tbuckley/cabot-search huggingface dataset:
Immunostimulatory Monoclonal Antibodies and Immunomodulation: Harvesting the Crop
Authors: Pedro Berraondo, María Carmen Ochoa, María Esperanza Rodriguez-Ruiz, Luna Minute, Juan José Lasarte, Ignacio Melero
Journal: Cancer Research (2016)

The recent approval by the FDA of the combination of anti-CTLA4 and anti-PD-1 mAbs for the treatment of BRAF-unmutated unresectable or metastatic melanoma is a landmark for the development of cancer immunotherapy. On October 18 to 22, 2015, a symposium was held in Pamplona (Spain) to present and discuss the basic and clinical discoveries that have brought us to this milestone and to explore other targets and immunotherapy strategies aimed at attaining more efficacious oncology practice in the short term. Cancer Res; 76(10); 2863-7. ©2016 AACR.
ARHGEF15 overexpression worsens the prognosis in patients with pancreatic ductal adenocarcinoma through enhancing the motility and proliferative activity of the cancer cells
Authors: Hiroto Fukushima, Makiko Yasumoto, Sachiko Ogasawara, Jun Akiba, Yuhei Kitasato, Masamichi Nakayama, Yoshiki Naito, Yusuke Ishida, Yoshinobu Okabe, Masafumi Yasunaga, Hiroyuki Horiuchi, Etsuko Sakamoto, Hiraku Itadani, Shinji Mizuarai, Shinji Oie, Hirohisa Yano
Journal: Molecular Cancer (2016)

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplastic diseases, associated with a remarkably poor prognosis. However, the molecular mechanisms underlying the development of PDAC remain elusive. The aim of this study was to identify genes whose expressions are correlated with a poor prognosis in PDAC patients, and to unravel the mechanisms underlying the involvement of these genes in the development of the cancer.Global gene expression profiling was conducted in 39 specimens obtained from Japanese patients with PDAC to identify genes whose expressions were correlated with a shorter overall survival. The effect of gene silencing or overexpression of ARHGEF15 in pancreatic cancer cell lines was examined by introducing siRNAs of ARHGEF15 or the ARHGEF15 expression vector. After assessing the effect of ARHGEF15 deregulation on the Rho-family proteins by pull-down assay, wound healing, transwell and cell viability assays were carried out to investigate the cellular phenotypes caused by the perturbation.The global mRNA expression profiling revealed that overexpression of ARHGEF15, a Rho-specific GEF, was significantly associated with a poor prognosis in patients with PDAC. We also found that the depletion of ARHGEF15 by RNA interference in pancreatic cancer cell lines downregulated the activities of molecules of the Rho signaling pathway, including RhoA, Cdc42 and Rac1. Then, we also showed that ARHGEF15 silencing significantly reduced the motility and viability of the cells, while its overexpression resulted in the development of the opposite phenotype in multiple pancreatic cancer cell lines.These data suggest that upregulation of ARHGEF15 contributes to the development of aggressive PDAC by increasing the growth and motility of the pancreatic cancer cells, thereby worsening the prognosis of these patients. Therefore, ARHGEF15 could serve as a novel therapeutic target in patients with PDAC.
Protein profiles of <scp>CCL</scp>5, <scp>HPGDS</scp>, and <scp>NPSR</scp>1 in plasma reveal association with childhood asthma
Authors: C. Hamsten, A. Häggmark, J. Grundström, M. Mikus, C. Lindskog, J. R. Konradsen, A. Eklund, G. Pershagen, M. Wickman, J. Grunewald, E. Melén, G. Hedlin, P. Nilsson, M. van Hage
Journal: Allergy (2016)

Asthma is a common chronic childhood disease with many different phenotypes that need to be identified. We analyzed a broad range of plasma proteins in children with well-characterized asthma phenotypes to identify potential markers of childhood asthma. Using an affinity proteomics approach, plasma levels of 362 proteins covered by antibodies from the Human Protein Atlas were investigated in a total of 154 children with persistent or intermittent asthma and controls. After screening, chemokine ligand 5 (CCL5) hematopoietic prostaglandin D synthase (HPGDS) and neuropeptide S receptor 1 (NPSR1) were selected for further investigation. Significantly lower levels of both CCL5 and HPGDS were found in children with persistent asthma, while NPSR1 was found at higher levels in children with mild intermittent asthma compared to healthy controls. In addition, the protein levels were investigated in another respiratory disease, sarcoidosis, showing significantly higher NPSR1 levels in sera from sarcoidosis patients compared to healthy controls. Immunohistochemical staining of healthy tissues revealed high cytoplasmic expression of HPGDS in mast cells, present in stroma of both airway epithelia, lung as well as in other organs. High expression of NPSR1 was observed in neuroendocrine tissues, while no expression was observed in airway epithelia or lung. In conclusion, we have utilized a broad-scaled affinity proteomics approach to identify three proteins with altered plasma levels in asthmatic children, representing one of the first evaluations of HPGDS and NPSR1 protein levels in plasma.
Sperm<i>Bindin</i>Divergence under Sexual Selection and Concerted Evolution in Sea Stars
Authors: Susana Patiño, Carson C. Keever, Jennifer M. Sunday, Iva Popovic, Maria Byrne, Michael W. Hart
Journal: Molecular Biology and Evolution (2016)

Selection associated with competition among males or sexual conflict between mates can create positive selection for high rates of molecular evolution of gamete recognition genes and lead to reproductive isolation between species. We analyzed coding sequence and repetitive domain variation in the gene encoding the sperm acrosomal protein bindin in 13 diverse sea star species. We found that bindin has a conserved coding sequence domain structure in all 13 species, with several repeated motifs in a large central region that is similar among all sea stars in organization but highly divergent among genera in nucleotide and predicted amino acid sequence. More bindin codons and lineages showed positive selection for high relative rates of amino acid substitution in genera with gonochoric outcrossing adults (and greater expected strength of sexual selection) than in selfing hermaphrodites. That difference is consistent with the expectation that selfing (a highly derived mating system) may moderate the strength of sexual selection and limit the accumulation of bindin amino acid differences. The results implicate both positive selection on single codons and concerted evolution within the repetitive region in bindin divergence, and suggest that both single amino acid differences and repeat differences may affect sperm–egg binding and reproductive compatibility.
Case 21-1971
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, J. Warren Harthorne, Robert L. Trelstad
Journal: New England Journal of Medicine (1971)

Presentation of CaseA 71-year-old woman was admitted to the hospital because of dyspnea.She had been well until seven years previously, when persistent fever developed. Evaluation at this hospital five months later disclosed a right-sided Horner syndrome, limited motion in multiple joints and a Grade 2 precordial systolic murmur, without radiation. The blood pressure was 200 systolic, 110 diastolic. An x-ray film of the chest showed slight cardiac enlargement and fusiform aneurysmal dilatation of the descending portion of the thoracic aorta (Fig. 1). No diagnosis to explain the fever was established, and the patient was discharged without specific treatment. . . .
Concurrent Changes in Growth-Related Biochemical Parameters During Regression of Hormone-Dependent Rat Mammary Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: M K Foecking, H Abou-Issa, T E Webb, J P Minton
Journal: JNCI Journal of the National Cancer Institute (1983)

The in vivo relationship was studied between these biochemical parameters which previous studies have separately implicated in the regression of hormone-dependent rat mammary tumors. Upon depletion of estrogen and suppression of prolactin levels by ovariectomy, there was a marked increase in the production of prostaglandin E2 (PGE2)(fourfold) and in the cyclic AMP (cAMP) content (twofold) in the regressing 7,12-dimethylbenz[a]anthracene-induced primary tumors. These two parameters appeared to be coupled since, in addition to this correlation, PGE2 stimulated adenylate cyclase and raised cAMP levels in both this primary tumor system and in another hormone-dependent transplantable rat mammary tumor (MTW9-A). Furthermore both the sensitivity of the adenylate cyclase system to PGE2 and the number of membrane binding sites for PGE2 increased upon induction of regression in these tumors. Under conditions where PGE2 and cAMP were elevated, (i.e., in regressing, but not growing, hormone-dependent mammary tumors), there was significant phosphorylation in the intact tissue of a 75,000-dalton nuclear protein, which appeared to be identical to the regression-associated protein shown by Cho-Chung and co-workers to undergo increased phosphorylation in response to elevated cAMP levels.
Olig2-Dependent Reciprocal Shift in PDGF and EGF Receptor Signaling Regulates Tumor Phenotype and Mitotic Growth in Malignant Glioma
Authors: Fanghui Lu, Ying Chen, Chuntao Zhao, Haibo Wang, Danyang He, Lingli Xu, Jincheng Wang, Xuelian He, Yaqi Deng, Ellen E. Lu, Xue Liu, Ravinder Verma, Hong Bu, Rachid Drissi, Maryam Fouladi, Anat O. Stemmer-Rachamimov, Dennis Burns, Mei Xin, Joshua B. Rubin, El Mustapha Bahassi, Peter Canoll, Eric C. Holland, Q. Richard Lu
Journal: Cancer Cell (2016)
Reply from Authors re: Julia Verne, Luke Hounsome, Roger Kockelbergh, Jem Rashbass. Improving Outcomes from Prostate Cancer: Unlocking the Treasure Trove of Information in Cancer Registries. Eur Urol 2016;69:1013–4
Authors: Giorgio Gandaglia, Freddie Bray, Matthew R. Cooperberg, R. Jeffrey Karnes, Michael J. Leveridge, Kim Moretti, Declan G. Murphy, David F. Penson, David C. Miller
Journal: European Urology (2015)
NK Cell Line Killing of Leukemia Cells Is Enhanced By Reverse Antibody Dependent Cell Mediated Cytotoxicity (R-ADCC) Via NKp30 and NKp44 and Target Fcγ Receptor II (CD32)
Authors: Brent A. Williams, Xinghua Wang, Bertrand Routy, Richard Cheng, Sonam Maghera, Armand Keating
Journal: Blood (2014)
Survival Benefit of Locoregional Treatment for Hepatocellular Carcinoma with Advanced Liver Cirrhosis
Authors: Satoshi Kitai, Masatoshi Kudo, Naoshi Nishida, Namiki Izumi, Michiie Sakamoto, Yutaka Matsuyama, Takafumi Ichida, Osamu Nakashima, Osamu Matsui, Yonson Ku, Norihiro Kokudo, Masatoshi Makuuchi
Journal: Liver Cancer (2016)

&lt;b&gt;&lt;i&gt;Background &amp;amp; Aims: &lt;/i&gt;&lt;/b&gt;Hepatocellular carcinoma (HCC) with decompensated liver cirrhosis (LC) is a life-threatening condition, which is amenable to liver transplantation (LT) as the standard first-line treatment. However, the application of LT can be limited due to a shortage of donor livers. This study aimed to clarify the effect of non-surgical therapy on the survival of patients with HCC and decompensated LC. &lt;b&gt;&lt;i&gt;Methods: &lt;/i&gt;&lt;/b&gt;Of the 58,886 patients with HCC registered in the nationwide survey of the Liver Cancer Study Group of Japan (January 2000-December 2005), we included 1,344 patients with primary HCC and Child-Pugh (C-P) grade C for analysis in this retrospective study. Among the patients analyzed, 108 underwent LT, 273 were treated by local ablation therapy (LAT), 370 were treated by transarterial chemoembolization (TACE), and 593 received best supportive care (BSC). The effect of LT, LAT, and TACE on overall survival (OS) was analyzed using multivariate and propensity score analyses. &lt;b&gt;&lt;i&gt;Results: &lt;/i&gt;&lt;/b&gt;Patient characteristics did not differ significantly between each treatment group and the BSC group, after propensity score matching. LAT (hazard ratio [HR]) =0.568; 95% confidence interval [CI], 0.40-0.80) and TACE (HR=0.691; 95% CI, 0.50-0.96) were identified as significant contributors to OS if the C-P score was less than 11 and tumor conditions met the Milan criteria. &lt;b&gt;&lt;i&gt;Conclusions: &lt;/i&gt;&lt;/b&gt;For patients with HCC within the Milan criteria and with a C-P score of 10 or 11, locoregional treatment can be used as a salvage treatment if LT is not feasible.
Treatment of schizophrenia with a vasopressin analogue
Authors: A C Iager, D G Kirch, L B Bigelow, C N Karson
Journal: American Journal of Psychiatry (1986)

Ten patients with chronic schizophrenia completed a 3-month double-blind, placebo-controlled trial with a vasopressin analogue. Modest improvement occurred, but several patients also experienced significant fluid and electrolyte imbalance.
Indication and management of allogeneic stem cell transplantation in primary myelofibrosis: a consensus process by an EBMT/ELN international working group
Authors: N M Kröger, J H Deeg, E Olavarria, D Niederwieser, A Bacigalupo, T Barbui, A Rambaldi, R Mesa, A Tefferi, M Griesshammer, V Gupta, C Harrison, H Alchalby, A M Vannucchi, F Cervantes, M Robin, M Ditschkowski, V Fauble, D McLornan, K Ballen, U R Popat, F Passamonti, D Rondelli, G Barosi
Journal: Leukemia (2015)
Pneumatic Retinopexy
Authors: Paul E. Tornambe, George F. Hilton, Daniel A. Brinton, Timothy P. Flood, Stuart Green, W. Sanderson Grizzard, Mark E. Hammer, Steven R. Leff, Leo Masciulli, Craig M. Morgan, David H. Orth, Kirk H. Packo, Lon S. Poliner, Douglas L. Taren, James S. Tiedeman, David L. Yarian
Journal: Ophthalmology (1991)
Usage of allergy codes in primary care electronic health records: a national evaluation in Scotland
Authors: M. Mukherjee, J. C. Wyatt, C. R. Simpson, A. Sheikh
Journal: Allergy (2016)

Background The UK's NHS intends to move from the current Read code system to the international, detailed Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) to facilitate more clinically appropriate coding of conditions and associated risk factors and outcomes. Given concerns about coding behaviour of general practitioners, we sought to study the current coding patterns in allergies and identify lessons for the future migration to SNOMED-CT. Methods Data from 2 014 551 primary care consultations in over 100 000 patients with one or more of 11 potentially allergic diseases (anaphylaxis, angioedema, asthma, conjunctivitis, drug allergies, eczema, food allergy, rhinitis, urticaria, venom allergy and other probable allergic disorders) from the Scottish Primary Care Clinical Informatics Unit Research (PCCIU-R) database were descriptively analysed and visualized to understand Read code usage patterns. Results We identified 352 Read codes for these allergic diseases, but only 36 codes (10%) were used in 95% of consultations; 73 codes (21%) were never used. Half of all usage was for Quality and Outcomes Framework codes for asthma. Despite 149 detailed codes (42%) being available for allergic triggers, these were infrequently used. Conclusions This analysis of Read codes use suggests that introduction of the more detailed SNOMED-CT, in isolation, will not improve the quality of allergy coding in Scottish primary care. The introduction of SNOMED-CT should be accompanied by initiatives aimed at improving coding quality, such as the definition of terms/codes, the availability of terminology browsers, a recommended list of codes and mechanisms to incentivize detailed coding of the condition and the underlying allergic trigger.
Frequency of Synaptic Autoantibody Accompaniments and Neurological Manifestations of Thymoma
Authors: Anastasia Zekeridou, Andrew McKeon, Vanda A. Lennon
Journal: JAMA Neurology (2016)

Thymoma is commonly recognized in association with paraneoplastic autoimmune myasthenia gravis (MG), an IgG-mediated impairment of synaptic transmission targeting the nicotinic acetylcholine receptor of muscle. Newly identified synaptic autoantibodies may expand the serological profile of thymoma.To investigate the frequency of potentially pathogenic neural synaptic autoantibodies in patients with thymoma.We retrospectively identified patients with histopathologically confirmed thymoma and serum available to test for synaptic autoantibodies (collected 1986-2014) at the Mayo Clinic Neuroimmunology Laboratory. We identified and classified 193 patients with thymoma into 4 groups: (1) lacking neurological autoimmunity (n = 43); (2) isolated MG (n = 98); (3) MG plus additional autoimmune neurological manifestations (n = 26); and (4) neurological autoimmunity other than MG (n = 26).Clinical presentation and serum profile of autoantibodies reactive with molecularly defined synaptic plasma membrane proteins of muscle, peripheral, and central nervous systems.Of the 193 patients with thymoma, mean patient age was 52 years and did not significantly differ by sex (106 women) or group. Myasthenia gravis was the most prevalent clinical manifestation (64%) followed by dysautonomia (16 patients [8%]) and encephalopathy (15 patients [8%]); 164 patients (85%) had at least 1 synaptic autoantibody, and 63 of these patients (38%) had at least 1 more. Muscle acetylcholine receptor was most frequent (78%), followed by ganglionic acetylcholine receptor (20%), voltage-gated Kv1 potassium channel-complex (13%), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (5%). Less frequent were aquaporin-4, voltage-gated Kv1 potassium channel-complex related proteins (leucine-rich glioma-inactivated 1 and contactin-associated protein-like 2), glycine receptor, and γ-aminobutyric acid-A receptor. Synaptic autoantibodies were significantly more frequent in patients with neurological autoimmunity than in those without and were most frequent in patients with neurological manifestations other than or in addition to MG.Synaptic autoantibodies, particularly those reactive with ion channels of the ligand-gated nicotinic acetylcholine receptor superfamily (namely α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, glycine, and γ-aminobutyric acid-A receptors), were prevalent in patients with thymoma. Autoantibodies of this extended spectrum may enhance autoimmune serological testing as an aid to preoperative thymoma diagnosis. Detection of currently known synaptic autoantibody specificities absent from this profile have potential algorithmic usefulness as negative predictors for thymoma (as recognized for neuronal voltage-gated calcium channel autoantibodies).
Efficacy of a Single-Dose, Inactivated Oral Cholera Vaccine in Bangladesh
Authors: Firdausi Qadri, Thomas F. Wierzba, Mohammad Ali, Fahima Chowdhury, Ashraful I. Khan, Amit Saha, Iqbal A. Khan, Muhammad Asaduzzaman, Afroza Akter, Arifuzzaman Khan, Yasmin A. Begum, Taufiqur R. Bhuiyan, Farhana Khanam, Mohiul I. Chowdhury, Taufiqul Islam, Atique I. Chowdhury, Anisur Rahman, Shah A. Siddique, Young A. You, Deok R. Kim, Ashraf U. Siddik, Nirod C. Saha, Alamgir Kabir, Alejandro Cravioto, Sachin N. Desai, Ajit P. Singh, John D. Clemens
Journal: New England Journal of Medicine (2016)

A single-dose regimen of the current killed oral cholera vaccines that have been prequalified by the World Health Organization would make them more attractive for use against endemic and epidemic cholera. We conducted an efficacy trial of a single dose of the killed oral cholera vaccine Shanchol, which is currently given in a two-dose schedule, in an urban area in which cholera is highly endemic.Nonpregnant residents of Dhaka, Bangladesh, who were 1 year of age or older were randomly assigned to receive a single dose of oral cholera vaccine or oral placebo. The primary outcome was vaccine protective efficacy against culture-confirmed cholera occurring 7 to 180 days after dosing. Prespecified secondary outcomes included protective efficacy against severely dehydrating culture-confirmed cholera during the same interval, against cholera and severe cholera occurring 7 to 90 versus 91 to 180 days after dosing, and against cholera and severe cholera according to age at baseline.A total of 101 episodes of cholera, 37 associated with severe dehydration, were detected among the 204,700 persons who received one dose of vaccine or placebo. The vaccine protective efficacy was 40% (95% confidence interval [CI], 11 to 60%; 0.37 cases per 1000 vaccine recipients vs. 0.62 cases per 1000 placebo recipients) against all cholera episodes, 63% (95% CI, 24 to 82%; 0.10 vs. 0.26 cases per 1000 recipients) against severely dehydrating cholera episodes, and 63% (95% CI, -39 to 90%), 56% (95% CI, 16 to 77%), and 16% (95% CI, -49% to 53%) against all cholera episodes among persons vaccinated at the age of 5 to 14 years, 15 or more years, and 1 to 4 years, respectively, although the differences according to age were not significant (P=0.25). Adverse events occurred at similar frequencies in the two groups.A single dose of the oral cholera vaccine was efficacious in older children (≥5 years of age) and in adults in a setting with a high level of cholera endemicity. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02027207.).
PTH-145 The effects of magic and laparoscopic surgery on anaemia and blood transfusions in oesophagectomy
Authors: O Ng, B Oakley, S Holmes, J Saunders, C Bowman, A Ayantunde, MJ Brookes, AG Acheson
Journal: Gut (2015)

<h3>Introduction</h3> The management of oesophageal cancer (OC) has evolved significantly in the last decade with MAGIC regimen chemotherapy and the increasing utilisation of minimally invasive techniques. Despite this, anaemia remains a common problem. This study examines how changes in the treatment of OC have impacted upon anaemia and blood transfusions, comparing two groups almost a decade apart. <h3>Method</h3> We conducted a retrospective review of patients diagnosed with OC from 2003–04 and 2012–13. Data on demographics, site and histology, TNM staging, treatment, pre-operative haemoglobin (Hb), rates of allogeneic blood transfusion and units cross matched were recorded. <h3>Results</h3> A total of 285 patients underwent oesophagectomy, 2003–04 (n = 145) and 2012–13 (n = 140). Patients were similar in age, sex, site of malignancy and histology. Patients in 2003–04 had more advanced disease at time of surgery (p &lt; 0.05) with TNM stage 3 disease in 55.9% (n = 81) vs. 42.1% (n = 59). This likely reflects down-staging from neoadjuvant chemotherapy with 41.1% (44/107) receiving neoadjuvant chemotherapy in 2003–04 vs. 55.7% (68/112) of patients in 2012–13 (p &lt; 0.05). Furthermore, those receiving chemotherapy mainly received the MAGIC regimen in the 2012–13 series whilst in 2003–4 the patients would have received 2 cycles of Cisplatin and 5 FU as per the OE-02 regimen. Mean pre-operative Hb was similar in 2003–04 to 2012–13, 12.9 g/dL (SD 1.7) vs 12.3 g/dL (SD1.7), p = 0.416. However, in those who had neoadjuvant chemotherapy, Hb was significantly different (p &lt; 0.05), 13.7 g/dL (SD 1.9) vs 12.2 g/dL (SD 1.7) from 2003–04 to 2012–2013. Consequently, patients in 2012–13 were significantly more likely to be anaemic pre-operatively (62.9% vs 38%, p &lt; 0.01), and rates more pronounced if only adenocarcinoma are analysed (65.2% vs 34.6%, p &lt; 0.01). There were also trends towards more transfusion in 2012–13 (60% vs 49%, p = 0.06) and more blood per patient 2.5u vs 2.2u, although these did not reach significance. No patients in 2003–04 had a laparoscopically assisted operation compared to 23 (16.4%) in 2012–13. 11/23 were transfused (47.8%) compared to 73/117 who received open procedures (62.4%). <h3>Conclusion</h3> Changes in the treatment of OC have increased the frequency of anaemia seen pre-operatively for patients undergoing elective oesophageal resections. This is likely due to MAGIC regimen neoadjuvant chemotherapy. While the benefits of MAGIC are recognised, peri-operative anaemia has implications on both morbidity and mortality. We now need to look at strategies to improve operative outcomes further by targeting this anaemia for treatment. <h3>Disclosure of interest</h3> None Declared.