tbuckley/cabot-search huggingface dataset:
CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells
Authors: Andreas Herrmann, Saul J. Priceman, Maciej Kujawski, Hong Xin, Gregory A. Cherryholmes, Wang Zhang, Chunyan Zhang, Christoph Lahtz, Claudia Kowolik, Steve J. Forman, Marcin Kortylewski, Hua Yu
Journal: Journal of Clinical Investigation (2014)

Intracellular therapeutic targets that define tumor immunosuppression in both tumor cells and T cells remain intractable. Here, we have shown that administration of a covalently linked siRNA to an aptamer (apt) that selectively binds cytotoxic T lymphocyte–associated antigen 4 (CTLA4apt) allows gene silencing in exhausted CD8+ T cells and Tregs in tumors as well as CTLA4-expressing malignant T cells. CTLA4 expression was upregulated in CD8+ T cells in the tumor milieu; therefore, CTLA4apt fused to a STAT3-targeting siRNA (CTLA4apt–STAT3 siRNA) resulted in internalization into tumor-associated CD8+ T cells and silencing of STAT3, which activated tumor antigen–specific T cells in murine models. Both local and systemic administration of CTLA4apt–STAT3 siRNA dramatically reduced tumor-associated Tregs. Furthermore, CTLA4apt–STAT3 siRNA potently inhibited tumor growth and metastasis in various mouse tumor models. Importantly, CTLA4 expression is observed in T cells of patients with blood malignancies, and CTLA4apt–STAT3 siRNA treatment of immunodeficient mice bearing human T cell lymphomas promoted tumor cell apoptosis and tumor growth inhibition. These data demonstrate that a CTLA4apt-based siRNA delivery strategy allows gene silencing in both tumor-associated T cells and tumor cells and inhibits tumor growth and metastasis.
Numerical abstractness and elementary arithmetic
Authors: Jamie I. D. Campbell, Arron W. S. Metcalfe
Journal: Behavioral and Brain Sciences (2009)

Abstract Like number representation, basic arithmetic seems to be a natural candidate for abstract instantiation in the brain. To investigate this, researchers have examined effects of numeral format on elementary arithmetic (e.g., 4+5 vs. four+five). Different numeral formats often recruit distinct processes for arithmetic, reinforcing the conclusion that number processing is not necessarily abstracted away from numeral format.
Patients with mantle cell lymphoma failing ibrutinib are unlikely to respond to salvage chemotherapy and have poor outcomes
Authors: C.Y. Cheah, D. Chihara, J.E. Romaguera, N.H. Fowler, J.F. Seymour, F.B. Hagemeister, R.E. Champlin, M.L. Wang
Journal: Annals of Oncology (2015)
From reinforcement of acts to reinforcement of social preferences
Authors: Daniel John Zizzo
Journal: Behavioral and Brain Sciences (2002)

Rachlin rightly highlights behavioural reinforcement, conditional cooperation, and framing. However, genes may explain part of the variance in altruistic behaviour. Framing cannot be used to support his theory of altruism. Reinforcement of acts is not identical to reinforcement of patterns of acts. Further, many patterns of acts could be reinforced, and Rachlin's altruism is not the most likely candidate.
Autoantibodies to T and B cell lines detected in serum samples from patients with systemic lupus erythematosus with lymphopenia and hypocomplementaemia.
Authors: M Noguchi, M Iwamori, T Hirano, S Kobayashi, H Hashimoto, S Hirose, Y Nagai
Journal: Annals of the Rheumatic Diseases (1992)

Antibodies to lymphocytes in serum samples from 88 patients with systemic lupus erythematosus (SLE) and 15 normal control subjects were examined by a cell enzyme linked immunosorbent assay (ELISA) with four human T and B cell lines as antigens. The antibodies reacted with the Wa B cell line and the T cell lines P12 (CD4-, CD8+), Jurkat (CD4-, CD8-), and Hut78 (CD4+, CD8-). Antibody titres in serum samples from patients with SLE were higher than in those from normal control subjects. Titres of antibodies to P12 were correlated with titres of antibodies to Wa, Jurkat, and Hut78 in serum samples from patients with SLE. IgG antibodies to P12 were associated with lymphopenia and reduced haemolytic complement. By thin layer chromatography immunostaining, the antibodies in serum samples from two of 10 patients with SLE with high titres of IgG antibodies to P12 and lymphopenia were shown to react with three monosialoglycosphingolipids and two neutral glycosphingolipids from P12 cells. Antibodies to lymphocytes in serum samples from patients with SLE react with T and B cell lines, recognise a series of cell membrane glycosphingolipids and are associated with the lymphopenia and hypocomplementaemia typical of active disease.
S<scp>UCCESSFUL</scp> W<scp>EIGHT</scp> L<scp>OSS</scp> M<scp>AINTENANCE</scp>
Authors: Rena R Wing, James O Hill
Journal: Annual Review of Nutrition (2001)

▪ Abstract Obesity is now recognized as a serious chronic disease, but there is pessimism about how successful treatment can be. A general perception is that almost no one succeeds in long-term maintenance of weight loss. To define long-term weight loss success, we need an accepted definition. We propose defining successful long-term weight loss maintenance as intentionally losing at least 10% of initial body weight and keeping it off for at least 1 year. According to this definition, the picture is much more optimistic, with perhaps greater than 20% of overweight/obese persons able to achieve success. We found that in the National Weight Control Registry, successful long-term weight loss maintainers (average weight loss of 30 kg for an average of 5.5 years) share common behavioral strategies, including eating a diet low in fat, frequent self-monitoring of body weight and food intake, and high levels of regular physical activity. Weight loss maintenance may get easier over time. Once these successful maintainers have maintained a weight loss for 2–5 years, the chances of longer-term success greatly increase.
Limitations of Conventional Methods of Self-Monitoring of Blood Glucose
Authors: Elizabeth Boland, Teresa Monsod, Maria Delucia, Cynthia A. Brandt, Sanjay Fernando, William V. Tamborlane
Journal: Diabetes Care (2001)

OBJECTIVE—Children with type 1 diabetes are usually asked to perform self-monitoring of blood glucose (SMBG) before meals and at bedtime, and it is assumed that if results are in target range, along with HbA1c measurements, then overall glycemic control is adequate. However, the brief glimpses in the 24-h glucose profile provided by SMBG may miss marked glycemic excursions. The MiniMed Continuous Glucose Monitoring System (CGMS) has provided a new method to obtain continuous glucose profiles and opportunities to examine limitations of conventional monitoring. RESEARCH DESIGN AND METHODS—A total of 56 children with type 1 diabetes (age 2–18 years) wore the CGMS for 3 days. Patients entered four fingerstick blood samples into the monitor for calibration and kept records of food intake, exercise, and hypoglycemic symptoms. Data were downloaded, and glycemic patterns were identified. RESULTS—Despite satisfactory HbA1c levels (7.7 ± 1.4%) and premeal glucose levels near the target range, the CGMS revealed profound postprandial hyperglycemia. Almost 90% of the peak postprandial glucose levels after every meal were &amp;gt;180 mg/dl (above target), and almost 50% were &amp;gt;300 mg/dl. Additionally, the CGMS revealed frequent and prolonged asymptomatic hypoglycemia (glucose &amp;lt;60 mg/dl) in almost 70% of the children. CONCLUSIONS—Despite excellent HbA1c levels and target preprandial glucose levels, children often experience nocturnal hypoglycemia and postprandial hyperglycemia that are not evident with routine monitoring. Repeated use of the CGMS may provide a means to optimize basal and bolus insulin replacement in patients with type 1 diabetes.
Endogenous Steroid Hormone Concentrations and Risk of Breast Cancer Among Premenopausal Women
Authors: A. Heather Eliassen, Stacey A. Missmer, Shelley S. Tworoger, Donna Spiegelman, Robert L. Barbieri, Mitch Dowsett, Susan E. Hankinson
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Higher levels of endogenous sex steroid hormones are associated with increased risks of breast cancer in postmenopausal women. Data for premenopausal women are sparse, in part because of the complexity of measuring hormone levels that vary cyclically. We prospectively evaluated associations between plasma sex hormone levels and breast cancer risk among premenopausal women in a case–control study nested within the Nurses' Health Study II. Methods: From 1996 to 1999, blood samples were collected from 18 521 premenopausal women during the early follicular and midluteal phases of their menstrual cycles. A total of 197 cases of breast cancer were diagnosed among these women after blood collection and before June 1, 2003; these case subjects were matched to 394 control subjects. Logistic regression models, controlling for breast cancer risk factors, were used to calculate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results: Women in the highest (versus the lowest) quartiles of follicular total and free estradiol levels had statistically significantly increased risks of breast cancer (RR = 2.1 [95% CI = 1.1 to 4.1], Ptrend = .08, and RR = 2.4 [95% CI = 1.3 to 4.5], Ptrend = .01, respectively); the associations were stronger for invasive breast cancer and for estrogen and progesterone receptor–positive (ER+/PR+) tumors. Luteal estradiol levels were not associated with breast cancer risk. Higher levels of total and free testosterone and androstenedione in both menstrual cycle phases were associated with modest, non–statistically significant increases in overall risk of breast cancer and with stronger, statistically significant increases in risks of invasive and ER+/PR+ cancers (e.g., RR of invasive cancers for the top [versus bottom] quartile of luteal total testosterone levels = 2.0 [95% CI = 1.1 to 3.6], Ptrend = .05, and RR of ER+/PR+ cancers = 2.9 [95% CI = 1.4 to 6.0], Ptrend = .02). Levels of estrone, estrone sulfate, progesterone, and sex hormone–binding globulin were not associated with breast cancer risk. The absolute number of cases observed over 3 years were 30 among women in the lowest 25% of follicular total estradiol levels and 50 among women in the highest 25%. Conclusions: Levels of circulating estrogens and androgens may be important in the etiology of premenopausal breast cancer.
Late neonatal lupus erythematosus onset in a child born of a mother with primary Sjogren's syndrome
Authors: Rolf Manthorpe, Åke Svensson, LE Wirestrand
Journal: Annals of the Rheumatic Diseases (2004)

The neonatal lupus syndrome can be present as congenital heart block (CHB) or as neonatal lupus erythematosus (NLE), both seldom passively acquired autoimmune diseases. CHB starts around week 20 of pregnancy and is a lifelong event, whereas NLE is self limiting and usually starts at the 6th week of the child's age-the maximum recorded up to week 20.An asymptomatic mother with primary Sjogren's syndrome and anti-SSA/Ro52, anti-SSA/Ro60, and anti-SSB/La autoantibodies is described who, at gestational week 23 during her first pregnancy, was diagnosed as having a male fetus with CHB due to third degree atrioventricular block. The boy from the second pregnancy developed skin eruptions which clinically and by biopsy were compatible with NLE at week 20+1 post partum.Our case of NLE, starting at week 20+1 of age, seems to be the latest reported clinical case of NLE. Development of CHB and NLE in two consecutive boy pregnancies is unusual.
Antitumor Activity of Cell-Permeable RUNX3 Protein in Gastric Cancer Cells
Authors: Junghee Lim, Tam Duong, Nga Do, Phuong Do, Jaetaek Kim, Hyuncheol Kim, Wael El-Rifai, H. Earl Ruley, Daewoong Jo
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Gastric cancer is a leading cause of cancer death worldwide. Limited therapeutic options highlight the need to understand the molecular changes responsible for the disease and to develop therapies based on this understanding. The goal of this study was to develop cell-permeable (CP-) forms of the RUNT-related transcription factor 3, RUNX3–a candidate tumor suppressor implicated in gastric and other epithelial cancers–to study the therapeutic potential of RUNX3 in the treatment of gastric cancer. Experimental Design: We developed novel macromolecule transduction domains (MTD) which were tested for the ability to promote protein uptake by mammalian cells and tissues and used to deliver of biologically active RUNX3 into human gastric cancer cells. The therapeutic potential CP-RUNX3 was tested in the NCI-N87 human tumor xenograft animal model. Results: RUNX3 fusion proteins, HM57R and HM85R, containing hydrophobic MTDs enter gastric cancer cells and suppress cell phenotypes (e.g., cell-cycle progression, wounded monolayer healing, and survival) and induce changes in biomarker expression (e.g., p21Waf1 and VEGF) consistent with previously described effects of RUNX3 on TGF-β signaling. CP-RUNX3 also suppressed the growth of subcutaneous human gastric tumor xenografts. The therapeutic response was comparable with studies augmenting RUNX3 gene expression in tumor cell lines; however, the protein was most active when administered locally, rather than systemically (i.e., intravenously). Conclusions: These results provide further evidence that RUNX3 can function as a tumor suppressor and suggest that practical methods to augment RUNX3 function could be useful in treating of some types of gastric cancer. Clin Cancer Res; 19(3); 680–90. ©2012 AACR.
At least some electrophysiological and behavioural data cannot be reconciled with the planning–control model
Authors: P. Paolo Battaglini, Paolo Bernardis, Nicola Bruno
Journal: Behavioral and Brain Sciences (2004)

The planning/control distinction is an important tool in the study of sensorimotor transformations. However, published data from our laboratories suggest that, contrary to what is predicted by the proposed model, (1) structures in the superior parietal lobe of both monkeys and humans can be involved in movement planning; and (2) fast pointing actions can be immune to visual illusions even if they are performed without visual feedback. The planning–control model as proposed by Glover is almost certainly too schematic.
Vitamin D reduces eosinophilic airway inflammation in nonatopic asthma
Authors: Jantina C. de Groot, Eric N.H. van Roon, Huib Storm, Nic J.G.M. Veeger, Aeilko H. Zwinderman, Pieter S. Hiemstra, Elisabeth H.D. Bel, Anneke ten Brinke
Journal: Journal of Allergy and Clinical Immunology (2015)
Strategies of Radioiodine Ablation in Patients with Low-Risk Thyroid Cancer
Authors: Martin Schlumberger, Bogdan Catargi, Isabelle Borget, Désirée Deandreis, Slimane Zerdoud, Boumediene Bridji, Stéphane Bardet, Laurence Leenhardt, Delphine Bastié, Claire Schvartz, Pierre Vera, Olivier Morel, Danielle Benisvy, Claire Bournaud, Fran\ccoise Bonichon, Catherine Dejax, Marie-Elisabeth Toubert, Sophie Leboulleux, Marcel Ricard, Ellen Benhamou
Journal: New England Journal of Medicine (2012)

It is not clear whether the administration of radioiodine provides any benefit to patients with low-risk thyroid cancer after a complete surgical resection. The administration of the smallest possible amount of radioiodine would improve care.
GROUP THERAPY IN SEXUAL MALADJUSTMENT
Authors: ABRAHAM STONE, LENA LEVINE
Journal: American Journal of Psychiatry (1950)

Group therapy in sexual maladjustment is a feasible and useful method. In some cases, it actually brings about a complete solution; in others, it serves to crystallize rapidly the areas of conflict. It affords the benefit that verbalization and catharsis have in clarifying a confusing problem. It relieves the feeling of inadequacy and isolation and provides an incentive for accepting a varying response. The group technique also emphasizes the universality of basic needs, as well as the uniqueness of the individual, and the resulting differences in behavior and attitudes to the same situation. This form of therapy, furthermore, offers a fertile field for research in the problems of sexual and other marital maladjustments, and can also be utilized in the training of students in the problems of marriage and the family.
Long-Term Outcome and Disability of Diabetic Patients Hospitalized for Diabetic Foot Ulcers
Authors: Edouard Ghanassia, Laetitia Villon, Jean-François Thuan dit Dieudonné, Catherine Boegner, Antoine Avignon, Ariane Sultan
Journal: Diabetes Care (2008)

The long-term outcome and functional status of subjects hospitalized for diabetic foot ulcers have been poorly studied and thus are the topics of this study.Ninety-four consecutive diabetic subjects hospitalized for diabetic foot ulcers between January 1998 and December 2000 were prospectively followed for mean +/- SD 79.5 +/- 13.3 months. We calculated rates of primary healing, new ulcers, amputations, mortality, and disability and evaluated the global therapeutic success (GTS) of foot care management as defined by the association of primary healing without recurrence or disability at the end of follow-up.Follow-up was successful in 89 of 94 subjects (63 men and 31 women; age 63.7 +/- 10.8 years). Of these, 69 (77.5%) experienced primary healing without major amputation, 39 (43.8%) underwent amputation (24 minor and 15 major), and 46 died (51.7%), including 23 from cardiovascular events. Forty-two of 69 patients who experienced primary healing (60.9%) had ulcer recurrence. At the end of the follow-up period, 25 patients (28.1%) were dependent and 40 subjects (44.9%) had achieved GTS. Multivariate analysis showed the role of age as an independent predictor of GTS (P < 0.05) and of impaired renal function/albuminuria as independent predictors of healing failure, first amputation, and mortality (P < 0.01).Despite a satisfactory initial healing rate, the global long-term outcome of patients hospitalized for diabetic foot ulcers was poor. Nephropathy appears to be an important predictor of long-term outcome. Further studies are needed to establish recognized criteria for therapeutic success going beyond just the evaluation of healing rate in the management of diabetic foot ulcers.
XVI International Cancer Congress opens in New Delhi, India
Authors: R. M. Romano
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article XVI International Cancer Congress opens in New Delhi, India Get access Rose Mary Romano Rose Mary Romano Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 20, 19 October 1994, Pages 1496–1497, https://doi.org/10.1093/jnci/86.20.1496 Published: 19 October 1994
Cancer Drug Development and the Evolving Regulatory Framework for Companion Diagnostics in the European Union
Authors: Francesco Pignatti, Falk Ehmann, Robert Hemmings, Bertil Jonsson, Micha Nuebling, Marisa Papaluca-Amati, Martin Posch, Guido Rasi
Journal: Clinical Cancer Research (2014)

Abstract The European Union (EU) legal framework for medical device regulation is currently under revision. The European Commission has proposed a new framework to ensure that medical devices serve the needs and ensure the safety of European citizens, aiming for a framework that is fit for purpose, more transparent, and better adapted to scientific and technological progress. The proposed new framework is described as an evolution of the current regime keeping the same legal approach. An important proposed change is that companion diagnostics will no longer be considered as low risk and subject to self-certification by the manufacturer. According to the new proposal, companion diagnostics will be classified as high individual risk or moderate public health risk (category C) and require conformity assessment by a notified body. It has also been proposed that evidence of the clinical utility of the device for the intended purpose should be required for companion diagnostics. In this article, we review the EU legal framework relevant for companion diagnostics, describe the proposed changes, and summarize the available scientific guidance from the European Medicines Agency and its regulatory experience with cancer drug development including companion diagnostics. See all articles in this CCR Focus section, “The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development.” Clin Cancer Res; 20(6); 1458–68. ©2014 AACR.
A rapid decrease in the expression of DMT1 and Dcytb but not Ireg1 or hephaestin explains the mucosal block phenomenon of iron absorption
Authors: D M Frazer
Journal: Gut (2003)

<b>Background:</b> A large oral dose of iron will reduce the absorption of a subsequent smaller dose of iron in a phenomenon known as mucosal block. Molecular analysis of this process may provide insights into the regulation of intestinal iron absorption. <b>Aims:</b> To determine the effect of an oral bolus of iron on duodenal expression of molecules associated with intestinal iron transport in rats and to relate this to changes in iron absorption. <b>Methods:</b> Rats were given an oral dose of iron and duodenal expression of divalent metal transporter 1 (DMT1), Dcytb, Ireg1, and hephaestin (Hp) was determined using the ribonuclease protection assay, western blotting, and immunofluorescence. Iron absorption was measured using radioactive <sup>59</sup>Fe. <b>Results:</b> A decrease in intestinal iron absorption occurred following an oral dose of iron and this was associated with increased enterocyte iron levels, as assessed by iron regulatory protein activity and immunoblotting for ferritin. Reduced absorption was also accompanied by a rapid decrease in expression of the mRNAs encoding the brush border iron transport molecules Dcytb and the iron responsive element (IRE) containing the splice variant of DMT1. No such change was seen in expression of the non-IRE splice variant of DMT1 or the basolateral iron transport molecules Ireg1 and Hp. Similar changes were observed at the protein level. <b>Conclusions:</b> These data indicate that brush border, but not basolateral, iron transport components are regulated locally by enterocyte iron levels and support the hypothesis that systemic stimuli exert their primary effect on basolateral transport molecules.