tbuckley/cabot-search huggingface dataset:
TGF-β Receptor II Loss Promotes Mammary Carcinoma Progression by Th17-Dependent Mechanisms
Authors: Sergey V. Novitskiy, Michael W. Pickup, Agnieszka E. Gorska, Philip Owens, Anna Chytil, Mary Aakre, Huiyun Wu, Yu Shyr, Harold L. Moses
Journal: Cancer Discovery (2011)

We report that IL-17 significantly increases the secretion of CXCL1 and CXCL5 from mammary carcinoma cells, which is downregulated by TGF-β through the type II TGF-β receptor (TβRII). Carcinoma cells with conditional knockout of TβRII (Tgfbr2(KO)) have enhanced sensitivity to IL-17a in the stimulation of chemokine secretion. During polyoma middle T (PyMT) induced tumor progression, levels of Th17 inducing cytokines TGF-β, IL-6, IL-23 were increased in PyMT/Tgfbr2(KO) tumors, which was associated with an increased number of Th17 cells. IL-17 increased the suppressive function of MDSCs on T cells through the upregulation of Arg, IDO, and COX2. Treatment of PyMT/Tgfbr2(KO) mice with anti-IL-17 Ab decreased carcinoma growth and metastatic burden. Analysis of human breast cancer transcriptome databases showed a strong association between IL-17 gene expression and poor outcome in lymph node positive, estrogen receptor negative or luminal B subtypes suggesting potential therapeutic approaches.
VASCULARIZATION OF THE CORNEA OF THE RAT IN RIBOFLAVIN DEFICIENCY, WITH A NOTE ON CORNEAL VASCULARIZATION IN VITAMIN A DEFICIENCY
Authors: O. A. Bessey, S. B. Wolbach
Journal: The Journal of Experimental Medicine (1939)

Vascularization of the cornea of the rat in the absence of antecedent pathology is probably a specific and the most reliable criterion of riboflavin deficiency. Its initiation and repair may be used for testing the biological activity of compounds structurally related to riboflavin. The facts that the invading capillaries are easily visible in the living animal and that the growth and regression of the blood vessels are under dietary control and for a considerable period of time unaccompanied by other pathological reactions, make this method very suitable for the study of problems related to capillary growth. We believe that the best hypothesis in explanation is that the vascularization is a response to asphyxia of the tunica propria.
Anticarbamylated protein antibodies can be detected in animal models of arthritis that require active involvement of the adaptive immune system
Authors: Jeroen N Stoop, Anita Fischer, Silvia Hayer, Martin Hegen, Tom WJ Huizinga, Guenter Steiner, Leendert A Trouw, René EM Toes
Journal: Annals of the Rheumatic Diseases (2015)

A key characteristic of rheumatoid arthritis (RA), is the occurrence of antibodies against post-translationally modified proteins. Citrullination and anti-citrullinated protein antibodies (ACPAs) have been studied extensively.1 Carbamylation is another type of post-translational modification. During carbamylation, isocyanic acid reacts with the amine group of an amino acid. This mostly results in the conversion of lysine into homocitrulline.2 A subset of patients with RA harbour anticarbamylated protein (anti-CarP) antibodies and the presence of these antibodies is predictive of worse disease progression in ACPA-negative patients.3 Anti-CarP antibodies can be present in patients with arthralgia and their presence predicts the development of RA.4 

A cornerstone of biomedical research is the use of animal models to explore basic pathophysiological mechanisms. Therefore, it is important to know whether antibodies against post-translationally modified proteins are present in these models. Although ACPAs were initially reported to be present in collagen-induced arthritis (CIA),5 ,6 this topic is now debated. Little is …
* Reducing capsule endoscopy reading times: efficacy of new playback functions
Authors: V. Subramanian, J. Mannath, E. Telakis, K. Ragunath, C. Hawkey
Journal: Gut (2011)

<h3>Introduction</h3> Capsule endoscopy (CE) has proven to be a valuable tool in the evaluation of obscure GI bleeding, suspected Crohn9s disease, coeliac disease and polyposis syndromes. The reading time and interpretation of video capsule data is very time consuming given that, in total, more than 50,000 images have to be reviewed. Recently, Olympus capsule endoscopy software systems have been equipped with auto-speed adjusted, express view and overview functions. The aim of this study was to evaluate the new functions by analysing the diagnostic yield of CE and the reading time of the new playback features by comparing it with conventional analysing systems. <h3>Methods</h3> Data on 42 patients who underwent CE were obtained, and two experienced CE readers (&gt;100 cases) analyzed the CE images independently using either the overview with express selected function or the overview with auto-speed adjusted function respectively. All CE videos were read blinded at 15 frames per second using the two new functions. The diagnostic yield was then compared to the conventionally read CE findings. All CE recording were done using the Olympus (Keymed UK) capsule endoscopy systems and read using the Olympus EndoCapsule software package. <h3>Results</h3> 42 patients (20 male, 22 female) with a mean age of 49.3(±21.2) years were included in the study. Clinically significant findings were found in 24/42 (60%) of patients. Using overview functions alone would have resulted in missing 6/24 (25%) clinically significant findings, while both express selected and auto-speed adjusted methods missed 1/24 (4%) clinically significant findings each. The average reading time for the auto-speed function plus overview was 35(±10) minutes and was significantly (p=0.01) more than that for express selected plus overview which was 20(±5) min. If the CE videos were read conventionally at 15 frames per second the average reading time based on the length of the recording would have been 47 (±14) min. <h3>Conclusion</h3> The diagnostic miss rate was high when overview functions alone were used. There was no significant difference in positive findings between auto-speed adjusted and express selected functions when used along with overview functions and the reading time using the new systems was significantly shorter than the conventional system. The new playback systems can efficaciously reduce reading times of CE with the express selected function reducing readings time significantly more than the auto-speed adjusted function.
Soft Tissue Sarcomas
Authors: Alain Spatz, Brigitte Bressac-de Paillerets, Eric Raymond
Journal: Journal of Clinical Oncology (2004)

4][5] It is usually encountered in adolescents and young adults between 15 and 35 years of age, with a predominance in females (female-male ratio, 2:1). 2 In adults, the lower extremities are most frequently affected, whereas it is uncommon to occur before the age of 5 years.The head and neck region is the most common site.Presentation as an orbital mass is extremely unusual except in children and infants in whom the orbit and tongue are the most common sites of origin.Early metastasis is not uncommon in ASPS, and lung, bone, and brain are the predominant sites of involvement. 5The deceptive clinical features of ASPS as a painless slowgrowing orbital mass with negative findings on both magnetic resonance imaging and positron-emission tomography scans pose significant challenges for diagnosis. 5,6Common differential diagnosis includes angiosarcoma, renal cell carcinoma, paraganglioma, granular cell tumor, malignant melanoma, and alveolar rhabdomyosarcoma. 3The myogenic origin is the most favorable theory, based on the ultrastructural similarity between the lattice crystals and the actin filaments, as well as the immunohistochemical positivity of some ASPSs for desmin, smooth muscle actin, myoglobulin, and MyoD1. 4,7Surgical excision is still the mainstay of therapy for localized ASPS.No adjuvant therapy has been offered in our case, as there is no consensus as to the efficacy of either chemotherapy or radiotherapy. 8,9
Insulin Resistance and Environmental Pollutants: Experimental Evidence and Future Perspectives
Authors: Tine L.M. Hectors, Caroline Vanparys, Luc F. Van Gaal, Philippe G. Jorens, Adrian Covaci, Ronny Blust
Journal: Environmental Health Perspectives (2013)

The metabolic disruptor hypothesis postulates that environmental pollutants may be risk factors for metabolic diseases. Because insulin resistance is involved in most metabolic diseases and current health care prevention programs predominantly target insulin resistance or risk factors thereof, a critical analysis of the role of pollutants in insulin resistance might be important for future management of metabolic diseases.We aimed to critically review the available information linking pollutant exposure to insulin resistance and to open the discussion on future perspectives for metabolic disruptor identification and prioritization strategies.We searched PubMed and Web of Science for experimental studies reporting on linkages between environmental pollutants and insulin resistance and identified a total of 23 studies as the prime literature.Recent studies specifically designed to investigate the effect of pollutants on insulin sensitivity show a potential causation of insulin resistance. Based on these studies, a summary of viable test systems and end points can be composed, allowing insight into what is missing and what is needed to create a standardized insulin resistance toxicity testing strategy.It is clear that current research predominantly relies on top-down identification of insulin resistance-inducing metabolic disruptors and that the development of dedicated in vitro or ex vivo screens to allow animal sparing and time- and cost-effective bottom-up screening is a major future research need.
Initial Treatment of Aggressive Lymphoma with High-Dose Chemotherapy and Autologous Stem-Cell Support
Authors: Noel Milpied, Eric Deconinck, Fanny Gaillard, Vincent Delwail, Charles Foussard, Christian Berthou, Remy Gressin, Virginie Lucas, Philippe Colombat, Jean-Luc Harousseau
Journal: New England Journal of Medicine (2004)

The efficacy of first-line intensive chemotherapy plus transplantation of autologous hematopoietic stem cells in adults with disseminated aggressive lymphoma is unknown.
Performance of Two Geriatric Screening Tools in Older Patients With Cancer
Authors: Cindy Kenis, Lore Decoster, Katrien Van Puyvelde, Jacques De Grève, Godelieve Conings, Koen Milisen, Johan Flamaing, Jean-Pierre Lobelle, Hans Wildiers
Journal: Journal of Clinical Oncology (2013)

To compare the diagnostic characteristics of two geriatric screening tools (G8 and Flemish version of the Triage Risk Screening Tool [fTRST]) to identify patients with a geriatric risk profile and to evaluate their prognostic value for functional decline and overall survival (OS).Patients ≥ 70 years old with a malignant tumor were included if a new cancer event occurred requiring treatment decision. Geriatric screening with G8 and fTRST (cutoff ≥ 1 [fTRST (1)] and ≥ 2 [fTRST (2)] evaluated) was performed in all patients, as well as a geriatric assessment (GA) evaluating social situation, functionality (activities of daily living [ADL] + instrumental activities of daily living [IADL]), cognition, depression, and nutrition. Functionality was re-evaluated 2 to 3 months after cancer treatment decision, and death rate was followed. Functional decline and OS were evaluated in relation to normal versus abnormal score on both screening tools.Nine hundred thirty-seven patients were included (October 2009 to July 2011). G8 and fTRST (1) showed high sensitivity (86.5% to 91.3%) and moderate negative predictive value (61.3% to 63.4%) to detect patients with a geriatric risk profile. G8 and fTRST (1) were strongly prognostic for functional decline on ADL and IADL, and G8, fTRST (1), and fTRST (2) were prognostic for OS (all P < .001). G8 had the strongest prognostic value for OS (hazard ratio for G8 normal v abnormal, 0.38; 95% CI, 0.27 to 0.52).Both geriatric screening tools, G8 and fTRST, are simple and useful instruments in older patients with cancer for identifying patients with a geriatric risk profile and have a strong prognostic value for functional decline and OS.
A Prospective Multivariate Analysis of Clinical Factors Associated With Pouchitis After Ileal Pouch–Anal Anastomosis
Authors: Phillip Fleshner, Andrew Ippoliti, Marla Dubinsky, Steven Ognibene, Eric Vasiliauskas, Marjorie Chelly, Ling Mei, Konstantinos A. Papadakis, Carol Landers, Stephan Targan
Journal: Clinical Gastroenterology and Hepatology (2007)
How To Do It: Get patients' consent to enter clinical trials
Authors: E. Wager, P. J H Tooley, M. B Emanuel, S. F Wood
Journal: BMJ (1995)

Gaining patients' consent to enter clinical trials is essential, but not easy. Giving careful thought to the design of the study itself, information which patients receive, and the use of a signed consent form may all help. To be properly informed, patients need to know something about their condition, the proposed study, and alternative options. The type and amount of information will vary and investigators need to judge the level appropriate for each person. Patients should understand that taking part in a clinical trial is voluntary and that their decision will not affect the quality of care they receive. The process of obtaining consent requires time and good communication. Working with young, elderly, or mentally impaired patients, or those particularly vulnerable to coercion, requires special sensitivity to the potential dangers.
Automatic tailoring of positive end-expiratory pressure (PEEP) by forced oscillation technique (FOT) during non-invasive ventilation: Effects of posture and exertion in COPD
Authors: Raffaele Dellaca, Bob Romano, Joe Garuccio, Cherian John, Ramesh Thimmiah, Melvin Saludes, Charles Cain
Journal: European Respiratory Journal (2012)

Expiratory Flow Limitation (EFL) promotes the development of intrinsic PEEP (PEEPi). EFL can be detected by FOT at 5 Hz from the difference between inspiratory and expiratory reactance (ΔXrs) during quiet breathing (ERJ 2004;23:232) and CPAP (ERJ 2006;27: 983). This non-invasive measurement has been incorporated in a mechanical ventilator (Synchrony, Philips/Respironics, USA) resulting in a prototype that continuously measures ΔXrs and automatically adjusts PEEP to the minimum pressure able to abolish EFL (PEEPopt).  The aim of this study was to measure PEEPopt in a group of COPD patients and to evaluate its alterations with changes in posture and during a six minute walking test (6MWT).  Eleven COPD patients (GOLD stage 2-4, BMI 30±10, FEV1%pred 48±12, FEV1/FVC 56±8) were initiated to nasal BiPAP with automatic PEEP adjustment. After adaptation, ventilation was applied for 10 minutes in the seated and supine positions and during a 6MWT. Data were recorded in the last minute for each condition.  At PEEP=2cmH2O, 8 patients showed EFL in the seated position, 10 in the supine and 9 in the last minute of the 6MWT. The average PEEPopt is reported in figure.  In mild to severe COPD, the development of EFL is greatly affected by posture and exertion and this results in major adjustments in the PEEP required to counteract PEEPi within the same patient.
Direct detection of endogenous hydroxyl radical production in cultured adult cardiomyocytes during anoxia and reoxygenation. Is the hydroxyl radical really the most damaging radical species?
Authors: M A Khalid, M Ashraf
Journal: Circulation Research (1993)

Isolated adult rat cardiac myocytes were subjected to anoxia and substrate deprivation for 15, 30, 60, 90, and 120 minutes and reoxygenation for 120 seconds. The supernatant and cell extract were analyzed for hydroxyl radicals (.OH) with high-performance liquid chromatography using salicylate as a trapping agent. The production of intracellular H2O2 as a possible precursor of .OH was also documented using the fluorescent probe dichlorofluorescein diacetate. The release of the cytosolic enzyme lactate dehydrogenase (LDH) and malondialdehyde (MDA) formation were used as cell injury markers. Trypan blue and horseradish peroxidase stains were used as markers for altered membrane permeability. Maximum formation of .OH was observed in myocytes subjected to 15 minutes of anoxia/reoxygenation (2.83 +/- 0.27 nmol/mg protein), at which time no injury was observed at light and ultramicroscopic levels. On the other hand, there was no correlation between the amount of .OH production and different parameters of cell injury in myocytes subjected to anoxia/reoxygenation longer than 15 minutes. Myocytes developed extensive blebbing, loss of cell membrane permeability, and ultrastructural damage. The enzyme leakage was minimal at 15 minutes (0.094 +/- 0.021 units/mg protein) and increased fivefold after 120 minutes (0.428 +/- 0.069 units/mg protein). Similarly, MDA increased from 0.78 +/- 0.14 nmol/mg protein at 15 minutes to 1.65 +/- 0.35 nmol/mg protein at 120 minutes. Incubation with 1 mM deferoxamine reduced the .OH production at all anoxic intervals, most significantly at 15 minutes, but did not decrease LDH and MDA release or provide ultrastructural preservation. However, preincubation with 2.5 microM diphenylphenylenediamine markedly reduced both LDH and MDA release and offered prominent ultrastructural protection. These results suggest that 1) myocytes were able to generate .OH endogenously; 2) maximum .OH was produced at 15 minutes after anoxic reoxygenation without compromising cell viability; 3) prolongation of the anoxic period exacerbated cell damage without parallel increase in .OH generation; 4) there was no significant production of .OH after 15 minutes of anoxia/reoxygenation with or without treatment of deferoxamine, suggesting that prolonged anoxia/reoxygenation does not induce additional .OH formation and thus mediate cell injury; and 5) it is likely that the damage to myocytes in this system was still mediated by free radicals other than .OH, as indicated by the protection by diphenylphenylenediamine against the cellular injury.
Cardiac Toxicity in Breast Cancer Survivors: Review of Potential Cardiac Problems
Authors: Brian R.J. Healey Bird, Sandra M. Swain
Journal: Clinical Cancer Research (2008)

Abstract As breast cancer survival is increased by the diagnosis of earlier-stage disease and treatments improve, the side effects of cancer treatments, such as cardiotoxicity, remain clinically important. Although physicians have known for 30 years that anthracyclines cause acute and chronic cardiotoxicity, the cardiotoxic effects of radiation therapy, hormonal therapy (including tamoxifen and the aromatase inhibitors), and chemotherapy with taxanes and trastuzumab treatment have emerged more recently. This review examines the cardiac toxicity of adjuvant therapy, monitoring for early changes and existing guidelines for monitoring cardiac function in patients with breast cancer.
The Treatment of Graves Disease
Authors: Frank O. Becker
Journal: JAMA (1975)

To the Editor.—  In a letter by Caswell and Maier (227:939, 1974) on the treatment of Graves disease, the authors conclude that the advantages of surgical treatment over radioactive iodine therapy and antithyroid drug treatment ensure that it will continue to be the standard by which other treatment methods are measured. They studied 72 patients with previous subtotal thyroidectomy for Graves disease and found a low incidence of postoperative hypothyroidism (10%) as well as a low incidence of recurrent hyperthyroidism (6%).1In support of this view, Griffiths et al,2studying 55 thyrotoxic patients following thyroidectomy, recently reported an 11% incidence of hypothyroidism and 3.5% incidence of recurrence. Successful treatment with radioactive iodine, on the other hand, is accompanied by an incidence of hypothyroidism of between 30% and 70% by 10 to 20 years of followup.3  It should be pointed out, however, that all studies are not in
Cancer therapy by resuscitating Notch immune surveillance
Authors: Anil Shanker, Duafalia F Dudimah, Samuel T Pellom, Roman V Uzhachenko, David P Carbone, Mikhail M Dikov
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts The immunosuppressive tumor microenvironment perturbs numerous immune regulatory networks and usurps host antitumor immunity. We discovered that tumor interferes with host hematopoietic Notch system in lung cancer patients [[1][1]]. The resultant decrease in immune Notch signaling
Plasma Bikunin As a Favorable Prognostic Factor in Ovarian Cancer
Authors: Hidenori Matsuzaki, Hiroshi Kobayashi, Tatsuo Yagyu, Kiyoshi Wakahara, Toshiharu Kondo, Noriyuki Kurita, Hideo Sekino, Kiyokazu Inagaki, Mika Suzuki, Naohiro Kanayama, Toshihiko Terao
Journal: Journal of Clinical Oncology (2005)

Bikunin is a multifunctional glycoprotein, which mediates suppression of tumor cell invasion and metastasis. The measurement of bikunin levels in the tissue of patients with malignant diseases has been introduced as a new and simple diagnostic tool for the evaluation of prognosis. The high bikunin expression in ovarian cancer tissue would enable the use of soluble bikunin protein present in the circulation of ovarian cancer patients as a biomarker of disease.We developed a double-antibody immunoassay for bikunin and detected its presence in normal human circulation. We quantified, by enzyme-linked immunosorbent assay and/or immunoblot assay bikunin in sera from 200 healthy women (controls), 200 patients with benign gynecologic diseases, and 327 patients with ovarian cancer before surgical removal of the tumor.When the values of bikunin corresponding to the median were used as the cutoff value (11.5 microg/mL), low plasma bikunin was strongly associated with late-stage, suboptimal debulking with large residual tumor (> 2 cm) and low response to chemotherapy. The median survival time of the patients with a high bikunin level was more than 60 months as compared with 26 months among those with low bikunin level (P = .002). This difference corresponded to a 2.2-fold increased risk of dying for the lower plasma bikunin patients (hazard ratio, 0.45; P = .023) and remained significant in multivariate analysis (hazard ratio, 0.63; P = .041).Preoperative plasma bikunin concentration is a strong and independent favorable prognostic marker for ovarian cancer.