tbuckley/cabot-search huggingface dataset:
Relationship between eGFR Decline and Hard Outcomes after Kidney Transplants
Authors: Philip A. Clayton, Wai H. Lim, Germaine Wong, Steven J. Chadban
Journal: Journal of the American Society of Nephrology (2016)

Trials designed to assess the effect of interventions on death and graft failure in kidney transplant recipients are not feasible, because these are predominantly late events. Here, we examined the potential of percentage decline in eGFR as a surrogate for hard outcomes. We obtained deidentified data from the Australia and New Zealand Dialysis and Transplant Registry and studied 7949 transplants performed from 1995 to 2009, including 71,845 patient-years of follow-up, 1121 graft losses, and 1192 deaths. We used adjusted Cox proportional hazards models to determine risks of death or death-censored graft failure related to percentage change in eGFR between years 1 and 3 after transplant. Percentage change in eGFR was modeled as a restricted cubic spline. Rate of eGFR decline associated with exponentially increased risks of graft failure and death. Compared with stable eGFR, a ≥30% decline in eGFR, detected in 10% of patients, strongly associated with subsequent death (hazard ratio, 2.20; 95% confidence interval, 1.87 to 2.60) and death-censored graft failure (hazard ratio, 5.14; 95% confidence interval, 4.44 to 5.95). Decline in eGFR was superior to other surrogates, including acute rejection, doubling of serum creatinine level, and eGFR at year 1 or year 2. We conclude that 30% decline in eGFR between years 1 and 3 after kidney transplant is common and strongly associated with risks of subsequent death and death-censored graft failure, which mirrors findings in CKD. Percentage decline in eGFR should be considered for use as a surrogate outcome in kidney transplant trials.
LOCAL UPPER THORACIC BIOIMPEDANCE: A POTENTIAL METHOD FOR LONG-TERM NON-INVASIVE HEMODYNAMIC MONITORING
Authors: Venkata Krishna Puppala, Dev Venugopal, Oana Dickinson, Samit S. Roy, Barry Detloff, Julie Dicken, Robert Patterson, David Benditt
Journal: Journal of the American College of Cardiology (2016)
Crafting Science: A Sociohistory of the Quest for the Genetics of Cancer, by Joan H Fujimura Between Bench and Bedside: Science, Healing, and Interleukin-2 in a Cancer Ward, by Ilana Lowy
Authors: S. Shapin
Journal: BMJ (1997)

Joan H Fujimura Harvard University Press, £29.95, pp 322 ISBN 0 674 15553 0

llana Lowy Harvard University Press, £26.50, pp 370 ISBN 0 674 06809 2

Many years ago, a friend who had just been interviewed by a sociologist said, more in sorrow than in anger, “She didn't seem interested in what I did.” What he meant was that he spent much of his day calculating the energies of subatomic particle interactions, and the sociologist never asked him anything about that. This was “technical stuff,” and, while you might not expect a sociologist know much about such things, this was what my friend was trained to do and what gave him his identity as a scientist of a certain kind. So, even if it was understandable that sociologists might choose to pass by on the other side of the technical, a sociology of science without the science still seemed an odd sort of enterprise.

About 25 years ago, sociologists began to agree: sociologists had to become “ethnographers,” hanging out where knowledge was made and learning the culture of those places. Science was still to be understood in its collective aspects—that's why sociologists tend to be interested in interactions rather than in individuals—but what made scientific collectivities communities of a certain sort was what they knew together and what they knew how to do together. There was no way to find out about that except by getting …
THU0426 Is contrast material needed for the mri scoring of synovitis of the hand in patients with rheumatoid arthritis? A systematic comparison of 0.23, 0.6, 1.5 and 3.0 tesla MRI
Authors: I. Eshed, S. Krabbe, M. Østergaard, P. Bøyesen, J. Møller, F. Therkildsen, O.R. Madsen, S. Juhl Pedersen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> With contrast-enhanced MRI as the reference method, to explore to which extent synovitis in wrists and metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis (RA) can be reliably assessed by unenhanced MRI. Furthermore, we explored the influence of different MRI field strengths, coil types and image resolutions. <h3>Methods</h3> 41 RA patients and 12 healthy controls underwent 7 MRI examinations (Coronal short tau inversion recovery (STIR) and T1-weighted (T1w) sequences) on 4 MRI units (0.23 T, 0.6 T, 1.5 T, and 3.0 T, with different coils, see table for details) within 24 hours. Additional post-contrast T1w sequence was performed at the 1.5T unit (gold standard). Images were scored according to OMERACT RA MRI score (RAMRIS) (1) by an experienced reader blinded to participant's details and MRI field strength. Gold standard images were scored on a different session. Intrareader reliability was evaluated on a subset of 18 patients and controls. <h3>Results</h3> Fair to good correlation (ICC=0.38-0.72) was seen between different STIR protocols and the gold standard reference (Table 1). The highest correlation was found using the 1.5T unit with the smaller voxel size and extremity coil. Sensitivity for the presence or absence of synovitis was moderate-high in all units (per patient: 0.8-1.0, per joint: 0.63-0.85) whereas the exact agreement on scores was poorer (0.5-0.66). <h3>Conclusions</h3> Unenhanced MRI, using STIR sequences, is only moderately reliable for assessing synovitis in RA MCP and wrist joints, when contrast-enhanced MRI is considered the gold standard reference. 0.6 T and 1.5 MRI performed best. <h3>References</h3> Ostergaard M. et al. J Rheumatol 2003;30:1385-6. <h3>Disclosure of Interest</h3> None Declared
Epidemiology of human leishmaniasis in Greece, 1981-2011
Authors: K Gkolfinopoulou, N Bitsolas, S Patrinos, L Veneti, A Marka, G Dougas, D Pervanidou, M Detsis, E Triantafillou, T Georgakopoulou, C Billinis, J Kremastinou, C Hadjichristodoulou
Journal: Eurosurveillance (2013)

Leishmaniasis is endemic and mandatorily notifiable in Greece. Epidemiological surveillance data for leishmaniasis in Greece between 1981 and 2011 are presented. In 1998, the notification system began distinguishing between visceral and cutaneous leishmaniasis. The mean annual incidence of reported leishmaniasis cases between 1998 and 2011 was 0.36 per 100,000 population. Of a total 563 leishmaniasis cases reported after 1998, 523 (93%) were visceral leishmaniasis cases. Incidence of reported visceral leishmaniasis cases fluctuated during this period, generally decreasing after 2007, with a small re-increase in 2011. The mean annual incidence rate of reported visceral leishmaniasis cases was significantly higher in less than four year-olds (p &lt;0.001). Leishmaniasis cases occurred both in the country mainland and islands. Between 1998 and 2011, Attica concentrated almost half of the reported visceral leishmaniasis cases, with incidence rates in western Attica and western Athens above 12.00 per 100,000 population. Compared to visceral leishmaniasis, cutaneous leishmaniasis had a rather sporadic distribution, with many prefectures appearing free of cases. From 2004, the notification also included risk factors and of 287 cases with known immune status, 44 (15%) were immunocompromised. Moreover having a dog at home was reported by 209 of 312 leishmaniasis cases (67%), whereas 229 of 307 cases (75%) reported the presence of stray dogs near their residence. Linking clinical surveillance data with laboratory data and improving collaboration with the veterinary public health sector are some of the future challenges for leishmaniasis surveillance in Greece.
A Global View of Health — An Unfolding Series
Authors: Harvey V. Fineberg, David J. Hunter
Journal: New England Journal of Medicine (2013)

This issue of the Journal includes the first article in a series of review articles on global health.1 In a journal that proudly bears the name of a U.S. domestic region, this series will show that local health and local health care are linked to sources of ill health elsewhere in the world. Today, not only are health problems global, but lessons, insights, and fresh solutions regarding such problems flow in all directions. The series is built around articles that explain the need for global health, the challenges to achieving it, and the solutions to problems related to it.The . . .
Per cent emphysema is associated with respiratory and lung cancer mortality in the general population: a cohort study
Authors: Elizabeth C Oelsner, J Jeffrey Carr, Paul L Enright, Eric A Hoffman, Aaron R Folsom, Steven M Kawut, Richard A Kronmal, David J Lederer, Joao A C Lima, Gina S Lovasi, Benjamin M Smith, Steven J Shea, R Graham Barr
Journal: Thorax (2016)

<h3>Background</h3> Emphysema on CT is a risk factor for all-cause mortality in persons with and without airflow obstruction; however, causes of death associated with emphysema remain uncertain, particularly in the general population. <h3>Aims</h3> To test associations between quantitatively assessed emphysema on CT and cause of death in persons with and without a substantial smoking history. <h3>Methods</h3> The Multi-Ethnic Study of Atherosclerosis recruited 6814 participants, aged 45–84 years and without clinical cardiovascular disease, in 2000–2002. Per cent emphysema was defined on cardiac CT as per cent of lung voxels less than −950 Hounsfield units; emphysema on CT was defined as per cent emphysema above the upper limit of normal. Cause of death was classified by administrative codes. Proportional-hazards models were adjusted for age, race/ethnicity, gender, body mass index, smoking status, pack-years, coronary artery calcium, site and education. Additional adjustment for lung function was made in a subset with spirometry from 2004 to 2006. <h3>Results</h3> There were 1091 deaths over 12 years median follow-up. Emphysema on CT was strongly associated with increased mortality due to respiratory diseases (adjusted HR 2.94, 95% CI 1.68 to 5.15), particularly chronic lower respiratory diseases (adjusted HR 9.54, 95% CI 4.70 to 19.35), and lung cancer (adjusted HR 1.84, 95% CI 1.09 to 3.12), but not cardiovascular disease. Associations persisted among participants with fewer than 10 pack-years and those without physician-diagnosed respiratory disease, and were similar after adjustment for airflow measures and in persons without airflow limitation. <h3>Conclusions</h3> Quantitatively assessed emphysema on CT is associated with greater respiratory disease and lung cancer mortality, even among persons without traditional risk factors.
Abstract 160: Modulation of the serum metabolomic profiles of breast cancer patients after receiving limonene intervention.
Authors: Jessica A. Miller, Kirk Pappan, Chengcheng Hu, Elizabeth J. Want, Hector Keun, Julie E. Lang, H-H Sherry Chow
Journal: Cancer Research (2013)

Abstract Background. Limonene is a bioactive food component found in citrus peel oil that has demonstrated chemopreventive and chemotherapeutic activities in preclinical studies. To better characterize its mechanism of action in the clinical setting, we measured the serum metabolomic profiles of breast cancer patients before and after receiving a short-term limonene intervention. Methods. Forty women with stage 0 - II breast cancer received 2 g QD limonene daily for 2 - 6 weeks (21.5 ± 8.8 days) before surgical resection of their tumor. Pre/post intervention blood draws were taken to assess serum metabolomic profiles. Metabolomic analysis was performed on the gas chromatography mass spectrometry and liquid chromatography mass spectrometry platforms established at Metabolon, Inc. Results. Of the 397 identified biochemicals, 71 changed significantly (p&amp;lt;0.05) from baseline to post limonene intervention. Pathway analysis revealed several key metabolic changes. Significant increases were noted in eight bile acid conjugates following limonene intervention, including a 3-fold elevation in taurocholate, taurodeoxycholate, and glycoursodeoxycholate. There were also significant decreases in a number of steroid hormones including dehydroisoandrosterone sulfate (DHEA-S), 4-androsten-3beta, 17beta-diol disulfate, epiandrosterone sulfate, androsterone sulfate, and pregnen-diol disulfate. In addition, markers of collagen remodeling or degradation were elevated following limonene intervention. Increased circulating vitamin C, improved insulin sensitivity and glycemic control, and reduced inflammatory potential were also noted following limonene treatment. An increase in plasma levels of ten different glycerophosphocholines and four carnitines were all significantly correlated to a decrease in cyclinD1 (all p's&amp;lt;0.01 and Rˆ2&amp;gt;0.4) in an exploratory analysis. Conclusions. This global metabolomic profiling study revealed several novel mechanistic insights into the potential clinical activities of limonene. Efforts are ongoing to correlate these metabolic changes to carcinogenesis, clinical characteristics, and risk markers measured in breast tissue and serum. Citation Format: Jessica A. Miller, Kirk Pappan, Chengcheng Hu, Elizabeth J. Want, Hector Keun, Julie E. Lang, H-H Sherry Chow. Modulation of the serum metabolomic profiles of breast cancer patients after receiving limonene intervention. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 160. doi:10.1158/1538-7445.AM2013-160
Case 27-2012
Authors: Thomas N. Byrne, Steven Jay Isakoff, Sandra P. Rincon, Thomas M. Gudewicz
Journal: New England Journal of Medicine (2012)

A 60-year-old woman was admitted to this hospital because of gradually progressive painful muscle spasms, weakness, and hyperreflexia in the legs. Brain and spine imaging revealed no parenchymal abnormalities. A diagnostic test was performed.
Abstract 632: The efficacy of IGF-I receptor monoclonal antibody for human gastrointestinal carcinomas is independent for mutation status of k-ras
Authors: Yasushi Adachi, Hiroyuki Yamamoto, Masanori Ii, Hua Li, Hirokazu Ohashhi, Yoshiaki Arimura, Takao Endo, Kohzoh Imai, David P. Carbone, Yasushisa Shinomura
Journal: Cancer Research (2011)

Abstract Background &amp; Aims: Insulin-like growth factor (IGF)-I receptor (IGF-IR) signaling is required for carcinogenicity and proliferation of many tumors, including gastrointestinal cancers. We have previously shown successful therapy for colorectal, pancreatic, gastric, and esophageal carcinomas using recombinant adenoviruses expressing dominant negative IGF-IR. Mutation in k-ras is one of key factors in the patients with gastrointestinal cancers. In this study, we sought to evaluate the effect of a new monoclonal antibody for IGF-IR, figitumumab (CP-751,871), on the progression of human gastrointestinal carcinomas with/without k-ras mutation. Methods: We assessed the effect of figitumumab on signal transduction, proliferation, and survival in 6 gastrointestinal cancer cell lines with or without k-ras mutation, colon and pancreatic adenocarcinoma, esophageal squamous cancer; and hepatoceller carcinoma. Combination effects of figitumumab and chemotherapy were studied. Then figitumumab was evaluated in the treatment for human gastrointestinal. cancer xenografts in nude mice. Results: Figitumumab blocked autophosphorylation of IGF-IR and the downstream signals. The antibody suppressed proliferation and tumorigenicity in all cell lines. The drug inhibited survival by itself and up-regulated chemotherapy (5-FU and gemcitabine) induced apoptosis in all cell lines. Moreover, the combination of the monoclonal antibody and chemotherapy was effective against tumors on mice. The effect of figitumumab is not influenced by the mutation stasis of k-ras. Figitumumab reduced expression of IGF-IR but not insulin receptor in tumors on mice. The drug did not affect on neither murine body weight nor blood concentrations of glucose, insulin, IGFBP-3, and growth hormone. Conclusions: IGF-IR might be a good molecular therapeutic target and figitumumab may thus have therapeutic utility in human gastrointestinal carcinomas even if k-ras mutated types. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 632. doi:10.1158/1538-7445.AM2011-632
THU0060 Clinical Phenotypes of Systemic Sclerosis Impact Telomere and Telosome Function in Distinct Patterns
Authors: J. Broen, L. McGlynn, L. Geurts-van Bon, R. Lafyatis, T. Radstake, P. Shiels
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic sclerosis is a immune mediated inflammatory disease culminating in vasculopathy and extensive fibrosis of the skin and internal organs. Telomere shortening has previously been described in small cohorts of SSc patients. <h3>Objectives</h3> To scrutinize previous findings in large cohort, investigate telomere shortening in multiple immune celltypes and scrutinize underlying aberrances in telosome gene expression. <h3>Methods</h3> We measured telomere length by qPCR in a cohort of 185 SSc patients and 100 healthy controls. Next we investigated plasmacytoid dendritic cells, T cells, B cells, monocytes and myeloid dendritic cells from 25 SSc patients for cell specific telomere attrition. Finally we investigated whether there were differences in expression of 31 genes involved in telomere pathways. <h3>Results</h3> A significant age related telomere attrition was observed in healthy controls and lcSSc patients (Both <i>p&lt;</i> 0.001), but not in dcSSc patients. We observed significant shorter telomeres in B cells and myeloid dendritic cells of both lcSSc and dcSSc patients (B-Cells <i>p=0.014, p=0.002</i> &amp; myDCs <i>p=0.019, p=0.004</i> respectively). PDCs and T cells had shorter telomeres in dcSSc patients only (<i>p=0.001</i> and <i>p=0.003</i>). In addition, we observed in early SSc, that B cells exhibit a significant upregulation of the telosome genes SIRT6, RIF1 and WRN (after correction for multiple testing <i>p=0.03</i>, <i>0.006</i> and <i>0.048</i> respectively). In later disease there is a significant higher expression of HDAC9 in monocytes from dcSSc compared to lcSSc patients. Intriguingly, in PDCs of diffuse SSc patients, regardless whether it is early or progressed disease the expression of SIRT1 is significantly lower (<i>p=0.002</i> in all comparisons). <h3>Image/graph</h3> <h3>Conclusions</h3> Aberrances in telomere shortening and biology are a feature of SSc, reflecting a difference in clinical subsets at the cellular level. <h3>Disclosure of Interest</h3> None Declared
Abstract 444: MACC1 as biomarker for progression and prognosis of human malignant glioma
Authors: Ulrike S. Stein, Steffen Fuchs, Camelia M. Monoranu, Pia Herrmann, Janice Smith, Ralf-Ingo Ernestus, Giles H. Vince, Carsten Hagemann
Journal: Cancer Research (2012)

Abstract Metastasis-associated in colon cancer-1 (MACC1) is a prognostic indicator for metastasis formation and metastasis-free survival of colon cancer patients. Patients with low MACC1 expressing primary tumors had a 5-year-survival of 80%, whereas subjects with high MACC1 expressing tumors had a 5-year-survival of only 15%. Correlations of MACC1 expression levels with tumor progression, recurrence and metastasis have meanwhile been reported for e.g. gastric, lung and hepatocellular cancer. However, no data are available concerning MACC1 expression in human astrocytic tumors. Glioblastoma multiforme (GBM) are the most prevalent brain tumors of adults either developing de novo without known precursor-lesion (primary GBM), or progressing from low grade astrocytomas (secondary GBM). Patients suffering from GBM have a very disadvantageous prognosis. Although these tumors rarely metastasize, they are characterized by rapid growth, and their invasive and migratory behavior is similar to those of metastatic cells of tumors with different origin. Therefore we tested our hypothesis on MACC1 involvement in progression of human gliomas. MACC1 mRNA expression increased concomitantly with increasing WHO grading, as demonstrated by semi-quantitative and quantitative RT-PCR of biopsies from human low grade astrocytomas and GBM. MACC1 protein expression allowed discrimination of dormant and recurrent LGA and of primary and secondary GBM, as shown by immunohistochemistry of an independent patients’ cohort. Furthermore, strong MACC1 expression was associated with reduced median patients’ survival. Finally, we performed real-time measurements of migration and proliferation in the MACC1-transfected GBM cell line U138/MACC1 and found promoted proliferation and migration. Therefore, MACC1 may be a new biomarker for progression and for prognosis of human malignant gliomas and might represent a new potential therapeutic target for inhibition of their proliferation and migration. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 444. doi:1538-7445.AM2012-444
Abstract 5440: Analyzing in vivo conformational changes of a transcription factor, c-Myb, using fluorescence resonance energy transfer (FRET) technology.
Authors: Olivia L. George, Scott A. Ness
Journal: Cancer Research (2013)

Abstract The c-myb proto-oncogene was first identified as the normal cellular counterpart to the v-myb oncogene identified in Avian Myeloblastosis virus (AMV), a retrovirus that transforms immature hematopoietic cells in tissue culture and induces leukemias in animals. However, the normal c-Myb protein is not oncogenic, in part because of conformational and auto-inhibitory interactions that keep its transforming activity in check. The c-Myb protein functions as both an activator and repressor of transcription and its regulation involves sequences found in the negative regulatory domain. We hypothesize that c-Myb protein undergoes conformational changes due to post-translational modifications and protein interactions that may help direct it to different sets of target gene promoters. In addition, there could also be upstream signaling pathways, for example the signals that direct cells either to proliferate or to undergo differentiation, that could contribute to its transforming potential. To address this, we are utilizing FRET technology to elucidate whether the intramolecular interactions of c-Myb or its interactions with various co-factors and co-activators change in vivo in response to extracellular signals that trigger a switch from proliferation to differentiation. The goal is to determine how the conformations and protein-protein interactions of c-Myb change in cells in response to signals that control cell fate. Citation Format: Olivia L. George, Scott A. Ness. Analyzing in vivo conformational changes of a transcription factor, c-Myb, using fluorescence resonance energy transfer (FRET) technology. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5440. doi:10.1158/1538-7445.AM2013-5440