tbuckley/cabot-search huggingface dataset:
Intrathecal triple therapy decreases central nervous system relapse but fails to improve event-free survival when compared with intrathecal methotrexate: results of the Children's Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the Children's Oncology Group
Authors: Yousif Matloub, Susan Lindemulder, Paul S. Gaynon, Harland Sather, Mei La, Emmett Broxson, Rochelle Yanofsky, Raymond Hutchinson, Nyla A. Heerema, James Nachman, Marilyn Blake, Linda M. Wells, April D. Sorrell, Margaret Masterson, John F. Kelleher, Linda C. Stork
Journal: Blood (2006)
Mitogen‐activated protein kinase kinase kinase 4 deficiency in intrahepatic cholangiocarcinoma leads to invasive growth and epithelial‐mesenchymal transition
Authors: Liu‐Xiao Yang, Qiang Gao, Jie‐Yi Shi, Zhi‐Chao Wang, Yong Zhang, Ping‐Ting Gao, Xiao‐Ying Wang, Ying‐Hong Shi, Ai‐Wu Ke, Guo‐Ming Shi, Jia‐Bin Cai, Wei‐Ren Liu, Meng Duan, Ying‐Jun Zhao, Yuan Ji, Dong‐Mei Gao, Kai Zhu, Jian Zhou, Shuang‐Jian Qiu, Ya Cao, Qi‐Qun Tang, Jia Fan
Journal: Hepatology (2015)

The molecular pathogenesis of intrahepatic cholangiocarcinoma (iCCA) is poorly understood, and its incidence continues to increase worldwide. Deficiency of mitogen‐activated protein kinase kinase kinase 4 (MAP3K4) has been reported to induce the epithelial‐mesenchymal transition (EMT) process of placental and embryonic development, yet its role in human cancer remains unknown. MAP3K4 has somatic mutation in iCCA so we sequenced all exons of MAP3K4 in 124 iCCA patients. We identified nine somatic mutations in 10 (8.06%) patients, especially in those with lymph node metastasis and intrahepatic metastasis. We also showed that messenger RNA and protein levels of MAP3K4 were significantly reduced in iCCA versus paired nontumor tissues. Furthermore, knockdown of MAP3K4 in cholangiocarcinoma cells markedly enhanced cell proliferation and invasiveness in vitro and tumor progression in vivo , accompanied by a typical EMT process. In contrast, overexpression of MAP3K4 in cholangiocarcinoma cells obviously reversed EMT and inhibited cell invasion. Mechanistically, MAP3K4 functioned as a negative regulator of EMT in iCCA by antagonizing the activity of the p38/nuclear factor κB/snail pathway. We found that the tumor‐inhibitory effect of MAP3K4 was abolished by inactivating mutations. Clinically, a tissue microarray study containing 322 iCCA samples from patients revealed that low MAP3K4 expression in iCCA positively correlated with aggressive tumor characteristics, such as vascular invasion and intrahepatic or lymph node metastases, and was independently associated with poor survival and increased recurrence after curative surgery. Conclusions: MAP3K4, significantly down‐regulated, frequently mutated, and potently regulating the EMT process in iCCA, was a putative tumor suppressor of iCCA. (H epatology 2015;62:1804‐1816)
Ten year follow-up study comparing conservative versus operative treatment of anterior cruciate ligament ruptures. A matched-pair analysis of high level athletes
Authors: D E Meuffels, M M Favejee, M M Vissers, M P Heijboer, M Reijman, J A N Verhaar
Journal: British Journal of Sports Medicine (2008)

Objective: To compare long term outcome of highly active patients with anterior cruciate ligament ruptures treated operatively versus non-operatively. Design: We reviewed high level athletes with an anterior cruciate ligament rupture on either MRI or arthroscopic evaluation more than 10 years previously, who were treated conservatively. They were pair-matched with patients who had had an anterior cruciate ligament reconstruction with bone-patella-tendon-bone, with respect to age, gender and Tegner activity score before injury. Participants: In total 50 patients were pair-matched. Results: We found no statistical difference between the patients treated conservatively or operatively with respect to osteoarthritis or meniscal lesions of the knee, as well as activity level, objective and subjective functional outcome. The patients who were treated operatively had a significantly better stability of the knee at examination. Conclusion: We conclude that the instability repair using a bone-patella-tendon-bone anterior cruciate ligament reconstruction is a good knee stabilising operation. Both treatment options however show similar patient outcome at 10 year follow up.
Don't Fence Me In. From Curse to Cure: Leprosy in Modern Times
Authors: Bhushan Kumar
Journal: BMJ (2005)

D on't Fence Me In is an account of the recent history of what many people still regard as a mysterious disease. Tony Gould tells the story of the anguished, fettered soul of a leprosy patient longing to be liberated. Fortunately today, after centuries of terrible existence, it stands almost completely free. This has been achieved through the untiring efforts of committed missionaries, social workers, epidemiologists, microbiologists, leprologists, reconstructive surgeons, and above all the patients themselves, who rose up from a “living hell.” Tony Gould Bloomsbury £20, pp 420 ISBN 0 7475 7510 X Rating:![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> Gould's narrative contains vivid accounts of the family life and suffering of people with leprosy, and of how complete ignorance about the disease created morbid fear in people's minds and an extreme degree of leprophobia. These accounts reveal the human tragedy of leprosy. They are heart rending, overwhelming at times, and are aptly summed up as follows: “Leprosy has stood as the most fearful of the human afflictions… Leprosy was not … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
The gut microbiota influences blood-brain barrier permeability in mice
Authors: Viorica Braniste, Maha Al-Asmakh, Czeslawa Kowal, Farhana Anuar, Afrouz Abbaspour, Miklós Tóth, Agata Korecka, Nadja Bakocevic, Lai Guan Ng, Parag Kundu, Balázs Gulyás, Christer Halldin, Kjell Hultenby, Harriet Nilsson, Hans Hebert, Bruce T. Volpe, Betty Diamond, Sven Pettersson
Journal: Science Translational Medicine (2014)

The intestinal microbiota helps to maintain the integrity of the blood-brain barrier in fetal and adult mice.
A cell-based bioassay for circulating bioactive IL-17: application to destruction in rheumatoid arthritis
Authors: Ndiémé Ndongo-Thiam, Pierre Miossec
Journal: Annals of the Rheumatic Diseases (2015)

Interleukin 17 (IL-17) plays an important role in many chronic inflammatory diseases such as psoriasis, psoriatic arthritis, ankylosing spondylitis and rheumatoid arthritis (RA).1 Measuring circulating IL-17 levels could be crucial to identifying patients who would benefit from IL-17-targeted therapies.2 Detection by ELISA has been difficult with high variability between studies. Furthermore, IL-17 function is critical to taking into consideration the contribution of activators (eg, tumour necrosis factor (TNF)-α acting in synergy with IL-17) and inhibitors (IL-25, autoantibodies).

In previous studies, human umbilical vein endothelial cells (HUVEC) were shown to be highly sensitive to IL-17 stimulation for the production of the chemokine IL-8.3 These cells were thus used in a functional bioassay to measure circulating bioactive IL-17. To determine the contribution of IL-17 in the IL-8-inducing activity, plasma samples at the dilution of 10% were first preincubated with or without an anti-IL-17 antibody at 10 µg/mL (R&D systems, Paris, France), before being added to HUVEC (see more details in figure 1 legend and in figure 1A, B). After 48 h of incubation, IL-8 production was measured in supernatants …
American Society of Clinical Oncology Guideline: Recommendations for Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer
Authors: Gary H. Lyman, Alok A. Khorana, Anna Falanga, Daniel Clarke-Pearson, Christopher Flowers, Mohammad Jahanzeb, Ajay Kakkar, Nicole M. Kuderer, Mark N. Levine, Howard Liebman, David Mendelson, Gary Raskob, Mark R. Somerfield, Paul Thodiyil, David Trent, Charles W. Francis
Journal: Journal of Clinical Oncology (2007)

To develop guideline recommendations for the use of anticoagulation in the prevention and treatment of venous thromboembolism (VTE) in patients with cancer.A comprehensive systematic review of the medical literature on the prevention and treatment of VTE in cancer patients was conducted and reviewed by a panel of content and methodology experts. Following discussion of the results, the panel drafted recommendations for the use of anticoagulation in patients with malignant disease.The results of randomized controlled trials of primary and secondary VTE medical prophylaxis, surgical prophylaxis, VTE treatment, and the impact of anticoagulation on survival of patients with cancer were reviewed. Recommendations were developed on the prevention of VTE in hospitalized, ambulatory, and surgical cancer patients as well as patients with established VTE, and for use of anticoagulants in cancer patients without VTE to improve survival.Recommendations of the American Society of Clinical Oncology VTE Guideline Panel include (1) all hospitalized cancer patients should be considered for VTE prophylaxis with anticoagulants in the absence of bleeding or other contraindications; (2) routine prophylaxis of ambulatory cancer patients with anticoagulation is not recommended, with the exception of patients receiving thalidomide or lenalidomide; (3) patients undergoing major surgery for malignant disease should be considered for pharmacologic thromboprophylaxis; (4) low molecular weight heparin represents the preferred agent for both the initial and continuing treatment of cancer patients with established VTE; and (5) the impact of anticoagulants on cancer patient survival requires additional study and cannot be recommended at present.
Arsenic trioxide inhibits nuclear receptor function via SEK1/JNK-mediated RXRα phosphorylation
Authors: Koren K. Mann, Alessandra M.S. Padovani, Qi Guo, April L. Colosimo, Ho-Young Lee, Jonathan M. Kurie, Wilson H. Miller Jr.
Journal: Journal of Clinical Investigation (2005)

We have previously published that 2 proven treatments for acute promyelocytic leukemia, As2O3 and retinoic acid, can be antagonistic in vitro. We now report that As2O3 inhibits ligand-induced transcription of the retinoic acid receptor, as well as other nuclear receptors that heterodimerize with the retinoid X receptor alpha (RXRalpha). As2O3 did not inhibit transactivation of the estrogen receptor or the glucocorticoid receptor, which do not heterodimerize with RXRalpha. We further show that As2O3 inhibits expression of several target genes of RXRalpha partners. Phosphorylation of RXRalpha has been reported to inhibit nuclear receptor signaling, and we show by in vivo labeling and phosphoamino acid detection that As2O3 phosphorylated RXRalpha in the N-terminal ABC region exclusively on serine residues. Consistent with our previous data implying a role for JNK in As2O3-induced apoptosis, we show that pharmacologic or genetic inhibition of JNK activation decreased As2O3-induced RXRalpha phosphorylation and blocked the effects of As2O3 on RXRalpha-mediated transcription. A mutational analysis indicated that phosphorylation of a specific serine residue, S32, was primarily responsible for inhibition of RXRalpha-mediated transcription. These data may provide some insight into the rational development of chemotherapeutic combinations involving As2O3 as well as into molecular mechanisms of arsenic-induced carcinogenesis resulting from environmental exposure.
Adenosine deaminase activity in rheumatoid pleural effusion.
Authors: I Ocana, E Ribera, J M Martinez-Vazquez, I Ruiz, E Bejarano, C Pigrau, A Pahissa
Journal: Annals of the Rheumatic Diseases (1988)

The activity of adenosine deaminase was studied in nine cases of rheumatoid pleural effusion, showing an increase in enzyme activity in all. Rheumatoid arthritis seems unique, however, as it cannot be differentiated from pleural tuberculosis on the basis of this test. Selective increase of adenosine deaminase in both conditions is attributed to stimulation of T lymphocytes in the pleural fluid.
Response to mTOR inhibition: activity of eIF4E predicts sensitivity in cell lines and acquired changes in eIF4E regulation in breast cancer
Authors: Sampoorna Satheesha, Victoria J Cookson, Louise J Coleman, Nicola Ingram, Brijesh Madhok, Andrew M Hanby, Charlotte AB Suleman, Vicky S Sabine, E Jane Macaskill, John MS Bartlett, J Michael Dixon, Jim N McElwaine, Thomas A Hughes
Journal: Molecular Cancer (2011)

Abstract Background Inhibitors of the kinase mTOR, such as rapamycin and everolimus, have been used as cancer therapeutics with limited success since some tumours are resistant. Efforts to establish predictive markers to allow selection of patients with tumours likely to respond have centred on determining phosphorylation states of mTOR or its targets 4E-BP1 and S6K in cancer cells. In an alternative approach we estimated eIF4E activity, a key effector of mTOR function, and tested the hypothesis that eIF4E activity predicts sensitivity to mTOR inhibition in cell lines and in breast tumours. Results We found a greater than three fold difference in sensitivity of representative colon, lung and breast cell lines to rapamycin. Using an assay to quantify influences of eIF4E on the translational efficiency specified by structured 5'UTRs, we showed that this estimate of eIF4E activity was a significant predictor of rapamycin sensitivity, with higher eIF4E activities indicative of enhanced sensitivity. Surprisingly, non-transformed cell lines were not less sensitive to rapamycin and did not have lower eIF4E activities than cancer lines, suggesting the mTOR/4E-BP1/eIF4E axis is deregulated in these non-transformed cells. In the context of clinical breast cancers, we estimated eIF4E activity by analysing expression of eIF4E and its functional regulators within tumour cells and combining these scores to reflect inhibitory and activating influences on eIF4E. Estimates of eIF4E activity in cancer biopsies taken at diagnosis did not predict sensitivity to 11-14 days of pre-operative everolimus treatment, as assessed by change in tumour cell proliferation from diagnosis to surgical excision. However, higher pre-treatment eIF4E activity was significantly associated with dramatic post-treatment changes in expression of eIF4E and 4E-binding proteins, suggesting that eIF4E is further deregulated in these tumours in response to mTOR inhibition. Conclusions Estimates of eIF4E activity predict sensitivity to mTOR inhibition in cell lines but breast tumours with high estimated eIF4E activity gain changes in eIF4E regulation in order to enhance resistance.
Increased risk of leukemia relapse with high dose cyclosporine after allogeneic marrow transplantation for acute leukemia: 10 year follow-up of a randomized study
Authors: Andrea Bacigalupo, Teresa Lamparelli, Francesca Gualandi, Stefania Bregante, AnnaMaria Raiola, Carmen di Grazia, Alida Dominietto, Chiara Romagnani, Domenico Occhini, Francesco Frassoni, Maria Teresa van Lint
Journal: Blood (2001)
Load-Dependent Myocyte Dysfunction
Authors: William H. Barry
Journal: Circulation (1998)

he term "cardiomyopathy of overload" was coined by Arnold Katz in 1990. 1 As he pointed out, it has been recognized since the time of Osler that in patients with chronic pressure or volume overload of the heart, a syndrome of progressive ventricular dysfunction can develop.Hypertrophy initially normalizes wall stress, 2 but eventually ventricular dilation occurs, resulting in a secondary increase in wall stress because of ventricular remodeling and associated increase in the radius of curvature of the ventricle.This increase in wall stress is proposed to cause further deterioration of ventricular function by a progressive sequence of hypertrophy3decreased ventricular function3dilation3increased wall stress3hypertro-phy3decreased ventricular function.This sequence of events may also account for the progressive nature of the ventricular enlargement and remodeling that can occur after loss of a significant component of functioning myocardium, or reduction in the number of myocytes as caused, for example, by myocardial infarction or myocarditis.Indeed, the well-recognized influence of depressed ventricular function and cardiac dilation on prognosis in patients with valvular disease, cardiomyopathy, and ischemic heart disease may in part be due to this process.
Medicine without doctors
Authors: A. Gonzalez
Journal: BMJ (2003)

“Treat Yourself”: an exhibition at the Science Museum, London SW7 Until 14 September 2003. Admission free www.sciencemuseum.org.uk/exhibitions/treatyourself/index.asp Rating:![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> The current obsession with health foods, vitamins, exercise, and spiritual relief from stress may come in for some stick from the scientific community, but how new is it? People have always faced acute and chronic illnesses, and they have not always left everything to doctors. This … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Infrequent K-<i>ras</i> codon 12 mutation in serrated adenomas of human colorectum
Authors: Y Ajioka, H Watanabe, J R Jass, Y Yokota, M Kobayashi, K Nishikura
Journal: Gut (1998)

Serrated adenoma is a new morphological subtype of colorectal adenoma. The lesion provides a distinct morphological route to carcinoma, but the underlying genetic changes have not yet been investigated.To determine the frequency of K-ras mutation in serrated adenoma.The frequency of K-ras codon 12 point mutation in 20 serrated adenomas, five atypical hyperplastic polyps, and 58 sporadic polypoid adenomas was investigated by nested polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods.Although most of the serrated adenomas were large (average size 11.4 mm) and polypoid, K-ras codon 12 point mutation was detected in only one of the 20 (5%), which is a significantly lower frequency than that in sporadic polypoid adenomas (18/60; 30%) (p = 0.017). No mutation was detected in the atypical hyperplastic polyps. Three of 20 (15%) serrated adenomas contained a focus of carcinoma in situ, indicating their malignant potential and the existence of a serrated adenoma-carcinoma sequence, but no mutation was detected in the foci of carcinoma in situ.K-ras mutation is uncommon in serrated adenomas, indicating a different spectrum of genetic alterations in these lesions from those in typical polypoid sporadic adenomas. This subtype of colorectal adenoma represents a new genetic pathway in the histogenesis of colorectal carcinoma.
A novel SCN5A mutation, F1344S, identified in a patient with Brugada syndrome and fever-induced ventricular fibrillation
Authors: D KELLER, H HUANG, J ZHAO, R FRANK, V SUAREZ, E DELACRETAZ, M BRINK, S OSSWALD, N SCHWICK, M CHAHINE
Journal: Cardiovascular Research (2006)

Brugada syndrome (BS) is an inherited electrical cardiac disorder characterized by right bundle branch block pattern and ST segment elevation in leads V1 to V3 on surface electrocardiogram that can potentially lead to malignant ventricular tachycardia and sudden cardiac death. About 20% of patients have mutations in the only so far identified gene, SCN5A, which encodes the alpha-subunit of the human cardiac voltage-dependent sodium channel (hNa(v)1.5). Fever has been shown to unmask or trigger the BS phenotype, but the associated molecular and the biophysical mechanisms are still poorly understood. We report on the identification and biophysical characterization of a novel heterozygous missense mutation in SCN5A, F1344S, in a 42-year-old male patient showing the BS phenotype leading to ventricular fibrillation during fever.The mutation was reproduced in vitro using site-directed mutagenesis and characterized using the patch clamp technique in the whole-cell configuration.The biophysical characterization of the channels carrying the F1344S mutation revealed a 10 mV mid-point shift of the G/V curve toward more positive voltages during activation. Raising the temperature to 40.5 degrees C further shifted the mid-point activation by 18 mV and significantly changed the slope factor in Na(v)1.5/F1344S mutant channels from -6.49 to -10.27 mV.Our findings indicate for the first time that the shift in activation and change in the slope factor at a higher temperature mimicking fever could reduce sodium currents' amplitude and trigger the manifestation of the BS phenotype.
Cetacean culture: Humans of the sea?
Authors: Peter L. Tyack
Journal: Behavioral and Brain Sciences (2001)

Rendell and Whitehead adopt a weak definition of culture to allow low standards of evidence for marine mammals, but they do not adequately rule out genetic factors or individual versus social learning. They then use these low standards to argue that some whales have unique cultures only matched by humans. It would have been more helpful to specify data gaps and suggest critical tests.
Alterations of the Arginine Metabolome in Asthma
Authors: Abigail Lara, Sumita B. Khatri, Zeneng Wang, Suzy A. A. Comhair, Weiling Xu, Raed A. Dweik, Melanie Bodine, Bruce S. Levison, Jeffrey Hammel, Eugene Bleecker, William Busse, William J. Calhoun, Mario Castro, Kian Fan Chung, Douglas Curran-Everett, Benjamin Gaston, Elliot Israel, Nizar Jarjour, Wendy Moore, Stephen P. Peters, W. Gerald Teague, Sally Wenzel, Stanley L. Hazen, Serpil C. Erzurum
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

As the sole nitrogen donor in nitric oxide (NO) synthesis and key intermediate in the urea cycle, arginine and its metabolic pathways are integrally linked to cellular respiration, metabolism, and inflammation.We hypothesized that arginine (Arg) bioavailability would be associated with airflow abnormalities and inflammation in subjects with asthma, and would be informative for asthma severity.Arg bioavailability was assessed in subjects with severe and nonsevere asthma and healthy control subjects by determination of plasma Arg relative to its metabolic products, ornithine and citrulline, and relative to methylarginine inhibitors of NO synthases, and by serum arginase activity. Inflammatory parameters, including fraction of exhaled NO (Fe(NO)), IgE, skin test positivity to allergens, bronchoalveolar lavage, and blood eosinophils, were also evaluated.Subjects with asthma had greater Arg bioavailability, but also increased Arg catabolism compared with healthy control subjects, as evidenced by higher levels of Fe(NO) and serum arginase activity. However, Arg bioavailability was positively associated with Fe(NO) only in healthy control subjects; Arg bioavailability was unrelated to Fe(NO) or other inflammatory parameters in severe or nonsevere asthma. Inflammatory parameters were related to airflow obstruction and reactivity in nonsevere asthma, but not in severe asthma. Conversely, Arg bioavailability was related to airflow obstruction in severe asthma, but not in nonsevere asthma. Modeling confirmed that measures of Arg bioavailabilty predict airflow obstruction only in severe asthma.Unlike Fe(NO), Arg bioavailability is not a surrogate measure of inflammation; however, Arg bioavailability is strongly associated with airflow abnormalities in severe asthma.