tbuckley/cabot-search huggingface dataset:
Molecular Determinants of Retinoic Acid Sensitivity in Pancreatic Cancer
Authors: Sonal Gupta, Dipankar Pramanik, Radha Mukherjee, Nathaniel R. Campbell, Sathyanarayanan Elumalai, Roeland F. de Wilde, Seung-Mo Hong, Michael G. Goggins, Ana De Jesus-Acosta, Daniel Laheru, Anirban Maitra
Journal: Clinical Cancer Research (2011)

Abstract Purpose: To identify a predictive molecular “signature” for sensitivity to retinoic acid in pancreatic cancer. Experimental Design: Fourteen patient-derived, low-passage pancreatic ductal adenocarcinoma (PDAC) lines with varied expression of fatty acid–binding protein 5 (FABP5) and cellular retinoic acid–binding protein 2 (CRABP2) were used to evaluate the response to all-trans retinoic acid (ATRA). Cell proliferation, apoptosis, and migration/invasion assays were used to measure the in vitro response. Tumor growth was monitored in subcutaneous xenografts in athymic nude mice for 4 weeks. Results: Response to ATRA was observed to be dependent upon differential expression of FABP5 versus CRABP2. Thus, elevated FABP5 expression was associated with minimal cytotoxicity and tumor growth inhibition and a paradoxical increase in migration and invasion. Conversely, CRABP2 expression in the absence of FABP5 was associated with significant tumor growth inhibition with ATRA, even in gemcitabine-resistant tumors. The ATRA-resistant phenotype of FABP5highCRABP2null cells could be circumvented by ectopic expression of CRABP2. Alternatively, reexpression of endogenous CRABP2 could be enabled in FABP5highCRABP2null PDAC lines by exposure to decitabine and trichostatin A, thereby relieving epigenetic silencing of the CRABP2 gene promoter. Immunohistochemical staining for FABP5 in archival human tissue microarrays identifies a subset of cases (13 of 63, ∼20%) which are negative for FABP5 expression and might be candidates for ATRA therapy. Conclusions: The widely used agent ATRA deserves a “second look” in PDAC, but needs to be targeted to patient subsets with biopsy-proven FABP5-negative tumors, or be combined with a chromatin-modifying agent to reexpress endogenous CRABP2. Clin Cancer Res; 18(1); 280–9. ©2011 AACR.
French patients gain access to medical records
Authors: A. Dorozynski
Journal: BMJ (2001)

The French parliament last week approved a bill to give patients access to their medical records. Currently, doctors can withhold any information they feel may be harmful to patients.

The proposed legislation states that any person has the right to access medical data about him or her kept by professionals or health establishments. The information includes reports, test results, surveillance records, and any correspondence between health professionals unless it contains information about …
Dietary consumption pattern of selected commonwealth probables with special reference to energy and protein
Authors: Deethu Sara Varghese, Venkataramana Yagnambhatt, Ashok Ahuja
Journal: British Journal of Sports Medicine (2010)

Optimal nutrition is important for athletes to maintain good performance and to attain a good health in latter life. The nutrient intake of an athlete should be adequate to cover the specific energy requirement of the sport as well as for tissue maintenance and repair. The nutritional data of international level athletes is sparse in India. Therefore, a case based study was done on the representative sample from boxing, wrestling and athletics who were preparing for commonwealth games (commonwealth probables) during the initial stage of the camp. A detailed study was done on the dietary consumption pattern of these athletes, especially on energy and protein intake levels. Both the protein and energy intake was found to be higher than the recommended levels. Even, cases in which the energy intake was found to be twofold and protein intake, more than fivefolds of the requirement was found when the nutritional data of the athletes were analysed individually. Despite of meeting their requirement of energy and protein from the diet alone, athletes were found to be consuming high amount of protein supplements. This extreme pattern of protein consumption will have deleterious effects on performance and health of the athletes. Hence, necessary dietary modifications were made to bring their energy and protein consumption to the recommended levels. It can be concluded that supplementation of energy and protein is not required if an athlete is consuming a balanced diet. To achieve this, proper awareness on nutrition should be imparted to the athletes and coaches.
Primary antiphospholipid syndrome: features of patients with raised anticardiolipin antibodies and no other disorder.
Authors: C G Mackworth-Young, S Loizou, M J Walport
Journal: Annals of the Rheumatic Diseases (1989)

Raised levels of serum antiphospholipid antibodies have most commonly been reported in patients with systemic lupus erythematosus (SLE). There remains, however, a group of patients with raised antiphospholipid antibody levels who do not have any other well defined disease, but do have clinical features associated with these raised antibodies. The clinical, haematological, and serological features of 20 such patients are reported. Antiphospholipid antibody levels were measured by a solid phase assay for anticardiolipin activity. Fourteen patients had raised IgG antiphospholipid antibodies, 12 had raised IgM, and six had both. Nine out of 19 had raised antinuclear antibody levels; however, non fulfilled criteria for the diagnosis of SLE. Seven patients had a history of venous thrombosis and five of definite or presumed arterial thrombosis-for example, stroke. Of the 15 female patients who underwent pregnancy, 12 experienced fetal loss with up to eight abortions each (mean 3.6). Six individuals had thrombocytopenia and four others had migraines. Other clinical features included livedo reticularis, cardiac and neuropsychiatric disorders, arthralgias, and Raynaud9s phenomenon. These findings confirm that the clinical features of individuals with what may be called the 9primary antiphospholipid syndrome9 are similar to those in patients with other diagnoses who have raised antiphospholipid antibodies. They indicate that the antiphospholipid syndrome may be related to SLE and other autoimmune diseases, but that, although it frequently overlaps with these disorders, it also exists as a distinct entity.
Merck discloses $3.7m paid to US doctors for speeches over three months
Authors: J. Hopkins Tanne
Journal: BMJ (2009)

Merck listed $3.7m in payments to US medical experts for speaking on behalf of the company or its products between 1 July and 30 September of this year. It followed Eli Lilly in disclosing payments to doctors who speak for companies.

Pfizer and GlaxoSmithKline have promised to make similar disclosures, according to the Associated Press news agency (www.ap.org, 19 Oct 2009, “Merck starts revealing payments to doctor-speakers”).

The list on Merck’s website discloses payments to 1078 doctors and other experts who took part in Merck speaking engagements during July-September. The list includes the names …
Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial
Authors: Richard K Burt, Sanjiv J Shah, Karin Dill, Thomas Grant, Mihai Gheorghiade, James Schroeder, Robert Craig, Ikuo Hirano, Karin Marshall, Eric Ruderman, Borko Jovanovic, Francesca Milanetti, Sandeep Jain, Kristin Boyce, Amy Morgan, James Carr, Walter Barr
Journal: The Lancet (2011)
A controlled study on batted ball speed and available pitcher reaction time in slowpitch softball
Authors: M McDowell, M V Ciocco
Journal: British Journal of Sports Medicine (2005)

Objectives: To investigate safety risks in slowpitch softball by conducting laboratory and experimental studies on the performance of high tech softball bats with polyurethane softballs. To compare the results with the recommended safety standards. Methods: ASTM standard compression testing of seven softball models was conducted. Using these seven softball models, bat/ball impact testing was performed using seven adult male softball players and six high tech softball bat models to determine mean batted ball speeds. Over 500 bat/ball impact measurements were recorded and analysed. Available pitcher reaction time was calculated from the mean batted ball speed measurements. Results: According to the United States Specialty Sports Association and the Amateur Softball Association, the maximum initial batted ball speed should be 137.2 km/h, which corresponds to a minimum pitcher reaction time of 0.420 second. These experiments produced mean batted ball speeds of 134.0–159.7 km/h, which correspond to available pitcher reaction times of 0.409–0.361 second. Conclusion: The use of high tech softball bats with polyurethane softballs can result in batted ball speeds that exceed the recommended safety limits, which correspond to decreased available pitcher reaction times.
Antiretroviral Therapy for HIV Infection in 1998
Authors: Charles C. J. Carpenter, Margaret A. Fischl, Scott M. Hammer, Martin S. Hirsch, Donna M. Jacobsen, David A. Katzenstein, Julio S. G. Montaner, Douglas D. Richman, Michael S. Saag, Robert T. Schooley, Melanie A. Thompson, Stefano Vella, Patrick G. Yeni, Paul A. Volberding
Journal: JAMA (1998)

Objective.—To provide recommendations for antiretroviral therapy based on information available in mid-1998.Participants.—An international panel of physicians with expertise in antiretroviral research and care of patients with human immunodeficiency virus (HIV) infection, first convened by the International AIDS Society–USA in December 1995.Evidence.—The panel reviewed available clinical and basic science study results (including phase 3 controlled trials; clinical, virologic, and immunologic end point data; data presented at research conferences; and studies of HIV pathophysiology); opinions of panel members were also considered. Recommendations were limited to drugs available in mid-1998.Consensus Process.—Panel members monitor new clinical research reports and interim results. The full panel meets regularly to discuss how the new information may change treatment recommendations. Updated recommendations are developed through consensus of the entire panel at each stage of development.Conclusions.—Accumulating data from clinical and pathogenesis studies continue to support early institution of potent antiretroviral therapy in patients with HIV infection. A variety of combination regimens show potency, expanding choices for initial regimens for individual patients. Plasma HIV RNA assays with increased sensitivity are important in monitoring therapeutic response; however, more data are needed to determine precisely the HIV RNA levels that define treatment failure. Long-term adverse drug effects are beginning to emerge, requiring ongoing attention. Some issues regarding optimal long-term approaches to antiretroviral management are unresolved. The increased complexity in HIV management requires ongoing monitoring of new data for optimal treatment of HIV infection.
Effects of Aerobic and Resistance Exercise in Breast Cancer Patients Receiving Adjuvant Chemotherapy: A Multicenter Randomized Controlled Trial
Authors: Kerry S. Courneya, Roanne J. Segal, John R. Mackey, Karen Gelmon, Robert D. Reid, Christine M. Friedenreich, Aliya B. Ladha, Caroline Proulx, Jeffrey K.H. Vallance, Kirstin Lane, Yutaka Yasui, Donald C. McKenzie
Journal: Journal of Clinical Oncology (2007)

Breast cancer chemotherapy may cause unfavorable changes in physical functioning, body composition, psychosocial functioning, and quality of life (QOL). We evaluated the relative merits of aerobic and resistance exercise in blunting these effects.We conducted a multicenter randomized controlled trial in Canada between 2003 and 2005 that randomly assigned 242 breast cancer patients initiating adjuvant chemotherapy to usual care (n = 82), supervised resistance exercise (n = 82), or supervised aerobic exercise (n = 78) for the duration of their chemotherapy (median, 17 weeks; 95% CI, 9 to 24 weeks). Our primary end point was cancer-specific QOL assessed by the Functional Assessment of Cancer Therapy-Anemia scale. Secondary end points were fatigue, psychosocial functioning, physical fitness, body composition, chemotherapy completion rate, and lymphedema.The follow-up assessment rate for our primary end point was 92.1%, and adherence to the supervised exercise was 70.2%. Unadjusted and adjusted mixed-model analyses indicated that aerobic exercise was superior to usual care for improving self-esteem (P = .015), aerobic fitness (P = .006), and percent body fat (adjusted P = .076). Resistance exercise was superior to usual care for improving self-esteem (P = .018), muscular strength (P < .001), lean body mass (P = .015), and chemotherapy completion rate (P = .033). Changes in cancer-specific QOL, fatigue, depression, and anxiety favored the exercise groups but did not reach statistical significance. Exercise did not cause lymphedema or adverse events.Neither aerobic nor resistance exercise significantly improved cancer-specific QOL in breast cancer patients receiving chemotherapy, but they did improve self-esteem, physical fitness, body composition, and chemotherapy completion rate without causing lymphedema or significant adverse events.
Effect of Uremia and Dialysis Modality on Mononuclear Cell Apoptosis
Authors: ALEJANDRO MARTÍN-MALO, JULIA CARRACEDO, RAFAEL RAMÍREZ, ALBERTO RODRIGUEZ-BENOT, SAGRARIO SORIANO, MARIANO RODRIGUEZ, PEDRO ALJAMA
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The aim of this study was to evaluate the effect of both uremia itself and hemodialysis (HD) membranes on the induction of apoptosis. Four groups of subjects were evaluated: 21 nondialyzed (Non-D) patients, 10 continuous ambulatory peritoneal dialysis (CAPD) patients, and 53 HD patients who were on hemophan, cuprophan, cellulose acetate, AN69, and polysulfone; control subjects were nine healthy volunteers. Circulating mononuclear cells were obtained before dialysis and cultured for 48 h. Mean percentage of apoptosis was analyzed by a FACScan flow cytometer using Annexin V-FITC. Cell apoptosis was increased in Non-D patients (11.5 ± 5.5%) compared with control subjects (2.1 ± 0.7%, P &lt; 0.001) and CAPD patients (7.0 ± 5.8%, P &lt; 0.05). In patients on HD with cuprophan, apoptosis was higher than in control subjects and Non-D and CAPD patients. In Non-D patients, apoptosis was inversely correlated with renal creatinine clearance ( r = -0.62, P = 0.003). Cell apoptosis was higher in hemophan than the other HD membranes. In seven patients on hemophan, switching to polysulfone resulted in decreased apoptosis ( P &lt; 0.01). Mononuclear cell circulation through mini-dialyzers made of different types of membranes (cuprophan, hemophan, cellulose acetate, AN69, and polysulfone) prouced a significant increase in apoptosis. However, there was a marked difference in the percentage of apoptosis induced by these five membranes, being significantly increased in hemophan and cuprohan compared with the other three membranes. Similar results were obtained when whole blood from healthy donors was circulated through the mini-dialyzers, showing that mononuclear cell apoptosis was increased in hemophan and cuprophan compared with polysulfone. In conclusion, uremia and membrane characteristics may independently affect the mononuclear cell apoptosis.
Prostacyclin production and mediation of adenylate cyclase activity in the pulmonary artery. Alterations after prolonged hypoxia in the rat.
Authors: P W Shaul, B Kinane, M A Farrar, L M Buja, R R Magness
Journal: Journal of Clinical Investigation (1991)

Prostacyclin is a critical mediator of structure and function in the pulmonary circulation, causing both the inhibition of vascular smooth muscle growth and vasodilation via the stimulation of adenylate cyclase. To examine the potential role of alterations in prostacyclin production or mechanism of action in chronic hypoxic pulmonary hypertension, we determined the effects of prolonged (7 d) in vivo hypoxia on in vitro prostacyclin synthesis and mediation of adenylate cyclase activity in rat main pulmonary arteries. In control arteries prostacyclin production exceeded that of prostaglandin (PG) E2 by 25-fold, with 42% originating from the endothelium. Studies utilizing indomethacin revealed that endogenous prostaglandins mediate at least 69% of basal adenylate cyclase activity. Prostacyclin-stimulated enzyme activity was enhanced by exogenous GTP, indicating that this is a receptor-mediated process involving G protein amplification. Comparable dose-related responses to prostacyclin and PGE2 suggest that these agents may activate a common receptor. After 7 d of in vivo hypoxia there was a 2.7-fold increase in in vitro prostacyclin production, with equivalent increases in synthesis in the endothelium and vascular smooth muscle. However, despite this increase there was no change in basal adenylate cyclase activity, and this was associated with attenuated sensitivity of the enzyme to prostacyclin stimulation. Concomitant diminution of the response to beta-adrenergic stimulation, with previously-demonstrated beta receptor downregulation and unaltered postreceptor-mediated activity, suggests that the blunted response to prostacyclin is due to receptor downregulation. Parallel studies of the thoracic aorta indicated that these changes are specific to the pulmonary artery. It is postulated that attenuation of the response of adenylate cyclase to prostacyclin may contribute to the structural changes and hypertension observed in the pulmonary vasculature of the rat with chronic hypoxia.
Antineutrophil cytoplasmic antibody and vasculitis: much more than a disease marker
Authors: Vivette D’Agati
Journal: Journal of Clinical Investigation (2002)

P-ANCA); cytoplasmic ANCA (C-ANCA); myeloperoxidase (MPO); proteinase 3 (PR3); mitogen-activated protein kinase (MAPK); extracellular signal-regulated kinase (ERK); intercellular adhesion molecule-1 (ICAM-1
Angiographical Follow-Up After Radioactive “Cold Ends” Stent Implantation
Authors: A.J. Wardeh, R. Albiero, I.P. Kay, A.H.M. Knook, W. Wijns, K. Kozuma, T. Nishida, V. Ferrero, P.C. Levendag, W.J. van der Giessen, A. Colombo, P.W. Serruys
Journal: Circulation (2002)

Background — Radioactive stents with an activity of 0.75 to 12 μCi have shown &gt;40% edge restenosis due to neointimal hyperplasia and negative remodeling. This trial evaluated whether radioactive Cold Ends stents might resolve edge restenosis by preventing remodeling at the injured extremities. Methods and Results — The 25-mm long (15-mm radioactive center and 5-mm nonradioactive ends) Cold Ends stents had an activity of 3 to 12 μCi at implantation. Forty-three stents were implanted in 43 patients with de novo native coronary artery disease. Two procedural, 1 subacute, and 1 late stent thrombosis occurred. A restenosis rate of 22% was observed with a shift of the restenosis, usually occurring at the stent edges of radioactive stents, into the Cold Ends stents. The most severe restenosis occurred at the transition zone from radioactive to nonradioactive segments, a region located in dose fall-off. Conclusion — Cold Ends stents did not resolve edge restenosis.
Specific Growth Rate versus Doubling Time for Quantitative Characterization of Tumor Growth Rate
Authors: Esmaeil Mehrara, Eva Forssell-Aronsson, Håkan Ahlman, Peter Bernhardt
Journal: Cancer Research (2007)

Abstract Doubling time (DT) is widely used for quantification of tumor growth rate. DT is usually determined from two volume estimations with measurement time intervals comparable with or shorter than DT. Clinical data show that the frequency distribution of DT in patients is positively skewed, with some very long DT values compared with the average DT. Growth rate can also be quantified using specific growth rate (SGR; %/d), equal to ln2/DT. The aim of this work was to compare DT and SGR as growth rate variables. Growth rate calculations were computer simulated for a tumor with DT of 100 days, measurement time interval of 1 to 200 days, and volume estimation uncertainty of 5% to 20%. Growth rate variables were determined and compared for previously published clinical data. The study showed that DT is not a suitable variable for tumor growth rate because (a) for short measurement time intervals, or high volume uncertainties, mean DT can either overestimate or underestimate the average growth rate; (b) DT is not defined if the consecutively estimated volumes are equal; and (c) the asymmetrical frequency distribution of DT makes it unsuitable for common statistical testing. In contrast, mean SGR and its equivalent DT give the correct values for average growth rate, SGR is defined for all tumor volume changes, and it has a symmetrical frequency distribution. SGR is also more accurate to use when discussing, for example, growth fraction, cell loss rate, and growth rate heterogeneities within the tumor. SGR should thus be used, instead of DT, to quantify tumor growth rate. [Cancer Res 2007;67(8):3970–5]
N-acetylcysteine versus fenoldopam mesylate to prevent contrast agent-associated nephrotoxicity
Authors: Carlo Briguori, Antonio Colombo, Flavio Airoldi, Anna Violante, Alfredo Castelli, Pasquale Balestrieri, Pietro Paolo Elia, Bruno Golia, Stefano Lepore, Guido Riviezzo, Pierfranco Scarpato, Mariateresa Librera, Amelia Focaccio, Bruno Ricciardelli
Journal: Journal of the American College of Cardiology (2004)
TLR9-Targeted STAT3 Silencing Abrogates Immunosuppressive Activity of Myeloid-Derived Suppressor Cells from Prostate Cancer Patients
Authors: Dewan M. S. Hossain, Sumanta K. Pal, Dayson Moreira, Priyanka Duttagupta, Qifang Zhang, Haejung Won, Jeremy Jones, Massimo D'Apuzzo, Stephen Forman, Marcin Kortylewski
Journal: Clinical Cancer Research (2015)

Recent advances in immunotherapy of advanced human cancers underscored the need to address and eliminate tumor immune evasion. The myeloid-derived suppressor cells (MDSC) are important inhibitors of T-cell responses in solid tumors, such as prostate cancers. However, targeting MDSCs proved challenging due to their phenotypic heterogeneity.Myeloid cell populations were evaluated using flow cytometry on blood samples, functional assays, and immunohistochemical/immunofluorescent stainings on specimens from healthy subjects, localized and metastatic castration-resistant prostate cancer patients.Here, we identify a population of Lin(-)CD15(HI)CD33(LO) granulocytic MDSCs that accumulate in patients' circulation during prostate cancer progression from localized to metastatic disease. The prostate cancer-associated MDSCs potently inhibit autologous CD8(+) T cells' proliferation and production of IFNγ and granzyme-B. The circulating MDSCs have high levels of activated STAT3, which is a central immune checkpoint regulator. The granulocytic pSTAT3(+) cells are also detectable in patients' prostate tissues. We previously generated an original strategy to silence genes specifically in Toll-like Receptor-9 (TLR9) positive myeloid cells using CpG-siRNA conjugates. We demonstrate that human granulocytic MDSCs express TLR9 and rapidly internalize naked CpG-STAT3siRNA, thereby silencing STAT3 expression. STAT3 blocking abrogates immunosuppressive effects of patients-derived MDSCs on effector CD8(+) T cells. These effects depended on reduced expression and enzymatic activity of Arginase-1, a downstream STAT3 target gene and a potent T-cell inhibitor.Overall, we demonstrate the accumulation of granulocytic MDSCs with prostate cancer progression and the feasibility of using TLR9-targeted STAT3siRNA delivery strategy to alleviate MDSC-mediated immunosuppression.