tbuckley/cabot-search huggingface dataset:
Abstract 2834: Cancer testis antigens-specific CD4+ T-cell immunity augmented by CTL-epitopes vaccination in cancer patients.
Authors: Yusuke Tomita, Akira Yuno, Yoshihiro Yoshitake, Hirotake Tsukamoto, Atsushi Irie, Satoru Senju, Koji Yoshida, Takuya Tsunoda, Yusuke Nakamura, Masanori Shinohara, Yasuharu Nishimura
Journal: Cancer Research (2013)

Abstract We identified novel cancer testis antigens (CTAs) including CDCA1, LY6K (URLC10) and KIF20A that are overexpressed in lung cancer, head and neck cancer (HNC), and other various malignancies, but not expressed in many adult normal tissues except for testis and fetal organs by using genome-wide cDNA microarray analyses. We identified CTAs-derived peptides that can activate tumor-reactive and HLA-A2 or -A24-restricted CTLs in both in vitro preclinical and in vivo clinical studies of peptide vaccine. It is well known that IL-2 and IFN-γ produced by Th1 cells have pivotal roles in efficient induction of memory CTLs and efficient infiltration of CTLs into the tumor. We identified these CTAs-derived promiscuous 20∼26-mer long peptides (LPs) that can induce both Th1 cells restricted by several frequent HLA class II and tumor-reactive CTLs restricted by HLA-A2 or -A24. The LPs were naturally processed from CTAs and presented by dendritic cells. In addition, these LPs induced propagation of CTA-specific CTLs by cross presentation in both human in vitro and HLA-class I transgenic mice in vivo. Furthermore, these LPs and Th1-cell clone enhanced induction of CTA-specific CTLs in vitro. Significant frequencies of CTA-specific Th1 cells were detected after short-term in vitro stimulation with LPs in HNC patients vaccinated with CTA-derived CTL-epitope peptides and cancer patients before vaccination but not in healthy donors; responses were augmented by repeated vaccinations. These results show for the first time the presence of novel CTAs-specific Th1 cell responses in cancer patients and suggest the potential utility of these LPs for propagation of CTAs-specific Th1 cells and CTLs. Citation Format: Yusuke Tomita, Akira Yuno, Yoshihiro Yoshitake, Hirotake Tsukamoto, Atsushi Irie, Satoru Senju, Koji Yoshida, Takuya Tsunoda, Yusuke Nakamura, Masanori Shinohara, Yasuharu Nishimura. Cancer testis antigens-specific CD4+ T-cell immunity augmented by CTL-epitopes vaccination in cancer patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2834. doi:10.1158/1538-7445.AM2013-2834
1195 HEALTHY VOLUNTEER FIRST-IN-HUMAN EVALUATION OF GS-5816, A NOVEL SECOND GENERATION BROAD-GENOTYPIC NS5A INHIBITOR WITH POTENTIAL FOR ONCE-DAILY DOSING
Authors: P. German, P. Pang, C. Yang, L. Han, J.O. Link, B.P. Kearney, A. Mathias
Journal: Journal of Hepatology (2013)
Food diversity in infancy and the risk of childhood asthma and allergies
Authors: Bright I. Nwaru, Hanna-Mari Takkinen, Minna Kaila, Maijaliisa Erkkola, Suvi Ahonen, Juha Pekkanen, Olli Simell, Riitta Veijola, Jorma Ilonen, Heikki Hyöty, Mikael Knip, Suvi M. Virtanen
Journal: Journal of Allergy and Clinical Immunology (2014)
Cutting the research budget
Authors: L. Dillner
Journal: BMJ (2010)

Will diminish the United Kingdom’s research pedigree and damage the economy

No sooner had Cambridge University ousted Harvard from the top of this years’ QS world university rankings, than Vince Cable, secretary of state for business in the United Kingdom, was making his first science, research, and innovation speech.1 In it he asked “How can we economise without damaging science?” When the results of the government’s comprehensive spending review are announced later this year few doubt, but few want to believe, that there will be serious reductions in research funding. Research quality is, after all, a factor in the QS rankings that puts six of the UK’s universities in the world’s top 25. Cable has already denied in a radio interview that 35% of the research budget will be cut. But rumours are circulating that the seven research councils that invest around £2.8bn (€3.38bn; $4.31bn) a year in research covering all academic disciplines, including medical and biological sciences, have been asked to prepare scenarios on the basis of funding reductions of 10%, 20%, and 30%.

Cable’s speech argued for prioritising the funding of only excellent research and that which …
Erythema elevatum diutinum, cryoglobulinaemia, and fixed urticaria on cooling
Authors: J.G.L. MORRISON, P.R. HULL, E. FOURIE
Journal: British Journal of Dermatology (1977)

A mixed cryoglobulin (IgG/IgM) was detected in a patient with erythema elevatum diutinum. Cold exposure activated the complement system and provoked a fixed urticarial reaction with the histology of a leukocytoclastic vasculitis.
758 CHARACTERIZATION OF RESISTANT MUTANTS SELECTED IN VITRO BY THE HCV NS3/4A PROTEASE INHIBITOR BI 201335
Authors: G. Kukolj, C. Bousquet, N. Dansereau, F. Dô, L. Lagacé, M. Llinàs-Brunet, M. Marquis, M.-J. Massariol, R. Maurice, C. Spickler, D. Thibeault, S. Zhao, P.W. White
Journal: Journal of Hepatology (2010)
Oral Contraceptives and Depression
Authors: Bernard M. Kaye
Journal: JAMA (1963)

<h3>To the Editor:</h3> —I have discussed the following problem with my psychiatric colleagues, and they feel that this matter should be brought to the attention of physicians in general. The use of the mixture norethynodrel with mestranol (Enovid) and other oral contraceptives is becoming more and more widespread. The usual side effects—nausea, bloating, and withdrawal bleeding—are well known. A less common complaint of some patients is severe depression. Within the last year I have had three patients complain about this symptom. Two of them had been under psychiatric care for depressions prior to the use of the norethynodrel mixture. Both patients also found the same effect from an experimental mixture of norethisterone acetate and ethinyl estradiol (Norlestrin). Because of depression, both patients were unable to tolerate the medications, and therefore discontinued their use. The third patient was originally given the norethynodrel mixture, 5 mg, to control premenstrual headaches, dysmenorrhea, and
415 Evolution of hepatitis C plasma quasispecies after liver transplantation does not reflect that of cell-associated quasispecies in human immunodeficiency virus co-infected patients
Authors: A.M. Roque-Afonso, E. Marchadier, E. Beaulieux, V. Mackiewicz, P. Vaghefi, D. Samuel, E. Dussaix
Journal: Journal of Hepatology (2006)
Poly(oligo-D-arginine) With Internal Disulfide Linkages as a Cytoplasm-sensitive Carrier for siRNA Delivery
Authors: Young-Wook Won, Sun-Mi Yoon, Kyung-Mi Lee, Yong-Hee Kim
Journal: Molecular Therapy (2010)

Small interfering RNA (siRNA) has emerged as a therapeutic strategy for various diseases due to its target-specific gene silencing; however, its relatively high molecular weight, negative charge, and low stability hamper in vitro and in vivo applications. Approaches to overcome those drawbacks have relied on nonviral siRNA carriers based on cationic polymers or peptides. Nevertheless, cationic polymer-based siRNA carriers have yet to resolve intrinsic problems such as cytotoxicity and immunogenicity. An environment-sensitive carrier was recently proposed to enhance siRNA bioactivity and to reduce the carrier safety issues. Only a few studies, however, have shown cytoplasm-sensitive dissociation of the polyplex. In the present study, we clearly demonstrated decondensation of siRNA/poly(oligo-D-arginine) polyplex in the cytoplasm in response to intracellular glutathione (GSH) and the enhanced bioactivity of siRNA against VEGF (siVEGF) used as a model both in vitro and in an animal model. Reducible poly(oligo-D-arginine) (rPOA) rapidly dissociated in the cytoplasm, resulting in fast siRNA release to its target location while maintaining siRNA bioactivity both in vitro and in vivo. Small interfering RNA (siRNA) has emerged as a therapeutic strategy for various diseases due to its target-specific gene silencing; however, its relatively high molecular weight, negative charge, and low stability hamper in vitro and in vivo applications. Approaches to overcome those drawbacks have relied on nonviral siRNA carriers based on cationic polymers or peptides. Nevertheless, cationic polymer-based siRNA carriers have yet to resolve intrinsic problems such as cytotoxicity and immunogenicity. An environment-sensitive carrier was recently proposed to enhance siRNA bioactivity and to reduce the carrier safety issues. Only a few studies, however, have shown cytoplasm-sensitive dissociation of the polyplex. In the present study, we clearly demonstrated decondensation of siRNA/poly(oligo-D-arginine) polyplex in the cytoplasm in response to intracellular glutathione (GSH) and the enhanced bioactivity of siRNA against VEGF (siVEGF) used as a model both in vitro and in an animal model. Reducible poly(oligo-D-arginine) (rPOA) rapidly dissociated in the cytoplasm, resulting in fast siRNA release to its target location while maintaining siRNA bioactivity both in vitro and in vivo.
Cholesterol Reduction in Coronary Artery Bypass Patients
Authors: Eugene R. Passamani
Journal: JAMA (1987)

This issue ofThe Journalcontains an article by Blanken-horn et al<sup>1</sup>that deserves, dear reader, your careful scrutiny. Aggressive diet and drug therapy appear to have led to sustained large reductions in blood cholesterol levels and, more importantly, to a reduced rate of development and progression of coronary artery and vein bypass graft lesions in patients who have undergone aortocoronary bypass graft surgery. The study is a substantial addition to the already extensive body of literature that links blood cholesterol level to atherosclerotic vascular disease in general and to coronary artery disease in particular.<sup>2-6</sup>The implications of this study for the several million individuals who have undergone coronary bypass surgery are substantial. Coronary artery disease remains a major public health problem in the United States, despite an encouraging 37% reduction in age-adjusted mortality rates noted during the last two decades.<sup>7</sup>In 1985, an estimated 540 000
Supervision registers for mentally ill people
Authors: G R Glover, A W McCulloch, R Jenkins
Journal: BMJ (1994)

Profiles ofriskfactors in users and non-users ofoestrogen in two studies CurrentPast Never user* user used Nurses' health study' Current smoker (0/%) 11-2 14-7 14-5 % With hypertension 23-2 25-0 21-8 % With diabetes 2-7 3-8 3-5 % With high serum cholesterol 9 9 11-2 7-6 % With parental myocardial infarction before age 60 10-6 100 93 % Taking vigorous physical activity -once per week 48-2 43-1 42-4 % With body mass index -29kg/m2 9-8 13-3 15-0 Lipid Research Clinics programme'* <High school education 16 25 % Smokers 33 31 % Taking regular exercise 12 10 % Drinking alcohol 82 79 Mean body mass index (kg/M2) 24-7 25-7 Mean age (years) 53-8 52-6 Mean systolic blood pressure (mm Hg) 129-0 127-7 Mean diastolic blood pressure (mm Hg) 79-9 79 5 Mean cholesterol 234-8 235-2 *In Lipid Research Clinics programme data for current and past users were combined.
Electron beam therapy in Arndt-Gottron's sclernmyxoedema
Authors: G.M. Kavanagh, L.M. Matheson, D.J. Thwaites, J.A.A. Hunter
Journal: British Journal of Dermatology (1997)

Journal Article Electron beam therapy in Arndt‐Gottron's sclernmyxoedema Get access G.M. Kavanagh, G.M. Kavanagh Department of Dermatology, The Royal Infirmary of Edinburgh NHS Trust Search for other works by this author on: Oxford Academic Google Scholar L.M. Matheson, L.M. Matheson Department of Clinical Oncology, Western General Hospitals NHS Trust, Edinburgh. U.K. Search for other works by this author on: Oxford Academic Google Scholar D.J. Thwaites, D.J. Thwaites Department of Oncology physics, The Royal Infirmary of Edinburgh NHS Trust Search for other works by this author on: Oxford Academic Google Scholar J.A.A. Hunter J.A.A. Hunter Department of Dermatology, The Royal Infirmary of Edinburgh NHS Trust Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 137, Issue 1, 1 July 1997, Pages 152–154, https://doi.org/10.1111/j.1365-2133.1997.tb03724.x Published: 01 July 1997
Factors Concerned with Postoperative Emesis and Its Prevention with Thiethylperazine
Authors: William C. North, Thomas H. Collawn, A.B. Hudnell, C.R. Stephen
Journal: JAMA (1963)

ONE OF THE OBJECTIONS to the use of antiemetics in the postanesthetic period has been their tendency to prolong return to consciousness or to induce a hypotensive episode. 1 When 2-ethyl-mercapto-10- [3′-(1″methyl-piperazinyl-4″)-propyl-1′] phenothiazine, thiethylperazine (Torecan), was proposed as a drug which acted specifically on the vomiting centers without causing sedation or hypotension, 2 it seemed that it was worthy of trial as a safe postoperative antiemetic.  It was evaluated by the use of a blind technique in which neither the individual administering the drug nor the observer knew what agent had been given. In no instance was the patient aware that he was part of a special study. The solutions were dispensed in 2 cc coded ampules. The codes were not broken until completion of the studies. The injections were all made intramuscularly.  In the initial series, 1,390 unselected surgical patients over the age of five were
Human leukocyte antigen-C genes and susceptibility to primary sclerosing cholangitis
Authors: Manus M. Moloney, Linda J. Thomson, Michael J. Strettell, Roger Williams, Peter T. Donaldson
Journal: Hepatology (1998)

Genetic susceptibility to primary sclerosing cholangitis (PSC) is associated with the extended HLA A1-B8-DR3 haplotype and also with the DRB3*0101-DRB1*0301-DQA1*0103-DQB1*0603 haplotype. However, very few studies have considered the role of HLA C which lies between HLA A and B, is highly polymorphic, and encodes proteins which play an important role in immunoregulation and in disease susceptibility. Traditional assignment of HLA Cw antigens by serology is both inaccurate and unreliable, with a high error rate. The aim of this study was to characterize the distribution of HLA C alleles in a large group of patients with primary sclerosing cholangitis by using a recently developed polymerase chain reaction-based genotyping technique. Ninety-three white adult patients of northern European origin with well characterized PSC and 100 geographically and racially matched controls were studied. HLA C and HLA DRB1 alleles were assigned by polymerase chain reaction-based genotyping, HLA A and B antigens by standard microlymphocytotoxicity test and extended haplotypes were constructed according to known patterns of linkage disequilibrium. The Cw*07 gene was found in 67.7% of patients versus 54% of controls (P = .051, OR = 1.79). This increase was a result of inheritance of the Cw*0701 allele which was found in 51.6% of patients compared with 34% of controls (P = .013, OR = 2.07). There were no significant differences in the frequencies of any of the other Cw alleles including the Cw*07 group: Cw*0702, Cw*0703, and Cw*0704. HLA-encoded genetic susceptibility to PSC is associated with the HLA Cw*0701 allele, but the association is weak and may simply reflect linkage disequilibrium with the HLA B8-DR3 haplotype. These findings indicate that the telomeric limit of HLA-encoded susceptibility to primary sclerosing cholangitis lies close to the HLA C locus.
Primary Angioplasty and Thrombolysis Are Both Reasonable Options in Acute Myocardial Infarction
Authors: James M. Brophy, Peter Bogaty
Journal: Annals of Internal Medicine (2004)

Primary angioplasty is increasingly being advocated as the preferred approach for treating acute ST-segment elevation myocardial infarction regardless of whether interinstitutional transfer is required. This review critically analyzes the evidence comparing primary angioplasty with thrombolytic therapy and concludes that reasonable health care professionals may still find considerable uncertainty about the superiority of primary angioplasty for all situations. The magnitude of benefit for primary angioplasty over thrombolysis is probably less than 1 to 2 lives saved/100 patients treated and largely depends on the choice of thrombolytic agent, time to treatment, place of treatment, and adjunctive therapy. There is little evidence that systematically transferring patients for primary angioplasty in routine practice will provide any health benefits over thrombolysis. Consequently, it may be most useful to view these treatments as complementary rather than competitive. Thrombolysis remains a clinically and economically attractive option for the treatment of acute myocardial infarction that does not require the radical restructuring of our health care systems.
Long term survival in gastro-oesophageal cancer
Authors: S. F. Neong, J. Deacon, I. R. Sargeant, D. L. Morris
Journal: Gut (2011)

<h3>Introduction</h3> One of the changes implemented following the publication of the Improving Outcome Guidances (IOG) is the centralisation of cancer services to ensure delivery of an effective management plan to all patients diagnosed with gastro-oesophageal cancer. With the high mortality, monitoring and auditing treatment outcomes is vital in ensuring that these patients receive the best available treatment. The recent publication of the National Oesophago-Gastric Cancer Audit data further re-iterates this and forms the crux of evidence-based management of patients diagnosed with gastro-oesophageal cancer. <h3>Methods</h3> The study aims to measure the survival outcome of patients diagnosed with both gastric and oesophageal cancer in our NHS trust who has a catchment population of 500 000 across the 2 district general hospitals. We retrospectively reviewed the medical notes, computerised notes of the multidisciplinary team (MDT) meetings as well as endoscopy reports of all patients diagnosed with gastro-oesophageal cancer in the 5-year period from 1 January 2004 to 31 December 2008. The date of death was noted and the number of survivors as of 15 July 2010 were taken into account. <h3>Results</h3> 234 and 139 patients were diagnosed with oesophageal and gastric cancer respectively, of which data from 6 patients were unavailable. As of 15 July 2010, 46 (12%) of all patients traced are still alive, 31 (13%) with oesophageal cancer and 15 (11%) with gastric cancer. For those that have died, the median survival was 156 days (2–1594) and 251 days (4–1413) for patients with gastric and oesophageal cancer respectively. For patients with oesophageal cancer, the median survival in those managed palliatively was 247 days (4–1022) while the median survival was 383 days (71–1413) in those that had neoadjuvant chemotherapy and surgery. Survival rates are shown below. <h3>Conclusion</h3> The improved survival after treatment with curative intent (surgery ± neoadjuvant chemotherapy or primary chemoradiotherapy) is encouraging. For oesophageal cancer, our 1-year survival rate (75%) in this group mirrors the results from the recently published National Oesophago-Gastric Cancer Audit 2010 (76.1%). There are more patients with gastric cancer being managed palliatively and this is reflected by the lower survival rates in this group. Centralisation of services in this trust occurred in 2009 and comparison with these data in future are vital in monitoring its success.
High Prevalence of Multidrug-Resistant Nonfermenters in Hospital-acquired Pneumonia in Asia
Authors: Doo Ryeon Chung, Jae-Hoon Song, So Hyun Kim, Visanu Thamlikitkul, Shao-Guang Huang, Hui Wang, Thomas Man-kit So, Rohani M. D. Yasin, Po-Ren Hsueh, Celia C. Carlos, Li Yang Hsu, Latre Buntaran, M. K. Lalitha, Min Ja Kim, Jun Yong Choi, Sang Il Kim, Kwan Soo Ko, Cheol-In Kang, Kyong Ran Peck
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) remain important causes of morbidity and mortality. Increasing antimicrobial resistance has aroused the concern of the failure of antibiotic treatment.To determine the distribution of the bacterial isolates of HAP and VAP, their antimicrobial resistance patterns, and impact of discordant antibiotic therapy on clinical outcome in Asian countriesA prospective surveillance study was conducted in 73 hospitals in 10 Asian countries from 2008-2009. A total of 2,554 cases with HAP or VAP in adults were enrolled and 2,445 bacterial isolates were collected from 1,897 cases. Clinical characteristics and antimicrobial resistance profiles were analyzed.Major bacterial isolates from HAP and VAP cases in Asian countries were Acinetobacter spp., Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae. Imipenem resistance rates of Acinetobacter and P. aeruginosa were 67.3% and 27.2%, respectively. Multidrug-resistant rates were 82% and 42.8%, and extensively drug-resistant rates were 51.1% and 4.9%. Multidrug-resistant rate of K. pneumoniae was 44.7%. Oxacillin resistance rate of S. aureus was 82.1%. All-cause mortality rate was 38.9%. Discordant initial empirical antimicrobial therapy increased the likelihood of pneumonia-related mortality (odds ratio, 1.542; 95% confidence interval, 1.127-2.110).Acinetobacter spp., P. aeruginosa, S. aureus, and K. pneumoniae are the most frequent isolates from adults with HAP or VAP in Asian countries. These isolates are highly resistant to major antimicrobial agents, which could limit the therapeutic options in the clinical practice. Discordant initial empirical antimicrobial therapy significantly increases the likelihood of pneumonia-related mortality.
Regional Brain Metabolic Correlates of α-Methylparatyrosine–Induced Depressive Symptoms
Authors: J. Douglas Bremner, Meena Vythilingam, Chin K. Ng, Eric Vermetten, Ahsan Nazeer, Dan A. Oren, Robert M. Berman, Dennis S. Charney
Journal: JAMA (2003)

ContextWe previously used positron emission tomography (PET) measurement of brain metabolism with 18fluorodeoxyglucose to show that patients receiving selective serotonin reuptake inhibitors (SSRIs) who have a tryptophan depletion–induced return of depressive symptoms have an acute decrease in metabolism in orbitofrontal cortex, dorsolateral prefrontal cortex, and thalamus. Many patients with depression in remission while taking norepinephrine reuptake inhibitors (NRIs) (but not SSRIs) experience a return of depressive symptoms with depletion of norepinephrine and dopamine using α-methylparatyrosine (AMPT).ObjectiveTo assess brain metabolic correlates of AMPT administration in patients with depression in remission while receiving NRIs.Design, Setting, and ParticipantsRandomized, controlled, double-blind trial in which 18 patients recruited in 1997-2000 from the general community who had depression in remission while taking NRIs had PET imaging in a psychiatric research unit following AMPT and placebo administration.InterventionsAfter initial medication with desipramine and follow-up until response, patients underwent active AMPT (five 1-g doses administered orally over 28 hours) and placebo (diphenhydramine hydrochloride, five 50- mg doses administered similarly) catecholamine depletion challenges in randomized order of assignment, after which PET imaging was performed on day 3 of each condition. Both study conditions were performed 1 week apart.Main Outcome MeasuresRegional brain metabolism rates in patients with and without AMPT-induced return of depressive symptoms.ResultsAMPT-induced return of depressive symptoms was experienced by 11 of the 18 patients and led to decreased brain metabolism in a number of cortical areas, with the greatest magnitude of effects in orbitofrontal (P = .002) and dorsolateral prefrontal (P = .03) cortex and thalamus (P = .006). Increased resting metabolism in prefrontal and limbic areas predicted vulnerability to return of depressive symptoms.ConclusionsDifferent neurochemical systems that mediate depression may have effects on a common brain circuitry. Baseline metabolism in successfully treated depressed patients may predict vulnerability to future episodes of depression.