tbuckley/cabot-search huggingface dataset:
Percutaneous radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation
Authors: David S. K. Lu, Nam C. Yu, Steven S. Raman, Charles Lassman, Myron J. Tong, Carolyn Britten, Francisco Durazo, Sammy Saab, Steven Han, Richard Finn, Jonathan R. Hiatt, Ronald W. Busuttil
Journal: Hepatology (2005)

Orthotopic liver transplantation (OLT) can be a definitive treatment for patients with hepatocellular carcinoma (HCC). Prolonged waiting times for cadaveric livers, however, may lead to dropout from the waiting list or worsened post-OLT prognosis as a result of interval tumor progression. Percutaneous radiofrequency ablation (RFA) is widely used for local control of small unresectable HCC, but its pretransplant role remains unclear. We studied the outcome of 52 consecutive patients accepted for OLT bearing 87 HCC nodules and treated with percutaneous RFA. On initial staging, the tumor burden exceeded the Milan criteria in 10 patients. Complete tumor coagulation was observed in 74 of 87 (85.1%) nodules based on postablation imaging. After a mean of 12.7 months (range: 0.3-43.5) on the waiting list, 3 of 52 patients (5.8%) had dropped out due to tumor progression. Forty-one patients had undergone transplantation, with 1- and 3-year post-OLT survival rates of 85% and 76%, respectively. No patient developed HCC recurrence. There were three major complications in 76 RFA procedures (hepatic arterial hemorrhage, small bowel perforation, and liver decompensation salvaged by OLT), without resultant death or dropout. In conclusion, percutaneous RFA is an effective bridge to OLT for patients with compensated liver function and safely accessible tumors. Tumor-related dropout rate and post-OLT outcome compared favorably with published controls of patients with early-stage disease. This can be attributed to the efficacy of RFA in producing local cure or curbing tumor progression during the waiting period. (HEPATOLOGY 2005;41:1130–1137.)
Troponin T and quantitative ST-segment depression offer complementary prognostic information in the risk stratification of acute coronary syndrome patients
Authors: Padma Kaul, L.Kristin Newby, Yuling Fu, Vic Hasselblad, Kenneth W Mahaffey, Robert H Christenson, Robert A Harrington, E.Magnus Ohman, Eric J Topol, Robert M Califf, Frans Van de Werf, Paul W Armstrong
Journal: Journal of the American College of Cardiology (2003)
Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk
Authors: Soumya Raychaudhuri, Brian P Thomson, Elaine F Remmers, Stephen Eyre, Anne Hinks, Candace Guiducci, Joseph J Catanese, Gang Xie, Eli A Stahl, Robert Chen, Lars Alfredsson, Christopher I Amos, Kristin G Ardlie, Anne Barton, John Bowes, Noel P Burtt, Monica Chang, Jonathan Coblyn, Karen H Costenbader, Lindsey A Criswell, J Bart A Crusius, Jing Cui, Phillip L De Jager, Bo Ding, Paul Emery, Edward Flynn, Pille Harrison, Lynne J Hocking, Tom W J Huizinga, Daniel L Kastner, Xiayi Ke, Fina A S Kurreeman, Annette T Lee, Xiangdong Liu, Yonghong Li, Paul Martin, Ann W Morgan, Leonid Padyukov, David M Reid, Mark Seielstad, Michael F Seldin, Nancy A Shadick, Sophia Steer, Paul P Tak, Wendy Thomson, Annette H M van der Helm-van Mil, Irene E van der Horst-Bruinsma, Michael E Weinblatt, Anthony G Wilson, Gert Jan Wolbink, Paul Wordsworth, David Altshuler, Elizabeth W Karlson, Rene E M Toes, Niek de Vries, Ann B Begovich, Katherine A Siminovitch, Jane Worthington, Lars Klareskog, Peter K Gregersen, Mark J Daly, Robert M Plenge
Journal: Nature Genetics (2009)
Requirement for T cells in the production of migration inhibitory factor.
Authors: B R Bloom, E Shevach
Journal: The Journal of Experimental Medicine (1975)

The question whether B lymphocytes are capable of being activated by antigen in the absence of functional T cells was investigated in a model that excludes participation of T cells by virtue of an immune response gene restriction. Strain 2 guinea pigs are capable of responding to immunization with DNP-PLL, whereas strain 13 animals are not. In the present experiments, animals of both strains were immunized with DNP-PLL complexed to ovalbumin (DNP-PLL-Ova) under conditions in which equal titers of antibodies to DNP were produced by both strains. The failure of T cells of strain 13 animals to respond to DNP-PLL was confirmed by the virus plaque assay. While spleen cells from both strains produced MIF after stimulation with DNP-PLL-Ova, in response to DNP-PLL only strain 2 spleens were able to produce MIF. Cells from neither strain could be activated by DNP-guinea pig albumin to produce MIF. We conclude that B lymphocytes are incapable of being stimulated by antigen in the absence of T cells, and that MIF production is a thymus-dependent response. While the results indicate that MIF production is a valid qualitative assay for T-cell competence, since MIF can be produced by B and T cells, the degree of migration inhibition cannot be regarded as a quantitative measure of T-cell function.
Phase I Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of the MEK Inhibitor RO4987655 (CH4987655) in Patients with Advanced Solid Tumors
Authors: Suzanne Leijen, Mark R. Middleton, Patricia Tresca, Françoise Kraeber-Bodéré, Veronique Dieras, Max E. Scheulen, Avinash Gupta, Vanesa Lopez-Valverde, Zhi-Xin Xu, Ruediger Rueger, Jean J.L. Tessier, Eliezer Shochat, Steve Blotner, Valerie Meresse Naegelen, Jan H.M. Schellens, Wilfried Ernst Erich Eberhardt
Journal: Clinical Cancer Research (2012)

This phase I study of the mitogen-activated protein/extracellular signal-regulated kinase inhibitor RO4987655 (CH4987655) assessed its maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety, pharmacokinetic/pharmacodynamic profile, and antitumor activity in patients with advanced solid tumors.An initial dose escalation was conducted using a once-daily dosing schedule, with oral RO4987655 administered at doses of 1.0 to 2.5 mg once daily over 28 consecutive days in 4-week cycles. Doses were then escalated from 3.0 to 21.0 mg [total daily dose (TDD)] using a twice-daily dosing schedule.Forty-nine patients were enrolled. DLTs were blurred vision (n = 1) and elevated creatine phosphokinase (n = 3). The MTD was 8.5 mg twice daily (TDD, 17.0 mg). Rash-related toxicity (91.8%) and gastrointestinal disorders (69.4%) were the most frequent adverse events. The pharmacokinetic profile of RO4987655 showed dose linearity and a half-life of approximately 4 hours. At the MTD, target inhibition, assessed by suppression of extracellular signal-regulated kinase phosphorylation in peripheral blood mononuclear cells, was high (mean 75%) and sustained (90% of time >IC(50)). Of the patients evaluable for response, clinical benefit was seen in 21.1%, including two partial responses (one confirmed and one unconfirmed). 79.4% of patients showed a reduction in fluorodeoxyglucose uptake by positron emission tomography between baseline and day 15.In this population of heavily pretreated patients, oral RO4987655 showed manageable toxicity, a favorable pharmacokinetics/pharmacodynamics profile, and promising preliminary antitumor activity, which has been further investigated in specific populations of patients with RAS and/or RAF mutation driven tumors.
Immunogenicity and safety of a quadrivalent human papillomavirus vaccine in patients with systemic lupus erythematosus: a case–control study
Authors: Chi Chiu Mok, Ling Yin Ho, Lai Shan Fong, Chi Hung To
Journal: Annals of the Rheumatic Diseases (2012)

To evaluate the immunogenicity and safety of GARDASIL, a quadrivalent human papillomavirus (HPV) vaccine, in patients with systemic lupus erythematosus (SLE).Women with SLE aged 18-35 years who had stable disease were recruited to receive GARDASIL vaccination and an equal number of age-matched healthy women were also vaccinated. Seroconversion rates of antibodies to HPV serotypes 6, 11, 16 and 18 at months 7 and 12 and adverse events (AEs) were compared between patients and controls. The rate of disease flares in SLE participants was compared with matched SLE controls.50 patients with SLE and 50 healthy controls were studied. The mean age and disease duration of the patients was 25.8±3.9 years and 6.6±4.5 years, respectively. At month 12 the seroconversion rates of anti-HPV serotypes 6, 11, 16 and 18 in patients and controls were 82%, 89%, 95%, 76% and 98%, 98%, 98%, 80%, respectively. In patients with SLE there were no significant changes in the titres of anti-dsDNA, complements, anti-C1q and SLE Disease Activity Index scores from baseline to months 2, 7 and 12. There was one mild/moderate SLE flare at months 0-2, two mild/moderate flares at months 3-6 and six mild/moderate and two severe flares at months 7-12. Disease flares in patients with SLE occurred at a similar frequency to that of 50 matched SLE controls (0.22/patient/year vs 0.20/patient/year, p=0.81). Injection site reaction was the commonest AE (5%), and the incidence of AEs was comparable between patients with SLE and controls.The quadrivalent HPV vaccine is well tolerated and reasonably effective in patients with stable SLE and does not induce an increase in lupus activity or flares.
Bronchoalveolar CD4+ T cell responses to respiratory antigens are impaired in HIV-infected adults
Authors: K. C. Jambo, E. Sepako, D. G. Fullerton, D. Mzinza, S. Glennie, A. K. Wright, R. S. Heyderman, S. B. Gordon
Journal: Thorax (2011)

<h3>Rationale</h3> HIV-infected adults are at an increased risk of lower respiratory tract infections. HIV infection impairs systemic acquired immunity, but there is limited information in humans on HIV-related cell-mediated immune defects in the lung. <h3>Objective</h3> To investigate antigen-specific CD4<sup>+</sup> T cell responses to influenza virus, <i>Streptococcus pneumoniae</i> and <i>Mycobacterium tuberculosis</i> antigens in bronchoalveolar lavage (BAL) and peripheral blood between HIV-infected individuals and HIV-uninfected Malawian adults. <h3>Methods</h3> We obtained BAL fluid and blood from HIV-infected individuals (n=21) and HIV-uninfected adults (n=24). We determined the proportion of T cell subsets including naive, memory and regulatory T cells using flow cytometry, and used intracellular cytokine staining to identify CD4<sup>+</sup> T cells recognising influenza virus-, <i>S pneumoniae</i>- and <i>M tuberculosis</i>-antigens. <h3>Main results</h3> CD4<sup>+</sup> T cells in BAL were predominantly of effector memory phenotype compared to blood, irrespective of HIV status (p&lt;0.001). There was immune compartmentalisation with a higher frequency of antigen-specific CD4<sup>+</sup> T cells against influenza virus, <i>S pneumoniae</i> and <i>M tuberculosis</i> retained in BAL compared to blood in HIV-uninfected adults (p&lt;0.001 in each case). Influenza virus- and <i>M tuberculosis</i>-specific CD4<sup>+</sup> T cell responses in BAL were impaired in HIV-infected individuals: proportions of total antigen-specific CD4<sup>+</sup> T cells and of polyfunctional IFN-γ and TNF-α-secreting cells were lower in HIV-infected individuals than in HIV-uninfected adults (p&lt;0.05 in each case). <h3>Conclusions</h3> BAL antigen-specific CD4<sup>+</sup> T cell responses against important viral and bacterial respiratory pathogens are impaired in HIV-infected adults. This might contribute to the susceptibility of HIV-infected adults to lower respiratory tract infections such as pneumonia and tuberculosis.
Breastfeeding and Childhood Leukemia Incidence
Authors: Efrat L. Amitay, Lital Keinan-Boker
Journal: JAMA Pediatrics (2015)

<h3>Importance</h3> Childhood cancer is a leading cause of mortality among children and adolescents in the developed world and the incidence increases by 0.9% each year. Leukemia accounts for about 30% of all childhood cancer but its etiology is still mostly unknown. <h3>Objective</h3> To conduct a meta-analysis of available scientific evidence on the association between breastfeeding and childhood leukemia. <h3>Data Sources</h3> A thorough search for articles published between January 1960 and December 2014 researching the association between breastfeeding and childhood leukemia was conducted on PubMed, the Cochrane Library, and Scopus (performed in July and December 2014), supplemented by manual searches of reference lists. <h3>Study Selection</h3> To be included in the meta-analyses, studies had to be case control; include breastfeeding as a measured exposure and leukemia as a measured outcome; include data on breastfeeding duration in months; and be published in a peer-reviewed journal with full text available in English. <h3>Data Extraction and Synthesis</h3> The search identified 24 relevant studies, 17 of which met all inclusion criteria. No publication bias or significant heterogeneity among these 17 studies were detected. The quality of each study that met the inclusion criteria was assessed using the Newcastle-Ottawa Scale. Multiple meta-analyses were conducted using the random effect model on raw data in the StatsDirect statistical program. <h3>Main Outcomes and Measures</h3> No or short duration of breastfeeding and the incidence of childhood leukemia. <h3>Results</h3> The meta-analysis of all 17 studies indicated that compared with no or shorter breastfeeding, any breastfeeding for 6 months or longer was associated with a 20% lower risk for childhood leukemia (odds ratio, 0.80; 95% CI, 0.72-0.90). A separate meta-analysis of 15 studies indicated that ever breastfed compared with never breastfed was associated with a 9% lower risk for childhood leukemia (odds ratio, 0.91; 95% CI, 0.80-1.04), although the definition of<i>never breastfed</i>differed between studies. All meta-analyses of subgroups of the 17 studies showed similar associations. Based on current meta-analyses results, 14% to 20% of all childhood leukemia cases may be prevented by breastfeeding for 6 months or more. <h3>Conclusions and Relevance</h3> Breastfeeding is a highly accessible, low-cost public health measure. This meta-analysis that included studies not featured in previous meta-analyses on the subject indicates that promoting breastfeeding for 6 months or more may help lower childhood leukemia incidence, in addition to its other health benefits for children and mothers.
Wittgensteinian developmental investigations
Authors: John Shotter
Journal: Behavioral and Brain Sciences (2004)

I criticize Carpendale &amp; Lewis's (C&amp;L) attempt to produce a Wittgensteinian theory, as an alternative to work in the “theory of mind” tradition, not because I disagree with it as theory, but because Wittgenstein would be critical of any attempt to make such a use of his work. His concern is with descriptions, not theories.
Pulmonary cryptococcosis mimicking solitary lung cancer in an immunocompetent patient
Authors: E-T Chang, A H Wang, C-B Lin, J-J Lee, S-H Liu
Journal: Thorax (2008)

A 48-year-old Chinese male henhouse keeper was admitted with dyspnoea. A plain chest radiograph and CT scan indicated a solitary right lung mass with invasion to the trachea (fig 1A and B). Positron emission tomography with 18F-fluoro-2-deoxy-D-glucose (FDG-PET) showed accumulation …
Systemic lupus erythematosus and thyrotoxicosis: a hitherto little recognised association.
Authors: S Rodrigue, H Laborde, P M Catoggio
Journal: Annals of the Rheumatic Diseases (1989)

Six patients are reported in whom systemic lupus erythematosus (SLE) and thyrotoxicosis coexisted. All had four or more American Rheumatism Association criteria (1982) for the diagnosis of SLE and had clinical manifestations and function test results characteristic of hyperthyroidism (except for one who had been thyroidectomised previously). In three patients the diagnosis of hyperthyroidism preceded that of SLE, in two patients both diseases began simultaneously, and only in one was the diagnosis of thyrotoxicosis made after that of SLE. It is suggested that hyperthyroidism associated with SLE may be a form of presentation of thyroiditis. This association may pass unnoticed because of the similarity of some clinical manifestations.
P181 Does The Degree Of Occupational Asbestos Exposure Affect The Outcome Of Radical Surgery For Malignant Pleural Mesothelioma?
Authors: A. Sharkey, R. Vaja, A. Nakas, D. Waller
Journal: Thorax (2014)

<h3>Introduction</h3> Malignant Pleural Mesothelioma (MPM) is associated with variable exposure to asbestos and a spectrum of prognosis which may be extended by radical surgery. Proportional mortality ratios have been used in the past to estimate the risk of developing mesothelioma, and more recently specific occupational risk groups have been described.<sup>1</sup> We aimed to determine whether those at highest risk of developing mesothelioma by virtue of working in high exposure occupations also fared worse after radical surgery for mesothelioma. <h3>Methods</h3> Case notes were reviewed for all patients undergoing radical surgery for MPM between 1999 and 2014. Prior asbestos exposure had been determined by histories taken by the multidisciplinary team. Patients were separated into one of 8 groups, using modified versions of the categories proposed by Rake <i>et al.</i> in 2009.<sup>1</sup> Comparative outcome was assessed for each group. <h3>Results</h3> History of asbestos exposure was available for 262 patients. Thirteen patients were excluded from further analysis having died in hospital. Of the remaining 249 patients, 84.3% were male, and median age was 62 years (range 14–81 years). The only significant intergroup difference was gender, with more females in the low risk and no exposure groups (p = 0.021). However, in our cohort of surgically treated patients, gender had no effect on survival (p = 0.476). There was a significant difference in survival between the low risk group and the high and medium risk groups combined (24.2 vs 14.5 months p = 0.031). Survival was similar between those with known asbestos exposure and those who reported no asbestos exposure; 14.7 vs 15.2 months p = 0.573. <h3>Conclusion</h3> This is the first study to demonstrate that those patients who worked in occupations at highest risk of developing mesothelioma also have the worst comparative survival from radical surgery. The causation remains a topic for further research. It is also of note that patients with no reported asbestos exposure had an unexpectedly poor survival. The importance of a careful occupational history of asbestos exposure is emphasised. <h3>Reference</h3> Rake C, Gilham C, Hatch J, Darnton A, Hodgson J, Peto J. Occupational, domestic and environmental mesothelioma risks in the British population: a case-control study. <i>Br J Cancer</i>. 2009 Apr 7;100(7):1175–83
Cancer: The Road to Amiens
Authors: David J. Stewart, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2008)

“The Battle of Amiens, which began on 8 August 1918, was the opening phase of the Allied offensive...that ultimately led to the end of World War I. Allied forces advanced over seven miles on the first day, one of the greatest advances of the war.” “The importance of this offensive in tactical terms was that it...provided a further example of the effectiveness of shifting from stagnant trench warfare to mobile multifaceted warfare.”
C1 inhibitor deficiency simulating systemic lupus erythematosus
Authors: S. SHIRAISHI, Y. NARA, Y. WATANABE, K. MATSUDA, Y. MIKI
Journal: British Journal of Dermatology (1982)

A 48–year‐old Japanese woman with systemic lupus erythematosus‐like lesions of the skin and lips was found to have hereditary angio‐oedema. Complement studies revealed low CH5O, C19, C4 and C1 inhibitor levels, with normal C3 and C5 levels. Dramatic clinical improvement followed fresh normal human blood transfusion and systemic betamethasone administration, while the deficient complement component levels were unchanged.
Novel Genetic Markers of Breast Cancer Survival Identified by a Genome-Wide Association Study
Authors: Xiao Ou Shu, Jirong Long, Wei Lu, Chun Li, Wendy Y. Chen, Ryan Delahanty, Jiarong Cheng, Hui Cai, Ying Zheng, Jiajun Shi, Kai Gu, Wen-Jing Wang, Peter Kraft, Yu-Tang Gao, Qiuyin Cai, Wei Zheng
Journal: Cancer Research (2012)

Abstract Only two genome-wide association studies (GWAS) have been conducted to date to identify potential markers for total mortality after diagnosis of breast cancer. Here, we report the identification of two single-nucleotide polymorphisms (SNP) associated with total mortality from a two-stage GWAS conducted among 6,110 Shanghai-resident Chinese women with tumor–node–metastasis (TNM) stage I to IV breast cancer. The discovery stage included 1,950 patients and evaluated 613,031 common SNPs. The top 49 associations were evaluated in an independent replication stage of 4,160 Shanghai patients with breast cancer. A consistent and highly significant association with total mortality was documented for SNPs rs3784099 and rs9934948. SNP rs3784099, located in the RAD51L1 gene, was associated with total morality in both the discovery stage (P = 1.44 × 10−8) and replication stage (P = 0.06; P-combined = 1.17 × 10−7). Adjusted HRs for total mortality were 1.41 [95% confidence interval (CI), 1.18–1.68] for the AG genotype and 2.64 (95% CI, 1.74–4.03) for the AA genotype, when compared with the GG genotype. The variant C allele of rs9934948, located on chromosome 16, was associated with a similarly elevated risk of total mortality (P-combined = 5.75 × 10−6). We also observed this association among 1,145 patients with breast cancer of European ancestry from the Nurses’ Health Study (NHS; P = 0.006); the association was highly significant in a combined analysis of NHS and Chinese data (P = 1.39 × 10−7). Similar associations were observed for these two SNPs with breast cancer–specific mortality. This study provides strong evidence suggesting that the RAD51L1 gene and a chromosome 16 locus influence breast cancer prognosis. Cancer Res; 72(5); 1182–9. ©2012 AACR.
Alternative Splicing and the Steady-State Ratios of mRNA Isoforms Generated by It Are under Strong Stabilizing Selection in Caenorhabditis elegans
Authors: S. Barberan-Soler, A. M. Zahler
Journal: Molecular Biology and Evolution (2008)

Evolutionary studies indicate that a high proportion of alternative splicing (AS) events are species-specific; just 28% of minor-form alternatively spliced exons are conserved between mice and humans. We employed a splicing-sensitive microarray to study the evolution of allele-specific AS in nematodes. We compared splicing levels among five distinct Caenorhabditis elegans lines. Our results indicate that AS is less variable between natural isolates (NIs) from England, Hawaii, and Australia than when compared with mutation accumulation lines (6% vs. 21%, respectively, vary compared with N2). This suggests that strong stabilizing selection shapes the evolution of the ratios of isoforms generated by AS in C. elegans. When we analyzed some of the splicing changes between the NIs, we found examples of changes in both cis and trans that lead to alterations in gene-specific AS. This indicates that both these mechanisms for changing AS are employed along the path toward speciation in nematodes.