tbuckley/cabot-search huggingface dataset:
Cost utility analysis of co-prescribed heroin compared with methadone maintenance treatment in heroin addicts in two randomised trials
Authors: Marcel G W Dijkgraaf, Bart P van der Zanden, Corianne A J M de Borgie, Peter Blanken, Jan M van Ree, Wim van den Brink
Journal: BMJ (2005)

<h3>Objectives</h3> To explore young adult women smokers’ cognitive and emotional response to using dark brown ‘plain’ cigarette packs in natural settings and whether plain packaging is associated with any short-term change in smoking behaviour. <h3>Design</h3> A naturalistic approach. Participants used plain cigarette packs provided to them for 1 week and for 1 week their own fully branded packs, but otherwise smoked and socialised as normal. Participants completed questionnaires twice a week. <h3>Setting</h3> The six most populated cities and towns in Scotland. <h3>Participants</h3> 301 young women smokers were recruited, with a final sample of 187 (62.1%). To meet the inclusion criteria women had to be between the ages of 18 and 35, daily cigarette smokers and provide a breath sample to confirm smoking status. <h3>Primary and secondary outcome measures</h3> Pack perceptions and feelings, feelings about smoking, salience and perceptions of health warnings and avoidant and cessation behaviours. <h3>Results</h3> In comparison to fully branded packaging, plain packaging was associated with more negative perceptions and feelings about the pack and about smoking (p&lt;0.001). No significant overall differences in salience, seriousness or believability of health warnings were found between the pack types, but participants reported looking more closely at the warnings on plain packs and also thinking more about what the warnings were telling them (p&lt;0.001). Participants reported being more likely to engage in avoidant behaviours, such as hiding or covering the pack (p&lt;0.001), and cessation behaviours, such as foregoing cigarettes (p&lt;0.05), smoking less around others (p&lt;0.001), thinking about quitting (p&lt;0.001) and reduced consumption (p&lt;0.05), while using the plain packs. Results did not differ by dependence level or socioeconomic status. <h3>Conclusions</h3> No research design can capture the true impacts of plain packaging prior to its introduction, but this study suggests that plain packaging may help reduce cigarette consumption and encourage cessation in the short term.
Tumor suppressor gene methylation in follicular lymphoma: a comprehensive review.
Authors: John Hayslip, Alberto Montero
Journal: Molecular Cancer (2006)

Transcriptional silencing of tumor suppressor genes, associated with DNA methylation, is a common epigenetic event in hematologic malignancies. Although DNA hypermethylation of CpG islands is well described in acute leukemias and myelodysplastic syndromes, much less is known of the specific methylation changes that commonly occur in follicular B cell lymphomas. Earlier methylation studies of follicular lymphoma involved only cell lines; however there is a growing literature of methylation changes in primary human FL samples. Published studies of primary follicular lymphoma specimens have demonstrated that: androgen receptor, SHP1, and death-associated protein kinase genes are commonly methylated. By contrast, the cyclin dependent kinase inhibitors p15, p16, and p57 are uncommon epigenetic events in follicular lymphoma. Methylation of cyclin dependent kinase inhibitors is more common in high grade lymphomas, and may be an important step in the progression and transformation of follicular lymphoma. Further methylation studies in follicular lymphoma should investigate the prognostic and therapeutic significance of these epigenetic changes and investigate methylation of other genes. Finally, reactivation of methylated tumor suppressor genes through the use of hypomethylating agents is a promising and novel approach to the treatment of indolent and transformed follicular lymphomas.
<i>BRAF</i> L597 Mutations in Melanoma Are Associated with Sensitivity to MEK Inhibitors
Authors: Kimberly Brown Dahlman, Junfeng Xia, Katherine Hutchinson, Charles Ng, Donald Hucks, Peilin Jia, Mohammad Atefi, Zengliu Su, Suzanne Branch, Pamela L. Lyle, Donna J. Hicks, Viviana Bozon, John A. Glaspy, Neal Rosen, David B. Solit, James L. Netterville, Cindy L. Vnencak-Jones, Jeffrey A. Sosman, Antoni Ribas, Zhongming Zhao, William Pao
Journal: Cancer Discovery (2012)

Abstract Kinase inhibitors are accepted treatment for metastatic melanomas that harbor specific driver mutations in BRAF or KIT, but only 40% to 50% of cases are positive. To uncover other potential targetable mutations, we conducted whole-genome sequencing of a highly aggressive BRAF (V600) and KIT (W557, V559, L576, K642, and D816) wild-type melanoma. Surprisingly, we found a somatic BRAFL597R mutation in exon 15. Analysis of BRAF exon 15 in 49 tumors negative for BRAFV600 mutations as well as driver mutations in KIT, NRAS, GNAQ, and GNA11, showed that two (4%) harbored L597 mutations and another two involved BRAF D594 and K601 mutations. In vitro signaling induced by L597R/S/Q mutants was suppressed by mitogen-activated protein (MAP)/extracellular signal–regulated kinase (ERK) kinase (MEK) inhibition. A patient with BRAFL597S mutant metastatic melanoma responded significantly to treatment with the MEK inhibitor, TAK-733. Collectively, these data show clinical significance to BRAFL597 mutations in melanoma. Significance: This study shows that cells harboring BRAFL597 mutants are sensitive to MEK inhibitor treatment, providing a rationale for routine screening and therapy of BRAFL597-mutant melanoma. Cancer Discov; 2(9); 791–7. ©2012 AACR. Read the Commentary on this article by Garraway and Baselga, p. 766. This article is highlighted in the In This Issue feature, p. 753.
Pulmonary gas transfer 20 years after pneumonectomy for pulmonary tuberculosis.
Authors: F Gimeno, J K Kraan, N G Orie, R Peset
Journal: Thorax (1977)

The changes in pulmonary function after pneumonectomy in 13 patients with pulmonary tuberculosis have been studied. The data at the time of two follow-up studies are compared with those obtained before the pneumonectomy. The first follow-up was carried out between 5 and 30 months postoperatively and the second between 20 and 24 years later. The results of this second follow-up show a relatively normal arterial oxygen saturation and gas transfer factor but an increased residual volume which cannot be explained by increasing age alone.
Capecitabine and Oxaliplatin for Advanced Esophagogastric Cancer
Authors: David Cunningham, Naureen Starling, Sheela Rao, Timothy Iveson, Marianne Nicolson, Fareeda Coxon, Gary Middleton, Francis Daniel, Jacqueline Oates, Andrew Richard Norman
Journal: New England Journal of Medicine (2008)

We evaluated capecitabine (an oral fluoropyrimidine) and oxaliplatin (a platinum compound) as alternatives to infused fluorouracil and cisplatin, respectively, for untreated advanced esophagogastric cancer.
IL-10–producing monocytes differentiate to alternatively activated macrophages and are increased in atopic patients
Authors: Antje Prasse, Martin Germann, Dmitri V. Pechkovsky, Anna Markert, Tibor Verres, Mirjam Stahl, Inga Melchers, Werner Luttmann, Joachim Müller-Quernheim, Gernot Zissel
Journal: Journal of Allergy and Clinical Immunology (2006)
Detection of hepatitis C virus antigen by immuno-histochemical staining: a histological marker of hepatitis C virus infection
Authors: Sing-Hiem Yap, Marc Willems, Joost Van den Oord, Winant Habets, Jaap M. Middeldorp, Jan-Albert Hellings, Frederik Nevens, Han Moshage, Valeer Desmet, Johan Fevery
Journal: Journal of Hepatology (1994)
The FLT3 ligand potently and directly stimulates the growth and expansion of primitive murine bone marrow progenitor cells in vitro: synergistic interactions with interleukin (IL) 11, IL-12, and other hematopoietic growth factors.
Authors: S E Jacobsen, C Okkenhaug, J Myklebust, O P Veiby, S D Lyman
Journal: The Journal of Experimental Medicine (1995)

The recently cloned murine flt3 ligand (FL) was studied for its ability to stimulate the growth of primitive (Lin-Sca-1+) and more committed (Lin-Sca-1-) murine bone marrow progenitor cells, alone and in combination with other hematopoietic growth factors (HGFs). Whereas FL was a weak proliferative stimulator alone, it potently synergized with a number of other HGFs, including all four colony-stimulating factor (CSF), interleukin (IL) 6, IL-11, IL-12, and stem cell factor (SCF), to promote the colony formation of Lin-Sca-1+, but not Lin-Sca-1- or erythroid progenitor cells. The synergistic activity of FL was concentration dependent, with maximum stimulation occurring at 250 ng/ml, and was observed when cells were plated at a concentration of one cell per culture, suggesting that its effects are directly mediated. 2 wk of treatment with FL in combination with IL-3 or SCF resulted in the production of a high proportion of mature myeloid cells (granulocytes and macrophages), whereas the combination of FL with G-CSF, IL-11, or IL-12 resulted predominantly in the formation of cells with an immature blast cell appearance. Accordingly, FL in combination with G-CSF or IL-11 expanded the number of progenitors more than 40-fold after 2 wk incubation. Thus, FL emerges as a potent synergistic HGF, that in combination with numerous other HGFs, can directly stimulate the proliferation, myeloid differentiation, and expansion of primitive hematopoietic progenitor cells.
A 10 year follow up study of patients transplanted for autoimmune hepatitis: histological recurrence precedes clinical and biochemical recurrence
Authors: J-C Duclos-Vallee
Journal: Gut (2003)

<b>Background and aim:</b> Autoimmune hepatitis (AIH) has been reported to recur after orthotopic liver transplantation (OLT) in 10–35% of patients in small series with a short follow up. The aim of the present study was to examine the clinical and histological outcome more than 10 years after OLT for AIH. <b>Patients and methods:</b> Seventeen women with a mean age of 30 (12) years at the time of OLT, selected from among 44 patients transplanted for AIH, were followed for more than 10 years. The criteria for definite AIH, as established by the International Autoimmune Hepatitis Group, were met in every case. Liver biopsies were performed 1, 2, 5, and 10 years after OLT, and when indicated by abnormal liver function tests. Specimens were examined for evidence of recurrent AIH, namely interface hepatitis, lobular activity, portal lymphoplasmocytic infiltration, and fibrosis. Other signs of recurrence included hypertransaminasaemia, serum autoantibodies, and the response to steroid reintroduction or significant steroid dose increments. <b>Results:</b> AIH recurred in 7 (41%) of 17 patients. In four patients histological abnormalities were detected by means of protocol biopsies 1–5 years before the onset of biochemical abnormalities. Two patients developed severe recurrences after 10 and 15 years, respectively, and required treatment with steroids and tacrolimus. In the other three patients histological recurrence was detected 0.6–3 years post-OLT, concomitantly with biochemical abnormalities. <b>Conclusions:</b> AIH recurred in 41% of patients followed for more than 10 years after OLT. As histological signs preceded biochemical abnormalities in four patients (23.5%), regular liver biopsy is warranted after OLT. Detection of isolated histological signs may call for closer follow up and/or a change in immunosuppressive therapy.
Infection of Embryonic Myogenic Cells With Murine Sarcoma Virus In Vitro2
Authors: P. J. Simons, E. J. Aw, J. M. Papadimitriou
Journal: JNCI Journal of the National Cancer Institute (1973)

The properties of serially passaged mouse embryonic myogenic cells in the presence or absence of murine sarcoma virus (Harvey) (MSV-H) were compared. The uninfected cultures rapidly lost their myogenic properties, as judged by their ability to form multinucleate strap cells. The infected cultures retained their myogenic character for up to 18 months (35 transfers). These results were discussed in relation to the pathogenesis of MSB-H-induced tumors in mice.
Cell Distance Mapping Identifies Functional T Follicular Helper Cells in Inflamed Human Renal Tissue
Authors: Vladimir M. Liarski, Natalya Kaverina, Anthony Chang, Daniel Brandt, Denisse Yanez, Lauren Talasnik, Gianluca Carlesso, Ronald Herbst, Tammy O. Utset, Christine Labno, Yahui Peng, Yulei Jiang, Maryellen L. Giger, Marcus R. Clark
Journal: Science Translational Medicine (2014)

T follicular helper (TFH) cells are critical for B cell activation in germinal centers and are often observed in human inflamed tissue. However, it is difficult to know if they contribute in situ to inflammation. Expressed markers define TFH subsets associated with distinct functions in vitro. However, such markers may not reflect in situ function. The delivery of T cell help to B cells requires direct cognate recognition. We hypothesized that by visualizing and quantifying such interactions, we could directly assess TFH cell competency in situ. Therefore, we developed computational tools to quantify spatial relationships between different cell subtypes in tissue [cell distance mapping (CDM)]. Analysis of inflamed human tissues indicated that measurement of internuclear distances between TFH and B cells could be used to discriminate between apparent cognate and noncognate interactions. Furthermore, only cognate-competent TFH cell populations expressed high levels of Bcl-6 and interleukin-21. These data suggest that CDM can be used to identify adaptive immune cell networks driving in situ inflammation. Such knowledge should help identify diseases, and disease subsets, that may benefit from therapeutic targeting of specific T cell-antigen-presenting cell interactions.
Rate of establishing the gut microbiota in infancy has consequences for future health
Authors: Shaillay Dogra, Olga Sakwinska, Shu-E Soh, Catherine Ngom-Bru, Wolfram M Brück, Bernard Berger, Harald Brüssow, Neerja Karnani, Yung Seng Lee, Fabian Yap, Yap-Seng Chong, Keith M Godfrey, Joanna D Holbrook
Journal: Gut Microbes (2015)

The gut of the human neonate is colonized rapidly after birth from an early sparse and highly distinct microbiota to a more adult-like and convergent state, within 1 to 3 years. The progression of colonizing bacterial species is non-random. During the first months of life several shifts commonly occur in the species prevalent in our guts. Although the sequential progression of these species is remarkably consistent across individuals and geographies, there is inter-individual variation in the rate of progression. Our study and others suggest that the rate is influenced by environmental factors, and influences our future health. In this article, we review our recent contribution to cataloging the developing infant gut microbiota alongside other important recent studies. We suggest testable hypotheses that arise from this synthesis.
High mRNA expressions of KLF2 improve post operative prognosis of pulmonary adenocarcinoma correlation with chemokine receptor CCR7 and genetical mutations of p53
Authors: Meiji Itakura, Yuya Terashima, Masato Shingyouji, Toshihiko Iizasa, Hideki Kimura
Journal: European Respiratory Journal (2012)

Purpose  Chemokines and chemokine receptors not only have the powerful ability in cancer metastasis and tumorigenesis, but also act as anti-tumorgenic ability. Lung Krueppel-like factor (LKLF, KLF2) is a member of the family of the Krueppel-like factors (KLFs). KLF2 was initially described as a lung-specific transcription factor. KLF2 is reported to regulate some malignant cells. We examined and evaluated the effect of KLF2 on pulmonary adenocarcinoma and the relationship of their mRNA expression with CCR7, EGFR and p53 genetical mutations in pulmonary adenocarcinoma.   Patients and Methods  120 patients of stage I to IV with pulmonary adenocarcinoma were included in this retrospective analysis. The expression of CCR7 and KLF2 mRNA expression in surgically resected pulmonary adenocarcinoma specimens were examined and evaluated the relation to prognosis, the effect of EGFR and p53 genetical mutations.   Results  High mRNA expression of KLF2 in lung cancer patients indicated significantly good prognosis than the groups of low expressions (p= 0.0066, HR= 2.008, 95% CI of ratio 1.215 to 3.319). The expression of KLF2 mRNA had relationships with CCR7, CCL21 and CCL19 mRNA expression in pulmonary adenocarcinoma. Moreover the mRNA expression of KLF2 in pulmonary adenocarcinoma specimens was influenced by the mutation of p53 mutation in lung cancer specimens.   Conclusion  We propose KLF2 as clinical good prognostic factors and that KLF2 has strong relation with CCR7, the ligands and p53 genetical mutation mRNA expression in pulmonary adenocarcinoma.
Sputum colour: a useful clinical tool in non-cystic fibrosis bronchiectasis
Authors: M. P. Murray, J. L. Pentland, K. Turnbull, S. MacQuarrie, A. T. Hill
Journal: European Respiratory Journal (2009)

This study explored the utility of sputum colour in clinically stable patients with bronchiectasis. Interpretation of sputum colour between the doctor and the patient was reliable (intraclass correlation coefficient 0.83 (95% confidence interval 0.76–0.89). Sputum colour predicted bacterial colonisation (5% in mucoid sputum; 43.5% in mucopurulent sputum; 86.4% in purulent sputum; p&lt;0.0001). On multivariate logistic regression analysis, independent factors associated with purulent sputum were bacterial colonisation, varicose or cystic bronchiectasis, forced expiratory volume in 1 s &lt;80% predicted and diagnosis of bronchiectasis aged &lt;45 yrs.
Limitations of Relative Apparent Synapomorphy Analysis (RASA) for Measuring Phylogenetic Signal
Authors: Mark P. Simmons, Christopher P. Randle, John V. Freudenstein, John W. Wenzel
Journal: Molecular Biology and Evolution (2002)

In this paper we use hypothetical and empirical data matrices to evaluate the ability of relative apparent synapomorphy analysis (RASA) to measure phylogenetic signal, select outgroups, and identify terminals subject to long-branch attraction. In all cases, except for equal character-state frequencies, RASA indicated extraordinarily high levels of phylogenetic information for hypothetical data matrices that are uninformative regarding relationships among the terminals. Yet, regardless of the number of characters or character-state frequencies, RASA failed to detect phylogenetic signal for hypothetical matrices with strong phylogenetic signal. In our empirical example, RASA indicated increasing phylogenetic signal for matrices for which the strict consensus of the most parsimonious trees is increasingly poorly resolved, clades are increasingly poorly supported, and for which many relationships are in conflict with more widely sampled analyses. RASA is an ineffective approach to identify outgroup terminal(s) with the most plesiomorphic character states for the ingroup. Our hypothetical example demonstrated that RASA preferred outgroup terminals with increasing numbers of convergent character states with ingroup terminals, and rejected the outgroup terminal with all plesiomorphic character states. Our empirical example demonstrated that RASA, in all three cases examined, selected an ingroup terminal, rather than an outgroup terminal, as the best outgroup. In no case was one of the two outgroup terminals even close to being considered the optimal outgroup by RASA. RASA is an ineffective means of identifying problematic long-branch terminals. In our hypothetical example, RASA indicated a terminal as being a problematic long-branch terminal in spite of the terminal being on a zero-length branch and having no possibility of undergoing long-branch attraction with another terminal. RASA also failed to identify actual problematic long-branch terminals that did undergo long-branch attraction, but only after following Lyons-Weiler and Hoelzer's (1997) three-step process to identify and remove terminals subject to long-branch attraction. We conclude that RASA should not be used for any of these purposes.
Role of Epidermal Growth Factor Receptor Degradation in Cisplatin-Induced Cytotoxicity in Head and Neck Cancer
Authors: Aarif Ahsan, Susan M. Hiniker, Susmita G. Ramanand, Shyam Nyati, Ashok Hegde, Abigail Helman, Radhika Menawat, Mahaveer S. Bhojani, Theodore S. Lawrence, Mukesh K. Nyati
Journal: Cancer Research (2010)

Abstract Cisplatin and its analogues are the most commonly used agents in the treatment of head and neck squamous cell carcinoma. In this study, we investigated a possible role of epidermal growth factor (EGF) receptor (EGFR) phosphorylation and degradation in cisplatin-induced cytotoxicity. Cisplatin treatment led to an increase in initial EGFR phosphorylation at Y1045, the binding site of ubiquitin ligase, Casitas B-lineage lymphoma (c-Cbl), followed by ubiquitination in the relatively cisplatin-sensitive cell lines. However, cisplatin-resistant cell lines underwent minimal EGFR phosphorylation at the Y1045 site and minimal ubiquitination. We found that EGFR degradation in response to cisplatin was highly correlated with cytotoxicity in seven head and neck cancer cell lines. Pretreatment with EGF enhanced cisplatin-induced EGFR degradation and cytotoxicity, whereas erlotinib pretreatment blocked EGFR phosphorylation, degradation, and cisplatin-induced cytotoxicity. Expression of a mutant Y1045F EGFR, which is relatively resistant to c-Cbl–mediated degradation, in Chinese hamster ovary cells and the UMSCC11B human head and neck cancer cell line protected EGFR from cisplatin-induced degradation and enhanced cell survival compared with wild-type (WT) EGFR. Transfection of WT c-Cbl enhanced EGFR degradation and cisplatin-induced cytotoxicity compared with control vector. These results show that cisplatin-induced EGFR phosphorylation and subsequent ubiquitination and degradation is an important determinant of cisplatin sensitivity. Our findings suggest that treatment with an EGFR inhibitor before cisplatin would be antagonistic, as EGFR inhibition would protect EGFR from cisplatin-mediated phosphorylation and subsequent ubiquitination and degradation, which may explain the negative results of several recent clinical trials. Furthermore, they suggest that EGFR degradation is worth exploring as an early biomarker of response and as a target to improve outcome. Cancer Res; 70(7); 2862–9
Diabetic Foot Infections: Microbiology Made Modern?
Authors: Benjamin A. Lipsky
Journal: Diabetes Care (2007)

Many aspects of managing foot infections in patients with diabetes have improved dramatically and are summarized in recently published guidelines (1–3). Yet, the basic methods of determining the causative microorganisms from these infections by culturing wound specimens have remained largely unchanged for over a century. Obtaining a proper wound culture specimen allows the clinician to define the pathogens involved and their antibiotic susceptibility. Unfortunately, results of cultures are generally not available for at least 2–3 days. Thus, most antibiotic therapy for infections is selected empirically (4). By the time culture results arrive, they are usually too late to influence the initial antibiotic choice. Many clinicians, therefore, feel compelled to select an antibiotic regimen that will cover most of the likely bacteria for all but the mildest infections, leading to an unnecessarily broad spectrum of therapy. This overprescribing increases the likelihood of adverse drug effects, drives antibiotic resistance, and increases the cost of treatment. To the contrary, some clinicians conclude that it is not worthwhile to obtain cultures, believing that the belated results are unhelpful. This approach, however, makes it difficult to properly select an alternative regimen if the patient is failing to respond to the initial agent(s).

The increasing incidence of antibiotic-resistant pathogens as causes of diabetic foot infections makes selecting empiric antibiotic therapy more difficult. Those who treat these patients are well aware of the growing problem of methicillin-resistant Staphylococcus aureus (MRSA), which is now frequently acquired in the community and in various types …