added together. This yielded each arm's summation dose-intensity (SDI), which was then correlated with treatment outcomes.In the single-agent trials, dose-response relationships were linear when the studies covered a range of dose-intensities. In the randomized trials that tested dose-intensity in metastatic disease, response rates and median survival correlated linearly with the SDIs of the treatment arms. An increment of one SDI unit increased CR + PR rate by approximately 30%, CR rate by 10%, and median survival by 3.75 months. Metastatic disease trials were negative if the difference between the arms was less than 0.54 SDI units. Adjuvant trials that tested a dose-intensity difference of less than 0.65 SDI units were also negative.A single-agent dose-response database can be derived from historic literature that enables comparison of the dose-intensity of all combination regimens on one scale. The dose-intensity increase required to improve outcome can then be identified in earlier trials that tested that variable. SDI methodology should be tested prospectively in contemporary patients, and may be useful in guiding dosage increases beyond the conventional range.
The mutational landscape of cutaneous T cell lymphoma and Sézary syndrome
Authors: Ana Carolina da Silva Almeida, Francesco Abate, Hossein Khiabanian, Estela Martinez-Escala, Joan Guitart, Cornelis P Tensen, Maarten H Vermeer, Raul Rabadan, Adolfo Ferrando, Teresa Palomero
Journal: Nature Genetics (2015)
Part 3: Ethical Issues
Authors: Mary E. Mancini, Douglas S. Diekema, Theresa A. Hoadley, Kelly D. Kadlec, Marygrace H. Leveille, Jane E. McGowan, Michele M. Munkwitz, Ashish R. Panchal, Michael R. Sayre, Elizabeth H. Sinz
Journal: Circulation (2015)
TIMING OF PCI IN PATIENTS WITH NON-ST-ELEVATION MYOCARDIAL INFARCTION: A SWEDEHEART STUDY
Authors: Christoph Varenhorst, Joakim Alfredsson, Oskar Angerås, Felix Böhm, Fredrik Calais, Stefan James, Sasha Koul, Bo Lagerqvist, Henrik Renlund, Giovanna Sarno, Daniel Lindholm
Journal: Journal of the American College of Cardiology (2016)
Type-I Diabetes: A Chronic Autoimmune Disease of Human, Mouse, and Rat
Authors: L Castaño, G S Eisenbarth
Journal: Annual Review of Immunology (1990)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Activation of the First Component of Complement
Authors: V N Schumaker, P Zavodszky, P H Poon
Journal: Annual Review of Immunology (1987)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Impact of treatment with biologic DMARDs on the risk of sepsis or mortality after serious infection in patients with rheumatoid arthritis
Authors: A Richter, J Listing, M Schneider, T Klopsch, A Kapelle, J Kaufmann, A Zink, A Strangfeld
Journal: Annals of the Rheumatic Diseases (2015)

This observational cohort study investigated the impact of biological (b) disease-modifying antirheumatic drugs (DMARDs) on the outcomes of serious infections (SIs) in patients with rheumatoid arthritis.We investigated outcomes of SIs observed in 947 patients enrolled in the German biologics register RABBIT(Rheumatoid arthritis: observation of biologic therapy). Outcomes were (1) recovery without complication, (2) sepsis following SI (≤30 days), and (3) death after SI without known sepsis (≤90 days). We applied a multinomial generalised estimating equation model for longitudinal data to evaluate the risks of sepsis and death simultaneously.Sepsis within 30 days after SI was reported in 135 out of 947 patients, 85 of these had a fatal outcome. Fifty-three patients died within 90 days after SI without known sepsis. The adjusted risk of developing sepsis increased with age and was higher in patients with chronic renal disease. Compared with conventional synthetic (cs)DMARDs, the risk was significantly lower when patients were exposed to bDMARDs at the time of SI (OR: 0.56, 95% CI 0.38 to 0.81). Risk factors of fatal SI were higher age, use of glucocorticoids at higher doses and heart failure. Patients treated with bDMARDs and those with better physical function had a significantly lower mortality risk.These results suggest a beneficial effect of bDMARDs on the risk of sepsis after SI and the risk of a fatal outcome. Successful immunosuppression may prevent an unregulated host response to SI, that is, the escalation to sepsis. Further investigation is needed to validate these results.
OP0118 Altered T Cell Plasticity Favors TH17 Cells in Rheumatoid Arthritis
Authors: J. Leipe, F. Pirronello, S. Hermann, M. Schiemann, H. Schulze-Koops, A. Skapenko
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Previously, T helper (Th) cell subsets have been regarded as irreversibly differentiated endpoints. However, evidence suggests that Th cell differentiation is a plastic process in response to certain (e.g. inflammatory) conditions. Mechanisms leading to the pathogenetic important predominance of Th17 cells in rheumatoid arthritis (RA) are not yet understood. <h3>Objectives</h3> Therefore, we investigated plasticity and underlying molecular mechanisms to address the question if an altered T cell plasticity contributes to the shift towards the Th17 phenotype in RA. <h3>Methods</h3> A unique cohort of 40 patients with early, active and untreated RA (to exclude effects of immunosuppressive drugs on T cells) and 41 age- and sex- matched healthy controls (HC) were studied. Viable <i>in vivo</i>-originated Th1, Th2 and Th17 cells were FACS-sorted and trans-differentiated under Th1-, Th2- or Th17-inducing conditions. The cytokine Th profile of the trans-differentiated cells was assessed by flow cytometry. Epigenetic modifications including histone modifications and DNA methylation of Th cell-associated cytokine and transcription factor gene loci were analyzed by ChiP assay and bisulfite sequencing. Relative expression of cytokine and transcription factors was measured by ELISA and qRT-PCR. <h3>Results</h3> Th17 cells from RA patients cultured under Th1 and Th2 conditions showed a strikingly diminished trans-differentiation capacity into both Th1 and Th2 phenotypes and retained their IL-17 expression to a significantly higher degree compared to Th17 cells from HC. Vice versa, RA Th1 and Th2 cells demonstrated an enhanced capacity to re-differentiate into Th17 cells. We found higher <i>RORC</i> expression in RA Th1 cells that were trans-differentiated under Th17 conditions as a basis for increased re-differentiation of Th1 to Th17 cells in RA. With regard to epigenetic regulation, an overrepresentation of the permissive histone modification H3 actetylation over the repressive H3K27 methylation was found in the <i>IL17</i> and <i>RORC</i> loci of T cells from RA patients. Moreover, DNA methylation was decreased in RA Th17 cells compared to HC enabling higher IL-17 expression. <h3>Conclusions</h3> Our data indicate that <i>in vivo</i>-originated Th17 cells in RA are resistant to changes in their phenotype, whereas other Th subsets are prone to Th17 cell trans-differentiation. Increased RORC expression, permissive histone modifications and a less DNA methylation at Th17 genes facilitating IL-17 expression might contribute to the altered Th plasticity in RA, thereby contributing to the pathogenic Th17 shift. <h3>Disclosure of Interest</h3> None declared
Insulin Resistance Syndrome Predicts Coronary Heart Disease Events in Elderly Type 2 Diabetic Men
Authors: Johanna Kuusisto, Päivi Lempiäinen, Leena Mykkänen, Markku Laakso
Journal: Diabetes Care (2001)

OBJECTIVE—To investigate whether cardiovascular risk factors cluster with hyperinsulinemia in elderly type 2 diabetic subjects and, if so, whether this clustering predicts coronary heart disease (CHD) events during a 7-year follow-up. RESEARCH DESIGN AND METHODS—Clustering of cardiovascular risk factors was analyzed by factor analysis. Cox regression models were used to investigate whether these clusters (factors) predict CHD events (CHD death or nonfatal myocardial infarction) during a 7-year follow-up in 229 type 2 diabetic subjects aged 65–74 years. RESULTS—There were 70 CHD events (21 in men and 49 in women) during the follow-up period. In diabetic men, components of the insulin resistance syndrome (IRS) loaded on Factor 1 (the insulin resistance factor), which reflected high fasting insulin, obesity (high BMI), central obesity (high waist-to-hip ratio), high total triglycerides, and a short duration of diabetes. Only this IRS factor predicted CHD events in multivariate Cox regression analysis (hazard ratio [HR] 1.71, 95% CI 1.08–2.71, P = 0.022). In diabetic women, components of IRS loaded on two factors, none of which predicted CHD events. In women, only Factor 4, characterized by advanced age, left ventricular hypertrophy on electrocardiogram, high alcohol consumption, high systolic blood pressure, and albuminuria, predicted CHD events in multivariate Cox regression analysis (1.34, 1.03–1.74, P = 0.03). CONCLUSIONS—IRS is a risk factor for CHD in elderly type 2 diabetic men.
Diagnosis and preoperative tagging of duodenal gastrinoma by endoscopic ultrasound
Authors: Rodica Gincul, Vincent Lepilliez, Thomas Walter, Maud Rabeyrin, Thierry Ponchon, Mustapha Adham, Jean-Alain Chayvialle
Journal: Endoscopy (2015)

Almost 50 % of sporadic duodenal gastrin-expressing neuroendocrine tumors (NETs), so-called gastrinomas, are associated with Zollinger–Ellison syndrome (ZES). The risk for lymph node metastasis is high (40 % – 70 %), even in tumors smaller than 10 mm [1]. We report the endoscopic ultrasound (EUS) diagnosis of a case of sporadic duodenal gastrinoma manifesting with ZES.