tbuckley/cabot-search huggingface dataset:
Objective Measurement and Clinical Significance of TILs in Non–Small Cell Lung Cancer
Authors: Kurt A. Schalper, Jason Brown, Daniel Carvajal-Hausdorf, Joseph McLaughlin, Vamsidhar Velcheti, Konstantinos N. Syrigos, Roy S. Herbst, David L. Rimm
Journal: JNCI Journal of the National Cancer Institute (2015)

Tumor-infiltrating lymphocytes (TILs) are usually measured using subjective methods. Studies suggest that TIL subtypes have independent roles in cancer and that they could support the use of novel immunostimulatory therapies. We simultaneously measured TIL subtypes in non–small cell lung cancer (NSCLC) samples using objective methods and determined their relationship with clinico-pathologic characteristics and survival. Using multiplexed quantitative fluorescence (QIF), we measured the levels of CD3, CD8, and CD20 in 552 NSCLC from two independent collections represented in tissue microarrays (YTMA79, n = 202 and YTMA140, n = 350). The level of TILs was obtained in different tumor compartments using cytokeratin stain to define tumor cells and 4’,6-Diamidino-2-Phenylindole. Association of TILs with clinical parameters was determined using univariate and multivariable analyses. All statistical tests were two-sided. In both NSCLC collections there was a low correlation between the three TIL markers (linear regression coefficients (R2) = 0.19–0.22, P < .001 for YTMA79 and R2 = 0.23–0.32, P < .001 for YTMA140). No consistent association between the level of TIL subtypes and age, sex, smoking history, tumor size, stage, and histology type was found. In univariate analysis, an elevated CD3 or CD8 signal was statistically significantly associated with longer survival in both collections. However, only CD8 was independent from age, tumor size, histology, and stage in multivariable analysis. High CD20 was associated with longer survival in the YTMA79 cohort. Increased levels of CD3 and CD8 + TILs are associated with better outcome in NSCLC, but only CD8 is independent from other prognostic variables. Objective measurement of TIL subpopulations could be useful to predict response or evaluate the local immune effect of anticancer immune checkpoint inhibitors.
Screening in health fairs. A critical review of benefits, risks, and costs
Authors: D. M. Berwick
Journal: JAMA (1985)

Health fairs provide multiphasic screening to more than 2 million Americans each year, and the number is growing rapidly. Nearly 40 different tests are in use, commonly including the measurement of up to 30 different blood chemistry levels. This report reviews the activities in a sample of 940 health fair sites and examines the experience regarding six specific screening procedures (blood pressure, anemia, blood chemistries, glaucoma, hearing, and fecal occult blood testing). Widespread use of these and other tests raises complex issues of cost, risk, and benefit. Rates of false alarm of healthy people and false reassurance of those at risk may be high for some tests, and the benefits of detecting new disease are easily overestimated. Detailed data collection and evaluation could help health fair sponsors to identify more rational screening strategies. (<i>JAMA</i>1985;254:1492-1498)
Erratum: IL-1 family nomenclature
Authors: Charles Dinarello, William Arend, John Sims, Dirk Smith, Hal Blumberg, Luke O'Neill, Raphaela Goldbach-Mansky, Theresa Pizarro, H Hoffman, Philip Bufler, Marcel Nold, Pietro Ghezzi, Alberto Mantovani, Cecilia Garlanda, Diana Boraschi, Anna Rubartelli, Mihai Netea, Jos van der Meer, Leo Joosten, Tom Mandrup-Poulsen, Marc Donath, Eli Lewis, Josef Pfeilschifter, Michael Martin, Michael Kracht, H Muehl, Daniela Novick, Miodrag Lukic, Bruno Conti, Alan Solinger, Kelk Peyman, Frank van de Veerdonk, Chiristopher Gabel
Journal: Nature Immunology (2011)
Lifestyle and youthful looks
Authors: D.A. Gunn, J.L. Dick, D. van Heemst, C.E.M. Griffiths, C.C. Tomlin, P.G. Murray, T.W. Griffiths, S. Ogden, A.E. Mayes, R.G.J. Westendorp, P.E. Slagboom, A.J.M. de Craen
Journal: British Journal of Dermatology (2015)

Journal Article Lifestyle and youthful looks Get access D.A. Gunn, D.A. Gunn Unilever R&D Colworth House Sharnbrook Bedfordshire MK44 1LQ U.K Correspondence David Andrew Gunn. E‐mail: david.gunn@unilever.com Search for other works by this author on: Oxford Academic Google Scholar J.L. Dick, J.L. Dick Unilever R&D Colworth House Sharnbrook Bedfordshire MK44 1LQ U.K Search for other works by this author on: Oxford Academic Google Scholar D. van Heemst, D. van Heemst Department of Gerontology and Geriatrics Leiden University Medical Center Leiden the Netherlands Search for other works by this author on: Oxford Academic Google Scholar C.E.M. Griffiths, C.E.M. Griffiths Dermatology Research Centre Salford Royal Hospital University of Manchester Manchester Academic Health Science Centre Manchester U.K Search for other works by this author on: Oxford Academic Google Scholar C.C. Tomlin, C.C. Tomlin Unilever R&D Colworth House Sharnbrook Bedfordshire MK44 1LQ U.K Search for other works by this author on: Oxford Academic Google Scholar P.G. Murray, P.G. Murray Unilever R&D Colworth House Sharnbrook Bedfordshire MK44 1LQ U.K Search for other works by this author on: Oxford Academic Google Scholar T.W. Griffiths, T.W. Griffiths Dermatology Research Centre Salford Royal Hospital University of Manchester Manchester Academic Health Science Centre Manchester U.K Search for other works by this author on: Oxford Academic Google Scholar S. Ogden, S. Ogden Dermatology Research Centre Salford Royal Hospital University of Manchester Manchester Academic Health Science Centre Manchester U.K Search for other works by this author on: Oxford Academic Google Scholar A.E. Mayes, A.E. Mayes Unilever R&D Colworth House Sharnbrook Bedfordshire MK44 1LQ U.K Search for other works by this author on: Oxford Academic Google Scholar R.G.J. Westendorp, R.G.J. Westendorp Department of Gerontology and Geriatrics Leiden University Medical Center Leiden the NetherlandsNetherlands Consortium for Healthy Aging (NCHA) the Netherlands Search for other works by this author on: Oxford Academic Google Scholar ... Show more P.E. Slagboom, P.E. Slagboom Netherlands Consortium for Healthy Aging (NCHA) the NetherlandsSection of Molecular Epidemiology Department of Medical Statistics and Bioinformatics Leiden University Medical Center Leiden the Netherlands Search for other works by this author on: Oxford Academic Google Scholar A.J.M. de Craen A.J.M. de Craen Department of Gerontology and Geriatrics Leiden University Medical Center Leiden the Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 5, 1 May 2015, Pages 1338–1345, https://doi.org/10.1111/bjd.13646 Published: 01 May 2015
INTESTINAL ANASTOMOSIS BY A NEW METHOD.
Authors: WILLIAM F. METCALF
Journal: JAMA (1898)

Since Lembert, about 1825, asserted that the union of serous surfaces was to be aimed at in intestinal anastomosis, many methods of suturing have been introduced and many mechanical substances used to facilitate the suturing, but no appliance has yet been invented in the use of which the union should not be fortified by suture. This being true, if device is to be used, it should possess the following qualifications: 1, it should be rigid so as to hold the parts firmly in apposition; 2, it should, as soon as its function is performed, as soon as the suturing is done, pass quickly away to leave the lumen of the gut free; 3, it should be easy of introduction. In gastrectomies upon dogs I found it difficult to make a satisfactory union between the intestine and esophagus. This led me to experiment with various appliances
Treatment outcome of multi-drug resistant tuberculosis in the United Kingdom: retrospective-prospective cohort study from 2004 to 2007
Authors: L F Anderson, S Tamne, J P Watson, T Cohen, C Mitnick, T Brown, F Drobniewski, I Abubakar
Journal: Eurosurveillance (2013)

United Kingdom (UK) guidelines recommend at least 18 months treatment for patients with multidrug-resistant tuberculosis (MDR-TB). Prior to 2008, data on treatment outcome were only available at 12 months and therefore the proportion completing treatment was unknown. This retrospective-prospective cohort study reports on treatment outcomes for MDR-TB patients notified between 2004 and 2007 and examines factors associated with successful outcomes. 70.6% (144/204) completed treatment in 24 months or more, 6.9% (14) stopped treatment, 6.9% (14) died, 7.8% (16) were lost to follow up, 0.5% (1) relapsed and 4.4% (9) were transferred overseas. Following adjustment for age, being non-UK born, non-compliance and having co-morbidities, treatment with a fluoroquinolone (OR 3.09; 95% CI 1.21-7.88; p<0.05) or bacteriostatic drug (OR 4.23; 95% CI 1.60-11.18; p<0.05) were independently associated with successful treatment outcome. Treatment completion for MDR-TB cases remains below the World Health Organization (WHO) target. Our findings support current WHO guidelines for MDR-TB treatment. The UK should consider adopting individualised regimens based on WHO recommended drugs, taking into account drug sensitivities. Improving treatment completion rates will be key to tackling further drug resistance and transmission from untreated infectious cases.
The molecular basis of chemical toxicity.
Authors: J D McKinney
Journal: Environmental Health Perspectives (1985)

Studies of structure-activity relationships and molecular mechanisms of action are fundamental to our understanding of the harmful effects of chemicals on the environment and their more direct effects on human health. It is important to identify factors that determine toxicological effects of foreign chemicals in biological systems and to assess our knowledge about chemical mechanisms of toxicity. Several fundamental mechanisms underlying toxic action are described, and the importance of studying receptor-substrate interactions is stressed. The Ah receptor is cited as an example of a protein-small molecule interaction associated with extreme acute toxicity in laboratory animals. It is recognized that reliable attempts at predictive toxicology across compound classes through structural and theoretical chemistry approaches must be based on sound knowledge about mechanisms of action at the molecular level. Such studies also contribute to the knowledge base in biomedical and physical sciences.
Barriers to Provider-Initiated Testing and Counselling for Children in a High HIV Prevalence Setting: A Mixed Methods Study
Authors: Katharina Kranzer, Jamilah Meghji, Tsitsi Bandason, Ethel Dauya, Stanley Mungofa, Joanna Busza, Karin Hatzold, Khameer Kidia, Hilda Mujuru, Rashida A. Ferrand
Journal: PLoS Medicine (2014)

Background There is a substantial burden of HIV infection among older children in sub-Saharan Africa, the majority of whom are diagnosed after presentation with advanced disease. We investigated the provision and uptake of provider-initiated HIV testing and counselling (PITC) among children in primary health care facilities, and explored health care worker (HCW) perspectives on providing HIV testing to children. Methods and Findings Children aged 6 to 15 y attending six primary care clinics in Harare, Zimbabwe, were offered PITC, with guardian consent and child assent. The reasons why testing did not occur in eligible children were recorded, and factors associated with HCWs offering and children/guardians refusing HIV testing were investigated using multivariable logistic regression. Semi-structured interviews were conducted with clinic nurses and counsellors to explore these factors. Among 2,831 eligible children, 2,151 (76%) were offered PITC, of whom 1,534 (54.2%) consented to HIV testing. The main reasons HCWs gave for not offering PITC were the perceived unsuitability of the accompanying guardian to provide consent for HIV testing on behalf of the child and lack of availability of staff or HIV testing kits. Children who were asymptomatic, older, or attending with a male or a younger guardian had significantly lower odds of being offered HIV testing. Male guardians were less likely to consent to their child being tested. 82 (5.3%) children tested HIV-positive, with 95% linking to care. Of the 940 guardians who tested with the child, 186 (19.8%) were HIV-positive. Conclusions The HIV prevalence among children tested was high, highlighting the need for PITC. For PITC to be successfully implemented, clear legislation about consent and guardianship needs to be developed, and structural issues addressed. HCWs require training on counselling children and guardians, particularly male guardians, who are less likely to engage with health care services. Increased awareness of the risk of HIV infection in asymptomatic older children is needed. Please see later in the article for the Editors' Summary
Topley and Wilson's Principles of Bacteriology, Virology and Immunity, vol 1: General Bacteriology and Immunity
Authors: Kenneth J. Ryan
Journal: JAMA (1991)

For over half a century, the appearance of a new edition of the British classic<i>Topley and Wilson's Principles of Bacteriology, Virology and Immunity</i>has been a major event for microbiologists on both sides of the Atlantic. Topley and Wilson's text has always embodied depth, accuracy, practical experience, and historical perspective in a way that sets it apart from other books in the field. It was not until the seventh edition (1983) that this text gave way to the inevitable multiauthor format, although the fifth and sixth editions by Wilson and Miles acknowledged "the help of" a small group including one of the current general editors, M. Tom Parker. The eighth edition has 128 contributors but follows the same organization as earlier editions, with separate sections (now volumes) devoted to general microbiology and immunology, systematic bacteriology, bacterial diseases, and virology (not reviewed here). A new, largerpage and -type format makes
FACTORS AFFECTING THE APPEARANCE AND PERSISTENCE OF VISIBLE CUTANEOUS REACTIVE HYPEREMIA IN MAN 1
Authors: W. F. Greenwood, A. C. Barger, J. R. DiPalma, J. Stokes, L. H. Smith
Journal: Journal of Clinical Investigation (1948)

Changes in cutaneous reactive hyperemia have been used successfully to identify certain local (1, 2) and general (3 to 5) abnormalities of the circulation.More recently it has been observed that cutaneous reactive hyperemia is altered con- spicuously in normal subjects by vigorous exer- cise, particularly as the circulatory stress of ex- haustion appears (6).Under these conditions venous pressure, cutaneous blood flow, and skin temperature were changing simultaneously and rapidly.Hence it was difficult to understand the mechanism by which cutaneous reactive hyperemia may be altered without more information on the factors which modify it in the normal subject un- der experimental conditions.This account describes the effects of environ- mental temperature, skin temperature, elevation of the arm, venous pressure, external pressure and epinephrine iontophoresis, on the appearance and persistence of visible cutaneous reactive hypere- mia.It indicates certain factors which should be kept constant when reactive hyperemia is used as a test to identify changes in cutaneous circulation. METHODSCutaneous reactive hyperemia was produced locally on the horizontal volar surface of the forearm by placing a weighted plastic ring on the skin for sufficient time to produce, after removal of the ring, a distinct annular redness of the skin as described by DiPalma et al. (7).The plastic ring itself had an outer diameter of 3.5 cm., an inner diameter of 2.5 cm., and a total surface area of 5 sq.cm.It was attached to the under surface of a 500 gm.weight.When resting freely on the skin the weight applied to the skin immediately beneath the ring a pres- sure equivalent to 73 mm.Hg, i.e., sufficient to collapse
Risk of breast cancer stabilising in UK, study shows
Authors: Roger Dobson
Journal: BMJ (2006)

The risk of developing breast cancer in the United Kingdom may be stabilising, even though most UK cancer registries are reporting an increased incidence after the introduction of mass screening, a study published online in the International Journal of Cancer shows (2006 Sep 8, doi:10.1002/ijc.22160).

The study, by researchers from the Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, calculated and estimated breast cancer trends in 10 European countries from 1970 to 2005. It found that regional differences in incidence seen in the 1970s persisted into the later years of the study, with the lowest incidence in Spain and Italy and the highest in the …
Pseudoxanthoma elasticum: evaluation of diagnostic criteria based on molecular data
Authors: S Christen-Zäch, M Huber, B Struk, K Lindpaintner, F Munier, R G Panizzon, D Hohl
Journal: British Journal of Dermatology (2006)

Pseudoxanthoma elasticum (PXE) is a genetic disorder due to mutations in the gene encoding the transmembrane transporter protein adenosine triphosphate binding cassette (ABC)-C6, resulting in calcification of elastic fibres in the skin, eyes and cardiovascular system.To evaluate the diagnostic criteria for PXE based on molecular data.Of 10 families with a positive history of PXE 142 subjects were investigated for clinical symptoms, histological findings and genetic haplotype analysis.Of these, 25 subjects were haplotypic homozygous for PXE and 23 had typical clinical and histopathological manifestations. Two of the 25 patients showed such marked solar elastosis and macular degeneration that PXE could not be confirmed clinically. Sixty-seven subjects were haplotypic heterozygous carriers and 50 were haplotypic homozygous unaffected. Of these 117 subjects, 116 showed no cutaneous or ophthalmological signs of PXE. In one of the 50 haplotypic homozygous unaffected patients important solar elastosis and scarring of the retina mimicked PXE lesions. Only four of the 67 haplotypic heterozygous carriers had biopsies of nonlesional skin; all were histopathologically normal.In our patients, PXE presents as an autosomal recessive genodermatosis. Correlation of haplotype and phenotype confirmed actual major diagnostic criteria. In patients with marked solar elastosis and/or severe macular degeneration clinical diagnosis can be impossible and molecular testing is needed to confirm the presence of PXE. To the best of our knowledge our large study compares for the first time clinical findings with molecular data.
Therapeutic use of etanercept in polyarticular course juvenile idiopathic arthritis over a two year period
Authors: D A Kietz
Journal: Annals of the Rheumatic Diseases (2002)

To analyse the treatment response to etanercept in patients with polyarticular course juvenile idiopathic arthritis (JIA).22 patients with polyarticular course JIA (19 females, three males; mean age 13.9 years; mean disease duration 6.3 years; 15 with polyarticular onset, seven with systemic onset, one with residual systemic activity; eight rheumatoid factor positive; eight with erosive disease) were treated with etanercept for up to 24 months. Etanercept was given subcutaneously at 0.4 mg/kg twice a week. Treatment response was ascertained in an open prospective study.All patients showed impressive clinical improvement, with a decrease in swollen joint count by an average of 10.1 joints (mean of 49% decrease), a decrease in tender joint count by 9.3 joints (mean of 94%), and decrease in total joint count by 11.2 joints (mean of 48%). Duration of morning stiffness decreased to less than 10 minutes. Furthermore, haemoglobin concentration increased on average by 14 g/l (mean of 15.3%) and packed cell volume increased by 0.035 (mean increase of 12%), and erythrocyte sedimentation rate decreased on average by 42.8 mm/1st h (mean decrease of 64%). No major side effects were noted.Etanercept continues to be clinically effective and well tolerated in patients with polyarticular course JIA over a two year period.
Prolonged Shedding of Multidrug-Resistant Influenza A Virus in an Immunocompromised Patient
Authors: David M. Weinstock, Larisa V. Gubareva, Gianna Zuccotti
Journal: New England Journal of Medicine (2003)

To the Editor: Immunocompromised patients can persistently shed influenza, increasing the potential for resistance to antiviral drugs and for nosocomial transmission.1,2 We report the case of a 23-...
Protein or amino acid deprivation differentially regulates the hepatic forkhead box protein A (FOXA) genes through an activating transcription factor-4-independent pathway
Authors: Nan Su, Michelle M. Thiaville, Keytam Awad, Altin Gjymishka, Jason O. Brant, Thomas P. Yang, Michael S. Kilberg
Journal: Hepatology (2009)

Abstract The FOXA (forkhead box A) proteins (FOXA1, FOXA2, and FOXA3) play a critical role in the development of the liver, and they also regulate metabolism in adult hepatic tissue. The liver responds to changes in nutrient availability by initiating a number of stress signaling pathways. The present studies demonstrated that in mouse dams fed a low-protein diet hepatic expression of FOXA2 and FOXA3 messenger RNA, but not FOXA1, was induced. Conversely, fetal liver did not exhibit this regulation. Amino acid deprivation of HepG2 hepatoma cells also enhanced transcription from the FOXA2 and FOXA3 genes. In contrast, endoplasmic reticulum stress inhibited the expression of FOXA1, only slightly induced FOXA2, and had no effect on FOXA3. The FOXA2 and FOXA3 messenger RNA induction by amino acid deprivation did not require activating transcription factor 4, a critical component of the conventional amino acid response (AAR) pathway, but their induction was partially dependent on CCAAT/enhancer-binding protein β. Simultaneous knockdown of both FOXA2 and FOXA3 by small interfering RNA did not affect the activation of other amino acid responsive genes, suggesting that the FOXA proteins are not required for the known AAR pathway. Collectively, the results document that the hepatic FOXA family of genes are differentially regulated by amino acid availability. (Hepatology 2009.)
Pre–Drug-Eluting Stent Debulking of Bifurcated Coronary Lesions
Authors: Etsuo Tsuchikane, Tadanori Aizawa, Hideo Tamai, Yasumi Igarashi, Kenji Kawajiri, Noriyuki Ozawa, Shigeru Nakamura, Koji Oku, Mikihiro Kijima, Takahiko Suzuki
Journal: Journal of the American College of Cardiology (2007)
Comparison of Pharmacokinetics and Dynamics of the Long-Acting Insulin Analogs Glargine and Detemir at Steady State in Type 1 Diabetes: a Double-Blind, Randomized, Crossover Study
Authors: Francesca Porcellati, Paolo Rossetti, Geremia B. Bolli, Carmine G. Fanelli
Journal: Diabetes Care (2008)

We thank Dr. Banarer (1) for his appreciation of our work (2) and for the opportunity to discuss his criticism.

The formula we used to describe the insulin activity profile was constructed to emphasize the ability of a basal insulin preparation to maintain plasma glucose at the target value during fasting, which is the clinical target of a basal insulin preparation. Accordingly, the second variable of the formula, plasma glucose concentration, was given greater power. The impact …