tbuckley/cabot-search huggingface dataset:
Exit of pediatric pre-B acute lymphoblastic leukaemia cells from the bone marrow to the peripheral blood is not associated with cell maturation or alterations in gene expression
Authors: Frida Hansson, Jacek Toporski, Robert Månsson, Bertil Johansson, Ulrika Norén-Nyström, Sten Eirik W Jacobsen, Thomas Wiebe, Marcus Larsson, Mikael Sigvardsson, Anders Castor
Journal: Molecular Cancer (2008)

Abstract Background Childhood pre-B acute lymphoblastic leukemia (ALL) is a bone marrow (BM) derived disease, which often disseminates out of the BM cavity, where malignant cells to a variable degree can be found circulating in the peripheral blood (PB). Normal pre-B cells are absolutely dependent on BM stroma for survival and differentiation. It is not known whether transformed pre-B ALL cells retain any of this dependence, which possibly could impact on drug sensitivity or MRD measurements. Results Pre-B ALL cells, highly purified by a novel method using surface expression of CD19 and immunoglobulin light chains, from BM and PB show a very high degree of similarity in gene expression patterns, with differential expression of vascular endothelial growth factor (VEGF) as a notable exception. In addition, the cell sorting procedure revealed that in 2 out of five investigated patients, a significant fraction of the malignant cells had matured beyond the pre-B cell stage. Conclusion The transition of ALL cells from the BM into the circulation does not demand, or result in, major changes of gene expression pattern. This might indicate an independence of BM stroma on the part of transformed pre-B cells, which contrasts with that of their normal counterparts.
Moral Aspects of Bariatric Surgery for Obese Children and Adolescents: The Urgent Need for Empirical–Ethical Research
Authors: S. M. van Geelen, L. L. E. Bolt, M. J. H. van Summeren
Journal: The American Journal of Bioethics (2010)

The article by Hofmann (2010) provides a timely and much-needed starting point for an analysis of major ethical aspects regarding bariatric surgery. Our aim in this commentary is to further highlig...
Reply to: “Pivotal preclinical trial of the spheroid reservoir bioartificial liver”
Authors: Jaime M. Glorioso, Shennen A. Mao, Brian Rodysill, Taufic Mounajjed, Walter K. Kremers, Faysal Elgilani, Raymond D. Hickey, Hakon Haugaa, Christopher F. Rose, Bruce Amiot, Scott L. Nyberg
Journal: Journal of Hepatology (2015)
Meiosis Gene Inventory of Four Ciliates Reveals the Prevalence of a Synaptonemal Complex-Independent Crossover Pathway
Authors: Jingyun Chi, Frédéric Mahé, Josef Loidl, John Logsdon, Micah Dunthorn
Journal: Molecular Biology and Evolution (2013)

To establish which meiosis genes are present in ciliates, and to look for clues as to which recombination pathways may be treaded by them, four genomes were inventoried for 11 meiosis-specific and 40 meiosis-related genes. We found that the set of meiosis genes shared by Tetrahymena thermophila, Paramecium tetraurelia, Ichthyophthirius multifiliis, and Oxytricha trifallax is consistent with the prevalence of a Mus81-dependent class II crossover pathway that is considered secondary in most model eukaryotes. There is little evidence for a canonical class I crossover pathway that requires the formation of a synaptonemal complex (SC). This gene inventory suggests that meiotic processes in ciliates largely depend on mitotic repair proteins for executing meiotic recombination. We propose that class I crossovers and SCs were reduced sometime during the evolution of ciliates. Consistent with this reduction, we provide microscopic evidence for the presence only of degenerate SCs in Stylonychia mytilus. In addition, lower nonsynonymous to synonymous mutation rates of some of the meiosis genes suggest that, in contrast to most other nuclear genes analyzed so far, meiosis genes in ciliates are largely evolving at a slower rate than those genes in fungi and animals.
Evolutionary Genetics of the Hydroid Allodeterminant alr2
Authors: Andrea Gloria-Soria, Maria A. Moreno, Philip O. Yund, Fadi G. Lakkis, Stephen L. Dellaporta, Leo W. Buss
Journal: Molecular Biology and Evolution (2012)

We surveyed genetic variation in alr2, an allodeterminant of the colonial hydroid Hydractinia symbiolongicarpus. We generated cDNA from a sample of 239 Hydractinia colonies collected at Lighthouse Point, Connecticut, and identified 473 alr2 alleles, 198 of which were unique. Rarefaction analysis suggested that the sample was near saturation. Most alleles were rare, with 86% occurring at frequencies of 1% or less. Alleles were highly variable, diverging on average by 18% of the amino acids in a predicted extracellular domain of the molecule. Analysis of 152 full-length alleles confirmed the existence of two structural types, defined by exons 4–8 of the gene. Several residues of the predicted immunoglobulin superfamily-like domains display signatures of positive selection. We also identified 77 unique alr2 pseudogene sequences from 85 colonies. Twenty-seven of these sequences matched expressed alr2 sequences from other colonies. This observation is consistent with pseudogenes contributing to alr2 diversification through sequence donation. A more limited collection of animals was made from a distant, relict population of H. symbiolongicarpus. Sixty percent of the unique sequences identified in this sample were found to match sequences from the Lighthouse Point population. The large number of alr2 alleles, their degree of divergence, the predominance of rare alleles in the population, their persistence over broad spatial and temporal scales, and the signatures of positive selection in multiple residues of the putative recognition domain paint a consistent picture of negative-frequency-dependent selection operating in this system. The genetic diversity observed at alr2 is comparable to that of the most highly polymorphic genetic systems known to date.
Surgeons' performance data: challenge and opportunity
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2015)

Last month, the Society for Cardiothoracic Surgery called for a rethink on the national policy of publishing performance data for cardiothoracic surgeons.1 Such calls are not new, indeed publication of these data has been resisted from the outset in 2004. Publishing performance data is now routine and other specialties allow it too, but dissenting voices remain. Transparency is fair enough, say the critics, but surgeons are now avoiding high risk procedures because of intense public scrutiny of individual surgeons' 30-day mortality rates.

Publication of any data is problematic. Many readers or users will not understand limitations of data or how best to interpret them. Performance data are especially tricky since they appear to offer a judgment on a clinician's competence, and risk creating anxiety in both doctor and patient. If high risk procedures are avoided, one of the stated objectives of publishing performance data, to discourage occasional practitioners, might well be achieved. But another consequence is that surgeons may be losing the courage to fail, as John Pepper and Aman Coonar explain in their editorial.2

This dilemma, they say, “represents a considerable challenge but also a great opportunity.” The challenge is clear, to present data in an understandable way to patients and surgeons that satisfies both parties but ultimately improves outcomes and protects patients. The opportunity might seem less obvious. Pepper and Coonar propose that the way ahead lies in greater patient partnership, multidisciplinary working, a focus on Atul Gawande's concept of “rescue from failure” instead of failure itself, and better definition of outcomes. Greater transparency with better quality data is required to foster an environment of candour and partnership.

David Misselbrook, who begins a two part series on virtue ethics, might ask whether the publication of performance data is Utilitarian or Deontological?3 Is there a third way characterised by virtue ethics? Medical ethics dates back at least to the time of Aristotle, although this month's paper from JRSM's archive only asks you to travel back fifty years. JP Shillingford describes the performance and operational challenges of one of the first coronary care units.4
Surgery Combined With Peritonectomy Procedures and Intraperitoneal Chemohyperthermia in Abdominal Cancers With Peritoneal Carcinomatosis: A Phase II Study
Authors: O. Glehen, F. Mithieux, D. Osinsky, A.C. Beaujard, G. Freyer, Ph. Guertsch, Y. Francois, P. Peyrat, G. Panteix, J. Vignal, F.N. Gilly
Journal: Journal of Clinical Oncology (2003)

Purpose: To evaluate the tolerance of peritonectomy procedures (PP) combined with intraperitoneal chemohyperthermia (IPCH) in patients with peritoneal carcinomatosis (PC), a phase II study was carried out from January 1998 to September 2001. Patients and Methods: Fifty-six patients (35 females, mean age 49.3) were included for PC from colorectal cancer (26 patients), ovarian cancer (seven patients), gastric cancer (six patients), peritoneal mesothelioma (five patients), pseudomyxoma peritonei (seven patients), and miscellaneous reasons (five patients). Surgeries were performed mainly on advanced patients (40 patients stages 3 and 4 and 16 patients stages 2 and 1) and were synchronous in 36 patients. All patients underwent surgical resection of their primary tumor with PP and IPCH (with mitomycin C, cisplatinum, or both) with a closed sterile circuit and inflow temperatures ranging from 46° to 48°C. Three patients were included twice. Results: A macroscopic complete resection was performed in 27 cases. The mortality and morbidity rates were one of 56 and 16 of 56, respectively. The 2-year survival rate was 79.0% for patients with macroscopic complete resection and 44.7% for patients without macroscopic complete resection (P = .001). For the patients included twice, two are alive without evidence of disease, 54 and 47 months after the first procedure. Conclusion: IPCH and PP are able to achieve unexpected long-term survival in patients with bulky PC. However, one must be careful when selecting the patients for such an aggressive treatment, as morbidity rate remains high even for an experienced team.
Stimulus-dependent Synergism of the Antiapoptotic Tumor Necrosis Factor Receptor–associated Factor 2 (TRAF2) and Nuclear Factor κB Pathways
Authors: Soo Young Lee, David R. Kaufman, Ana L. Mora, Angela Santana, Mark Boothby, Yongwon Choi
Journal: The Journal of Experimental Medicine (1998)

Tumor necrosis factor (TNF) signaling leads to pleiotropic responses in a wide range of cell types, in part by activating antiapoptotic and proapoptotic signaling pathways. Thus, although TNF can cause apoptosis and may prove useful in the treatment of malignancies, most cells are resistant to TNF-induced cell death unless de novo protein synthesis is inhibited. Previous studies suggested that TNF activation of the nuclear factor (NF)-κB transcription factor family antagonizes the proapoptotic signals initiated by TNF-α. TNF receptor–associated factor (TRAF)2 has also been shown to mediate crucial antiapoptotic signals during TNF stimulation, yet is not essential in activation of NF-κB under physiologic conditions, thus raising questions about the relationship between these antiapoptotic pathways. We report here that inhibition of TRAF2 and NF-κB function in primary cells, by coexpression of a constitutive repressor of multiple NF-κB/Rel proteins (IκBα.DN) and a dominant negative form of TRAF2 (TRAF2.DN), synergistically enhanced TNF-induced apoptosis. The effects were stimulus dependent, such that neither inhibitory molecule affected Fas- and daunorubicin-induced apoptosis to the same degree as TNF-induced death. These findings indicate that the NF-κB and TRAF2 pathways activate independent antiapoptotic mechanisms which act in concert to suppress the proapoptotic signals induced by TNF-α.
Folic Acid‐Modified Mesoporous Silica Nanoparticles for Cellular and Nuclear Targeted Drug Delivery
Authors: Fabiola Porta, Gerda E. M. Lamers, Jess Morrhayim, Antonia Chatzopoulou, Marcel Schaaf, Hans den Dulk, Claude Backendorf, Jeffrey I. Zink, Alexander Kros
Journal: Advanced Healthcare Materials (2012)

Folic acid-modified mesoporous silica nanoparticles are designed for cellular and nuclear targeted drug delivery. Camptothecin is efficiently delivered to human cancer cells resulting in apoptosis without premature leakage. The folic acid moiety is an integral part of a rotaxane structure, which locks the drug molecules in the pores, preventing premature release. Upon folate receptor-mediated cell uptake, esterases cleave the rotaxane valves and camptothecin is released, resulting in apoptosis. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Strontium-containing hydroxyapatite bioactive bone cement in revision hip arthroplasty
Authors: G.X. Ni, K.Y. Chiu, W.W. Lu, Y. Wang, Y.G. Zhang, L.B. Hao, Z.Y. Li, W.M. Lam, S.B. Lu, K.D.K. Luk
Journal: Biomaterials (2006)
Analgesic effect of indomethacin shown using the nociceptive flexion reflex in humans.
Authors: R Guieu, O Blin, J Pouget, G Serratrice
Journal: Annals of the Rheumatic Diseases (1992)

This study investigated whether indomethacin has an analgesic effect on the central nervous system. As analgesics which affect the central nervous system produce a correlated decrease in the subjective sensation of pain and in the nociceptive reflex in humans, the amplitude of the nociceptive flexion of the biceps femoris was studied. Eight patients (six men, two women) aged 35-70 years (mean 51) with rheumatic diseases were included in the study. Each patient was his or her own control and was given a single intramuscular injection of either 50 mg of indomethacin or a placebo. A placebo controlled, double blind experimental design was used. Patients were evaluated before and 30, 60, and 75 minutes after the injection. Seventy five minutes after injection, indomethacin gave a 54% decrease in the amplitude of the nociceptive reflex, whereas the placebo produced a decrease of only 12%. This suggests that indomethacin exerts a depressive effect on the amplitude of the nociceptive reflex and affects the central nervous system as part of its analgesic action.
Tumor-Induced Activation of Lymphatic Endothelial Cells via Vascular Endothelial Growth Factor Receptor-2 Is Critical for Prostate Cancer Lymphatic Metastasis
Authors: Yiping Zeng, Kenneth Opeskin, Jeremy Goad, Elizabeth D. Williams
Journal: Cancer Research (2006)

Abstract Prostate cancer disseminates initially and primarily to regional lymph nodes. However, the nature of interactions between tumor cells and lymphatic endothelial cells (LEC) is poorly understood. In the current study, we have isolated prostate LECs and developed a series of two-dimensional and three-dimensional in vitro coculture systems and in vivo orthotopic prostate cancer models to investigate the interactions of prostate cancer cells with prostate LECs. In vitro, highly lymph node metastatic prostate cancer cell lines (PC-3 and LNCaP) and their conditioned medium enhanced prostate LEC tube formation and migration, whereas poorly lymph node metastatic prostate cancer cells (DU145) or normal prostate epithelial cells (RWPE-1) or their conditioned medium had no effect. In vivo, the occurrence of lymphatic invasion and lymph node metastasis was observed in PC-3 and LNCaP xenografts but not in DU145 xenografts. Furthermore, vascular endothelial growth factor (VEGF) receptor (VEGFR)-2 is expressed by prostate LECs, and its ligands VEGF-A, VEGF-C, and VEGF-D are up-regulated in highly lymph node metastatic prostate cancer cells. Recombinant VEGF-A and VEGF-C, but not VEGF-C156S, potently promoted prostate LEC tube formation, migration, and proliferation in vitro, indicating that signaling via VEGFR-2 rather than VEGFR-3 is involved in these responses. Consistent with this, blockade of VEGFR-2 significantly reduced tumor-induced activation of LECs. These results show that the interaction of prostate tumor cells with LECs via VEGFR-2 modulates LEC behavior and is related to the ability of tumor cells to form lymph node metastases. (Cancer Res 2006; 66(19): 9566-75)
Atenolol versus Losartan in Children and Young Adults with Marfan's Syndrome
Authors: Ronald V. Lacro, Harry C. Dietz, Lynn A. Sleeper, Anji T. Yetman, Timothy J. Bradley, Steven D. Colan, Gail D. Pearson, E. Seda Selamet Tierney, Jami C. Levine, Andrew M. Atz, D. Woodrow Benson, Alan C. Braverman, Shan Chen, Julie De Backer, Bruce D. Gelb, Paul D. Grossfeld, Gloria L. Klein, Wyman W. Lai, Aimee Liou, Bart L. Loeys, Larry W. Markham, Aaron K. Olson, Stephen M. Paridon, Victoria L. Pemberton, Mary Ella Pierpont, Reed E. Pyeritz, Elizabeth Radojewski, Mary J. Roman, Angela M. Sharkey, Mario P. Stylianou, Stephanie Burns Wechsler, Luciana T. Young, Lynn Mahony
Journal: New England Journal of Medicine (2014)

Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers.
Factors That Predict Short-term Intensive Care Unit Mortality in Patients With Cirrhosis
Authors: Ranjeeta Bahirwani, Marwan Ghabril, Kimberly A. Forde, Hemant Chatrath, Karen M. Wolf, Lindsay Uribe, K. Rajender Reddy, Barry Fuchs, Naga Chalasani
Journal: Clinical Gastroenterology and Hepatology (2013)
Longitudinal Tracing of Spontaneous Regression and Anti-angiogenic Response of Individual Microadenomas during Colon Tumorigenesis
Authors: Jin Woo Choi, Pilhan Kim, Jun Ki Kim, Yi Rang Kim, Dai Fukumura, Seok Hyun Yun
Journal: Theranostics (2015)

Angiogenesis is essential for the progression of cancer, but its involvement in the initial phase of colon tumorigenesis is not well understood.Using intravital endomicroscopy, we visualized the natural history of early pre-tumorous lesions and adenomas in the colon of conditional Apc-knockout and Apc/Kras double mutant mouse models.Early lesions emerged about 4 weeks after the onset of somatic mutations, accompanying vascular dilation when the size of lesions reached about 200 µm, but most lesions regressed spontaneously and cleared within 10 weeks after their emergence.Anti-angiogenic treatments with vascular endothelial growth factor receptor (VEGFR) antagonists reduced the size of the early lesions and the number of polyps.We found surprisingly that anti-angiogenic treatments delayed the natural clearance of transient lesions by up to several weeks in both genetic models.The results represent the previously unexpected role of early angiogenesis on the spontaneous regression of early-stage colon tumors.
Genome Analysis of Elysia chlorotica Egg DNA Provides No Evidence for Horizontal Gene Transfer into the Germ Line of This Kleptoplastic Mollusc
Authors: Debashish Bhattacharya, Karen N. Pelletreau, Dana C. Price, Kara E. Sarver, Mary E. Rumpho
Journal: Molecular Biology and Evolution (2013)

The sea slug Elysia chlorotica offers a unique opportunity to study the evolution of a novel function (photosynthesis) in a complex multicellular host. Elysia chlorotica harvests plastids (absent of nuclei) from its heterokont algal prey, Vaucheria litorea. The "stolen" plastids are maintained for several months in cells of the digestive tract and are essential for animal development. The basis of long-term maintenance of photosynthesis in this sea slug was thought to be explained by extensive horizontal gene transfer (HGT) from the nucleus of the alga to the animal nucleus, followed by expression of algal genes in the gut to provide essential plastid-destined proteins. Early studies of target genes and proteins supported the HGT hypothesis, but more recent genome-wide data provide conflicting results. Here, we generated significant genome data from the E. chlorotica germ line (egg DNA) and from V. litorea to test the HGT hypothesis. Our comprehensive analyses fail to provide evidence for alga-derived HGT into the germ line of the sea slug. Polymerase chain reaction analyses of genomic DNA and cDNA from different individual E. chlorotica suggest, however, that algal nuclear genes (or gene fragments) are present in the adult slug. We suggest that these nucleic acids may derive from and/or reside in extrachromosomal DNAs that are made available to the animal through contact with the alga. These data resolve a long-standing issue and suggest that HGT is not the primary reason underlying long-term maintenance of photosynthesis in E. chlorotica. Therefore, sea slug photosynthesis is sustained in as yet unexplained ways that do not appear to endanger the animal germ line through the introduction of dozens of foreign genes.
Current Management of Calcific Aortic Stenosis
Authors: Brian R. Lindman, Robert O. Bonow, Catherine M. Otto
Journal: Circulation Research (2013)

Calcific aortic stenosis is a progressive disease with no effective medical therapy that ultimately requires aortic valve replacement (AVR) for severe valve obstruction. Echocardiography is the primary diagnostic approach to define valve anatomy, measure aortic stenosis severity, and evaluate the left ventricular response to chronic pressure overload. In asymptomatic patients, markers of disease progression include the degree of leaflet calcification, hemodynamic severity of stenosis, adverse left ventricular remodeling, reduced left ventricular longitudinal strain, myocardial fibrosis, and pulmonary hypertension. The onset of symptoms portends a predictably high mortality rate unless AVR is performed. In symptomatic patients, AVR improves symptoms, improves survival, and, in patients with left ventricular dysfunction, improves systolic function. Poor outcomes after AVR are associated with low-flow low-gradient aortic stenosis, severe ventricular fibrosis, oxygen-dependent lung disease, frailty, advanced renal dysfunction, and a high comorbidity score. However, in most patients with severe symptoms, AVR is lifesaving. Bioprosthetic valves are recommended for patients aged >65 years. Transcatheter AVR is now available for patients with severe comorbidities, is recommended in patients who are deemed inoperable, and is a reasonable alternative to surgical AVR in high-risk patients.
Conceptual Framework for Cutting the Pancreatic Cancer Fuel Supply
Authors: Anne Le, N.V. Rajeshkumar, Anirban Maitra, Chi V. Dang
Journal: Clinical Cancer Research (2012)

Pancreatic ductal adenocarcinoma (a.k.a. pancreatic cancer) remains one of the most feared and clinically challenging diseases to treat despite continual improvements in therapies. The genetic landscape of pancreatic cancer shows near ubiquitous activating mutations of KRAS, and recurrent inactivating mutations of CDKN2A, SMAD4, and TP53. To date, attempts to develop agents to target KRAS to specifically kill cancer cells have been disappointing. In this regard, an understanding of cellular metabolic derangements in pancreatic cancer could lead to novel therapeutic approaches. Like other cancers, pancreatic cancer cells rely on fuel sources for homeostasis and proliferation; as such, interrupting the use of two major nutrients, glucose and glutamine, may provide new therapeutic avenues. In addition, KRAS-mutant pancreatic cancers have been documented to depend on autophagy, and the inhibition of autophagy in the preclinical setting has shown promise. Herein, the conceptual framework for blocking the pancreatic fuel supply is reviewed.