tbuckley/cabot-search huggingface dataset:
A NOTE ON PETROFF'S CULTURAL METHOD FOR THE ISOLATION OF TUBERCLE BACILLI FROM SPUTUM AND ITS APPLICATION TO THE EXAMINATION OF MILK
Authors: F. Constance Stewart
Journal: The Journal of Experimental Medicine (1917)

1. Tubercle bacilli were isolated by the Petroff method from 64.8 per cent of the sputa which were found to be positive by the direct microscopic method. 2. The organism was recovered from 69.2 per cent of the samples of milk that were artificially infected. 3. Of the milk obtained through the New Haven Health Department Laboratory 8.4 per cent of the samples were found to contain tubercle bacilli, while none of the twenty-nine samples from the State Laboratory gave positive cultures. 4. All the guinea pigs (thirteen), except one, which were used as control animals died without any visible signs of tuberculosis. 5. Petroff's method for the isolation of tubercle bacilli from sputum may be applied successfully to the examination of milk. With slight modifications, the method should prove constant and reliable. The need of such a method for the examination of milk and milk products is apparent.
Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4
Authors: Rikke B. Holmgaard, Dmitriy Zamarin, David H. Munn, Jedd D. Wolchok, James P. Allison
Journal: The Journal of Experimental Medicine (2013)

The cytotoxic T lymphocyte antigen-4 (CTLA-4)–blocking antibody ipilimumab results in durable responses in metastatic melanoma, though therapeutic benefit has been limited to a fraction of patients. This calls for identification of resistance mechanisms and development of combinatorial strategies. Here, we examine the inhibitory role of indoleamine 2,3-dioxygenase (IDO) on the antitumor efficacy of CTLA-4 blockade. In IDO knockout mice treated with anti–CTLA-4 antibody, we demonstrate a striking delay in B16 melanoma tumor growth and increased overall survival when compared with wild-type mice. This was also observed with antibodies targeting PD-1–PD-L1 and GITR. To highlight the therapeutic relevance of these findings, we show that CTLA-4 blockade strongly synergizes with IDO inhibitors to mediate rejection of both IDO-expressing and nonexpressing poorly immunogenic tumors, emphasizing the importance of the inhibitory role of both tumor- and host-derived IDO. This effect was T cell dependent, leading to enhanced infiltration of tumor-specific effector T cells and a marked increase in the effector-to-regulatory T cell ratios in the tumors. Overall, these data demonstrate the immunosuppressive role of IDO in the context of immunotherapies targeting immune checkpoints and provide a strong incentive to clinically explore combination therapies using IDO inhibitors irrespective of IDO expression by the tumor cells.
Molecular Pathways: Comparing the Effects of Drugs and T Cells to Effectively Target Oncogenes
Authors: Kathleen Anders, Thomas Blankenstein
Journal: Clinical Cancer Research (2012)

Mutant cancer-driving oncogenes are the best therapeutic targets, both with drugs like small-molecule inhibitors (SMI) and adoptive T-cell therapy (ATT), the most effective form of immunotherapy. Cancer cell survival often depends on oncogenes, which implies that they are homogeneously expressed by all cancer cells and are difficult to select against. Mutant oncogene-directed therapy is relatively selective, as it targets preferentially the oncogene-expressing cancer cells. Both SMI and ATT can be highly effective in relevant preclinical models as well as selected clinical situations, and both share the risk of therapy resistance, facilitated by the frequent genetic instability of cancer cells. Recently, both therapies were compared in the same experimental model targeting the same oncogene. It showed that the oncogene-inactivating drug selected resistant clones, leading eventually to tumor relapse, whereas ATT eradicated large established tumors completely. The mode of tumor destruction likely explained the different outcome with only ATT destroying the tumor vasculature. Elucidating the cellular and molecular mechanisms responsible for tumor regression and relapse will define optimal conditions for the clinic. We argue that the ideal conditions of ATT in the experimental cancer model can be translated to individuals with cancer.
Genealogy, kinship, and knowledge: A cautionary note about causation
Authors: Stephen M. Lyon
Journal: Behavioral and Brain Sciences (2010)

Abstract The choice of emphasis in kinship studies has often resulted in incompatible theoretical models of kinship that are mutually undermining and contradictory. Jones' attempts to reconcile disparate approaches to kinship using OT is useful, however; seeing kinship as a specialized system for representing genealogy may be unwarranted in the light of recent advances in mathematical approaches to kinship terminologies.
The UK prevalence of hereditary haemorrhagic telangiectasia and its association with sex, socioeconomic status and region of residence: a population-based study
Authors: J W Donaldson, T M McKeever, I P Hall, R B Hubbard, A W Fogarty
Journal: Thorax (2013)

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder of aberrant blood vessel development characterised by arteriovenous malformations. HHT is associated with significant morbidity due to complications including epistaxis, gastrointestinal bleeding and stroke. We explored the hypothesis that a diagnosis of HHT is associated with sex, socioeconomic status and geographical location.We used The Health Improvement Network, a longitudinal, computerised general practice database covering 5% of the UK population to calculate prevalence estimates for HHT stratified by age, sex, socioeconomic status and geographical location.The 2010 UK point prevalence for HHT was 1.06/10 000 person years (95% CI 0.95 to 1.17) or 1 in 9400 individuals. The diagnosed prevalence of HHT was significantly higher in women compared with men (adjusted prevalence rate ratio (PRR) 1.53, 95% CI 1.24 to 1.88) and in those from the most affluent socioeconomic group compared with the least (adjusted PRR 1.74, 95% CI 1.14 to 2.64). The PRR varied between different regions of the UK, being highest in the South West and lowest in the West Midlands (adjusted PRR for former compared with latter 1.86, 95% CI 1.61 to 2.15).HHT prevalence is more common in the UK population than previously demonstrated, though this updated figure is still likely to be an underestimate. HHT appears to be significantly under-diagnosed in men, which is likely to reflect their lower rates of consultation with primary care services. There is under-diagnosis in patients from lower socioeconomic groups and a marked variation in the prevalence of diagnosis between different geographical regions across the UK that requires further investigation.
Conclusions and validity of data cannot be judged
Authors: J. F Stratton, H Gordon, M Logue
Journal: BMJ (1995)

EDITOR,—Tine Brink Henriksen and colleagues fail to give adequate clinical information so that we can judge the validity of their data and their conclusions on changes in the use of episiotomy.1 First and foremost is their failure to analyse their results for primigravidas and multigravidas separately.

As most parturients who require episiotomy are primigravidas, combining the results for both groups may mask important underlying differences and outcomes. The high incidence of pudendal …
Target discovery for T cell therapy: next steps to advance Immunotherapies
Authors: Adrian Bot, Joanna E Brewer, Zelig Eshhar, Stanley R Frankel, Emma Hickman, Achim A Jungbluth, Richard Morgan, Yoav Peretz, Laszlo Radvanyi, Carlos A Ramos, Paul F Robbins, Kai W Wucherpfennig
Journal: Journal for ImmunoTherapy of Cancer (2015)

Investigators from academia and industry gathered on August 14, 2014, in Boston at the Inaugural ImVacS conference entitled “Target Discovery for T Cell Therapy: Next Step to Advance Immunotherapies”. Novel targets, discovery strategies and enabling technologies were presented and discussed.
Adipose Tissue ATP Binding Cassette Transporter A1 Contributes to High-Density Lipoprotein Biogenesis In Vivo
Authors: Soonkyu Chung, Janet K. Sawyer, Abraham K. Gebre, Nobuyo Maeda, John S. Parks
Journal: Circulation (2011)

Adipose tissue (AT) is the body's largest free cholesterol reservoir and abundantly expresses ATP binding cassette transporter A1 (ABCA1), a key cholesterol transporter for high-density lipoprotein (HDL) biogenesis. However, the extent to which AT ABCA1 expression contributes to HDL biogenesis in vivo is unknown.Adipocyte-specific ABCA1 knockout mice (ABCA1(-A/-A)) were generated by crossing ABCA1(floxed) mice with aP2Cre transgenic mice. AT from ABCA1(-A/-A) mice had <10% of wild-type ABCA1 protein expression but normal hepatic and intestinal expression. Deletion of adipocyte ABCA1 resulted in a significant decrease in plasma HDL cholesterol (approximately 15%) and apolipoprotein A-I (approximately 13%) concentrations. AT from ABCA1(-A/-A) mice had a 2-fold increase in free cholesterol content compared with wild-type mice and failed to efflux cholesterol to apolipoprotein A-I. However, cholesterol efflux from AT to plasma HDL was similar for both genotypes of mice. Incubation of wild-type AT explants with apolipoprotein A-I resulted in the formation of multiple discrete-sized nascent HDL particles ranging in diameter from 7.1 to 12 nm; similar incubations with ABCA1(-A/-A) AT explants resulted in nascent HDL <8 nm. Plasma decay and tissue uptake of wild-type (125)I-HDL tracer were similar in both genotypes of recipient mice, suggesting that adipocyte ABCA1 deficiency reduces plasma HDL concentrations solely by reducing nascent HDL particle formation.We provide in vivo evidence that AT ABCA1-dependent cholesterol efflux and nascent HDL particle formation contribute to systemic HDL biogenesis and that AT ABCA1 expression plays an important role in adipocyte cholesterol homeostasis.
Comparison the quality and efficacy of recruited CXR and routine CXR in mechanically ventilated ICU patients
Authors: Ali Sharifpour, Abdol-Rasool Alaee, Masood Aliali, Siavash Abedi, Neda Karimi
Journal: European Respiratory Journal (2013)

Back ground : Whether chest radiographs (CXRs) in mechanically ventilated patients should be routinely obtained or only when an abnormality is anticipated remains debated. We aimed to compare the diagnostic, therapeutic and outcome efficacy of routin of CXRs with that of a recutment forced respiratory prescription, focusing on delayed diagnoses and treatments potentially related to the patterns.   Methods : The study was desined on ICU paitients in 2012 on emam hospital who taked ventilator.the number of study was 75 ones and get in two pattern of CXR:1-routin one and with manipulated mechanical system of ventilator at supine position.  :Intensive care unit of the Teaching Hospital, Imam Hospital sari.iran.  RESULTS: The mean age of the paitients was63.5±14 years old and 43 cases were man and the other were wemen that this was not difference analysis. For each CXR, a questionnaire was completed addressing the reason for the CXR, the new findings, and any subsequent therapeutic intervention. The endpoints were the rates of new findings, the rates of new findings that prompted therapeutic intervention, the rate of delayed diagnoses, and mortality.16 patients were included in the routine prescription group showed the points on the ventilator.  CONCLUSIONS: It is finded that as most comertial benefits and in the critical situations using the CXR as difined ventilator needed paitients can be usefull nad easy way to manage them and reaching the optimal endpoints.
The effect of menopause on the lung function among Korean women; the fourth Korean National Health and Nutrition Examination Survey (KHANES IV)
Authors: Won Jai Jung, Young Sam Kim, Ji Ye Jung, Kyung Su Jung, Eun Young Kim, Se Kyu Kim, Joon Chang
Journal: European Respiratory Journal (2012)

Background  – Sex hormones appear to play an important role in women9s lung health. But the literature on menopause and lung health is scarce, especially lung function. Some studies showed improvement or no change in forced expiratory volume in the first second (FEV1), forced volume capacity (FVC) in association with hormone therapy. And a few studies showed that postmenopausal women had significantly lower FEV1 and FVC, especially among lean women. This study examined whether menopausal status was related to the lung function.   Design & Methods  – Data were obtained from the 4th Korean National Health and Nutrition Examination Survey of 2007-9. A total of 1382 Women aged 44 to 61 years not receiving hormone replacement (712 premenopausal women and 670 postmenopausal women) were included in this analysis. Women who were current pregnancy, lactation, amenorrhea induced by hysterectomy were excluded. In our study, a postmenopausal woman was defined as a woman whose current age was 1 year than her age of menopause.Age,height, BMI, smoking status were adjusted by multiple linear regression analysis   Results  – Postmenopausal status is not significantly associated with lower FVC (-33mL, p-value = 0.353), but associated with lower FEV1(-77mL, p-value = 0.032).   Conclusion  - Postmenopausal status can be related with lower lung function in this study.
Anti‐IgE‐Induced Histamine Release from Human Basophilic Leukocytes: Inhibition Depends on Nature and Concentration of Inhibitor and Secretagogue
Authors: Håkan Bergstrand, Anette Björnsson, Inga‐Maria Frick, Britta Lundquist, BengtÅke Petersson
Journal: Allergy (1982)

Histamine release from human basophilic leukocytes was induced by increasing concentrations of anti-IgE in the presence of various concentrations of 2-deoxyglucose (2-DOG), the histamine H2-receptor agonist dimaprit, theophylline, or enprofylline (a new antiasthmatic xanthine derivative). The results show that the degree of inhibition produced by each agent differed with the concentration of anti-IgE used and with the nature and concentration of the inhibitor. These data indicate that great care should be used when characterizing an inhibitor of mediator release by simply giving a figure for the per cent inhibition of release observed in its presence.
H2S stimulates cytokine expression in fibroblast-like synoviocytes via an ERK-dependent but NF- B-independent pathway
Authors: B. Kloesch, M. Liszt, G. Steiner, J. Broell
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Rheumatoid arthritis (RA) is an autoimmune disease characterised by inflammation of the synovial membrane, resulting in progressive joint destruction. Fibroblast-like synoviocytes (FLSs) play a crucial role in the joint inflammation and destructive processes. An established treatment for patients with different forms of arthritis is sulphur bath therapy which belongs to the oldest forms of treatment for chronic inflammatory diseases and is still used today in many parts of the world. The fact that scientific reports about the potential beneficial effects of this kind of therapy are controversial and rare encouraged us to investigate the effects of an exogenous H<sub>2</sub>S donor (NaHS) on FLSs isolated from synovial tissues of RA and OA patients. <h3>Material and methods</h3> RA and OA-FLSs were isolated from synovial tissues obtained at joint replacement surgery and were cultivated under standard conditions. FLSs were utilised between the third and twelfth passage. Cells were incubated for 20–60 min with different concentrations of NaHS (0.06–1.0 mM) after which medium was changed and cells were further incubated for 12 h. After 1, 3, 6 and 12 h cell culture supernatants were collected and IL-6 levels were quantified by ELISA. Additionally, RNA levels were analysed by quantitative real time PCR. NF-kB and MAPK activation (p38 MAPK and ERK1/2) were analysed by PathScan Sandwich ELISA Kits (Cell signaling) and Western blot experiments. <h3>Results</h3> RA-FLSs constitutively expressed high levels of IL-6. In contrary, IL-6 expression of OA-FLSs was very low and not detecable. After incubation of cells for 20 min with high concentrations of H<sub>2</sub>S (from 0.5 to 1.0 mM) IL-6 expression was dramatically upregulated in both cell types. H<sub>2</sub>S concentrations below 0.5 mM had no stimulatory effects. Interestingly, when cells were incubated for 60 min with the same concentrations of H<sub>2</sub>S stimulatory effects failed. Activation of IL-6 expression was accompanied by simultaneous phosphorylation of extra cellular signal regulated kinase (ERK1/2). However, activation of p38 MAPK and NF-kBp65 could not be observed. <h3>Conclusion</h3> Data presented here shows that H<sub>2</sub>S stimulated cytokine expression in RA and OA-FLSs via an ERK-dependent but NF-κB-independent pathway. Our data seem of importance for studying (patho-) physiological functions of H<sub>2</sub>S and for re-evaluating sulphur spa therapy as one of the oldest forms of therapy for rheumatic disorders.
Phase I Dose-Escalation Study of Intravenous Aflibercept in Combination with Docetaxel in Patients with Advanced Solid Tumors
Authors: Nicolas Isambert, Gilles Freyer, Sylvie Zanetta, Benoît You, Pierre Fumoleau, Claire Falandry, Laure Favier, Sylvie Assadourian, Karen Soussan-Lazard, Samira Ziti-Ljajic, Veronique Trillet-Lenoir
Journal: Clinical Cancer Research (2012)

Abstract Purpose: This phase I study cohort investigated aflibercept in combination with docetaxel in patients with advanced solid tumors. Materials and Methods: Eligible patients had metastatic or nonresectable cancer for which docetaxel was considered appropriate. Patients received intravenous aflibercept (either 2, 4, 5, 6, 7, or 9 mg/kg) with docetaxel (75 mg/m2) on day 1 every 3 weeks until disease progression or unacceptable toxicity. Primary objectives were to evaluate dose-limiting toxicities (DLT) during cycle 1 and to determine the aflibercept recommended phase II trial dose (RP2D) for combination with docetaxel. Pharmacokinetics, tolerability, and antitumor activity were also investigated. Results: Fifty-four patients (mean age, 56 y) were enrolled. Most had prior chemotherapy (96%) and most (24.1%) had breast cancer. In the dose-escalation phase (n = 34), there were three DLTs: grade 4 neutropenic infection (2 mg/kg), grade 3 dysphonia (7 mg/kg), and grade 2 hypertension (9 mg/kg). An excess of free-over-bound aflibercept was observed at doses of 5 mg/kg or more. The pharmacokinetics of aflibercept and docetaxel were not modified by coadministration. Aflibercept (6 mg/kg) was defined as the RP2D based on DLT and pharmacokinetic data. Overall, the most frequent grade 3/4 adverse events (AE) were neutropenia (85.2%), leukopenia (74.1%), hypertension (18.5%), and stomatitis (16.7%). AEs associated with vascular endothelial growth factor blockade included epistaxis (all grades, 83.3%), proteinuria (68.5%), dysphonia (68.5%), and hypertension (53.7%). Seven patients had partial responses, and 32 patients had stable disease (&amp;gt;3 months in 18 patients). Conclusion: On the basis of findings from this study, aflibercept (6 mg/kg) was the dose recommended for further clinical development. Clin Cancer Res; 18(6); 1743–50. ©2012 AACR.
Expanded identification and characterization of mammalian circular RNAs
Authors: Junjie U Guo, Vikram Agarwal, Huili Guo, David P Bartel
Journal: Genome biology (2014)

Abstract Background The recent reports of two circular RNAs (circRNAs) with strong potential to act as microRNA (miRNA) sponges suggest that circRNAs might play important roles in regulating gene expression. However, the global properties of circRNAs are not well understood. Results We developed a computational pipeline to identify circRNAs and quantify their relative abundance from RNA-seq data. Applying this pipeline to a large set of non-poly(A)-selected RNA-seq data from the ENCODE project, we annotated 7,112 human circRNAs that were estimated to comprise at least 10% of the transcripts accumulating from their loci. Most circRNAs are expressed in only a few cell types and at low abundance, but they are no more cell-type-specific than are mRNAs with similar overall expression levels. Although most circRNAs overlap protein-coding sequences, ribosome profiling provides no evidence for their translation. We also annotated 635 mouse circRNAs, and although 20% of them are orthologous to human circRNAs, the sequence conservation of these circRNA orthologs is no higher than that of their neighboring linear exons. The previously proposed miR-7 sponge, CDR1as, is one of only two circRNAs with more miRNA sites than expected by chance, with the next best miRNA-sponge candidate deriving from a gene encoding a primate-specific zinc-finger protein, ZNF91. Conclusions Our results provide a new framework for future investigation of this intriguing topological isoform while raising doubts regarding a biological function of most circRNAs.
In Vivo–Generated Antigen-Specific Regulatory T Cells Treat Autoimmunity Without Compromising Antibacterial Immune Response
Authors: Shimpei Kasagi, Pin Zhang, Li Che, Brittany Abbatiello, Takashi Maruyama, Hiroko Nakatsukasa, Peter Zanvit, Wenwen Jin, Joanne E. Konkel, WanJun Chen
Journal: Science Translational Medicine (2014)

Antigen-specific regulatory T cells induced in vivo have therapeutic effects in mice with established autoimmune diseases.
The transcription factors IRF8 and PU.1 negatively regulate plasma cell differentiation
Authors: Sebastian Carotta, Simon N. Willis, Jhagvaral Hasbold, Michael Inouye, Swee Heng Milon Pang, Dianne Emslie, Amanda Light, Michael Chopin, Wei Shi, Hongsheng Wang, Herbert C. Morse, David M. Tarlinton, Lynn M. Corcoran, Philip D. Hodgkin, Stephen L. Nutt
Journal: The Journal of Experimental Medicine (2014)

Activated B cells undergo immunoglobulin class-switch recombination (CSR) and differentiate into antibody-secreting plasma cells. The distinct transcriptomes of B cells and plasma cells are maintained by the antagonistic influences of two groups of transcription factors: those that maintain the B cell program, including BCL6 and PAX5, and plasma cell–promoting factors, such as IRF4 and BLIMP-1. We show that the complex of IRF8 and PU.1 controls the propensity of B cells to undergo CSR and plasma cell differentiation by concurrently promoting the expression of BCL6 and PAX5 and repressing AID and BLIMP-1. As the PU.1–IRF8 complex functions in a reciprocal manner to IRF4, we propose that concentration-dependent competition between these factors controls B cell terminal differentiation.
Chimerism and clinical outcomes of 110 recipients of unrelated donor bone marrow transplants who underwent conditioning with low-dose, single-exposure total body irradiation and cyclophosphamide
Authors: Mark Girgis, Chris Hallemeier, William Blum, Randy Brown, Hsiu-san Lin, Hanna Khoury, L. Tim Goodnough, Ravi Vij, Steve Devine, Marita Wehde, Stacey Postma, Aarti Oza, John DiPersio, Douglas Adkins
Journal: Blood (2004)
U-500 Regular Insulin
Authors: Mayer B. Davidson, Maria D. Navar, Diana Echeverry, Petra Duran
Journal: Diabetes Care (2009)

OBJECTIVE To describe the clinical experience and the pharmacokinetics of U-500 regular insulin in severely insulin-resistant obese type 2 diabetic patients. RESEARCH DESIGN AND METHODS Patients requiring &amp;gt;200 units of insulin with A1C levels &amp;gt;8.0% were switched to U-500 regular insulin. For the pharmacokinetic study, fasting subjects received 100 units of U-500 regular insulin subcutaneously, and samples drawn before and every 30–60 min for glucose, insulin, and C-peptides until glucose fell below 100 mg/dl. RESULTS U-500 regular insulin doses were adjusted using the same approach as for adjusting NPH insulin doses. Mean values at baseline and at minimum A1C levels were, respectively, A1C 9.9 and 7.1%, 3.2 and 3.3 units/kg, and weight 98.6 and 102.8 kg. Pharmacokinetically, insulin concentrations rose briskly by 30 min and remained elevated for at least 7 h. CONCLUSIONS Uncontrolled severely insulin-resistant obese type 2 diabetic patients can be satisfactorily controlled with U-500 regular insulin.