tbuckley/cabot-search huggingface dataset:
First European data from the network of severe allergic reactions (<scp>NORA</scp>)
Authors: M. Worm, A. Moneret‐Vautrin, K. Scherer, R. Lang, M. Fernandez‐Rivas, V. Cardona, M. L. Kowalski, M. Jutel, I. Poziomkowska‐Gesicka, N. G. Papadopoulos, K. Beyer, T. Mustakov, G. Christoff, M. B. Bilò, A. Muraro, J. O. B. Hourihane, L. B. Grabenhenrich
Journal: Allergy (2014)

Occurrence, elicitors and treatment of severe allergic reactions are recognized and reported differently between countries. We aimed to collect standardized data throughout Europe on anaphylaxis referred for diagnosis and counselling.Tertiary allergy, dermatology and paediatric units in 10 European countries took part in this pilot phase of the first European Anaphylaxis Registry, from June 2011 to March 2014. An online questionnaire was used to collect data on severe allergic reactions based on the medical history and diagnostics.Fifty-nine centres reported 3333 cases of anaphylaxis, with 26.7% below 18 years of age. Allergic reactions were mainly caused by food (children and adults 64.9% and 20.2%, respectively) and insect venom (20.2% and 48.2%) and less often by drugs (4.8% and 22.4%). Most reactions occurred within 30 min of exposure (80.5%); a delay of 4+ hours was mainly seen in drug anaphylaxis (6.7%). Symptom patterns differed by elicitor, with the skin being affected most often (84.1%). A previous, usually milder reaction to the same allergen was reported by 34.2%. The mainstay of first-line treatment by professionals included corticoids (60.4%) and antihistamines (52.8%). Only 13.7% of lay- or self-treated reactions to food and 27.6% of insect anaphylaxis received on-site adrenaline.This pilot phase of a pan-European registry for severe allergic reactions provides for the first time data on anaphylaxis throughout Europe, demonstrates its potential functionality and allows a comparison of symptom patterns, elicitors and treatment habits between referral centres and countries.
Innate immune responses in hepatitis C virus-exposed healthcare workers who do not develop acute infection
Authors: Jens Martin Werner, Theo Heller, Ann Marie Gordon, Arlene Sheets, Averell H. Sherker, Ellen Kessler, Kathleen S. Bean, M'Lou Stevens, James Schmitt, Barbara Rehermann
Journal: Hepatology (2013)

Hepatitis C virus (HCV) infection typically results in chronic disease with HCV outpacing antiviral immune responses. Here we asked whether innate immune responses are induced in healthcare workers who are exposed to small amounts of HCV, but do not develop systemic infection and acute liver disease. Twelve healthcare workers with accidental percutaneous exposure to HCV-infected blood were prospectively studied for up to 6 months for phenotype and function of natural killer T (NKT) and NK cells, kinetics of serum chemokines, and vigor and specificity of HCV-specific T-cell responses. Eleven healthcare workers tested negative for HCV RNA and HCV antibodies. All but one of these aviremic cases displayed NKT cell activation, increased serum chemokines levels, and NK cell responses with increased CD122, NKp44, NKp46, and NKG2A expression, cytotoxicity (as determined by TRAIL and CD107a expression), and interferon-gamma (IFN-γ) production. This multifunctional NK cell response appeared a month earlier than in the one healthcare worker who developed high-level viremia, and it differed from the impaired IFN-γ production, which is typical for NK cells in chronic HCV infection. The magnitude of NKT cell activation and NK cell cytotoxicity correlated with the magnitude of the subsequent HCV-specific T-cell response. T-cell responses targeted nonstructural HCV sequences that require translation of viral RNA, which suggests that transient or locally contained HCV replication occurred without detectable systemic viremia.Exposure to small amounts of HCV induces innate immune responses, which correlate with the subsequent HCV-specific T-cell response and may contribute to antiviral immunity.
Sentinel Lymph Node Procedure Is Highly Accurate in Squamous Cell Carcinoma of the Vulva
Authors: J.A. de Hullu, H. Hollema, D.A. Piers, R.H. M. Verheijen, P.J. van Diest, M.J. E. Mourits, J.G. Aalders, A.G. J. van der Zee
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine the diagnostic accuracy of the sentinel lymph node procedure in patients with squamous cell carcinoma of the vulva and to investigate whether step sectioning and immunohistochemistry of sentinel lymph nodes increase the sensitivity for detection of metastases. PATIENTS AND METHODS: Between July 1996 and July 1999, 59 patients with primary vulvar cancer were entered onto a two-center prospective study. All patients underwent sentinel lymph node procedure with the combined technique (preoperative lymphoscintigraphy with technetium-99m–labeled nanocolloid and intraoperative blue dye). Radical excision of the primary tumor with uni- or bilateral inguinofemoral lymphadenectomy was performed subsequently. Sentinel lymph nodes and lymphadenectomy specimens were sent for histopathologic examination separately. Sentinel lymph nodes, negative at the time of routine pathologic examination, were re-examined with step sectioning and immunohistochemistry. RESULTS: In 59 patients, 107 inguinofemoral lymphadenectomies were performed (11 unilateral and 48 bilateral). All sentinel lymph nodes, as observed on preoperative lymphoscintigram, were identified successfully intraoperatively. Routine histopathologic examination showed lymph node metastases in 27 groins, all of which were detected by the sentinel lymph node procedure. The negative predictive value for a negative sentinel lymph node was 100% (97.5% confidence interval [CI], 95% to 100%). Step sectioning and immunohistochemistry showed four additional metastases in 102 sentinel lymph nodes (4%; 95% CI, 1% to 9%) that were negative at the time of routine histopathologic examination. CONCLUSION: Sentinel lymph node procedure with the combined technique is highly accurate in predicting the inguinofemoral lymph node status in patients with early-stage vulvar cancer. Future trials should focus on the safe clinical implementation of the sentinel lymph node procedure in these patients. Step sectioning and immunohistochemistry slightly increase the sensitivity of detecting metastases in sentinel lymph nodes and should be included in these trials.
Cyclosporin A, FK-506, and Rapamycin: Pharmacologic Probes of Lymphocyte Signal Transduction
Authors: N H Sigal, F J Dumont
Journal: Annual Review of Immunology (1992)

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
Bio++: Efficient Extensible Libraries and Tools for Computational Molecular Evolution
Authors: Laurent Guéguen, Sylvain Gaillard, Bastien Boussau, Manolo Gouy, Mathieu Groussin, Nicolas C. Rochette, Thomas Bigot, David Fournier, Fanny Pouyet, Vincent Cahais, Aurélien Bernard, Céline Scornavacca, Benoît Nabholz, Annabelle Haudry, Loïc Dachary, Nicolas Galtier, Khalid Belkhir, Julien Y. Dutheil
Journal: Molecular Biology and Evolution (2013)

Efficient algorithms and programs for the analysis of the ever-growing amount of biological sequence data are strongly needed in the genomics era. The pace at which new data and methodologies are generated calls for the use of pre-existing, optimized—yet extensible—code, typically distributed as libraries or packages. This motivated the Bio++ project, aiming at developing a set of C++ libraries for sequence analysis, phylogenetics, population genetics, and molecular evolution. The main attractiveness of Bio++ is the extensibility and reusability of its components through its object-oriented design, without compromising the computer-efficiency of the underlying methods. We present here the second major release of the libraries, which provides an extended set of classes and methods. These extensions notably provide built-in access to sequence databases and new data structures for handling and manipulating sequences from the omics era, such as multiple genome alignments and sequencing reads libraries. More complex models of sequence evolution, such as mixture models and generic n-tuples alphabets, are also included.
Continuous inhalation of nitric oxide protects against development of pulmonary hypertension in chronically hypoxic rats.
Authors: C Kouyoumdjian, S Adnot, M Levame, S Eddahibi, H Bousbaa, B Raffestin
Journal: Journal of Clinical Investigation (1994)

Exposure to hypoxia and subsequent development of pulmonary hypertension is associated with an impairment of the nitric oxide (NO) mediated response to endothelium-dependent vasodilators. Inhaled NO may reach resistive pulmonary vessels through an abluminal route. The aim of this study was to investigate if continuous inhalation of NO would attenuate the development of pulmonary hypertension in rats exposed to chronic hypoxia. In conscious rats previously exposed to 10% O2 for 3 wk, short-term inhalation of NO caused a dose-dependent decrease in pulmonary artery pressure (PAP) from 44 +/- 1 to 32 +/- 1 mmHg at 40 ppm with no changes in systemic arterial pressure, cardiac output, or heart rate. In normoxic rats, acute NO inhalation did not cause changes in PAP. In rats simultaneously exposed to 10% O2 and 10 ppm NO during 2 wk, right ventricular hypertrophy was less severe (P < 0.01), and the degree of muscularization of pulmonary vessels at both alveolar duct and alveolar wall levels was lower (P < 0.01) than in rats exposed to hypoxia alone. Tolerance to the pulmonary vasodilator effect of NO did not develop after prolonged inhalation. Brief discontinuation of NO after 2 wk of hypoxia plus NO caused a rapid increase in PAP. These data demonstrate that prolonged inhalation of low concentrations of NO induces sustained pulmonary vasodilation and reduces pulmonary vascular remodeling in response to chronic hypoxia.
Immunohistochemical and functional correlations of renal cyclooxygenase-2 in experimental diabetes
Authors: Radko Komers, Jessie N. Lindsley, Terry T. Oyama, William E. Schutzer, John F. Reed, Scott L. Mader, Sharon Anderson
Journal: Journal of Clinical Investigation (2001)

Prostaglandins (PGs) generated by the enzyme cyclooxygenase (COX) have been implicated in the pathological renal hemodynamics and structural alterations in diabetes mellitus, but the role of individual COX isoenzymes in diabetic nephropathy remains unknown. We explored COX-1 and COX-2 expression and hemodynamic responses to the COX-1 inhibitor valeryl salicylate (VS) or the COX-2 inhibitor NS398 in moderately hyperglycemic, streptozotocin-diabetic (D) and control (C) rats. Immunoreactive COX-2 was increased in D rats compared with C rats and normalized by improved glycemic control. Acute systemic administration of NS398 induced no significant changes in mean arterial pressure and renal plasma flow in either C or D rats but reduced glomerular filtration rate in D rats, resulting in a decrease in filtration fraction. VS had no effect on renal hemodynamics in D rats. Both inhibitors decreased urinary excretion of PGE2. However, only NS398 reduced excretion of thromboxane A2. In conclusion, we documented an increase in renal cortical COX-2 protein expression associated with a different renal hemodynamic response to selective systemic COX-2 inhibition in D as compared with C animals, indicating a role of COX-2–derived PG in pathological renal hemodynamic changes in diabetes.
Use of the Medical Futility Rationale in Do-Not-Attempt-Resuscitation Orders
Authors: J. Randall Curtis, David R. Park, Melissa R. Krone, Robert A. Pearlman
Journal: JAMA (1995)

To describe the use of the medical futility rationale in do-not-attempt-resuscitation (DNAR) orders written for medical inpatients.Structured interviews with medical residents.Second- and third-year internal medicine residents (n = 44) were telephoned weekly and briefly interviewed about each patient who received a DNAR order in the preceding week.Two university-affiliated hospitals: a veterans affairs medical center and a municipal hospital.One hundred forty-five medical inpatients for whom DNAR orders were written during their hospitalization.Residents stated that the medical futility rationale applied for 91 patients (63%), but this rationale was invoked independent of patient or surrogate choice for only 17 patients (12%). Of the 91 patients for whom futility applied, both quantitative futility (low probability of success) and qualitative futility (poor quality of life if cardiopulmonary resuscitation [CPR] were performed) applied to 45 (49%), quantitative futility alone to 30 (33%), and qualitative futility alone to 16 (18%). Residents report that they discussed resuscitation issues with all communicative patients for whom the medical futility rationale was invoked. Among patients for whom quantitative futility applied, residents' predictions of the probability that patients would survive to hospital discharge after CPR varied from 0% (for 60% of patients) to 75%. For 32% of these patients, residents predicted survival at 5% or more. Logistic regression modeling showed that the presence of organ failure (odds ratio [OR], 8.9; 95% confidence interval [CI], 3.3 to 23.9), the residents' estimates of the probability of surviving CPR (OR, 0.94; 95% CI, 0.88 to 0.99), and nonwhite race (OR, 2.7; 95% CI, 1.1 to 6.3) were associated with the determination of quantitative futility. In one third of the cases where qualitative futility applied, residents made the judgment of qualitative futility without discussing quality of life with communicative patients. Logistic regression modeling showed immobility (OR, 3.2; 95% CI, 1.1 to 9.0) and age > or = 75 years (OR, 0.3; 95% CI, 0.1 to 0.8) to be associated with the determination of qualitative futility.While residents did not appear to use the medical futility rationale to avoid discussing DNAR issues with patients, we found evidence of important misunderstandings of the concepts of both quantitative and qualitative futility. If the futility rationale is to be applied to withholding or withdrawing medical interventions, practice guidelines for its use should be developed, and education about medical futility must be incorporated into medical school, residency training, and continuing medical education programs.
The Schedule-Dependent Effects of the Novel Antifolate Pralatrexate and Gemcitabine Are Superior to Methotrexate and Cytarabine in Models of Human Non-Hodgkin's Lymphoma
Authors: Lorraine E. Toner, Radovan Vrhovac, Emily A. Smith, Jeffrey Gardner, Mark Heaney, Mithat Gonen, Julie Teruya-Feldstein, Frank Sirotnak, Owen A. O'Connor
Journal: Clinical Cancer Research (2006)

Methotrexate is known to synergize with cytarabine [1-beta-D-arabinofuranosylcytosine (ara-C)] in a schedule-dependent manner. The purpose of this article is to compare and contrast the activity of pralatrexate (10-propargyl-10-deazaminopterin)/gemcitabine to the standard combination of methotrexate/ara-C and to determine if schedule dependency of this combination is important in lymphoma.Cytotoxicity assays using the standard trypan blue exclusion assay were used to explore the in vitro activity of pralatrexate and gemcitabine against a panel of lymphoma cell lines. Both severe combined imunodeficient beige and irradiated nonobese diabetic/severe combined imunodeficient mouse xenograft models were used to compare and contrast the in vivo activity of these combinations as a function of schedule. In addition, apoptosis assays were conducted.Compared with methotrexate-containing combinations, pralatrexate plus gemcitabine combinations displayed improved therapeutic activity with some schedule dependency. The combination of pralatrexate and gemcitabine was superior to any methotrexate and ara-C combination in inducing apoptosis and in activating caspase-3. In vivo, the best therapeutic effects were obtained with the sequence of pralatrexate --> gemcitabine. Complete remissions were only appreciated in animals receiving pralatrexate followed by gemcitabine.These data show that the combination of pralatrexate followed by gemcitabine was superior to methotrexate/ara-C in vitro and in vivo, and was far more potent in inducing apoptosis in a large B-cell lymphoma. These data provide strong rationale for further study of this combination in lymphomas where methotrexate and ara-C are used.
Reply to A. Ocana et al
Authors: Javier Cortés, Antonio Llombart-Cussac, Emiliano Calvo
Journal: Journal of Clinical Oncology (2013)

We have read with interest the letter from Ocana et al in reaction to our article entitled “Progress Against Solid Tumors in Danger: The Metastatic Breast Cancer Example.” We appreciate their comments in support of our main arguments. We agree with Ocana et al about the inclusion of composite end points of progression-free survival (PFS), and patient-reported outcome as reasonable approaches in the design of clinical trials. However, Ocana et al comment on the case of trastuzumab emtansine as second-line therapy in metastatic breast cancer or the pertuzumab story as examples of increased overall survival (OS), even with long postprogression survival times. These examples are not comparable with bevacizumab; in fact, with the same argumentation, should lapatinib, which is another human epidermal growth factor receptor 2–targeted agent that has not shown survival gain in its two approved indications, follow the same path? There are dozens of active drugs with a strong impact on PFS without translation into an increase in OS. We strongly believe that the most important issue is the concept and not particular cases. We also agree with the importance of biomarker discovery as stated in the summary of our article. In the meantime, we cannot forget that a considerable number of patients might experience benefit from bevacizumab. Everolimus, which was recently approved in metastatic breast cancer, is a mammalian target of rapamycin inhibitor that has been shown to improve PFS in combination with exemestane in nonsteroidal aromatase-inhibitor– resistant patients. However, no biomarkers have been identified, and thousands of women are already being treated with this approach. Ocana et al also express their concern about safety and tolerability of bevacizumab. However, as previously published, the toxicity profile of bevacizumab in patients with breast cancer seems to be better than the ones reported in other tumor types in which bevacizumab is approved. Although the real-world benefit and efficacy-effectiveness gap is always intriguing, this is inherent to all drugs in clinical trials. We should try to treat patients according to guidelines, which generally take into account inclusion and exclusion criteria from clinical trials. However, is there any difference in this with respect to bevacizumab compared with other agents? Finally, we completely agree, as discussed in our article, that the high prices of drugs are of concern. This situation is clearly not sustainable, and we should do all our best to redefine economic strategies, but value and price should not be confused when solely evaluating the antitumor efficacy of drugs by regulatory agencies. Although some drugs have unrealistic prices and are not cost effective, we should be transparent and consistent in the drug approval processes. Otherwise, our progress against solid tumors will be in danger.
LaTulippe--a case study of a one hundred and sixty kilometre runner.
Authors: W. J. O'Hara, C. Allen, R. J. Shephard, J. W. Gill
Journal: British Journal of Sports Medicine (1977)

A 55 year old runner covered 160 km within a 20 hour period. His speed averaged 8.16 km/h, at an estimated 59.1% of maximum oxygen intake. After the first four hours of running, one of five fluids was taken in rotation every twelve minutes. Volumes ingested whe heart rate for the final four hours (125/min) was not increased relative to oxygen consumption for this portion of the run. Constancy of heart rate, continued urine production and formal fluid balance calculations all indicate that hydration was well maintained over the run. Caloric intake averaged 480 kcal/h (2.01 MJH), being greatest fro the ice-creas/syrup mixture; the energy deficit (56/KA/H, 235 kJ/h) was small during that part of the run in which food was provided.
Immune Recruitment and Therapeutic Synergy: Keys to Optimizing Oncolytic Viral Therapy?
Authors: Jay D. Naik, Christopher J. Twelves, Peter J. Selby, Richard G. Vile, John D. Chester
Journal: Clinical Cancer Research (2011)

Abstract Oncolytic viruses consist of a diverse range of DNA and RNA viruses traditionally thought to mediate their effects by exploiting aberrations in tumor pathways, allowing preferential viral replication in, and killing of, tumor cells. Clinical development has progressed to late-phase trials, potentially heralding their introduction into clinical practice. However, despite this promise, the activity of oncolytic viruses has yet to achieve the potential suggested in preclinical models. To address this disparity, we need to recognize the complex interaction among oncolytic viruses, tumor, chemotherapy, and host immune system, and appreciate that direct oncolysis may not be the only factor to play an important role in oncolytic virus-mediated antitumor efficacy. Although key in inactivating viruses, the host immune system can also act as an ally against tumors, interacting with oncolytic viruses under the right conditions to generate useful and long-lasting antitumor immunity. Preclinical data also suggest that oncolytic viruses show synergy with standard therapies, which may offer improved clinical response rates. Here, we explore clinical and preclinical data on clinically relevant oncolytic viruses, highlighting areas of progress, uncertainty, and translational opportunity, with respect to immune recruitment and therapeutic synergy. Clin Cancer Res; 17(13); 4214–24. ©2011 AACR.
Skeletal Muscle Index (Smi) is a Prognostic Factor in Metastatic Renal Cell Carcinoma (Mrcc) Patients Treated with Everolimus: a Retrospective Study
Authors: E. Auclin, C. Bourillon, L. Fournier, M. Auvray, P. Combe, R. Elaidi, A. Angelergues, E. Fabre, S. Oudard, Y. Vano
Journal: Annals of Oncology (2014)