tbuckley/cabot-search huggingface dataset:
OC-059 Prevalence of Bile Acid Malabsorption as a Cause of Diarrhoea in Consecutive new Patient Referrals to a Gastroenterology Clinic: Abstract OC-059 Table 1
Authors: U Shivaji, F Chowdhury, A C Ford
Journal: Gut (2013)

<h3>Introduction Background</h3> Diarrhoea is a common presenting complaint in the Gastroenterology outpatient department. The potential causes are numerous, but include irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), coeliac disease, and colorectal cancer. Interest in bile acid malabsorption (BAM) as a cause of diarrhoea has increased recently. However, guidelines from the British Society of Gastroenterology do not recommend routine exclusion of this condition using 23-seleno-25-homo-tauro-cholic acid (SeHCAT) scanning. <h3>Methods</h3> Review of consecutive unselected new patient referrals to a single Gastroenterologists’ outpatient clinic during a 2-year period, from January 2010 to December 2011. All clinic letters were reviewed retrospectively, and symptoms reported by the patient at the initial consultation were recorded. Radiology, endoscopy, chemical pathology, and histopathology databases were then cross-examined in order to ascertain the final diagnosis following full investigation, to the level deemed appropriate by the consulting physician. We defined BAM using a SeHCAT retention value of &lt; 15% at 7 days. <h3>Results</h3> Of 397 consecutive unselected new patient referrals to a single Gastroenterologist between January 2010 and December 2011, 102 (25.7%) reported diarrhoea. After investigation the final diagnoses are listed in Table 1. The second commonest cause of diarrhoea, after IBS, was BAM. Eight (53.3%) of 15 patients with BAM reported lower abdominal pain or discomfort. In 10 (66.7%) patients there was no obvious cause of BAM, and these were classified as idiopathic, or type II, BAM. <h3>Conclusion</h3> BAM was the commonest underlying cause of diarrhoea after IBS. Idiopathic BAM was commoner than coeliac disease. More than 50% of patients with BAM reported lower abdominal pain or discomfort, which may lead to misdiagnosis as IBS unless further investigations are performed. BAM should be considered as a likely diagnosis in all patients with diarrhoea, and SeHCAT scanning should be moved up the hierarchy of diagnostic tests in such patients. <h3>Disclosure of Interest</h3> None Declared
Classification of molecular subtypes of triple-negative breast cancer using reverse phase protein arrays (RPPAs).
Authors: Hiroko Masuda, Yuan Qi, Shuying Liu, Naoki Hayashi, Takahiro Kogawa, Gabriel N. Hortobagyi, Vicente Valero, Ana M. Gonzalez-Angulo, Naoto T. Ueno
Journal: Journal of Clinical Oncology (2014)

1121 Background: Gene expression analyses have identified molecular subtypes of triple-negative breast cancer (TNBC), such as the basal-like subtype and the 7 molecular subtypes that are refining our understanding of breast cancer biology. However, these subtypes are not well defined enough to enable development of targeted therapy or prediction of prognosis in a clinical setting. Reverse phase protein array (RPPA) analysis could be easily adapted to a clinical setting for this purpose because it allows investigation of potential targets at the protein level and can lead to the development of immunohistochemical assays. Methods: We used 80 TNBC RPPAs obtained from patients at The MD Anderson Cancer Center between 03/87 and 04/06. RPPA analysis showed 154 breast cancer related proteins, including both total and phosphorylated proteins. We classified the TNBC samples using 2 types of clustering analysis, k-means and hierarchical, and silhouette width analysis. To assess the biological features of each TNBC subtype, we mapped antibody names from the RPPA dataset to HGNC gene symbols and fit a Gene Set Enrichment Analysis. We also performed correlation analysis between each TNBC subtype and recurrence-free survival (RFS) and overall survival (OS). Results: Results of both clustering showed that the optimal number of subtypes in the TNBC RPPA dataset was 2-3. Clusters of k = 2 from the k-means and hierarchical clustering methods showed the same, indicating that these 2 clusters were stable and sufficiently different and therefore could be reproduced using different methods. The top canonical pathways, which were associated with 2 clusters, were the DNA repair and replication pathway (cluster 1) and the immune response and adipocytokine signaling pathways (cluster 2). OS and DFS rates were different between the 2 clusters, but the differences were not significant (DFS: p = 0.3; OS: p = 0.1), probably owing to small sample size. Conclusions: Two types of clustering analysis showed that we identified 2 stable TNBC subtypes at the protein level. These results indicate that distinguishing between basal and stromal subtypes is a useful first step in identifying TNBC heterogeneity in the clinical setting.
<i>MET</i> Exon 14 Mutation Encodes an Actionable Therapeutic Target in Lung Adenocarcinoma
Authors: Xinyuan Lu, Nir Peled, John Greer, Wei Wu, Peter Choi, Alice H. Berger, Sergio Wong, Kuang-Yu Jen, Youngho Seo, Byron Hann, Angela Brooks, Matthew Meyerson, Eric A. Collisson
Journal: Cancer Research (2017)

Targeting somatically activated oncogenes has revolutionized the treatment of non-small cell lung cancer (NSCLC). Mutations in the gene mesenchymal-epithelial transition (MET) near the exon 14 splice sites are recurrent in lung adenocarcinoma and cause exon skipping (METΔ14). Here, we analyzed 4,422 samples from 12 different malignancies to estimate the rate of said exon skipping. METΔ14 mutation and transcript were most common in lung adenocarcinoma. Endogenously expressed levels of METΔ14 transformed human epithelial lung cells in a hepatocyte growth factor-dependent manner. In addition, overexpression of the orthologous mouse allele induced lung adenocarcinoma in a novel, immunocompetent mouse model. Met inhibition showed clinical benefit in this model. In addition, we observed a clinical response to crizotinib in a patient with METΔ14-driven NSCLC, only to observe new missense mutations in the MET activation loop, critical for binding to crizotinib, upon clinical progression. These findings support genomically selected clinical trials directed toward METΔ14 in a fraction of NSCLC patients, confirm second-site mutations for further therapeutic targeting prior to and beyond acquired resistance, and provide an in vivo system for the study of METΔ14 in an immunocompetent host. Cancer Res; 77(16); 4498-505. ©2017 AACR.
Targeted Therapy as an Alternative to Whole-Brain Radiotherapy in <i>EGFR</i>-Mutant or <i>ALK</i>-Positive Non–Small-Cell Lung Cancer With Brain Metastases
Authors: Pablo Martínez, Raymond H. Mak, Geoffrey R. Oxnard
Journal: JAMA Oncology (2017)

Is up-front whole-brain radiotherapy required to treat multiple brain metastases from non-small-cell lung cancer when highly active targeted therapies are available?Patients with EGFR-mutant or ALK-positive non-small-cell lung cancer with brain metastases now have the potential to achieve a prolonged survival. Through use of highly active targeted therapies, whole-brain radiotherapy can be safely postponed, diminishing toxic effects that could impair quality of life.
X-linked carriers of chronic granulomatous disease: Illness, lyonization, and stability
Authors: Beatriz E. Marciano, Christa S. Zerbe, E. Liana Falcone, Li Ding, Suk See DeRavin, Janine Daub, Samantha Kreuzburg, Lynne Yockey, Sally Hunsberger, Ladan Foruraghi, Lisa A. Barnhart, Kabir Matharu, Victoria Anderson, Dirk N. Darnell, Cathleen Frein, Danielle L. Fink, Karen P. Lau, Debra A. Long Priel, John I. Gallin, Harry L. Malech, Gulbu Uzel, Alexandra F. Freeman, Douglas B. Kuhns, Sergio D. Rosenzweig, Steven M. Holland
Journal: Journal of Allergy and Clinical Immunology (2017)
Association of inducible nitric oxide synthase with asthma severity, total serum immunoglobulin E and blood eosinophil levels
Authors: J. Batra, T. Pratap Singh, U. Mabalirajan, A. Sinha, R. Prasad, B. Ghosh
Journal: Thorax (2006)

<b>Background:</b> Nitric oxide is released by immune, epithelial and endothelial cells, and plays an important part in the pathophysiology of asthma. <b>Objective:</b> To investigate the association of inducible nitric oxide synthases (<i>iNOS)</i> gene repeat polymorphisms with asthma. <b>Methods:</b> 230 families with asthma (842 individuals) were recruited to identify and establish the genetic association of <i>iNOS</i> repeats with asthma and associated phenotypes. Serum nitric oxide levels in selected individuals were measured and correlated with specific genotypes. Multiple logistic regression analysis was performed to determine the effect of age and sex. <b>Results:</b> A total of four repeats—a (CCTTT)n promoter repeat, a novel intron 2 (GT)n repeat (BV680047), an intron 4 (GT)n repeat (AFM311ZB1) and an intron 5 (CA)n repeat (D17S1878)—were identified and genotyped. A significant transmission distortion to the probands with asthma was seen for allele 3 of the <i>AFM311ZB1</i> gene (p = 0.006). This allele was also found to be significantly associated with percentage blood eosinophils (p&lt;0.001) and asthma severity (p = 0.04). Moreover, it was functionally correlated with high serum nitric oxide levels (p = 0.006). Similarly, the promoter repeat was found to be associated with serum total immunoglobulin (Ig)E (p = 0.028). Individuals carrying allele 4 of this repeat have high serum IgE (p&lt;0.001) and nitric oxide levels (p = 0.03). <b>Conclusion:</b> This is the first study to identify the repeat polymorphisms in the <i>iNOS</i> gene that are associated with severity of asthma and eosinophils. The functional relevance of the associated alleles with serum nitric oxide levels was also shown. Therefore, these results could be valuable in elucidating the role of nitric oxide in asthma pathogenesis.
Asthma refractory to glucocorticoids: The role of newer immunosuppressants
Authors: C J Corrigan
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Asthma is orchestrated by cytokine products of activated T cells. Glucocorticoids are thought to ameliorate asthma at least partly through T cell inhibition. Consequently, other T cell immunomodulatory agents have been assessed for asthma therapy. Since these agents may have serious unwanted effects, attention has been focused on patients with severe asthma refractory to maximal topical, and additional systemic glucocorticoid therapy. Although gold salts show a modest but significant glucocorticoid-sparing effect in severe asthma, lung function is not improved and not all patients respond. The minimum duration of a valid trial of therapy is probably 6 months. Unwanted effects include dermatitis, hepatic dysfunction, proteinuria and interstitial pneumonitis. Meta-analysis of trials of methotrexate in oral glucocorticoid-dependent asthma have confirmed that concomitant weekly methotrexate for a minimum of 3 to 6 months enables significant (approximately 20%) overall reduction in oral glucocorticoid requirements, although only approximately 60% of patients show a significant response. There is little effect on lung function. Blood count and liver function must be monitored. Opportunistic infection is rare but potentially fatal. Cyclosporine, administered for at least 3 months, is effective in only a proportion of patients with oral glucocorticoid-dependent asthma, where it may improve disease severity and/or enable oral glucocorticoid dosage reductions. Regular monitoring of renal function, blood pressure and blood concentrations of cyclosporine is required. The evidence that intravenous immunoglobulin (Ig) is of any benefit in patients with glucocorticoid-dependent asthma is at present equivocal. The therapy is expensive and associated with a high incidence of unwanted effects (fever, aseptic meningitis, urticaria). The macrolides tacrolimus (FK506) and sirolimus (rapamycin) have end effects similar to those of cyclosporine. Brequinar sodium, mycophenolate mofetil and leflunomide are inhibitors of de novo synthesis of pyrimidines and purines, to which T cells are particularly sensitive. Such drugs may in theory be beneficial for therapy of patients with oral glucocorticoid-dependent asthma. Humanized anti-CD4, anti-IgE and anti-interleukin (IL)-5 monoclonal antibodies, and other cytokine inhibitors such as soluble IL-4 receptor have entered early trials. The worth of current immunomodulatory drugs is limited since: (i) not all patients respond, and response cannot be predicted a priori; (ii) the high incidence of unwanted effects makes it difficult to assess overall benefit/risk ratios; (iii) there is increased risk of opportunistic infection and (theoretically) neoplasia; (iv) there are many relative and absolute contraindications to therapy; and (v) there is lack of knowledge about the long-term effects, beneficial or otherwise, of therapy.
Hepatitis B Surface Antigen Screening Among Pregnant Women and Care of Infants of Hepatitis B Surface Antigen–Positive Mothers — Guam, 2014
Authors: Winston E. Abara, Susan Cha, Tasneem Malik, Mia S. DeSimone, Bernadette Schumann, Esther Mallada, Michael Klemme, Vince Aguon, Anne Marie Santos, Melissa Collier, Mary Kamb
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Hepatitis B virus (HBV) infection is endemic among adults in the U.S. territory of Guam (1,2). Perinatal HBV transmission, which occurs at birth from an infected mother to her newborn infant, is a major mode of HBV transmission and maintains HBV endemicity (3). Approximately 90% of HBV-infected infants will develop chronic HBV infection, and approximately 25% of those will die prematurely from liver failure or hepatocellular carcinoma (4,5). Since 1988, the Advisory Committee on Immunization Practices has recommended that all pregnant women be screened for hepatitis B surface antigen (HBsAg), an indicator of HBV infection, and that infants of women who screen positive (HBsAg-positive women) receive postexposure prophylaxis (PEP) (hepatitis B vaccine and hepatitis B immunoglobulin [HBIG]). When received within 12 hours of birth, PEP is 85%-95% effective in preventing perinatal HBV transmission (5,6). Hepatitis B vaccine provides long-term active immunity to HBV infection and HBIG provides short-term passive immunity to HBV infection until the infant responds to the vaccine (5). Hepatitis B vaccine was introduced into the routine universal infant vaccination schedule in Guam in 1988 (1).
ADA2 deficiency (DADA2) as an unrecognised cause of early onset polyarteritis nodosa and stroke: a multicentre national study
Authors: Roberta Caorsi, Federica Penco, Alice Grossi, Antonella Insalaco, Alessia Omenetti, Maria Alessio, Giovanni Conti, Federico Marchetti, Paolo Picco, Alberto Tommasini, Silvana Martino, Clara Malattia, Romina Gallizi, Rosa Anna Podda, Annalisa Salis, Fernanda Falcini, Francesca Schena, Francesca Garbarino, Alessia Morreale, Manuela Pardeo, Claudia Ventrici, Chiara Passarelli, Qing Zhou, Mariasavina Severino, Carlo Gandolfo, Gianluca Damonte, Alberto Martini, Angelo Ravelli, Ivona Aksentijevich, Isabella Ceccherini, Marco Gattorno
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To analyse the prevalence of <i>CECR1</i> mutations in patients diagnosed with early onset livedo reticularis and/or haemorrhagic/ischaemic strokes in the context of inflammation or polyarteritis nodosa (PAN). Forty-eight patients from 43 families were included in the study. <h3>Methods</h3> Direct sequencing of <i>CECR1</i> was performed by Sanger analysis. Adenosine deaminase 2 (ADA2) enzymatic activity was analysed in monocyte isolated from patients and healthy controls incubated with adenosine and with or without an ADA1 inhibitor. <h3>Results</h3> Biallelic homozygous or compound heterozygous <i>CECR1</i> mutations were detected in 15/48 patients. A heterozygous disease-associated mutation (p.G47V) was observed in two affected brothers. The mean age of onset of the genetically positive patients was 24 months (6 months to 7 years). Ten patients displayed one or more cerebral strokes during their disease course. Low immunoglobulin levels were detected in six patients. Thalidomide and anti-TNF (tumour necrosis factor) blockers were the most effective drugs. Patients without <i>CECR1</i> mutations had a later age at disease onset, a lower prevalence of neurological and skin manifestations; one of these patients displayed all the clinical features of adenosine deaminase 2deficiency (DADA2) and a defective enzymatic activity suggesting the presence of a missed mutation or a synthesis defect. <h3>Conclusions</h3> DADA2 accounts for paediatric patients diagnosed with PAN-like disease and strokes and might explain an unrecognised condition in patients followed by adult rheumatologist. Timely diagnosis and treatment with anti-TNF agents are crucial for the prevention of severe complications of the disease. Functional assay to measure ADA2 activity should complement genetic testing in patients with non-confirming genotypes.
Esophageal Cancer Diagnosed by Thyroid Scintigraphy
Authors: María de la Cinta Calvo-Morón, Francisco Javier García-Gómez, Pablo Antonio de la Riva-Pérez, Juan Castro-Montaño
Journal: Clinical Nuclear Medicine (2017)

We report a 34-year-old man referred because of increasing dysphagia secondary to goiter. Thyroid scintigraphy and SPECT/CT images helped to recognize an unsuspected esophageal dilation due to a poorly differentiated adenocarcinoma arising at the lower end of the esophagus. Further examinations are mandatory when abnormal activities are observed during thyroid scintigraphy.
STUDIES ON OXIDATION AND REDUCTION BY PNEUMOCOCCUS
Authors: James M. Neill, Oswald T. Avery
Journal: The Journal of Experimental Medicine (1924)

1. Certain enzymes of Pneumococcus are destroyed by oxidizing agents formed when sterile extracts of the cellular substances are exposed to air. The carbohydrate-hydrolyzing enzymes (sucrase, raffinase, inulase, and amylase) are the most easily inactivated under these conditions, although the bacteriolytic enzyme is also reduced in activity. Similar treatment is without effect upon the active concentration of pneumococcus lipase and peptonase. 2. The enzymes which are destroyed during the oxidation of unwashed cell extracts are themselves non-reactive with molecular oxygen. The reactions by which they are destroyed seem to represent oxidations of a type similar to those proposed in previous papers for the oxidation of hemotoxin and of hemoglobin. 3. A study has been made of the relative resistance of different pneumococcus enzymes to heat and to the action of hydrogen peroxide. 4. The various enzymes may be arranged in the same order of relative resistance whether the rating be made from the standpoint of resistance to heat or of resistance to oxidation. Nevertheless, it appears that by a proper regulation of conditions of oxidation, certain labile constituents of a mixture of cellular enzymes may be inactivated with less effect upon the activity of other constituents of the mixture than when inactivation is brought about by heat.
Thrombotic events in metastatic colorectal cancer patients treated with FOLFIRI plus bevacizumab.
Authors: Humaid O. Al-Shamsi, Mahraz Anjum, Abdulaziz Mohammed Al Farsi, Hua Shen, Richard J. Cook, Lori-Ann Linkins, Pierre Major
Journal: Journal of Clinical Oncology (2013)

e14630 Background: To determine the incidence and risk factors for thrombotic events (TEs) (arterial and venous) in patients with metastatic colorectal cancer (mCRC) who received Bevacizumab and FOLFIRI (Leucovorin, Fluorouracil and Irinotican ) compared to FOLFIRI alone. Methods: Single institution retrospective study of 450 mCRC patients who received either Bevacizumab plus FOLFIRI or FOLFIRI alone between October 2006 and September 2012. Demographics , TE risk factors and treatment data were abstracted from patients records. Multivariate analysis was used to determine factors that contributed to increased TE incidence. Results: 261 mCRC patients received Bevacizumab plus FOLFIRI ( 64.8 % males , mean Body Mass Index (BMI) 26.1 ) compared to 189 control patients who received FOLFIRI alone ( 61.1 % males ,BMI 27). The incidence of TEs was 15 % (arterial 1.8% + venous 13.2%) in the Bevacizumab plus FOLFIRI group compared to 15.8% (arterial 2.1% + venous 13.7%) in the control groups. Multivariate analysis controlled for age, BMI, gender, malignancy, metastatic sites , line of treatment, and risk factors did not suggest a significant increase in risk of TE associated with Bevacizumab (OR=0.83 95% CI: 0.40 - 1.70; p=0.602). No difference in locations of TEs was observed between both groups . The only statistically significant factor for thrombosis in Bevacizumab group was increased BMI (OR=1.05; 95% CI: 1.01- 1.10; p=0.016). Conclusions: Our data suggest that bevacizumab did not significantly increase the rate of thrombosis in patients with mCRC when added to FOLFIRI. To our knowledge this is the first study reporting the rate of TEs (arterial and venous) in this population.Our data suggest that BMI may be a risk factor for increase risk of thrombosis in patients treated with bevacizumab . Clinician should consider risk factors assessment prior to initiating bevacizumab .
Dendritic cells enter lymph vessels by hyaluronan-mediated docking to the endothelial receptor LYVE-1
Authors: Louise A Johnson, Suneale Banerji, William Lawrance, Uzi Gileadi, Gennaro Prota, Kayla A Holder, Yaowaluck M Roshorm, Tomáš Hanke, Vincenzo Cerundolo, Nicholas W Gale, David G Jackson
Journal: Nature Immunology (2017)
Clinical and Pathological Features and Differential Diagnosis of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): a Series of Cases
Authors: Gabriela Cesarman-Maus, Carmen Lome, Karla Adriana Espinosa, Carmen Marcela Quezada-Fiallos, Silvia Rivas, Roxana Quezda
Journal: Blood (2016)
Targeting miR-21 with Sophocarpine Inhibits Tumor Progression and Reverses Epithelial-Mesenchymal Transition in Head and Neck Cancer
Authors: Wei Liu, Beilei Zhang, Guo Chen, Wenjiao Wu, Lin Zhou, Yaru Shi, Qi Zeng, Yanqiu Li, Youwei Sun, Xingming Deng, Fu Wang
Journal: Molecular Therapy (2017)

A major challenge for cancer chemotherapy is the development of safe and clinically effective chemotherapeutic agents. With its low toxicity profile, sophocarpine (SC), a naturally occurring tetracyclic quinolizidine alkaloid derived from Sophora alopecuroides L, has shown promising therapeutic properties, including anti-inflammatory, anti-nociceptive, and antivirus activities. However, the antitumor efficacy of SC and its underlying mechanisms have not been completely delineated. In the present study, the inhibitory effect of SC on head and neck squamous cell carcinoma (HNSCC) progression and possible mechanisms for this effect involving microRNA-21 (miR-21) regulation were investigated. By cell viability, Transwell, and wound healing assays, we show that SC effectively inhibited proliferation, invasion, and migration of HNSCC cells. Moreover, SC exerted its growth-inhibitory effect via the downregulation of miR-21 expression by blocking Dicer-mediated miR-21 maturation. Furthermore, SC treatment led to the increased expression of PTEN and p38MAPK phosphorylation as well as the reversal of epithelial-mesenchymal transition (EMT), which was rescued by ectopic expression of miR-21 in cells. Notably, SC dramatically repressed tumor growth without observable tissue cytotoxicity in a mouse xenograft model of HNSCC. Our findings offer a preclinical proof of concept for SC as a leading natural agent for HNSCC cancer therapy.