tbuckley/cabot-search huggingface dataset:
Adjuvant Chemotherapy for Gastric Cancer with S-1, an Oral Fluoropyrimidine
Authors: Shinichi Sakuramoto, Mitsuru Sasako, Toshiharu Yamaguchi, Taira Kinoshita, Masashi Fujii, Atsushi Nashimoto, Hiroshi Furukawa, Toshifusa Nakajima, Yasuo Ohashi, Hiroshi Imamura, Masayuki Higashino, Yoshitaka Yamamura, Akira Kurita, Kuniyoshi Arai
Journal: New England Journal of Medicine (2007)

Advanced gastric cancer can respond to S-1, an oral fluoropyrimidine. We tested S-1 as adjuvant chemotherapy in patients with curatively resected gastric cancer.Patients in Japan with stage II or III gastric cancer who underwent gastrectomy with extended (D2) lymph-node dissection were randomly assigned to undergo surgery followed by adjuvant therapy with S-1 or to undergo surgery only. In the S-1 group, administration of S-1 was started within 6 weeks after surgery and continued for 1 year. The treatment regimen consisted of 6-week cycles in which, in principle, 80 mg of oral S-1 per square meter of body-surface area per day was given for 4 weeks and no chemotherapy was given for the following 2 weeks. The primary end point was overall survival.We randomly assigned 529 patients to the S-1 group and 530 patients to the surgery-only group between October 2001 and December 2004. The trial was stopped on the recommendation of the independent data and safety monitoring committee, because the first interim analysis, performed 1 year after enrollment was completed, showed that the S-1 group had a higher rate of overall survival than the surgery-only group (P=0.002). Analysis of follow-up data showed that the 3-year overall survival rate was 80.1% in the S-1 group and 70.1% in the surgery-only group. The hazard ratio for death in the S-1 group, as compared with the surgery-only group, was 0.68 (95% confidence interval, 0.52 to 0.87; P=0.003). Adverse events of grade 3 or grade 4 (defined according to the Common Toxicity Criteria of the National Cancer Institute) that were relatively common in the S-1 group were anorexia (6.0%), nausea (3.7%), and diarrhea (3.1%).S-1 is an effective adjuvant treatment for East Asian patients who have undergone a D2 dissection for locally advanced gastric cancer. (ClinicalTrials.gov number, NCT00152217 [ClinicalTrials.gov].).
Clinical and Biological Efficacy of Recombinant Human Interleukin-21 in Patients with Stage IV Malignant Melanoma without Prior Treatment: A Phase IIa Trial
Authors: Ian D. Davis, Ben Brady, Richard F. Kefford, Michael Millward, Jonathan Cebon, Birte K. Skrumsager, Ulrik Mouritzen, Lasse Tengbjerg Hansen, Kresten Skak, Dorthe Lundsgaard, Klaus Stensgaard Frederiksen, Paul E.G. Kristjansen, Grant McArthur
Journal: Clinical Cancer Research (2009)

Human interleukin-21 (IL-21) is a class I cytokine that mediates activation of CD8(+) T cells, natural killer (NK) cells, and other cell types. We report final clinical and biological results of a phase II study of recombinant human IL-21 (rIL-21) in patients with metastatic melanoma.Open-label, single-arm, two-stage trial.unresectable metastatic melanoma, measurable disease by Response Evaluation Criteria in Solid Tumors, no prior systemic therapy (adjuvant IFN permitted), adequate major organ function, good performance status, no significant autoimmune disease, and life expectancy at least 4 months.antitumor efficacy (response rate).safety, blood biomarkers, and generation of anti-rIL-21 antibodies. rIL-21 (30 microg/kg/dose) was administered by intravenous bolus injection in 8-week cycles (5 dosing days followed by 9 days of rest for 6 weeks and then 2 weeks off treatment).Stage I of the study comprised 14 patients. One confirmed complete response (CR) was observed, and as per protocol, 10 more patients were accrued to stage II (total n = 24: 10 female and 14 male). Best tumor response included one confirmed CR and one confirmed partial response, both with lung metastases. Treatment was overall well tolerated. Biomarker analyses showed increases in serum soluble CD25, frequencies of CD25(+) NK and CD8(+) T cells, and mRNA for IFN-gamma, perforin, and granzyme B in CD8(+) T and NK cells.rIL-21 administered at 30 microg/kg/d in 5-day cycles every second week is biologically active and well tolerated in patients with metastatic melanoma. Confirmed responses, including one CR, were observed.
GPs need training and funding in caring for refugees and asylum seekers
Authors: Srinivasa Vittal Katikireddi, Raj Bhopal, Julia A Quickfall
Journal: BMJ (2004)

EDITOR—UK asylum seekers and refugees have the same rights to health care as the settled population. None the less, refugees report difficulties accessing health care—for example, in registering with a general practitioner.1 They are also sometimes registered as temporary residents, which is detrimental for continuity of care.2

We sent a postal questionnaire to all 129 general practitioners in Lothian, an area in Scotland with an estimated …
An Open-Label Trial of Riluzole in Patients With Treatment-Resistant Major Depression
Authors: Carlos A. Zarate, Jennifer L. Payne, Jorge Quiroz, Jonathan Sporn, Kirk K. Denicoff, David Luckenbaugh, Dennis S. Charney, Husseini K. Manji
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: This study was conducted to determine the efficacy and safety of riluzole, a glutamate-modulating agent, in patients with recurrent major depression. METHOD: After a 1-week drug-free period, subjects 18 years or older with a diagnosis of recurrent major depression and a Montgomery-Åsberg Depression Rating Scale score ≥20 received riluzole monotherapy (100–200 mg/day) openly for 6 weeks. RESULTS: Nineteen treatment-resistant depressed patients, 53% of whom were classified as having stage 2 treatment resistance or greater, received riluzole at a mean dose of 169 mg/day. Significant improvement occurred during weeks 3 through 6 for all patients and weeks 2 through 6 for completers. CONCLUSIONS: Although preliminary, these results indicate that riluzole may have antidepressant properties in some patients.
Lipopeptides from Bacillus and Paenibacillus spp.: A Gold Mine of Antibiotic Candidates
Authors: Stephen A. Cochrane, John C. Vederas
Journal: Medicinal Research Reviews (2014)

Abstract The emergence of multidrug‐resistant bacteria has placed a strain on health care systems and highlighted the need for new classes of antibiotics. Bacterial lipopeptides are secondary metabolites, generally produced by nonribosomal peptide synthetases that often exhibit broad‐spectrum antimicrobial activity. Only two new structural types of antibiotics have entered the market in the last 40 years, linezolid and the bacterial lipopeptide daptomycin. A wide variety of bacteria produce lipopeptides, however Bacillus and Paenibacillus spp. in particular have yielded several potent antimicrobial lipopeptides. Many of the lipopeptides produced by these bacteria have been known for decades and represent a potential gold mine of antibiotic candidates. This list includes the polymyxins, octapeptins, polypeptins, iturins, surfactins, fengycins, fusaricidins, and tridecaptins, as well as some novel examples, including the kurstakins. These lipopeptides have a wide variety of activities, ranging from antibacterial and antifungal, to anticancer and antiviral. This review presents a reasonably comprehensive list of each class of lipopeptide and their known homologues. Emphasis has been placed on their antimicrobial activities, as well other potential applications for this interesting class of substances.
Honour subcultures and the reciprocal model
Authors: James Steele
Journal: Behavioral and Brain Sciences (1998)

Tests of models of reciprocal interactions of testosterone and behaviour patterns in honour subcultures, if based on adult samples measured at a single point in time, would be aided by measures of behaviour in such samples that indirectly index basal testosterone levels at earlier developmental ages, for example, hand preference and other measures of cerebral dominance. Such models raise questions about the social preconditions of honour subcultures, and their indirect effects on health.
Abstract P5-11-06: Combination of insulin-like growth factor 1 receptor and PI3K/mTOR inhibition in triple-negative breast cancers
Authors: T Liu, LD Taliaferro-Smith, R O'Regan
Journal: Cancer Research (2013)

Abstract Triple-negative (TN) breast cancers account for 15%-20% of all breast cancers with limited treatment options and poor prognosis. The poor outcomes seen with TN breast cancers (TNBCs) are in part due to a lack of viable therapeutic targets. Overexpression of insulin-like growth factor 1 receptors results in mammary tumorigenesis and is common in breast carcinomas. However, the use of IGF1R inhibitor alone has produced limited effects on TNBC cells inhibition. NVP-BEZ235 is a potent PI3K/mTOR dual inhibitor and has been shown to be effective in TNBC cell lines, especially for the mesenchymal-like and luminal-androgen receptor subtypes. Unlike rapamycin, which produces a feedback activation of Akt, NVP-BEZ235 alone successfully blocks the Akt activation and effectively inhibits the cells proliferation. Methods: In this study, we examined the effects of a selective IGF1R small molecule inhibitor picropodophyllin (PPP) in combination with NVP-BEZ235 on human MDA-MB-231, MDA-MB-468, HCC1806 and BT549 TNBC cell lines. SRB cell survival assays were performed following PPP or NVP-BEZ235 treatments alone and PPP in combination with NVP-BEZ235. Western blotting was used to detect expression and phosphorylation of down-stream signaling proteins and fluorescence-activated cell sorting (FACS) analysis to assess effects on apoptosis following treatments. Results: The combined IGF1R inhibition with PPP and PI3K/mTOR inhibition with NVP-BEZ235 resulted in significantly greater cytotoxicity than either PPP or NVP-BEZ235 alone in all four cell lines compared to single agent treatments. Notably, this difference was more pronounced at lower concentrations of both drugs (between 7.8 nM-62.5 nM). The combination of PPP and NVP-BEZ235 inhibitors also significantly increased apoptosis via induction of cleaved caspase-3 and suppressed the PI3K/Akt and MEK/ERK signaling cascades in these TNBC cell lines. Conclusion: These results suggest that the combined inhibition of IGF1R and PI3K/mTOR may be a more effective strategy than single inhibition for TNBC treatments and warrant further investigation in in vivo animal studies. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-11-06.
Lectures on Diseases of the Gall Bladder and Bile Ducts: Delivered at the Royal College of Surgeons of England
Authors: A. W. M. Robson
Journal: BMJ (1897)

BILE DUCTS. HAD time permitted, the anatomy of the gall bladder bile ducts would have formed a subject of sufficient for my first lecture, but the number and importance matters I propose to consider clearly demonstrate an impossibility, if I am to nearly complete my Some of the more important anatomical points, must not omit.Congqenital Malformations.-There is apparently no the biliary apparatus, except the liver, which may absent.While it is not to be wondered at in the MRDWALB.JL]
Evolution of “The Guideline Advantage”: Lessons Learned From the Front Lines of Outpatient Performance Measurement
Authors: Vincent Bufalino, Mary Ann Bauman, Jay H. Shubrook, Alan J. Balch, Christopher Boone, Katy Vennum, Sarah Bradley, Richard C. Wender, Regan Minners, Donna Arnett
Journal: Diabetes Care (2014)

Heart disease, cancer, stroke, and diabetes mellitus collectively account for >1.37 million U.S. deaths each year (1). Compounding the tragedy is the knowledge that many of those deaths could be avoided through better application of clinical guidelines related to primary and secondary prevention or disease management. The combined control of blood pressure, lipids, and glucose has been shown to substantially reduce mortality and cardiovascular events (2,3). Screening for colon, cervical, breast, and lung cancer has been proven to reduce age-adjusted mortality from these diseases (4). In recognition of the common risk factors across these disease areas, the chief executive officers of the American Cancer Society, American Diabetes Association, and American Heart Association formed the Preventive Health Partnership in 2004. The 3 organizations have been working closely ever since to increase public awareness about healthy lifestyles, support policies that increase funding for and access to prevention programs and research, and increase the focus on prevention among healthcare providers.

The American Cancer Society, American Diabetes Association, and American Heart Association have long developed scientific statements and evidence-based guidelines that promote public health services and clinical interventions of known efficacy for improving patient outcomes. Thus, maximizing adherence to quality-of-care guidelines is a high priority for each organization, because this will save lives and improve quality of life. This common purpose has served as a focal point for much of the collaborative work undertaken by the 3 organizations, including The Guideline Advantage (TGA).

Launched in 2011, TGA is a jointly operated program designed to promote consistent use of evidence-based practice guidelines through existing healthcare technology in the outpatient setting. The ultimate goal of this undertaking is to improve patient care through quality improvement programs that provide feedback to clinicians and their practices on performance across various quality measures. The data gathered through …
Obstructive sleep apnea syndrome (OSA) and hypercoagulability - What is the impact of sole OSA in the absence of comorbities?
Authors: Nadine Baschung, Corinne Roth, Anne-Kathrin Brill, Thomas Geiser, Matthias Gugger, Sebastian Ott
Journal: European Respiratory Journal (2013)

Aim:   OSA is a known risk factor for cardiovascular morbidity and mortality. Among others, OSA-induced hypercoagulability has been identified as a potentially unterlying mechanism. So far, it remains unclear whether changes in the coagulation system are caused by OSA alone or by OSA-associated comorbidities. The aim of this study was to investigate the influence of sole OSA on various hemostatic parameters and markers of platelet activation (INR, aPTT, prothrombin time (PT), plasminogen, plasminogen activator inhibitor-1, fibrinogen, sCD40 ligand, platelet derived microparticles).   Methods : We studied 10 otherwise healthy male patients with newly diagnosed OSA and 10 male non-OSAS controls with comparable demographics. OSA was proven or excluded by full-night polysomnography (PSG). Following PSG, fasting blood was drawn between 6:00 a.m. and 7:00 a.m. prior to physical activity.   Results : Most parameters of hemostasis and platelet activation did not differ between sole OSA patients and healthy controls. Only PT (12.0±0.6 s vs. 12.8±0.5 s, p   Conclusions : Our data suggest that sole OSA contributes only a small proportion to the previously described procoagulatory state, thus, limiting the hitherto assumed direct impact of OSA on the coagulation system. OSA associated comorbidities and simultaneously existing cardiovascular risk factors are probably the major contributors to hypercoagulability in OSA patients, possibly aggravated by a concomittant OSA.
The effects of ultraviolet radiation on the human immune system
Authors: None Duthie, None Kimber, None Norval
Journal: British Journal of Dermatology (1999)

The adverse outcome of increased ultraviolet (UV) irradiation on human health is currently of concern. While many experiments have been carried out in rodent models, fewer have been designed to test the effects of UV exposure in human subjects. This review concentrates on the modulations induced in the human immune system by UV, and outlines changes in antigen presentation by Langerhans cells and macrophages, in the activities of natural killer cells and T cells, and in cytokine regulation. Precautionary measures which might be taken to help protect people against the immunosuppressive action of UV irradiation are considered.
Severe Pulmonary Hypertension and Chronic Obstructive Pulmonary Disease
Authors: Ari Chaouat, Anne-Sophie Bugnet, Nabila Kadaoui, Roland Schott, Irina Enache, Alain Ducoloné, May Ehrhart, Romain Kessler, Emmanuel Weitzenblum
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Severe pulmonary hypertension occurs occasionally in patients with chronic obstructive pulmonary disease (COPD), but no detailed description of these patients is available.To identify and characterize patients with COPD and severe pulmonary hypertension.Retrospective study of 27 patients with COPD with severe pulmonary hypertension (pulmonary artery mean pressure [Ppa], > or = 40 mm Hg) among 998 patients who underwent right heart catheterization between 1990 and 2002 as part of a workup for chronic respiratory failure during a period of disease stability.Of the 27 patients, 16 had another disease capable of causing pulmonary hypertension. The remaining 11 (11 of 998, 1.1%) patients had COPD as the only cause of pulmonary hypertension, with a median Ppa of 48 mm Hg (interquartile range, 46-50). They had an unusual pattern of cardiopulmonary abnormalities with mild to moderate airway obstruction, severe hypoxemia, hypocapnia, and a very low diffusing capacity for carbon monoxide (p < 0.01 compared with a control group of patients with COPD). Exertional dyspnea was more severe (p < 0.01) and survival was shorter (p = 0.0026) than in the control subjects.Severe pulmonary hypertension is uncommon in patients with COPD. When it occurs, another cause must be sought. COPD with severe pulmonary hypertension and no other possible cause shares features with pulmonary vascular diseases, such as idiopathic pulmonary hypertension.
Hypermutation of Immunoglobulin Genes in Memory B Cells of DNA Repair–deficient Mice
Authors: Heinz Jacobs, Yosho Fukita, Gijsbertus T.J. van der Horst, Jan de Boer, Geert Weeda, Jeroen Essers, Niels de Wind, Bevin P. Engelward, Leona Samson, Sjef Verbeek, Josiane Ménissier de Murcia, Gilbert de Murcia, Hein t e Riele, Klaus Rajewsky
Journal: The Journal of Experimental Medicine (1998)

To investigate the possible involvement of DNA repair in the process of somatic hypermutation of rearranged immunoglobulin variable (V) region genes, we have analyzed the occurrence, frequency, distribution, and pattern of mutations in rearranged Vλ1 light chain genes from naive and memory B cells in DNA repair–deficient mutant mouse strains. Hypermutation was found unaffected in mice carrying mutations in either of the following DNA repair genes: xeroderma pigmentosum complementation group (XP)A and XPD, Cockayne syndrome complementation group B (CSB), mutS homologue 2 (MSH2), radiation sensitivity 54 (RAD54), poly (ADP-ribose) polymerase (PARP), and 3-alkyladenine DNA-glycosylase (AAG). These results indicate that both subpathways of nucleotide excision repair, global genome repair, and transcription-coupled repair are not required for somatic hypermutation. This appears also to be true for mismatch repair, RAD54-dependent double-strand–break repair, and AAG-mediated base excision repair.
The Finding of Premalignant Lesions is Not Associated with Smoking Cessation in Chemoprevention Study Volunteers
Authors: Romane M. Schook, Berber B.M. Postmus, Remco M. van den Berg, Thomas G. Sutedja, Frances S. Man de, Egbert F. Smit, Pieter E. Postmus
Journal: Journal of Thoracic Oncology (2010)
Changing Health Insurance Trends
Authors: John K. Iglehart
Journal: New England Journal of Medicine (2002)

With health care expenditures growing far more rapidly than the economy, employers and the health insurers whose plans employers purchase are implementing new ways to reconcile the strong demand for medical services with the means to pay for them. The changes fall short of a grand strategy, but they do underscore the emergence of a set of beliefs that will influence the shape of private insurance for the foreseeable future. Their centerpiece is a conviction that individual consumers of health care should assume greater financial responsibility for the decisions they make when selecting insurance benefits and seeking medical treatment. Central . . .
Intraprostatic Androgens and Androgen-Regulated Gene Expression Persist after Testosterone Suppression: Therapeutic Implications for Castration-Resistant Prostate Cancer
Authors: Elahe A. Mostaghel, Stephanie T. Page, Daniel W. Lin, Ladan Fazli, Ilsa M. Coleman, Lawrence D. True, Beatrice Knudsen, David L. Hess, Colleen C. Nelson, Alvin M. Matsumoto, William J. Bremner, Martin E. Gleave, Peter S. Nelson
Journal: Cancer Research (2007)

Abstract Androgen deprivation therapy (ADT) remains the primary treatment for advanced prostate cancer. The efficacy of ADT has not been rigorously evaluated by demonstrating suppression of prostatic androgen activity at the target tissue and molecular level. We determined the efficacy and consistency of medical castration in suppressing prostatic androgen levels and androgen-regulated gene expression. Androgen levels and androgen-regulated gene expression (by microarray profiling, quantitative reverse transcription-PCR, and immunohistochemistry) were measured in prostate samples from a clinical trial of short-term castration (1 month) using the gonadotropin-releasing hormone antagonist, Acyline, versus placebo in healthy men. To assess the effects of long-term ADT, gene expression measurements were evaluated at baseline and after 3, 6, and 9 months of neoadjuvant ADT in prostatectomy samples from men with localized prostate cancer. Medical castration reduced tissue androgens by 75% and reduced the expression of several androgen-regulated genes (NDRG1, FKBP5, and TMPRSS2). However, many androgen-responsive genes, including the androgen receptor (AR) and prostate-specific antigen (PSA), were not suppressed after short-term castration or after 9 months of neoadjuvant ADT. Significant heterogeneity in PSA and AR protein expression was observed in prostate cancer samples at each time point of ADT. Medical castration based on serum testosterone levels cannot be equated with androgen ablation in the prostate microenvironment. Standard androgen deprivation does not consistently suppress androgen-dependent gene expression. Suboptimal suppression of tumoral androgen activity may lead to adaptive cellular changes allowing prostate cancer cell survival in a low androgen environment. Optimal clinical efficacy will require testing of novel approaches targeting complete suppression of systemic and intracrine contributions to the prostatic androgen microenvironment. [Cancer Res 2007;67(10):5033–41]