tbuckley/cabot-search huggingface dataset:
Cost-Effectiveness of Rapid Syphilis Screening in Prenatal HIV Testing Programs in Haiti
Authors: Bruce R Schackman, Christopher P Neukermans, Sandy N. Nerette Fontain, Claudine Nolte, Patrice Joseph, Jean W Pape, Daniel W Fitzgerald
Journal: PLoS Medicine (2007)

New rapid syphilis tests permit simple and immediate diagnosis and treatment at a single clinic visit. We compared the cost-effectiveness, projected health outcomes, and annual cost of screening pregnant women using a rapid syphilis test as part of scaled-up prenatal testing to prevent mother-to-child HIV transmission in Haiti.A decision analytic model simulated health outcomes and costs separately for pregnant women in rural and urban areas. We compared syphilis syndromic surveillance (rural standard of care), rapid plasma reagin test with results and treatment at 1-wk follow-up (urban standard of care), and a new rapid test with immediate results and treatment. Test performance data were from a World Health Organization-Special Programme for Research and Training in Tropical Diseases field trial conducted at the GHESKIO Center Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes in Port-au-Prince. Health outcomes were projected using historical data on prenatal syphilis treatment efficacy and included disability-adjusted life years (DALYs) of newborns, congenital syphilis cases, neonatal deaths, and stillbirths. Cost-effectiveness ratios are in US dollars/DALY from a societal perspective; annual costs are in US dollars from a payer perspective. Rapid testing with immediate treatment has a cost-effectiveness ratio of $6.83/DALY in rural settings and $9.95/DALY in urban settings. Results are sensitive to regional syphilis prevalence, rapid test sensitivity, and the return rate for follow-up visits. Integrating rapid syphilis testing into a scaled-up national HIV testing and prenatal care program would prevent 1,125 congenital syphilis cases and 1,223 stillbirths or neonatal deaths annually at a cost of $525,000.In Haiti, integrating a new rapid syphilis test into prenatal care and HIV testing would prevent congenital syphilis cases and stillbirths, and is cost-effective. A similar approach may be beneficial in other resource-poor countries that are scaling up prenatal HIV testing.
A very British congress
Authors: J. O. Drife
Journal: BMJ (1998)

Normally I am cynical about spas and large congresses. Both have something a little too artificial about them for my taste. Nevertheless, at the end of June there I was in our local watering place, wearing a name badge with a long ribbon marked “chairman,” and awaiting the arrival of a thousand obstetricians.



Four years ago, it had seemed a good idea. The British Congress last came to Leeds in 1952, when (according to his Lancet obituary)one of my predecessors presided over it with grace and charm. That sounded fun, and anyway my colleagues and I thought that …
CD4<sup>+</sup>CD25<sup>+</sup> regulatory T lymphocytes in allergy and asthma
Authors: H.‐Z. Shi, X.‐J. Qin
Journal: Allergy (2005)

Allergic asthma is characterized by airway hyper‐responsiveness and chronic mucosal inflammation mediated by CD4 + Th2 lymphocytes. Regulatory CD4 + CD25 + T cells are important components of the homeostasis of the immune system, as impaired CD4 + CD25 + T cell activity can cause autoimmune diseases and allergy. The mechanism of suppression by CD4 + CD25 + T cells remains controversial; different in vivo and in vitro studies raise possible roles for the immunosuppressive cytokines interleukin‐10 and transforming growth factor‐ β , forkhead transcription factor Foxp3, glucocorticoid‐induced tumor necrosis factor receptor, cytotoxic lymphocyte associated antigen‐4, 4‐1BB costimulator receptor, a CD4‐related molecule LAG‐3, and neuropilin‐1. Current data suggest that Th2 responses to allergens are normally suppressed by CD4 + CD25 + T cells. Suppression by CD4 + CD25 + T cells is decreased in allergic individuals. Furthermore, CD4 + CD25 + T cells play a key role in regulating airway eosinophilic inflammation. The immunomodulatory properties of CD4 + CD25 + T cells do extend to Th2 responses, most notably by limiting the development of a proinflammatory CD4 + Th2 phenotype characterized by reduced cytokine production. An understanding of the roles of CD4 + CD25 + T cells in vivo could provide better insight into the design of novel approaches to modulate the chronic airway inflammatory reaction evident in bronchial asthma.
Cheek swab can detect early signs of cancer, study indicates
Authors: J. Wise
Journal: BMJ (2015)

DNA damage caused by smoking can be detected in cheek swab samples, a study published in JAMA Oncology concludes.1

Researchers from University College London analysed buccal samples from 790 women all born in 1946 and 152 matched blood samples from the Medical Research Council’s National Survey of Health and Development. Smoking history and smoking status were also collected.

They found that buccal cells in women who had …
Venous thromboembolism prophylaxis in medically ill patients and the development of strategies to improve prophylaxis rates
Authors: Jason M. Stinnett, Robert Pendleton, LeAnne Skordos, Michelle Wheeler, George M. Rodgers
Journal: American Journal of Hematology (2005)

Venous thromboembolism (VTE) is common but often unrecognized in medically ill patients. Over the past 5 years, three large-scale placebo-controlled trials enrolling a total of 5500 medically ill patients have highlighted the risk of VTE in this group. These trials have helped to define a specific at-risk patient profile, including those admitted to the hospital with severe congestive heart failure, respiratory illness, acute infection, and inflammatory bowel disease. We performed a retrospective review of patients admitted to the medical service at our tertiary care center to define how common the at-risk medical patient is and to evaluate and improve prophylaxis rates in this patient group. The study was conducted in two phases. Based on admission characteristics, patients were stratified into high-risk or low-risk groups for the development of VTE. During the pre-intervention phase, 75% of patients admitted to the medical service were characterized as increased risk for VTE, yet only 43% of these high-risk patients received prophylaxis of any sort. After interventions designed to increase awareness of VTE, we conducted a second review period. In this post-intervention phase, where 79% of patients were at risk for VTE, prophylaxis rates improved to 72%. Based on these results, we conclude that the majority of patients admitted to the medical service at our tertiary care center constitute a high-risk population that warrants consideration for VTE prophylaxis. Implementation of strategies to improve prophylaxis rates, including educational sessions and risk stratification guidelines, can be successful and improve identification and prophylaxis of this population. Am. J. Hematol. 78:167–172, 2005. © 2005 by Wiley Periodicals, Inc.
When at rest: “Event-free” active inference may give rise to implicit self-models of coping potential
Authors: Ryan J. Murray, Philip Gerrans, Tobias Brosch, David Sander
Journal: Behavioral and Brain Sciences (2015)

Abstract Kalisch and colleagues highlight coping potential (CP) as a principle resilience mechanism during event engagement. We complement this discussion by exploring generative implicit CP self-models, arguably emerging during “resting-state,” subsequent and prior to events. Resting-state affords a propitious environment for Bayesian learning, wherein appraisals/reappraisals may update active inferential CP self-models, which then mediate appraisal style organization and resilience factor valuation.
Lung Cancer Cell Lines as Tools for Biomedical Discovery and Research
Authors: Adi F. Gazdar, Luc Girard, William W. Lockwood, Wan L. Lam, John D. Minna
Journal: JNCI Journal of the National Cancer Institute (2010)

Lung cancer cell lines have made a substantial contribution to lung cancer translational research and biomedical discovery. A systematic approach to initiating and characterizing cell lines from small cell and non-small cell lung carcinomas has led to the current collection of more than 200 lung cancer cell lines, a number that exceeds those for other common epithelial cancers combined. The ready availability and widespread dissemination of the lines to investigators worldwide have resulted in more than 9000 citations, including multiple examples of important biomedical discoveries. The high (but not perfect) genomic similarities between lung cancer cell lines and the lung tumor type from which they were derived provide evidence of the relevance of their use. However, major problems including misidentification or cell line contamination remain. Ongoing studies and new approaches are expected to reveal the full potential of the lung cancer cell line panel.
All antihistamines cross blood-brain barrier
Authors: J G Ramaekers, A Vermeeren
Journal: BMJ (2000)

<h3>Introduction and objectives</h3> Bedaquiline and delamanid were centrally commissioned by NHS England for management of MDR and XDR-TB, within specified criteria (including age 16–65, pulmonary disease, discussion in BTS MDR-TB forum and six months usage) in Aug 2015. We sought to determine ease of availability, obstacles faced and off licence use by prescribing centres. <h3>Methods</h3> An electronic survey was sent to the leads or nominated deputy of MDR-TB centres in England, and the responses analysed using the Surveymonkey web tool. <h3>Results</h3> Response rate was 64% (18/28). Of the respondents, 8 centres (44%) had not used the drugs since Aug 2015. Of the remainder, indications in all cases were either drug resistance (90% of centres) or intolerance (70% of centres). Intolerance was usually hearing loss from second line injectable agents and tendonitis from fluoroquinolones; a minority of patients also could not tolerate prolonged linezolid. 90% of cases had been discussed in the BTS MDR-TB forum; the exception was a case of non tuberculous mycobacterial(NTM) disease(<i>M.abscessus</i>) which was discussed with other NTM experts. There was minimal delay (&lt;2 weeks) between the MDR-TB forum decision to use the drugs and NHS England approval when used for licenced indications; one delay occurred when requesting an extension beyond 6 months (7 weeks delay). There was minimal delay (&lt;2 weeks) between NHS England approval and the patient actually receiving the drug. Both drugs were used in the same patient by two centres (20%). The drugs had been used ‘off licence’ by 6/10 centres. Details in Table 1. Free text responses highlighted difficulty in obtaining the outcome of individualised funding request decisions, difficulty obtaining funding for children (being paid for by the children’s hospital in one case), and two rejections of the use in NTM disease. <h3>Conclusions</h3> Access to bedaquiline and delamanid within licenced indications seems to have minimal delay. Difficulties may arise when the drug needs to be used for ≥6 months. Problems are also reported with funding in children. There is emerging evidence of benefit in difficult NTM disease; this is an unlicensed indication that may expand in the future. Consideration may need to be given to a forum for difficult NTM disease.
The Clinical Course of Alcoholism in 243 Mission Indians
Authors: Cindy L. Ehlers, Tamara L. Wall, Michelle Betancourt, David A. Gilder
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: This study was conducted to describe the order of appearance and the progression of alcohol-related life events in Mission Indian men and women with a lifetime diagnosis of alcohol dependence. METHOD: A total of 407 participants completed a structured interview that gathered information on alcohol diagnoses, remissions, abstinences, and treatments as well as alcohol-related life events. RESULTS: A total of 70% of the men and 50% of the women sampled met lifetime diagnostic criteria for alcohol dependence. The age at onset of alcohol dependence was younger (20 years) and the course proceeded more rapidly (6 years) than what has been described in other large studies of alcoholics. A high degree of similarity in the type and progression of alcohol-related life events was found between Mission Indian men and women and alcoholics from the Collaborative Study on the Genetics of Alcoholism (COGA). However, Mission Indians in this study were significantly more likely than alcoholics in the COGA to experience binge drinking, physical fighting, driving while intoxicated, and alcohol-related health problems and were less likely to consider themselves excessive drinkers, drinking where and when they had not intended to, and to experience guilt concerning their drinking. Rates of abstention after an alcohol dependence diagnosis (61%) and remission from alcohol dependence symptoms (77%) were also high in Mission Indians. CONCLUSIONS: Understanding the course of Mission Indian alcoholism can help identify unique alcohol-related phenotypes as well as guide the development of treatment and prevention programs in this underserved population.
A STUDY OF THE MECHANISMS OF DNA AND THYMINE DEGRADATION IN CULTURED HUMAN CELLS INFECTED WITH A LIPOVIRUS
Authors: R. Shihman Chang, H. Liepins
Journal: The Journal of Experimental Medicine (1962)

DNA and thymine degradation on cultured human, mouse, and chick cells were studied. Significant increase in DNA-degrading activity was demonstrated in human embryonic cells killed by freeze-thawing, liver cells killed with mitomycin C, mouse embryonic cells infected with encephalomyocarditis virus, and in all cells killed by the lipovirus. Twelve other viral agents, actinomycin D, and 5-fluorodeoxyuridine failed to produce a similar increase. Thymidine-2-C14-labeled cultures, either live, killed, or infected by 19 different physical-chemical and biological agents, did not release detectable quantity of C14C2. Following infection with the lipovirus 20 to 60 per cent of the total radioactivity of thymidine-2-C14-labeled cultures was liberated as C14O2. It was postulated that the lipovirus introduced into the host cells the missing genetic information necessary for the synthesis of one or more enzymes responsible for the reductive catabolism of thymine.
Rapid reprogramming of epigenetic and transcriptional profiles in mammalian culture systems
Authors: Colm E Nestor, Raffaele Ottaviano, Diana Reinhardt, Hazel A Cruickshanks, Heidi K Mjoseng, Rhoanne C McPherson, Antonio Lentini, John P Thomson, Donncha S Dunican, Sari Pennings, Stephen M Anderton, Mikael Benson, Richard R Meehan
Journal: Genome biology (2015)

The DNA methylation profiles of mammalian cell lines differ from those of the primary tissues from which they were derived, exhibiting increasing divergence from the in vivo methylation profile with extended time in culture. Few studies have directly examined the initial epigenetic and transcriptional consequences of adaptation of primary mammalian cells to culture, and the potential mechanisms through which this epigenetic dysregulation occurs is unknown.We demonstrate that adaptation of mouse embryonic fibroblasts to cell culture results in a rapid reprogramming of epigenetic and transcriptional states. We observed global 5-hydroxymethylcytosine (5hmC) erasure within three days of culture initiation. Loss of genic 5hmC was independent of global 5-methylcytosine (5mC) levels and could be partially rescued by addition of vitamin C. Significantly, 5hmC loss was not linked to concomitant changes in transcription. Discrete promoter-specific gains of 5mC were also observed within seven days of culture initiation. Against this background of global 5hmC loss we identified a handful of developmentally important genes that maintained their 5hmC profile in culture, including the imprinted loci Gnas and H19. Similar outcomes were identified in the adaption of CD4(+) T cells to culture.We report a dramatic and novel consequence of adaptation of mammalian cells to culture in which global loss of 5hmC occurs, suggesting rapid concomitant loss of methylcytosine dioxygenase activity. The observed epigenetic and transcriptional re-programming occurs much earlier than previously assumed, and has significant implications for the use of cell lines as faithful mimics of in vivo epigenetic and physiological processes.
Role of the Human High-Affinity Copper Transporter in Copper Homeostasis Regulation and Cisplatin Sensitivity in Cancer Chemotherapy
Authors: Macus Tien Kuo, Siqing Fu, Niramol Savaraj, Helen H.W. Chen
Journal: Cancer Research (2012)

Abstract The high-affinity copper transporter (Ctr1; SCLC31A1) plays an important role in regulating copper homeostasis because copper is an essential micronutrient and copper deficiency is detrimental to many important cellular functions, but excess copper is toxic. Recent research has revealed that human copper homeostasis is tightly controlled by interregulatory circuitry involving copper, Sp1, and human (hCtr1). This circuitry uses Sp1 transcription factor as a copper sensor in modulating hCtr1 expression, which in turn controls cellular copper and Sp1 levels in a 3-way mutual regulatory loop. Posttranslational regulation of hCtr1 expression by copper stresses has also been described in the literature. Because hCtr1 can also transport platinum drugs, this finding underscores the important role of hCtr1 in platinum-drug sensitivity in cancer chemotherapy. Consistent with this notion is the finding that elevated hCtr1 expression was associated with favorable treatment outcomes in cisplatin-based cancer chemotherapy. Moreover, cultured cell studies showed that elevated hCtr1 expression can be induced by depleting cellular copper levels, resulting in enhanced cisplatin uptake and its cell-killing activity. A phase I clinical trial using a combination of trientine (a copper chelator) and carboplatin has been carried out with encouraging results. This review discusses new insights into the role of hCtr1 in regulating copper homeostasis and explains how modulating cellular copper availability could influence treatment efficacy in platinum-based cancer chemotherapy through hCtr1 regulation. Cancer Res; 72(18); 4616–21. ©2012 AACR.
Regulation of liver regeneration and hepatocarcinogenesis by suppressor of cytokine signaling 3
Authors: Kimberly J. Riehle, Jean S. Campbell, Ryan S. McMahan, Melissa M. Johnson, Richard P. Beyer, Theo K. Bammler, Nelson Fausto
Journal: The Journal of Experimental Medicine (2007)

Suppressor of cytokine signaling 3 (SOCS3) down-regulates several signaling pathways in multiple cell types, and previous data suggest that SOCS3 may shut off cytokine activation at the early stages of liver regeneration (Campbell, J.S., L. Prichard, F. Schaper, J. Schmitz, A. Stephenson-Famy, M.E. Rosenfeld, G.M. Argast, P.C. Heinrich, and N. Fausto. 2001.J. Clin. Invest. 107:1285–1292). We developed Socs3 hepatocyte-specific knockout (Socs3 h-KO) mice to directly study the role of SOCS3 during liver regeneration after a two-thirds partial hepatectomy (PH). Socs3 h-KO mice demonstrate marked enhancement of DNA replication and liver weight restoration after PH in comparison with littermate controls. Without SOCS3, signal transducer and activator of transcription 3 (STAT3) phosphorylation is prolonged, and activation of the mitogenic extracellular signal-regulated kinase 1/2 (ERK1/2) is enhanced after PH. In vitro, we show that SOCS3 deficiency enhances hepatocyte proliferation in association with enhanced STAT3 and ERK activation after epidermal growth factor or interleukin 6 stimulation. Microarray analyses show that SOCS3 modulates a distinct set of genes, which fall into diverse physiological categories, after PH. Using a model of chemical-induced carcinogenesis, we found that Socs3 h-KO mice develop hepatocellular carcinoma at an accelerated rate. By acting on cytokines and multiple proliferative pathways, SOCS3 modulates both physiological and neoplastic proliferative processes in the liver and may act as a tumor suppressor.
Safety of antitumour necrosis factor (anti-TNF) therapy in patients with chronic viral infections: hepatitis C, hepatitis B, and HIV infection
Authors: L H Calabrese
Journal: Annals of the Rheumatic Diseases (2004)

Tumour necrosis factor α (TNFα) is a pivotal cytokine in host defences with broad ranging effects on the innate and adaptive immune systems. Clinically, TNFα inhibitors have demonstrated remarkable efficacy in a wide range of autoimmune and inflammatory disorders but clearly at the cost of heightened susceptibility to a variety of infections in those treated with these agents. Most reports to date have described increased susceptibility to intracellular pathogens in patients with underlying chronic viral infections, but little in the way of adverse event reporting in these patients has occurred. While the reported experience to date is rather limited, TNFα inhibitors have displayed a reasonable safety profile in the setting of some chronic viral infections and in certain circumstances have demonstrated adjunctive activity in the treatment of these infections. Given the high prevalence of chronic viral infections in patients who are candidates for anti-TNF therapy and the potential for these agents in the treatment of chronic viral illness, additional studies are urgently needed to assess the risks and benefits of such therapy in these populations.
Increased Expression of IL-12 Receptor mRNA in Active Pulmonary Tuberculosis and Sarcoidosis
Authors: RAME A. TAHA, ELEANOR M. MINSHALL, RON OLIVENSTEIN, DAIZO IHAKU, BENOÎT WALLAERT, ANNE TSICOPOULOS, ANDRÉ-BERNARD TONNEL, ROBERTA DAMIA, DICK MENZIES, QUTAYBA A. HAMID
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Cytokines have been implicated in the pathophysiology and development of pulmonary diseases such as tuberculosis and sarcoidosis. In particular, the numbers of cells expressing Th1-type cytokines such as IFN- γ and IL-12 are increased within the lungs of patients with these granulomatous diseases. As a factor promoting the commitment of naive lymphocytes to a Th1-type profile of cytokine expression, IL-12 may be pivotal in the cascade of proinflammatory events within the airways. In this study, we examined the expression of the IL-12 receptor (IL-12R) mRNA in bronchoalveolar lavage (BAL) fluid from patients with active pulmonary tuberculosis (n = 6) and active pulmonary sarcoidosis (n = 6), and from allergic asthmatics (n = 6) and normal control subjects (n = 6). Bronchoscopy with BAL was undertaken, and cell cytospins were examined using the technique of in situ hybridization. There was a significant increase in the numbers of cells expressing mRNA for both β1 and β2 subunits of the IL-12R in active pulmonary sarcoidosis (p < 0.02, p < 0.01, respectively) and active pulmonary tuberculosis (p < 0.01, p < 0.005, respectively) compared with normal control subjects. In contrast, the allergic asthmatic patients exhibited a significant decrease in the number of IL-12R mRNA-positive cells (both β1 and β2 subunits (p < 0.01, p < 0.005, respectively), compared with the normal control subjects. These patients did, however, exhibit a significant increase in IL-4R mRNA, which was not evident in those with either tuberculosis or sarcoidosis when compared with normal subjects (p < 0.05). Colocalization studies demonstrated that CD8 + ve cells are a principal site for the expression of IL-12R in tuberculosis. In sarcoidosis, IL-12R was expressed both on CD4 + ve and CD8 + ve cells. The increased expression of receptors for IL-12 in granulomatous diseases such as pulmonary tuberculosis and sarcoidosis provides evidence supporting the commitment of lymphocytes to a Th1-type cytokine profile in vivo.
Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study
Authors: Karen A Gelmon, Marc Tischkowitz, Helen Mackay, Kenneth Swenerton, André Robidoux, Katia Tonkin, Hal Hirte, David Huntsman, Mark Clemons, Blake Gilks, Rinat Yerushalmi, Euan Macpherson, James Carmichael, Amit Oza
Journal: The Lancet Oncology (2011)