tbuckley/cabot-search huggingface dataset:
Neonatal Respiratory Syncytial Virus Infection
Authors: Caroline Breese Hall, Arthur E. Kopelman, R. Gordon Douglas, Joyce M. Geiman, Mary Pat Meagher
Journal: New England Journal of Medicine (1979)

Respiratory syncytial virus infections are thought to be uncommon in the first month of life. During a community outbreak, we prospectively studied such infection in our neonatal units. Of 82 neonates studied, 66 were hospitalized for six days or longer, and 23 (35 per cent) acquired this virus. Four infants died, two unexpectedly. Infected infants had a significantly shorter gestation and birth weight. Illness was often atypical, with nonspecific signs, especially in infants under three weeks of age, who had significantly less lower-respiratory-tract involvement and lower quantities of virus in their nasal washes. The titer of virus shed correlated with the infants' postnatal, but not gestational, age. Infection was also acquired by 34 per cent of the staff, who appeared to be important in the spread of the virus. These findings suggest that respiratory syncytial virus may readily infect neonates, but the disease may be atypical and may be overlooked. (N Engl J Med 300:393–396, 1979)
FDG PET/CT of Bilateral Testicular Lymphoma
Authors: Chun-Jiang Dang, Feng-Hua Zhan, Ya-Jun Li
Journal: Clinical Nuclear Medicine (2011)

Testicular lymphoma is a rare extranodal presentation of non-Hodgkin lymphoma. The most common type is diffuse large B-cell lymphoma. A 58-year-old man presented with painless enlargement of bilateral scrotums for about 6 months and a mass in the left neck for a month. The patient underwent an F-18 FDG PET/CT scan to evaluate the situation. The PET/CT scan demonstrated intense hypermetabolic activity in the bilateral enlarged testes, enlarged left adrenal gland, and multiple enlarged lymph nodes in the left neck, retroperitoneum, and bilateral inguinal region. Subsequent radical orchiectomy and pathologic examination revealed a large B-cell lymphoma infiltrating the testicular parenchyma.
A2.23 Blockade of increased autophagy in juvenile arthritis synovial fluid T cells reduces cellular activation and cytokine production
Authors: JGC Peeters, N de Graeff, BJ Prakken, J van Loosdregt, S de Roock
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Juvenile Idiopathic Arthritis (JIA) is a debilitating autoimmune disease with an important role for aberrant T cell homeostasis in the pathogenesis. Autophagy is a process of lysosomal degradation that is important for (T) cellular homeostasis that has previously been genetically correlated to several auto-immune diseases. We investigated the role of autophagy in JIA synovial inflammation and its effect on T cell activity. <h3>Materials and methods</h3> PBMC from healthy donors, and PBMC and Synovial fluid cells (SFMC) from 21 JIA patients were used. Cells were cultured overnight with or without hydroxychloroquin to investigate the autophagic flux. Synovial fluid was added to HC cell cultures to investigate the role of inflammatory mediators on autophagy. Autophagy was measured with flow cytometry using the specific dye Cyto-ID or by western blot of LC3-II. The importance of autophagy for inflammatory activity of T cells in the synovium was investigated by blockade of autophagy during anti-CD3 activation and measuring proliferation and cytokine production during 4 day cultures. <h3>Results</h3> Autophagy was significantly increased in CD4<sup>+</sup>, and CD8<sup>+</sup> T cells from SFMC which was due to a higher basal level of autophagy in SFMC and not to an increase in susceptibility to HCQ. Culturing HC and JIA PBMC and SFMC with SF or inflammatory cytokines did not affect autophagy levels, indicating that the increased autophagy in SFMC is related to a cell intrinsic phenomenon rather than induced by soluble mediators of inflammation. Indeed, cellular activation related to levels of autophagy. Additionally, blocking autophagy reduced proliferation and cytokine production. <h3>Conclusions</h3> T cells from the inflamed synovium of JIA patients show significantly increased autophagy. This phenomenon is not affected by cytokines in the SF or SF itself, but is related to cellular activation. Moreover, blocking autophagy reduces cellular activity and cytokine production. We conclude that targeting autophagy in JIA has a major potential for future therapy.
PTH-035 Pulmonary Misplacement Of Nasogastric Tubes: A 2 Year Audit Of Service Delivery, Feedback Intervention And Patient Outcome
Authors: F Mansour, M Virta, P Neild, T Marshall
Journal: Gut (2014)

<h3>Introduction</h3> Although nasogastric feeding will continue to be the preferred method of assisted nutrition, after oral intake, better understanding of the risks associated with pulmonary misplacement and how to improve delivery of service is required. It is well known that feeding through a pulmonary placed NGT can lead to serious harm or mortality. The National Patient Safety Agency (NPSA) issued guidelines in 2011 to try to reduce reported cases of feeding into the lungs. However,it is unknown whether the introduction of an NG tube into the lungs,in itself can introduce infection. <h3>Methods</h3> We conducted two snapshot audits at a tertiary centre between 2012–2013. Between these audits, organised training of nursing and core medical trainees was conducted. Audits involved spot-checks on 34 wards, assessing notes of all patients with NGTs <i>in situ</i> that day. These were then compared to NPSA guidelines. We also did a retrospective study on the outcome of cases with pulmonary misplaced tubes, between 2012–2013. To identify these, chest X-ray reports were searched. Patient mortality and cases that later developed sepsis or chest infection were calculated. They were then compared to a group of controls that did have correctly placed NGTs. <h3>Results</h3> The number of patients with NG tubes <i>in situ</i> were 38 and 46 in 2012 and 2013 respectively. None of these had cases of pulmonary misplacement. After the training that staff received there was a remarkable improvement in guideline adherence in 2013. Documentation of insertion increased by 46% (p &lt; 0.001), and length of NGT recording increased by 53.9% (p &lt; 0.001). pH checks being the first line confirmation of position, rather than X-ray, increased by 33.8% (p = 0.002). In the 18 patients that had pH checks in 2013, 7 patients did not require a second line Xray to check position. From the radiology search there were 27 patients that did have pulmonary misplacement out of a total of 1332 (2.03%). For mortality RR = 1.33 (95% CI: 0.8424 – 2.1077, P = 0.2199). For development of infection the RR = 1.94 which was statistically significant (95% CI: 1.1362 – 3.3207, P = 0.0152). Direct logistic regression was performed on patient age to assess the impact on the likelihood of developing disease. However, this was not found to be statistically significant. <h3>Conclusion</h3> It appears that training of both nursing and medical staff can have a huge benefit in increasing adherence to guidance. This study suggests that patients are nearly twice as likely to develop chest infection or sepsis after pulmonary misplacement of their NGT. Although other factors such as age have been shown to have little affect on this outcome, factors such as patient morbidity before misplacement could not be assessed. <h3>Disclosure of Interest</h3> None Declared.
AB0878 Self-reported productivity at work and sick leave in patients with spondyloarthritis:
Authors: E. Haglund, S. Bergman, A. Bremander, L.T. Jacobsson, B. Strömbeck, I.F. Petersson
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Spondyloarthritis (SpA) causes impaired function, activity limitation, decreased health related quality of life and work disability. Little is known of the relations between registered sick leave and self-reported productivity limitations and associations with disease severity, functioning and general health. <h3>Objectives</h3> To study self reported productivity at work and registered sick leave and associated factors expected to influence the productivity and sick leave in patients with SpA also related to subgroups. <h3>Methods</h3> A questionnaire survey was performed in 2009 including all health care seeking subjects aged ≥18 years with a diagnosis of SpA (according to specified ICD 10 codes during the years 2003 to 2007) in the Skane Region, Sweden (n=3711) identified by a regional health care register. The questionnaires included self-reported presenteeism (from the WPAI questionnaire) defined as the percentage reduced productivity while working (0-100), 0=no impact on productivity level). Register data of sick leave from a 3 month period including the survey response date was obtained from the Swedish Social Insurance Agency. Evaluated possible associated factors were age, disease duration, disease activity (BASDAI) physical function (BASFI), health related quality of life (EQ5D), anxiety (HAD-A), depression (HAD-D) and ASES pain and symptom. <h3>Results</h3> Response rate was 77% whereof 684 patients (18%) declined participation and 2167 (58%), returned the questionnaire. Out of these, 1821 SpA patients in working age (18-67 years), mean age 50 years and 48% men were included in the analysis. Disease duration was mean 13 years (SD 10), mean EQ5D score was 0.75 (SD 0.16), BASDAI mean 4.4 (SD 2.2) and BASFI mean 3.0 (SD 2.4). Self-reported productivity limitation at work was mean 43% (95% CI 40-45) with statistically non-significant differences between men and women and between disease subgroups. Sick leave levels ranged from 0-91 days per three months, mean 20 days (95% CI 19-21). Patients with the subtype psoriatic arthritis had the lowest level of sick leave days (table). In correlation analysis, factors associated with self-reported productivity limitation in patients with SpA were EQ5D r= -0.47 (p&lt;0.001), BASDAI r=0.55 (p&lt;0.001), BASFI r=0.55 (p&lt;0.001), while none of the studied variables correlated to sick leave (r &lt;0.07). <h3>Conclusions</h3> Self reported productivity loss at work was associated with lower levels of health-related quality of life, increased self-reported disease activity and impaired function while there were no associations with registered levels of sick leave. The results indicate that self reported productivity and sick leave capture different dimensions of work and absence in patients with SpA. <h3>Disclosure of Interest</h3> None Declared
Prediction of Early Death in Patients with Early-Stage NSCLC—Can We Select Patients without a Potential Benefit of SBRT as a Curative Treatment Approach?
Authors: Rainer J. Klement, José Belderbos, Inga Grills, Maria Werner-Wasik, Andrew Hope, Meredith Giuliani, Hong Ye, Jan-Jakob Sonke, Heike Peulen, Matthias Guckenberger
Journal: Journal of Thoracic Oncology (2016)
4D nucleomes in single cells: what can computational modeling reveal about spatial chromatin conformation?
Authors: Monika Sekelja, Jonas Paulsen, Philippe Collas
Journal: Genome biology (2016)

Genome-wide sequencing technologies enable investigations of the structural properties of the genome in various spatial dimensions. Here, we review computational techniques developed to model the three-dimensional genome in single cells versus ensembles of cells and assess their underlying assumptions. We further address approaches to study the spatio-temporal aspects of genome organization from single-cell data.
NCI Appropriation For 1990 Nearly Settled
Authors: C. McClave
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article NCI Appropriation For 1990 Nearly Settled Get access Cathy McClave Cathy McClave Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 22, 15 November 1989, Page 1694, https://doi.org/10.1093/jnci/81.22.1694 Published: 15 November 1989
Abstract 3889: Direct evidence that the MRN complex is required for a pathway that processes Top2 covalent complexes
Authors: Eroica Soans, Margarita Mishina, John L. Nitiss
Journal: Cancer Research (2011)

Abstract Drugs targeting topoisomerase II (Top2) such as etoposide or doxorubicin generate enzyme mediated DNA damage. During the normal Top2 reaction, the enzyme forms a covalent enzyme DNA intermediate consisting of a 5’ phosphotyrosyl linkage between the enzyme and DNA. Many compounds that generate Top2 mediated damage inhibit the enzyme-catalyzed religation step leading to DNA breaks. Therefore an important aspect of the repair of Top2 mediated damage includes removal of the protein covalently bound to DNA. One way of eliminating that protein is by proteolysis. Liu and colleagues have clearly demonstrated that proteolysis plays a role in repairing Top2 beta damage1 and it is likely that proteolysis is also important for repairing Top2 alpha mediated damage. Proteolysis cannot remove all of the peptide bound to DNA; therefore nucleolytic enzymes are also needed for repairing Top2 damage. Since the MRN complex is required for nucleolytic removal of the meiotic Top2-like protein Spo11, it has been hypothesized that the MRN complex also participates in removal of Top2 protein from DNA following cellular treatment with Top2 poisons. However, there is no direct evidence for processing of Top2 mediated damage by the MRN complex. We have used the ICE assay to directly measure Top2 covalent complexes in mammalian cells treated with Top2 poisons such as etoposide. The ICE assay uses CSCl centrifugation to isolate protein:DNA covalent complexes. We have combined this assay with siRNA knockdowns to assess whether specific protein complexes are required for processing Top2 covalent complexes. Since this assay depends on recognition of Top2 epitopes by monoclonal antibodies directed towards Top2 isoforms, we have examined levels of Top2 complexes in cells treated with the proteasome inhibitor, MG132. In cells treated with siRNA directed against Mre11, we observed an increase in Top2:DNA covalent complexes following treatment with either etoposide or mAMSA. These results provide direct evidence that the MRN complex is required for at least one pathway for removal of Top2 covalent complexes. It is likely that this MRN dependent pathway is capable of removing Top2 bound to DNA without proteolytic processing of the covalent complex. We are currently using this approach to assess other recently described processing pathways including pathways requiring CtiP and pathways requiring Tdp2. (1) Mao, Y.; Desai, S. D.; Ting, C. Y.; Hwang, J.; Liu, L. F. J Biol Chem 2001, 276, 40652. 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 3889. doi:10.1158/1538-7445.AM2011-3889
Familial Adenomatous Polyposis With Malignant Change Seen With Ga-67 Imaging
Authors: T Hirano, K Ichikawa, A Suzuki, H Nariko, K Kunitomo, Y Yamamoto, Y Omori
Journal: Clinical Nuclear Medicine (1997)

A 41-year-old woman had a history of familial adenomatous polyposis of the colon. She recently reported lower abdominal pain when moving her bowels. Ga-67 citrate scintigraphy demonstrated an area of increased uptake in the lower pelvis and diffusely increased uptake in the ascending and transverse colon on whole-body and spot images. A barium enema study showed multiple polyps in the entire colon with focal area of concentric narrowing and mucosal irregularity at the sigmoid colon. Biopsy of the lesion in the sigmoid colon revealed well-differentiated adenocarcinoma.
TGR5 is essential for bile acid-dependent cholangiocyte proliferation in vivo and in vitro
Authors: Maria Reich, Kathleen Deutschmann, Annika Sommerfeld, Caroline Klindt, Stefanie Kluge, Ralf Kubitz, Christoph Ullmer, Wolfram T Knoefel, Diran Herebian, Ertan Mayatepek, Dieter Häussinger, Verena Keitel
Journal: Gut (2015)

<h3>Objective</h3> Cholestatic liver diseases in humans as well as bile acid (BA)-feeding and common bile duct ligation (CBDL) in rodents trigger hyperplasia of cholangiocytes within the portal fields. Furthermore, elevation of BA levels enhances proliferation and invasiveness of cholangiocarcinoma (CCA) cells in animal models, thus promoting tumour progression. TGR5 is a G-protein coupled BA receptor, which is highly expressed in cholangiocytes and postulated to mediate the proliferative effects of BA. <h3>Design</h3> BA-dependent cholangiocyte proliferation was examined in TGR5-knockout and wild type mice following cholic acid (CA)-feeding and CBDL. TGR5-dependent proliferation and protection from apoptosis was studied in isolated cholangiocytes and CCA cell lines following stimulation with TGR5 ligands and kinase inhibitors. TGR5 expression was analysed in human CCA tissue. <h3>Results</h3> Cholangiocyte proliferation was significantly reduced in TGR5-knockout mice in response to CA-feeding and CBDL. Taurolithocholic acid and TGR5-selective agonists induced cholangiocyte proliferation through elevation of reactive oxygen species and cSrc mediated epidermal growth factor receptor transactivation and subsequent Erk1/2 phosphorylation only in wild type but not in TGR5-knockout-derived cells. In human CCA tissue TGR5 was overexpressed and the pathway of TGR5-dependent proliferation via epidermal growth factor receptor and extracellular signal-regulated kinase (ERK)1/2 activation also translated to CCA cell lines. Furthermore, apoptosis was inhibited by TGR5-dependent CD95 receptor serine phosphorylation. <h3>Conclusions</h3> TGR5 is an important mediator of BA-induced cholangiocyte proliferation in vivo and in vitro. Furthermore, TGR5 protects cholangiocytes from death receptor-mediated apoptosis. These mechanisms may protect cholangiocytes from BA toxicity under cholestatic conditions, however, they may trigger proliferation and apoptosis resistance in malignantly transformed cholangiocytes, thus promoting CCA progression.
AB0069 Conditioned media from adipose-derived mesenchymal stem cells decreases senescence and enhances collagen ii expression in osteoarthritic chondrocytes
Authors: M. I. Guillen, J. Platas, V. Mirabet, M. A. Castejon, F. Gomar, M. J. Alcaraz
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Adipose-derived mesenchymal stem cells (ASC) might act as a cellular source of soluble factors exerting anti-inflammatory or trophic effects on cells. Osteoarthritis (OA) is characterized by the progressive loss of structure and functionality of articular cartilage. <h3>Objectives</h3> In the present study we explored the effect of conditioned medium from adipose-derived mesenchymal stem cells (ASC-CM) on the metabolism of OA chondrocytes in primary culture. <h3>Methods</h3> ADC were isolated from adipose tissue of patients subjected to abdominal lipectomy surgery, by collagenase treatment. Cells were incubated in DMEM/F12 + 15% human serum. Cell phenotype was analysed by flow cytometry with specific antibodies anti-CD105-PE, anti-CD90PerCP-eFluo 710, anti-CD34APC, and anti-CD45-PE (International Society of Cellular Therapy), and cellular viability with propidium iodide. ASC-CM was collected after 48h of culture, centrifuged and stored at -80°C in sterile conditions. Protocols were approved by the Institutional Ethical Committee. Chondrocytes were isolated from knee cartilage samples from patients with diagnosis of advanced OA. OA chondrocytes in primary culture were stimulated with 10 ng/ml interleukin (IL)-1β for 1 or 5 days. We have evaluated the senescence marker β-galactosidase by histochemical staining of cells. Collagen II production was analyzed by immunofluorescence, gene expression by real-time qPCR and protein expression by ELISA. <h3>Results</h3> The percentage of senescent chondrocytes was increased by IL-1β treatment after 1 or 5 days whereas ASC-CM significantly counteracted this effect. When OA chondrocytes were treated with IL-1β and/or ASC-CM for 5 days, we observed a significant maintenance of collagen II expression in chondrocytes cultured with ASC-CM either in basal conditions or in the presence of IL-1β stimulation. Cytokine stimulation of chondrocytes augmented gene expression and protein release into the culture medium of matrix metalloproteinases (MMPs). Our data indicate that ASC-CM significantly decreased the production of MMP-13. In addition, AC-CM reduced gene expression and protein levels of the pro-inflammatory cytokine IL-6 and enhanced the production of the anti-inflammatory cytokine IL-10. <h3>Conclusions</h3> We have shown that ASC-CM treatment of OA chondrocytes prevents the appearance of senescence features and the production of degradative mediators. These findings suggest a protective role for ASC-CM in OA chondrocytes. <h3>Acknowledgements</h3> This work was funded by grants SAF2010-22048 (MINECO), RETICEF RD06/0013/2001 (MINECO, ISCIII, FEDER), and Prometeo2010-047 (Generalitat Valenciana). <h3>Disclosure of Interest</h3> None Declared
Abstract 4951: 2-Methoxyestradiol (2-ME2) induces microRNA alterations in prostate cancer cells: Role for miRs in 2-ME2-induced biological effects
Authors: Jianping Xie, Rita Ghosh, Addanki P. Kumar
Journal: Cancer Research (2011)

Abstract Prostate cancer is the second most common cause of death related to cancer in Western societies. 2-Methoxyestradiol (2-ME2), an endogenous metabolite of 17-β estradiol inhibits tumor cell proliferation in various cancer cells, including the prostate. Previous studies from our laboratory showed that 2-ME2 (i) inhibits proliferation of both androgen responsive and independent cells through induction of apoptosis involving G2/M check point block; (ii) prevents the development of prostate tumors in transgenic adenocarcinoma of mouse prostate (TRAMP) model. Although various molecular targets have been proposed, the mechanism of action behind its antiproliferative activity is still uncertain. Here we investigated the possible role for 2-ME2 induced antiproliferative activity by examining the altered regulation of microRNA (miRNAs). MicroRNAs are small non-coding RNAs that down regulate gene expression during cellular processes including proliferation and apoptosis. We compared the microRNA profile in non-tumorigenic (RWPE-1), androgen responsive (LNCaP) and androgen independent (PC-3) cells in response to 2-ME2 treatment in the presence and absence of androgen-stimulation (only in LNCaP cells) using the stem-loop RT-PCR based Taqman® Array Human MicroRNA Cards (Array A and B) representing 754 unique assays specific to human mature miRNAs (Applied Biosystems, Foster City, CA). Analysis of these data identified expression of only 50% of miRs in prostate cancer cells. About 26% and 12% of these are upregulated; 20.5% and 26% were down regulated in LNCaP and PC-3 cells respectively. However androgen stimulation of LNCaP cells resulted in upregulation of 34.2% and 15% down regulation of miRs whereas 2-ME2 treatment down regulated 28.7% of miRs. Target transcripts for these miRs have been identified. To the best of our knowledge this is the first study to report in-depth investigation of global miR changes in response to 2-ME2 induced biological effects. These data demonstrate that 2-ME2 suppresses proliferation and induces apoptosis in prostate cancer cells through modulation of microRNA signature. Supported by NIH CA 135451 (APK). 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 4951. doi:10.1158/1538-7445.AM2011-4951