tbuckley/cabot-search huggingface dataset:
Achieving excellence in colorectal cancer care through performance improvement: KP Georgia's implementation of the national vision.
Authors: Juliane Tomlin, Joanne E. Schottinger, Michele Lagana, Violeta Rabrenovich
Journal: Journal of Clinical Oncology (2016)

207 Background: The Care Management Institute and The Permanente Federation have partnered over the past two years to develop an Improvement Portfolio for Colorectal Cancer, with the objective of accelerating improvement of Colorectal Cancer Care quality, timeliness, reliability, and the member care experience across the continuum, from prevention, reliable screening and diagnosis, through treatment and survivorship. The portfolio includes: 1) National clinical algorithms for diagnosis and treatment (colon), and for survivorship (colon and rectal); 2) Timeliness metrics for Time to Diagnosis, Time to Initial Treatment, and Time from Surgery to Adjuvant; 3) Patient Friendly Pathway. Methods: The National team has partnered with KP Georgia's clinical and operational leaders to successfully operationalize the Colon Cancer Diagnostic Clinical Algorithm using KP's Performance Improvement methodology. Results: KP Georgia improved time from diagnosis to treatment by 40.3% and reduced variation by 60.5%. Conclusions: Development of the National CRC Improvement Portfolio consisting of clinical algorithms, and timeliness metrics within the same scope of the colorectal cancer care journey, has provided KP regions with the basic tools and resources to significantly improve the quality, timeliness, reliability, and member care experience across the cancer continuum.
Scar Detection by Pulse-Cancellation Echocardiography
Authors: Nicola Gaibazzi, Michele Bianconcini, Nicola Marziliano, Iris Parrini, Maria Rosa Conte, Carmine Siniscalchi, Giacomo Faden, Pompilio Faggiano, Filippo Pigazzani, Francesca Grassi, Lisa Albertini
Journal: JACC. Cardiovascular imaging (2016)
Biochemical Study on the Mucosubstance in Diabetic Vascular Lesion
Authors: Mahito Kawamura, Masahiro Kawanishi, Makoto Nagano
Journal: Circulation (1969)

For the elucidation of the pathogenesis of the diabetic vascular complication, direct chemical analysis of mucosubstance, which characterize the specific lesion of this complication, were attempted in this study. Renal glomeruli, which were isolated from the kidney obtained at autopsy by the Krakower's method, were digested with Pronase-p. Released polysaccharides and glycopeptides were isolated and fractionated with Sephadex column. From normal glomeruli, two fractions of glycopeptides were obtained. Increased amount of both fractions of glycopeptides was noted in diabetic glomerulosclerosis, but no qualitative changes were observed in diabetics and nondiabetics. Total acid mucopolysaccharide content in glomeruli were also increased in diabetic glomerulosclerosis and remarkable changes were observed in the distribution of their fraction. From these data nature of mucosubstances in diabetic glomerulosclerosis was discussed.
Long-term toluene abuse
Authors: J D Lewis, D Moritz, L P Mellis
Journal: American Journal of Psychiatry (1981)

The authors briefly review the literature on the use of toluene as an intoxicating agent. They describe two cases in which the habit of sniffing toluene vapors extended over many years, discuss the rarity of this condition, and speculate about the conditions that might account for both the rarity and the occurrence of long-term toluene abuse.
Azole-resistant Aspergillus fumigatus due to TR46/Y121F/T289A mutation emerging in Belgium, July 2012
Authors: E Vermeulen, J Maertens, H Schoemans, K Lagrou
Journal: Eurosurveillance (2012)

A new azole resistance mechanism in Aspergillus fumigatus consisting of a TR46/Y121F/T289A alteration in the cyp51A gene was recently described in the Netherlands. Strains containing these mutations are associated with invasive infection and therapy failure. This communication describes the first case of fatal invasive aspergillosis caused by TR46/Y121F/T289A outside the Netherlands, in the neighboring country of Belgium, suggesting geographical spread. TR46/Y121F/T289A leads to a recognisable phenotypic susceptibility pattern which should trigger cyp51A genotyping to monitor further spread.
Osteogenic growth peptide increases blood and bone marrow cellularity and enhances engraftment of bone marrow transplants in mice
Authors: O Gurevitch, S Slavin, A Muhlrad, A Shteyer, D Gazit, M Chorev, M Vidson, M Namdar-Attar, E Berger, I Bleiberg, I Bab
Journal: Blood (1996)
Abstract B08: Genomics analyses of less common epithelial ovarian cancer subtypes.
Authors: Kylie L. Gorringe, Matthew Wakefield, Sally M. Hunter, Georgina L. Ryland, Dane Cheasley, Michael S. Anglesio, Michael Christie, Raghwa Sharma, Antill Yoland, Simone M. Rowley, Jason Li, Blake Gilks, Prue E. Allan, Andrew N. Stephens, Sumi Ananda, Jan Pyman, Martin Koebel, Jessica McAlpine, Charlie Gourley, David G. Huntsman, Anna deFazio, David DL Bowtell, Ian G. Campbell, Clare Scott
Journal: Clinical Cancer Research (2016)

Abstract While the genomics of high-grade serous carcinoma are well-studied in large international consortia, the less common subtypes have been neglected. We have sought to rectify this gap by analyzing international collections of low-grade serous and mucinous ovarian carcinomas and their putative benign and borderline precursors. Exome sequencing and copy number analysis of low-grade serous carcinomas (n=9) and serous borderline tumours (n=13) and targeted sequencing and copy number analysis in additional carcinomas (n=10) and borderline tumours (n=44) identified recurrent mutations in novel drivers such as EIF1AX and USP9X, as well as the known drivers KRAS, BRAF and NRAS. Copy number changes including 9p and 1p losses were significantly associated with progression from borderline to carcinoma. Exome and targeted sequencing analysis of mucinous carcinomas (GAMuT study) found a surprisingly high proportion (~50%) with TP53 mutations, and mutations in new drivers like RNF43 and ELF3. Despite similarities in early RAS/RAF pathway oncogenic drivers and CDKN2A disruption, the genetics of these two subtypes are otherwise distinct, suggesting differing etiologies and selective pressures. We also present here the first whole-genome sequencing analysis of a high-grade mucinous ovarian carcinoma collected from multiple sites at autopsy (CASCADE study). The patient, aged just 41 when diagnosed with Stage I mucinous ovarian carcinoma, had a 26-month progression-free interval, including normal CA125 and CA19-9 measurements at 21 months. The primary tumor was mostly borderline in appearance, with only a small focus of carcinoma. At autopsy, the carcinoma was widespread in the body, and whole-genome sequencing data was obtained from deposits in the omentum, iliac lymph node, para-aortic lymph node and upper diaphragm. These data were compared to the primary ovarian tumor and nine other sites sampled at autopsy. Citation Format: Kylie L. Gorringe, Matthew Wakefield, Sally M. Hunter, Georgina L. Ryland, Dane Cheasley, Michael S. Anglesio, Michael Christie, Raghwa Sharma, Antill Yoland, Simone M. Rowley, Jason Li, Blake Gilks, Prue E. Allan, Andrew N. Stephens, Sumi Ananda, Jan Pyman, Martin Koebel, Jessica McAlpine, Charlie Gourley, David G. Huntsman, Anna deFazio, David DL Bowtell, Ian G. Campbell, Clare Scott. Genomics analyses of less common epithelial ovarian cancer subtypes. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B08.
Abstract B2-24: OVOL: A brake on EMT, driver of MET and expander of the hybrid E/M phenotype
Authors: Dongya Jia, Mohit Kumar Jolly, Marcelo Boareto, Princy Parsana, Steven Mooney, Kenneth J. Pienta, Herbert Levine, Eshel Ben-Jacob
Journal: Cancer Research (2015)

Abstract Aberrant activation of Epithelial to Mesenchymal Transition (EMT) and its reverse MET is a hallmark of cancer metastasis. Also, the carcinoma cells can undergo partial transitions to attain a hybrid epithelial/mesenchymal (E/M) phenotype, which can allow them to migrate collectively and form clusters of Circulating Tumor Cells (CTCs). These clusters can be up to 50 times more metastatic compared to cells that undergo complete EMT or individually migrating CTCs. Here, using experimental data and bioinformatics, we devised a dedicated model to study the role of transcription factor OVOL in regulating these bidirectional epithelial-hybrid-mesenchymal transitions. The new model incorporates the coupling between OVOL and miR-200/ZEB - the three-way EMT/MET decision-making switch that allows for three phenotypes (E, M and E/M). We found that OVOL operates as a brake holder of complete EMT and as an expander of the hybrid E/M phenotype (it extends the range of physiological parameters for which the cells can attain the hybrid E/M phenotype). Inhibition of OVOL, for example by Wg signaling, removes that brake and supports a complete EMT. Conversely, overexpression of OVOL, for example by BMP7/Smad4, leads to the reverse of EMT, i.e. MET. In addition, OVOL elevates the phenotypic plasticity of cells by turning both EMT and MET into a two-step process (E to E/M to M, and M to E/M to E). We show that depending on the context-specific coupling manner of OVOL with miR-200/ZEB, OVOL can shepherd cellular plasticity in multiple ways - by driving MET, by restricting EMT, and by expanding the existence of the hybrid E/M phenotype. In particular, we explain how the differences between the observed effects of OVOL in breast and prostate cancer are associated with the results of different miR-200/ZEB/OVOL couplings. Our computational framework can be tailored to include other signals such as p53, TGF-beta, inflammation and hypoxia that affect the cellular plasticity during metastasis, thus providing a platform to design novel anti-metastasis therapies. Citation Format: Dongya Jia, Mohit Kumar Jolly, Marcelo Boareto, Princy Parsana, Steven Mooney, Kenneth J. Pienta, Herbert Levine, Eshel Ben-Jacob. OVOL: A brake on EMT, driver of MET and expander of the hybrid E/M phenotype. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B2-24.
Economic evaluation and randomised controlled trial of extracorporeal membrane oxygenation: UK collaborative trial Commentary: Concurrent economic evaluations are rare but should be standard practice
Authors: T. E Roberts, T. Jefferson
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To compare the resource implications and short term outcomes of extracorporeal membrane oxygenation and conventional management for term babies with severe respiratory failure. <b>Design:</b> Cost effectiveness evaluation alongside a randomised controlled trial. <b>Setting:</b> 55 approved recruiting hospitals in the United Kingdom. These hospitals provided conventional management, but infants randomised to extracorporeal membrane oxygenation were transferred to one of five specialist centres. <b>Subjects:</b> 185 mature newborn infants (gestational age at birth &gt;35 weeks, birth weight &gt;2 kg) with severe respiratory failure (oxygenation index &gt;40) recruited between 1993 and 1995. The commonest diagnoses were persistent pulmonary hypertension due to meconium aspiration, congenital diaphragmatic hernia, isolated persistent fetal circulation, sepsis, and idiopathic respiratory distress syndrome. <b>Main outcome measure:</b> Cost effectiveness based on survival at 1 year of age without severe disability. <b>Results:</b> 63 (68%) of the 93 infants randomised to extracorporeal membrane oxygenation survived to 1 year compared with 38 (41%) of the 92 infants who received conventional management. Of those that survived, one infant in each arm was lost to follow up and the proportion with disability at 1 year was similar in the two arms of the trial. One child in each arm had severe disability. The estimated additional cost of extracorporeal membrane oxygenation per additional surviving infant without severe disability was £51 222 and the cost per surviving infant with no disability was £75 327. <b>Conclusions:</b> Extracorporeal membrane oxygenation for term neonates with severe respiratory failure would increase overall survival without disability. Although the policy will increase costs of neonatal health care, it is likely to be as cost effective as other life extending technologies.
Abstract B02: Oxidized hemoglobin promotes survival of ROS-stressed and DNA damaged fallopian tube epithelial cells with p53 loss, resulting in a copy number variation phenotype of HGSC.
Authors: Hsuan-Shun Huang, Che-Fang Hsu, Tang-Yuan Chu
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Ovulation is a strong risk factor for high grade serous carcinoma (HGSC) of ovary known to largely originate from the fallopian tube fimbriae. Previously, we have showed ROS in the mature follicular fluid (FF) is mutagenic and cytotoxic to fimbria epithelial cells, and induces DNA double strand breaks (DSB) in the context of p53 loss. We hypothesized that hemoglobin (Hb) in FF accumulated in cul-de-sac (CDS) after ovulatory bleeding may protect the bathed fimbria from cell death and enhance cancer initiation. Results: Peritoneal fluids collected from the CDS after ovulation contained high level of oxidized Hb and ROS, so did ovarian FFs retrieved from IVF patients. When treating E6/E7-immortalized fimbria secretory cells (FE25) with FFs with various ROS levels ranging from 100-1200 μM of H2O2 equivalence, a positive correlation of Hb levels (ranging from 100-1100 μg/ml) in FF and cell viability was observed. This was further confirmed in treating FE25 cells with H2O2 where Hb dose-dependently rescued cell death. As a consequence, FE25 cells treated with either Hb-high FF or with H2O2 plus Hb accumulated high level of DSB and showed an extensive DNA copy number variation compatible with the copy number variation (CNV) phenotype of HGSC. The resulted DNA aneuploidy rates were 50±5% and 65±7% in FE25 treated with 500 μM H2O2 supplemented with 100 μg/ml Hb or 3% Hb-hgih FF, respectively; as compared to 15±2% at baseline and 31±8% with H2O2 only. In the case of primary fimbria epithelial cells the figures were 2±0.3% and 1.3±0.2%, respectively. Finally, the p53 deficiency dependent rescuing effect of Hb on ROS-stressed tubal epithelial cells, and the consequent CNV phenotype were confirmed ex vivo with oviducts of wild type and Trp53-null mice. Conclusion: While ROS in FF induces DNA damage and cytotoxicity of p53-deficient fimbria epithelial cells, oxidized Hb in peritoneal fluid rescues cells from death and results in a CNV phenotype, a major characteristic of HGSC. Citation Format: Hsuan-Shun Huang, Che-Fang Hsu, Tang-Yuan Chu. Oxidized hemoglobin promotes survival of ROS-stressed and DNA damaged fallopian tube epithelial cells with p53 loss, resulting in a copy number variation phenotype of HGSC. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B02.
Psychiatric education in Eastern Europe
Authors: D R Hawkins
Journal: American Journal of Psychiatry (1981)

Psychiatry and psychiatric education in the Eastern European countries are determined by the cultural practices and tradition of the region and the organizational principles of the U.S.S.R. Medical schools have been separated from the universities and are under the jurisdiction of the Ministry of Health. Soviet psychiatry is less developed in medical education as compared to the West. A unique feature of Soviet medical education is the development of student scientific societies where opportunities exist for more in-depth work in a specialty. Except for a few select students, postgraduate psychiatric training is shorter and less rigorous than in the West. Refresher education at a facility far advanced training is required at 5-year intervals.
Obesity and Cardiovascular Disease
Authors: Francisco B. Ortega, Carl J. Lavie, Steven N. Blair
Journal: Circulation Research (2016)

The prevalence of obesity has increased worldwide over the past few decades. In 2013, the prevalence of obesity exceeded the 50% of the adult population in some countries from Oceania, North Africa, and Middle East. Lower but still alarmingly high prevalence was observed in North America (≈30%) and in Western Europe (≈20%). These figures are of serious concern because of the strong link between obesity and disease. In the present review, we summarize the current evidence on the relationship of obesity with cardiovascular disease (CVD), discussing how both the degree and the duration of obesity affect CVD. Although in the general population, obesity and, especially, severe obesity are consistently and strongly related with higher risk of CVD incidence and mortality, the one-size-fits-all approach should not be used with obesity. There are relevant factors largely affecting the CVD prognosis of obese individuals. In this context, we thoroughly discuss important concepts such as the fat-but-fit paradigm, the metabolically healthy but obese (MHO) phenotype and the obesity paradox in patients with CVD. About the MHO phenotype and its CVD prognosis, available data have provided mixed findings, what could be partially because of the adjustment or not for key confounders such as cardiorespiratory fitness, and to the lack of consensus on the MHO definition. In the present review, we propose a scientifically based harmonized definition of MHO, which will hopefully contribute to more comparable data in the future and a better understanding on the MHO subgroup and its CVD prognosis.
Abstract A24: Brain tumor induction after somatic inactivation of rb1 in zebrafish
Authors: Staci L. Solin, Heather R. Shive, Jeffrey J. Essner, Maura McGrail
Journal: Cancer Research (2015)

Abstract Purpose: We found that targeted somatic inactivation of rb1 leads to solid tumor formation in the central nervous system of adult zebrafish. The purpose of our study was to characterize the histological and genetic features of the tumors. Methods: Zebrafish rb1 tumor suppressor was inactivated in somatic tissue by injection of transcription activator-like effector nucleases (TALENs) targeting exon 2 and exon 3 at the one-cell stage. Histopathology and immunohistochemistry with s100 and pH3 was performed on tumor tissue. To confirm TALEN-mediated editing of the targeted rb1 loci and characterize the frequency and type of indel alleles in tumor and somatic tissues we sequenced cloned amplicons from each locus. Results: Zebrafish injected with TALENs targeting exon 2 or exon 3 of rb1 presented with cranial tumors beginning at six months of age. By one year the frequency of adults with tumors was 33-50% and 11%, respectively. Histopathological analyses of tumors from eight exon 2-targeted and six exon 3-targeted fish revealed a range of undifferentiated and differentiated tumor phenotypes. Seven tumors exhibited features suggestive of primitive neuroectodermal tumors (PNET). The remainder exhibited more differentiated tumor phenotypes resembling glioma. S100 was detected in a subset of the tumors. pH3 labeled regions of high mitotic activity in each of the tumors. In 4 out of 4 tumors the frequency of rb1 mutant alleles (61%-87% of cloned amplicons) was consistently higher than wild type. However, only one or two specific rb1 alleles were present in 3 out of 4 tumors. In contrast, the mutation frequency in retinal, muscle, and germline tissues was highly variable (3%-100%), and represented by up to seven different mutant rb1 alleles. Conclusion: Somatic inactivation of rb1 resulted in brain tumors showing varying degrees of differentiation suggesting the possibility that transformed neural progenitors give rise to tumors. rb1 allele frequency is consistent with clonal expansion contributing to tumor growth. Predisposing zebrafish to brain tumors by somatic inactivation of rb1 with site-specific nucleases suggests a simple method for investigating pathways cooperating in tumor progression. Citation Format: Staci L. Solin, Heather R. Shive, Jeffrey J. Essner, Maura McGrail. Brain tumor induction after somatic inactivation of rb1 in zebrafish. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr A24.
Homozygous hemoglobin Knossos (alpha 2 beta 227(B9) Ala----Ser): a new variety of beta+-thalassemia intermedia associated with delta degree- thalassemia
Authors: F Baklouti, E Dorleac, L Morle, P Laselve, D Peyramond, M Aubry, J Godet, J Delaunay
Journal: Blood (1986)
Human OX40 ligand fusion protein (MEDI6383) as a potent OX40 agonist and immuno-modulator in vitro and in vivo.
Authors: Scott A Hammond, Chad Morris, Catherine Auge, Qun Du, Kathy Mulgrew, Kelly McGlinchey, Steven Eck, Nicholas Buss, James Hair, Christina Stracener, Lolke De Haan, Melissa Damschroder, Andrew Weinberg, Michael D Oberst
Journal: Journal of Clinical Oncology (2015)

3056 Background: OX40 is a tumor necrosis factor receptor found primarily on activated T effector (Teff) cells and regulatory T (Treg) cells including lymphocytes infiltrating mouse and human tumors. Costimulation of OX40 by agonist molecules is hypothesized to improve antitumor immunity by enhancing Teff cell activity and inhibiting Treg cell suppression. MEDI6383 is a novel, agonist, human OX40 ligand fusion protein currently undergoing early phase clinical testing for the treatment of advanced solid malignancies. Methods: Preclinical pharmacological properties of MEDI6383 were assessed using in vitro and in vivo models. Results: MEDI6383 bound specifically and with high affinity to human and monkey OX40 expressed on the cell surface of T cells, and did not bind to OX40 expressed on the cell surface of either rat or mouse T cells. The OX40 signaling pathway was activated by MEDI6383, as measured by NFκB signaling in human OX40-expressing Jurkat T reporter cells. Co-culture of reporter cells with cells that express Fcγ receptors enhanced OX40 signaling, demonstrating that clustering of MEDI6383 by Fcg receptors increased the OX40 intracellular signaling strength and magnitude of response. MEDI6383 enhanced T cell receptor mediated (co-stimulatory) activation of primary human CD4+ T cells as demonstrated by the induction of cell proliferation and cytokine release, and reduced Treg cell suppression in T cell co-cultures. MEDI6383 showed no such activity in the absence of concomitant CD3/T cell receptor complex signaling. MEDI6383 demonstrated potent in vivo antitumor activity that was dependent on the addition of alloreactive human T cells in a xenograft mouse model of human cancer. Intravenous administration of MEDI6383 to rhesus monkeys in the absence of a define antigen challenge resulted in the proliferation of both CD4+ and CD8+ total memory T-cell populations as measured by induction of the cell-proliferation marker Ki67, and by an increase in absolute numbers of these T cell populations. Conclusions: These results demonstrate that MEDI6383 is a potent, soluble agonist of the OX40 pathway that may be utilized to boost anti-tumor immunity in patients with cancer.