tbuckley/cabot-search huggingface dataset:
Varying Estimates of Sepsis Mortality Using Death Certificates and Administrative Codes — United States, 1999–2014
Authors: Lauren Epstein, Ray Dantes, Shelley Magill, Anthony Fiore
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Sepsis is a clinical syndrome caused by a dysregulated host response to infection (1). Because there is no confirmatory diagnostic test, the diagnosis of sepsis is based on evidence of infection and clinical judgement. Both death certificates and health services utilization data (administrative claims) have been used to assess sepsis incidence and mortality, but estimates vary depending on the surveillance definition and data source. To highlight the challenges and variability associated with estimating sepsis mortality, CDC compared national estimates of sepsis-related mortality based on death certificates using the CDC WONDER database with published sepsis mortality estimates generated using administrative claims data from hospital discharges reported in the Nationwide Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality (2). During 2004-2009, using data rounded to thousands, the annual range of published sepsis-related mortality estimates based on administrative claims data was 15% to 140% higher (range = 168,000-381,000) than annual estimates generated using death certificate data (multiple causes) (range = 146,000-159,000). Differences in sepsis-related mortality reported using death certificates and administrative claims data might be explained by limitations inherent in each data source. These findings underscore the need for a reliable sepsis surveillance definition based on objective clinical data to more accurately track national sepsis trends and enable objective assessment of the impact of efforts to increase sepsis awareness and prevention.
PREDICTORS OF 2-YEAR MORTALITY AFTER SURGICAL AND ENDOVASCULAR REVASCULARIZATION FOR INFRAINGUINAL ARTERY DISEASE IN HEMODIALYSIS PATIENTS WITH CRITICAL LIMB ISCHEMIA
Authors: Tatsuya Shiraki, Osamu Iida, Yoshimitsu Soga, Terutoshi Yamaoka, Masaaki Uematsu
Journal: Journal of the American College of Cardiology (2015)
Demonstration of a Dual A-V Nodal Conduction System in the Isolated Rabbit Heart
Authors: CARLOS MENDEZ, GORDON K. MOE
Journal: Circulation Research (1966)

The intranodal propagation of atrial and ventricular echoes in in-vitro preparations of the rabbit heart was traced from microelectrode records at many puncture sites. Composite records indicate that the upper part of the node can be functionally and spatially dissociated into two pathways (α and β), which communicate with a final common pathway (FCP) about halfway between the atrium and the His bundle. Atrial echoes, induced by premature atrial stimulation, traverse the α pathway and return to the atrium from the middle part of the node over the β route; echoes can occur without propagation of the premature response to the ventricle. Ventricular echoes, induced by premature stimulation of the His bundle, pass from the FCP to the atrium over the α route, and back to the FCP over the β route. Repetitive reciprocation, in the nature of an intranodal circus movement, was commonly observed. The results completely substantiate previous conclusions based on indirect observations in the dog heart.
Abstract 134: miRNA-708 suppresses prostate cancer growth through Akt2 signaling pathways
Authors: Sharanjot Saini, Shahana Majid, Varahram Shahryari, Sumit Arora, Soichiro Yamamura, Inik Chang, Saif Zaman, Guoren Deng, Yuichiro Tanaka, Peter R. Carroll, Rajvir Dahiya
Journal: Cancer Research (2012)

Abstract MicroRNAs have been implicated in the etiology, progression and metastasis of various malignancies. We identify miR-708, a little studied member of a set of microRNAs that have been implicated in stress control, as an important tumor suppressor in prostate cancer. In this study we identify that miR-708 expression is significantly attenuated in prostate cancer cell lines and human prostate clinical specimens. To evaluate the functional significance of decreased miR-708 expression, miR-708 was reintroduced in prostate cancer cell lines followed by functional assays. Restoration of miR-708 expression in prostate cancer cell lines decreased cell growth, clonability, invasion, migration and elicited a dramatic increase in apoptosis. Moreover, intratumoral delivery of miR-708 was sufficient to trigger in vivo regression of established tumors in a murine xenograft model of human prostate cancer. Further, analysis of putative miR-708 targets showed that miR-708 targets the serine/threonine kinase Akt2/PKBβ, a member of the PI3K/Akt signaling pathway that plays a key role in cellular survival. Phenocopy experiments in prostate cancer cell lines suggest that Akt2 is a functionally relevant target of miR-708 in prostate cancer. In conclusion, our data suggests that miR-708 is a tumor suppressor microRNA that inhibits prostate cancer growth both in vitro and in vivo through targeting Akt2 pathways. 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 134. doi:1538-7445.AM2012-134
Publishers should offer subscription discounts to universities that pay author fees, government agrees
Authors: Z. Kmietowicz
Journal: BMJ (2013)

Institutions that carry out publicly funded research and opt to publish their findings in journals that use the “author pay model” of open access should get a discount on their subscriptions to the same publisher’s journals, the UK government has said.

The statement was made in response to a report by the House of Commons Business, Innovation and Skills Committee, published in September, in which MPs said that the government acted too quickly in favouring a “gold” model of open access that risked curbing access and increasing costs to universities.1

The United Kingdom is moving towards a system of open access so that research will be made freely available at …
Abstract 1653: Regulation of autophagy and apoptosis by a natural triterpenoid in diffuse large B-cell lymphoma.
Authors: Bently Doonan, Azim Hossain, Faisal Radwan, Azizul Haque
Journal: Cancer Research (2013)

Abstract Diffuse large B-cell lymphoma (DLBCL), a subtype of non-Hodgkin's lymphoma, is the most common lymphoid malignancy in the western world. Treatment of DLBCL has been greatly improved in recent years with the addition of the monoclonal antibody Rituximab to the gold standard CHOP chemotherapy regimen, but these treatments are often ineffective in patients with highly aggressive disease or in patients of advanced age. A real problem given the population of DLBCL patients is largely 60 years of age or older, these chemotherapeutics also present the issue of severe toxicity to the patient(s). Thus, studies have focused lately on natural products that can selectively kill malignant lymphomas while displaying a reduced host toxicity profile. Here, we report that a natural extract from the Ganoderma lucidum mushroom, GA-DM, induces apoptosis in human DLBCL cell lines and primary tumors, and activates an orchestrated autophagy/apoptosis pathway in the murine B-cell lymphoma cell line A20. Antitumor efficacy of GA-DM was also investigated in vivo in a murine B-cell lymphoma model using the A20 cell line, where GA-DM (50mg/kg) treatment reduced both the number of tumor metastases and the overall tumor burden in diseased mice. These findings support the potential use of GA-DM as a novel chemotherapeutic in the treatment of DLBCL and could improve the treatment of higher risk patients with advanced disease who can't tolerate current chemotherapy treatment. Citation Format: Bently Doonan, Azim Hossain, Faisal Radwan, Azizul Haque. Regulation of autophagy and apoptosis by a natural triterpenoid in diffuse large B-cell lymphoma. [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 1653. doi:10.1158/1538-7445.AM2013-1653
Hepatorenal Cutaneous Syndrome Demonstrated by 99mTc Macro Aggregated Albumin Whole-Body Scintigraphy
Authors: S. Padma, Shanmuga Sundaram Palaniswamy, Sunny Gandhi, Sanjay Babu K.
Journal: Clinical Nuclear Medicine (2013)

Hepatopulmonary syndrome, also known as hepatorenal syndrome, is a triad of liver disease, impaired oxygenation, and intrapulmonary vascular abnormalities. Forty-seven percent of patients with end-stage liver disease may have hepatopulmonary syndrome, an independent predictor of poor prognosis. Gross dilatation of pulmonary precapillary and capillary vessels, as well as an absolute increase in the number of dilated vessels, is the classic pathological description. We report a young man with cirrhosis demonstrating extrapulmonary shunting of 99mTc-MAA to kidneys with extensive peripheral arteriovenous (cutaneous) vasodilation, which we prefer to name as the “mosaic sign” in the absence of spider nevi or erythema.
P224 DIFFERENT PROFILE OF NATURAL RESISTANCE TO NS3 PROTEASE INHIBITORS IN HEPATITIS C SUBTYPES 1A AND 1C
Authors: S. Bagaglio, E. Messina, A. Smacchia, L. Della Torre, A. Galli, M. Merli, H. Hasson, A. Lazzarin, C. Uberti-Foppa, G. Morsica
Journal: Journal of Hepatology (2014)
Seizures and Other Neurologic Sequelae of Bacterial Meningitis in Children
Authors: Scott L. Pomeroy, Sandra J. Holmes, Philip R. Dodge, Ralph D. Feigin
Journal: New England Journal of Medicine (1990)

Although the mortality rate among children with bacterial meningitis has decreased dramatically in recent decades, some patients are left with neurologic sequelae. It has not been clearly established which features of the acute illness predict the chronic neurologic sequelae, including late seizures or epilepsy.
Excision of basal cell carcinoma: Who does it best?
Authors: M. Chowdhry, R. Shah, P. Dziewulski, N. El-Muttardi
Journal: International Journal of Surgery (2015)

s / International Journal of Surgery 23 (2015) S15eS134 S94 no drain group. The combined complication risk was almost identical between groups (10.9% drain Vs 11% no-drain group). Conclusion: The use of drains has been subject to debate. Studies increasingly support that drains offer no increased recovery benefits and are associated with discomfort and infection risks. High-level studies are required to evaluate drain use in free-flap breast reconstruction, allowing the development of appropriate guidelines. 0762: EXCISION OF BASAL CELL CARCINOMA: WHO DOES IT BEST? M. Chowdhry, R. Shah, P. Dziewulski, N. El-Muttardi. Broomfield Hospital,
Abstract 2733: KITENIN and ErbB4 contribute to further malignant changes in colorectal cancer through c-Jun/AP-1 activation
Authors: Jeong A Bae, Eun Gene Sun, Hangun Kim, So Yeon Park, Hyun Jong Lee, Hee Won Ryu, Kyung Keun Kim
Journal: Cancer Research (2011)

Abstract KITENIN (KAI1 C-terminal interacting tetraspanin, Vangl1) is not only a major component of PCP pathway but also a functional protein promoting colorectal cancer (CRC) cell motility and invasiveness. Here, we report the mechanism of which KITENIN leads further malignant changes in CRC progression after loss of tumor suppressor Adenomatous polyposis coli (APC). KITENIN increases the level of AP-1 activity through interaction with Dvl2, which is subsequently being degraded. Decreasing Dvl2 via interaction with KITENIN or via treatment of si-RNA to Dvl2 significantly increases the AP-1 activity through elevating the level of c-jun and c-jun phosphorylation. EGF acts upstream of KITENIN/AP-1 signaling and induces synergic AP-1 activation in the presence of elevated KITENIN, which requires the interaction of KITENIN with ErbB4. The morphological characteristics of adenocarcinoma were observed in intestinal tumor tissues from compound villin-KITENIN transgenic/APCmin/+ mice but not from APCmin/+ mice, both of which express the elevated level of ErbB4. This result demonstrates that further malignant phenotype of intestinal tumor can be induced by elevated KITENIN and ErbB4 via promoting c-Jun/AP-1 activation within an APC loss-associated tumor microenvironment. Our present results suggest the possibility of the addition of anti-KITENIN therapy to the use of EGFR inhibitors in the treatment of CRC patients with APC mutation. 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 2733. doi:10.1158/1538-7445.AM2011-2733
Abstract 1496: Oxidatively induced DNA base damage in colorectal carcinoma
Authors: Guldal Kirkali, Didem Keles, Aras Emre Canda, Cem Terzi, Pawel Jaruga, Miral Dizdaroglu, Gulgun Oktay
Journal: Cancer Research (2010)

Abstract Molecular pathways that play a role in the development of colorectal cancer involve multiple genetic changes in cancer-related genes that may be caused by overproduction of reactive oxygen species (ROS) including free radicals. Various types of ROS are capable of damaging DNA and other biomolecules. Increased formation of ROS can contribute to genetic instability and promote the development of malignancy. These facts led us to hypothesize that oxidatively induced DNA damage may accumulate in colorectal cancer patients. To test this hypothesis, we investigated oxidatively induced DNA damage in colon and rectum tissues of cancer patients in comparison with their normal paired tissues. DNA was isolated from 51 colorectal cancer tissues. The levels of oxidatively induced DNA lesions such as 4,6-diamino-5-formamidopyrimidine (FapyAde), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua), 8-hydroxyguanine (8-OH-Gua) and (5′S)-8,5′-cyclo-2′-deoxyadenosine (S-cdA) were measured by gas chromatography/isotope-dilution mass spectrometry and liquid chromatography/isotope-dilution mass spectrometry. We found that the level of 8-OH-Gua, FapyAde and FapyGua were significantly lower in cancer tissues than those in paired normal tissues (p=0.002, p=0.019 and p=0.005, respectively), whereas the S-cdA levels showed no significant difference between both tissues. These DNA base damages correlated with clinical and pathological data such as tumor location, tumor stage, gender and perineural invasion. The low levels of DNA base damage in tumor tissues when compared to their normal counterparts suggest an increase in DNA repair capacity in malignant tumors that may contribute to the resistance to therapeutic agents. This finding may lead to development of new therapeutic approaches. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1496.
SAT0327 Predicting hip osteoarthritis progression using active appearance modelling (AAM) applied to hip DXA images from the auckland calcium study:
Authors: K. Yoshida, J.S. Gregory, B. Mason, I.R. Reid, D.M. Reid
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Dual energy Xray absorptiometry (DXA) scanners are used to assess osteoporosis but recently, DXA images have also been shown to adequately assess osteoarthritis (OA) and Active Shape modelling (ASM) to predict hip OA progression<sup>1</sup>. AAM is an extension of ASM incorporating information on both bone shape and density. <h3>Objectives</h3> To identify hip OA cases and determine if AAM applied to hip DXA images can predict the progression of hip OA. <h3>Methods</h3> Hip DXA scans taken at 30 month intervals over 5 years from postmenopausal women participating in the Auckland Calcium Study<sup>2</sup>were scored for the presence of hip OA using Kellgren Lawrence grades (KL). Hip OA progression was defined as a) Hip arthroplasty (excluding hip fracture and avascular necrosis) or b) KL change of ≥1/2 grade based on progressive OA features and KL≥2 on follow up scan. Frequency matching for age was used to obtain 1:3 ratio of OA progression cases (a and b) to never OA controls (n=378). 48-point proximal femur AAM was applied to the DXA images. <h3>Results</h3> Significant correlations (<i>P</i>&lt;0.001) were found between baseline KL grade and Appearance modes (App)1,6,8,13,15 and 16 (rho=0.23, -0.17, 0.20, -0.24, -0.21, 0.16). When OA progression was defined as hip arthroplasty of the scanned hip (n=21; controls including 41 non-progressive hip OA cases, n=419) App7,8,13,16,18 and 19 were respectively found to be significant predictors, but only App16,18 and 19 remained statistically significant after adjustment for KL. When controls were widened to include all nonarthroplasty cases (n=495), App7,8,13,16,18 and 19 were found to be significant predictors of hip arthroplasty but only App13 and 16 remained significant after KL adjustment. When new incident hip OA was defined as KL≥2 at follow up in absence of baseline OA (n=47), both App7 and 13 remained significant after adjustment. When OA cases were most broadly defined as KL change≥1/2 grade or arthroplasty (n=126) and controls included non-progressive hip OA cases (n=419), 6 modes (App7,13,16 inclusive) remained significant after KL adjustment (Table 1). <h3>Conclusions</h3> AAM applied to hip DXA images can predict the incidence and progression of hip OA. <h3>References</h3> Reid IR et al. American Journal of Medicine. 2006;119(9):777-85 Barr RJ et al. doi:10.1093/rheumatology/ker382 <h3>Disclosure of Interest</h3> None Declared
Abstract 5215: Detection of circulating tumor cells in peripheral blood of patients with renal cell carcinoma
Authors: Steffen Goebel, Karen Bluemke, Udo Bilkenroth, Axel Meye, Susanne Fuessel, Christine Lautenschlaeger, Andres Melchior, Hans Heynemann, Paolo Fornara, Helge Taubert
Journal: Cancer Research (2011)

Abstract Detection of circulating tumor cells in peripheral blood of patients with renal cell carcinoma The aim of this study was to evaluate the clinical relevance of the presence of disseminated tumor cells in peripheral blood, so called circulating tumor cells (CTCs), for renal cell carcinoma (RCC) patients. 233 peripheral blood samples from 154 RCC patients were investigated for the presence of disseminated tumor cells (DTCs) by autoMACS technique and immunocytochemical (ICC) staining of cytokeratin. The frequency of CTCs was analyzed statistically for correlation with relevant clinical data. Two kinds of tumor cells were detected: those with expression of cytokeratin 8/18 (CK+), but also cells without a detectable CK+ expression, which we called large blue stained (Bl+) cells with a tumor-like morphology. After following the CD45 autoMACS depletion protocol, we identified CTCs in 96 out of 233 peripheral blood samples (41%), which originated from 81 out of 154 (53%) RCC patients. A significant correlation between the detection of CTCs and positive lymph node status (p &amp;lt; 0.001; Chi-square test) and the presence of synchronous metastases at the time of primary tumor resection (p &amp;lt; 0.02; Chi-square test) was found. In a multivariate Cox's regression hazard model, presence of CK+ CTCs was significantly correlated with poor overall survival for RCC patients (RR=2.3; p &amp;lt; 0.05). The presence of CTCs correlated to lymph node status and presence of synchronous metastases in RCC. It is important to evaluate CK+ and Bl+ tumor cells together to determine the role of CTCs in tumor behavior and disease progression. Detection of CK+ CTCs in peripheral blood is a significant and independent prognostic factor for RCC. 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 5215. doi:10.1158/1538-7445.AM2011-5215
A4.03 The GPR22 receptor, genetically linked to osteoarthritis stimulates chondrocyte hypertrophy and decreases protein kinase a activity
Authors: LA Guns, D Calebiro, MJ Lohse, RJ Lories, F Cailotto
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Purpose</h3> A genome-wide association study (GWAS) identified an association between osteoarthritis and a gene cluster on chromosome 7 in which we proposed a role for G protein coupled receptor (GPR)22. This orphan receptor was found in OA cartilage while not in healthy cartilage. Activated GPR22 signals through the G inhibitory pathway resulting in inhibition of adenylcyclase and consequently decreases protein kinase A (PKA) activity. The cholecystokinin (CCK) receptors A and B are paralogues of this orphan receptor. <h3>Methods</h3> The ATDC5 chondrogenic cell line was used as model system. ATDC5 cells stably overexpressing <i>Gpr22</i> were cultured as high density micromasses (200,000 cells/10 µl)&nbsp;in triplicate. The chemical compound AG-041R (at 1, 3 or 10 µM) was used as a potential antagonist. Gene expression of <i>Ccka</i> and <i>Cckb, </i>of&nbsp;chondrogenic markers was analysed&nbsp;in both undifferentiated and differentiated ATDC5 cells. Sulfated proteoglycan, mineralization and collagen content were quantified. PKA activity was determined with a fluorescence-based assay. Real-time PKA concentrations and kinetics were measured by fluorescence resonance energy transfer (FRET) imaging by expressing FRET-based PKA sensors in ATDC5 cells. <h3>Results</h3> ATDC5 cells stably&nbsp;overexpressing&nbsp;<i>Gpr22 </i>showed a 30% increased in mineralization and a 50% decrease in proteoglycan content after 21 days of differentiation in the micromass model. Gene expression studies demonstrated a decrease in&nbsp;<i>Agg</i> and <i>Col</i><i>a1&nbsp;</i>mRNA at day 1, 7, 14 and 21. <i>Col10a1</i> and <i>Mmp13</i> expression were increased suggesting an earlier and enhanced shift of the cells towards hypertrophy. PKA activity was 40% reduced in the&nbsp;<i>Gpr22 </i>overexpressing cells. The effect of <i>Gpr22 </i>overexpression in the differentiating cells within the micromass&nbsp;was antagonised by AG-041R treatment. FRET imaging confirmed the neutralising effect of AG-041R on intracellular PKA concentration in <i>Gpr22&nbsp;</i>overexpressing cells using a forskolin titration model. <h3>Conclusions</h3> GPR22, an orphan G-coupled protein receptor has been linked to osteoarthritis. Overexpression of this receptor reduces PKA activity in differentiating chondrocytes and shifts the differentiation program towards hypertrophy, a deleterious outcome in the context of osteoarthritis. The effects of GPR22 can be antagonised by cholecystokinin antagonist AG-041R.
1331 “HEALTHY LIVER” IN MORBIDLY OBESE: TRANSITION TO NASH IN THE CONTEXT OF INSULIN RESISTANCE AS PREREQUISITE FOR HEPATIC STEATOSIS REQUIRES ADDITIONAL TRIGGERS
Authors: W. von Schonfels, M. Ahrens, M. Laudes, B. Sipos, K. Balschun, M. Brosch, H. Hinrichsen, J.-H. Egberts, K. Tiemann, S. Schreiber, T. Becker, C. Rocken, F. Stickel, C. Schafmayer, J. Hampe
Journal: Journal of Hepatology (2012)