tbuckley/cabot-search huggingface dataset:
Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas
Authors: Marcus Renner, Thomas Wolf, Hannah Meyer, Wolfgang Hartmann, Roland Penzel, Alexis Ulrich, Burkhard Lehner, Volker Hovestadt, Esteban Czwan, Gerlinde Egerer, Thomas Schmitt, Ingo Alldinger, Eva Kristin Renker, Volker Ehemann, Roland Eils, Eva Wardelmann, Reinhard Büttner, Peter Lichter, Benedikt Brors, Peter Schirmacher, Gunhild Mechtersheimer
Journal: Genome biology (2013)

Abstract Background High-grade soft tissue sarcomas are a heterogeneous, complex group of aggressive malignant tumors showing mesenchymal differentiation. Recently, soft tissue sarcomas have increasingly been classified on the basis of underlying genetic alterations; however, the role of aberrant DNA methylation in these tumors is not well understood and, consequently, the usefulness of methylation-based classification is unclear. Results We used the Infinium HumanMethylation27 platform to profile DNA methylation in 80 primary, untreated high-grade soft tissue sarcomas, representing eight relevant subtypes, two non-neoplastic fat samples and 14 representative sarcoma cell lines. The primary samples were partitioned into seven stable clusters. A classification algorithm identified 216 CpG sites, mapping to 246 genes, showing different degrees of DNA methylation between these seven groups. The differences between the clusters were best represented by a set of eight CpG sites located in the genes SPEG , NNAT , FBLN2 , PYROXD2 , ZNF217 , COL14A1 , DMRT2 and CDKN2A . By integrating DNA methylation and mRNA expression data, we identified 27 genes showing negative and three genes showing positive correlation. Compared with non-neoplastic fat, NNAT showed DNA hypomethylation and inverse gene expression in myxoid liposarcomas, and DNA hypermethylation and inverse gene expression in dedifferentiated and pleomorphic liposarcomas. Recovery of NNAT in a hypermethylated myxoid liposarcoma cell line decreased cell migration and viability. Conclusions Our analysis represents the first comprehensive integration of DNA methylation and transcriptional data in primary high-grade soft tissue sarcomas. We propose novel biomarkers and genes relevant for pathogenesis, including NNAT as a potential tumor suppressor in myxoid liposarcomas.
FIELD TRIAL OF ORAL CHOLERA VACCINES IN BANGLADESH
Authors: JohnD Clemens, JeffreyR Harris, M.R Khan, BradfordA Kay, Md Yunus, Ann-Mari Svennerholm, DavidA Sack, J Chakraborty, BonitaF Stanton, M.U Khan, William Atkinson, Jan Holmgren
Journal: The Lancet (1986)
Cardiovascular malformations with lithium use during pregnancy
Authors: Morton R. Weinstein, Michael D. Goldfield
Journal: American Journal of Psychiatry (1975)

The 143 cases of lithium use during pregnancy collected by the Register of Lithium Babies show that infants exposed to lithium appear to have a higher than expected ratio of cardiovascular anomalies to all anomalies and may have an increased risk of congenital heart disease. The authors believe that these findings justify a conservative policy on the use of lithium with fertile and pregnant women.
Myths, Presumptions, and Facts about Obesity
Authors: Krista Casazza, Kevin R. Fontaine, Arne Astrup, Leann L. Birch, Andrew W. Brown, Michelle M. Bohan Brown, Nefertiti Durant, Gareth Dutton, E. Michael Foster, Steven B. Heymsfield, Kerry McIver, Tapan Mehta, Nir Menachemi, P.K. Newby, Russell Pate, Barbara J. Rolls, Bisakha Sen, Daniel L. Smith, Diana M. Thomas, David B. Allison
Journal: New England Journal of Medicine (2013)

Many beliefs about obesity persist in the absence of supporting scientific evidence (presumptions); some persist despite contradicting evidence (myths). The promulgation of unsupported beliefs may yield poorly informed policy decisions, inaccurate clinical and public health recommendations, and an unproductive allocation of research resources and may divert attention away from useful, evidence-based information.Using Internet searches of popular media and scientific literature, we identified, reviewed, and classified obesity-related myths and presumptions. We also examined facts that are well supported by evidence, with an emphasis on those that have practical implications for public health, policy, or clinical recommendations.We identified seven obesity-related myths concerning the effects of small sustained increases in energy intake or expenditure, establishment of realistic goals for weight loss, rapid weight loss, weight-loss readiness, physical-education classes, breast-feeding, and energy expended during sexual activity. We also identified six presumptions about the purported effects of regularly eating breakfast, early childhood experiences, eating fruits and vegetables, weight cycling, snacking, and the built (i.e., human-made) environment. Finally, we identified nine evidence-supported facts that are relevant for the formulation of sound public health, policy, or clinical recommendations.False and scientifically unsupported beliefs about obesity are pervasive in both scientific literature and the popular press. (Funded by the National Institutes of Health.).
Systemic Therapy in Men With Metastatic Castration-Resistant Prostate Cancer: American Society of Clinical Oncology and Cancer Care Ontario Clinical Practice Guideline
Authors: Ethan Basch, D. Andrew Loblaw, Thomas K. Oliver, Michael Carducci, Ronald C. Chen, James N. Frame, Kristina Garrels, Sebastien Hotte, Michael W. Kattan, Derek Raghavan, Fred Saad, Mary-Ellen Taplin, Cindy Walker-Dilks, James Williams, Eric Winquist, Charles L. Bennett, Ted Wootton, R. Bryan Rumble, Stacie B. Dusetzina, Katherine S. Virgo
Journal: Journal of Clinical Oncology (2014)

Purpose To provide treatment recommendations for men with metastatic castration-resistant prostate cancer (CRPC). Methods The American Society of Clinical Oncology and Cancer Care Ontario convened an expert panel to develop evidence-based recommendations informed by a systematic review of the literature. Results When added to androgen deprivation, therapies demonstrating improved survival, improved quality of life (QOL), and favorable benefit-harm balance include abiraterone acetate/prednisone, enzalutamide, and radium-223 ( 223 Ra; for men with predominantly bone metastases). Improved survival and QOL with moderate toxicity risk are associated with docetaxel/prednisone. For asymptomatic/minimally symptomatic men, improved survival with unclear QOL impact and low toxicity are associated with sipuleucel-T. For men who previously received docetaxel, improved survival, unclear QOL impact, and moderate to high toxicity risk are associated with cabazitaxel/prednisone. Modest QOL benefit (without survival benefit) and high toxicity risk are associated with mitoxantrone/prednisone after docetaxel. No benefit and excess toxicity are observed with bevacizumab, estramustine, and sunitinib. Recommendations Continue androgen deprivation (pharmaceutical or surgical) indefinitely. Abiraterone acetate/prednisone, enzalutamide, or 223 Ra should be offered; docetaxel/prednisone should also be offered, accompanied by discussion of toxicity risk. Sipuleucel-T may be offered to asymptomatic/minimally symptomatic men. For men who have experienced progression with docetaxel, cabazitaxel may be offered, accompanied by discussion of toxicity risk. Mitoxantrone may be offered, accompanied by discussion of limited clinical benefit and toxicity risk. Ketoconazole or antiandrogens (eg, bicalutamide, flutamide, nilutamide) may be offered, accompanied by discussion of limited known clinical benefit. Bevacizumab, estramustine, and sunitinib should not be offered. There is insufficient evidence to evaluate optimal sequences or combinations of therapies. Palliative care should be offered to all patients.
VH gene family utilization is regulated by a locus outside of the VH region.
Authors: G E Wu, C J Paige
Journal: The Journal of Experimental Medicine (1988)

We have used the RNA colony blot method to examine VH usage in colonies derived from primary splenic B cells. We found that there are strain-specific differences in the pattern of VH usage. Using parental F1, congenic, and recombinant inbred strains we demonstrate that the genetic element that causes the observed phenotype is: (a) stably expressed; (b) not due to maternal influence; (c) not due to dominate diffusible factors; (d) not linked to cloning efficiency; and (e) outside the Igh locus.
Novel heat shock protein Hsp70L1 activates dendritic cells and acts as a Th1 polarizing adjuvant
Authors: Tao Wan, Xiangyang Zhou, Guoyou Chen, Huazhang An, Taoyong Chen, Weiping Zhang, Shuxun Liu, Yingming Jiang, Feng Yang, Yanfeng Wu, Xuetao Cao
Journal: Blood (2003)
Infectious discitis caused by Enterobacter cloacae.
Authors: R Solans, P Simeon, R Cuenca, V Fonollosa, J Bago, M Vilardell
Journal: Annals of the Rheumatic Diseases (1992)

The case is reported of a patient who developed a vertebral osteomyelitis caused by Enterobacter cloacae. The organism was isolated in cultures of blood and vertebral puncture biopsy samples. The patient was satisfactorily treated with trimethroprim and sulphamethoxazole. Enterobacter cloacae, a Gram negative organism, has been confirmed as the cause of bacteremia in patients with burns, urinary infections, in adults with pneumonia, and in children with joint infections. Spondylodiscitis caused by Enterobacter cloacae has not previously been described.
Impact of correcting peak flow for nonlinear errors on air pollutant effect estimates from a panel study
Authors: DJ Ward, MR Miller, S Walters, RM Harrison, JG Ayres
Journal: European Respiratory Journal (2000)

Air pollutant effects are commonly investigated using panel studies employing daily measurement of changes in peak expiratory flow (PEF). Variable orifice PEF meters are inaccurate with a nonlinear relationship to actual PEF. The impact on a panel study of correcting these errors was examined. Twice-daily PEF readings were taken by 147 9-yr old children for 8 weeks and corrected using an equation derived from the response of 32 Vitalograph meters to a servomechanism-controlled pump. Pollutant effect estimates for corrected and uncorrected readings were derived using a regression approach incorporating appropriate confounders. Correction impacted little on mean PEF values (333.1-334.2 L x min(-1)), but did alter effect sizes. Nonsignificant nitrogen dioxide estimates for the entire panel decreased by up to 73%, but, for symptomatic/atopic children, a significant 5-day mean result was lost (decrease in effect size from -2.53 to -0.90% per 10 parts per billion (ppb)) and lag 0 became significant (decrease from -0.51 to -1.22% per 10 ppb). Mass concentration estimates of particles with a 50% cut-off aerodynamic diameter of 2.5 microm moved in both directions (-0.22 changed to 0.11% per 10 microg x m(-1) lag 3 and -0.29 to -0.73% per 10 microg x m(-3) for the 5-day mean). Correction of nonlinearity of peak expiratory flow meters influenced the overall outcome of this panel study, and the changes in effect estimates would be sufficient to alter the interpretation of some studies. For adults, a greater change in effect estimates may follow the larger correction required for their usual peak expiratory flow range.
Parenteral nutrition via an arteriovenous bypass graft
Authors: S M Turner
Journal: Gut (2003)

Delivery of nutritional support via prolonged venous access can often pose a significant problem. We report a case of polytetrafluroethylene (PTFE) grafting from the axillary artery to the inferior vena cava (IVC) to provide parental nutrition to a young patient with intestinal failure. HISTORY A 19 year old woman was first admitted with non-specific abdominal pain. She repeatedly presented with recurrent small bowel obstruction thought to be secondary to inflammatory adhesions. In 1997, a Hartmann’s procedure was performed for a perforated distal sigmoid colon.Histology was suggestive of Crohn’s disease (CD). Over the next two years she was treated for CD. Once symptom free and without evidence of active CD she underwent subtotal colectomy with ileorectal anastomosis. Subsequent admissions with non-specific abdominal pain and weight loss failed to respond to steroid maintenance. Barium follow through showed slow small bowel transit with a lack of small bowel tonicity resulting in dilatation and no features of CD. Initial investigations revealed no specific cause for her gut dysmotility and malabsorption. She was initially diagnosed with unexplained intestinal failure. Later a full thickness small bowel biopsy would determine the presence of vacuolated longitudinal and transverse muscle fibres,thus establishing the diagnosis of intestinal myopathy. In view of her significant malabsorption and an initial body mass index of 15 kg/m 2
Inferring steady state single-cell gene expression distributions from analysis of mesoscopic samples.
Authors: Jessica C Mar, Renee Rubio, John Quackenbush
Journal: Genome biology (2006)

A great deal of interest has been generated by systems biology approaches that attempt to develop quantitative, predictive models of cellular processes. However, the starting point for all cellular gene expression, the transcription of RNA, has not been described and measured in a population of living cells.Here we present a simple model for transcript levels based on Poisson statistics and provide supporting experimental evidence for genes known to be expressed at high, moderate, and low levels.Although the model describes a microscopic process occurring at the level of an individual cell, the supporting data we provide uses a small number of cells where the echoes of the underlying stochastic processes can be seen. Not only do these data confirm our model, but this general strategy opens up a potential new approach, Mesoscopic Biology, that can be used to assess the natural variability of processes occurring at the cellular level in biological systems.
Targeting Mitochondrial Metabolism by Inhibiting Autophagy in <i>BRAF</i>-Driven Cancers
Authors: Anne M. Strohecker, Eileen White
Journal: Cancer Discovery (2014)

Abstract Metabolomic analyses of human tumors and mouse models of cancer have identified key roles for autophagy in supporting mitochondrial metabolism and homeostasis. In this review, we highlight data suggesting that autophagy inhibition may be particularly effective in BRAF-driven malignancies. Catalytic BRAF inhibitors have profound efficacy in tumors carrying activating mutations in Braf but are limited by the rapid emergence of resistance due in part to increased mitochondrial biogenesis and heightened rates of oxidative phosphorylation. We suggest that combined inhibition of autophagy and BRAF may overcome this limitation. Significance: Braf V600E-driven tumors require autophagy and likely autophagy-provided substrates to maintain mitochondrial metabolism and to promote tumor growth, suggesting that autophagy ablation may improve cancer therapy. Cancer Discov; 4(7); 766–72. ©2014 AACR.
The Frequency of Muir-Torre Syndrome Among Lynch Syndrome Families
Authors: C. D. South, H. Hampel, I. Comeras, J. A. Westman, W. L. Frankel, A. de la Chapelle
Journal: JNCI Journal of the National Cancer Institute (2008)

Lynch syndrome is the predisposition to visceral malignancies that are associated with deleterious germline mutations in DNA mismatch repair genes, including MLH1, MSH2, MSH6, and PMS2. Muir-Torre syndrome is a variant of Lynch syndrome that includes a predisposition to certain skin tumors. We determined the frequency of Muir-Torre syndrome among 50 Lynch syndrome families that were ascertained from a population-based series of cancer patients who were newly diagnosed with colorectal or endometrial carcinoma. Histories of Muir-Torre syndrome-associated skin tumors were documented during counseling of family members. Muir-Torre syndrome was observed in 14 (28%) of 50 families and in 14 (9.2%) of 152 individuals with Lynch syndrome. Four (44%) of nine families with MLH1 mutations had a member with Muir-Torre syndrome compared with 10 (42%) of 24 families with MSH2 mutations (P = .302). Families who carried the c.942+3A>T MSH2 gene mutation had a higher frequency of Muir-Torre syndrome than families who carried other mutations in the MSH2 gene (75% vs 25%; P = .026). Muir-Torre syndrome was not found in families with mutations in the MSH6 or PMS2 genes. Our results suggest that Muir-Torre syndrome is simply a variant of Lynch syndrome. Screening for Muir-Torre syndrome-associated skin lesions among patients with Lynch syndrome is recommended.
Eve-3: A liver enriched suppressor of Ras/MAPK signaling
Authors: James A.J. King, Niall M. Corcoran, Giovanna M. D'Abaco, Andrew F. Straffon, Craig T. Smith, Carole L.C. Poon, Michael Buchert, Stacey I, Nathan E. Hall, Peter Lock, Christopher M. Hovens
Journal: Journal of Hepatology (2005)
Transduction of Soluble <b> <i>Flt-1</i> </b> Gene to Peritoneal Mesothelial Cells Can Effectively Suppress Peritoneal Metastasis of Gastric Cancer
Authors: Akihiro Sako, Joji Kitayama, Hiroyuki Koyama, Hikaru Ueno, Hiroaki Uchida, Hirofumi Hamada, Hirokazu Nagawa
Journal: Cancer Research (2004)

Abstract The prognosis of gastric cancer with peritoneal metastasis has not improved. Despite many promising studies, gene therapy has limited clinical application because of the lack of suitable vector systems to enable selective gene transduction to tumor cells. The aim of this study was to clarify whether gene therapy targeted to peritoneal mesothelial cells (PMCs) can inhibit peritoneal dissemination of gastric cancer. In vitro experiments showed that adenovirus expressing LacZ infected human omental tissue-derived PMCs more efficiently than human gastric cancer cell lines MKN1 and MKN45. When adenovirus expressing LacZ was injected into the peritoneal cavity of nude mice, the expression was detected in the peritoneum for at least 4 weeks. Furthermore, when adenovirus expressing soluble Flt-1 (Ad-sFLT-1) was i.p. administered in vivo, a high level of sFlt-1 protein could be detected in peritoneal lavage for 8 weeks. When MKN45 cells were i.p. inoculated 3 days after adenoviral vector injection, Ad-sFLT-1 markedly reduced the number of metastatic nodules larger than 1 mm in diameter on the peritoneal surface, and significantly prolonged the survival of nude mice without any significant side effects. Thus, peritoneal dissemination was significantly suppressed by a single i.p. injection of Ad-sFlt-1. Anti-angiogenic gene therapy targeted to PMCs could be a novel and practical strategy against peritoneal dissemination of gastric cancer, because it does not require tumor-specific gene transfer.
Neoadjuvant Paclitaxel, Ifosfamide, and Cisplatin Chemotherapy for Metastatic Penile Cancer: A Phase II Study
Authors: Lance C. Pagliaro, Dallas L. Williams, Danai Daliani, Michael B. Williams, William Osai, Michael Kincaid, Sijin Wen, Peter F. Thall, Curtis A. Pettaway
Journal: Journal of Clinical Oncology (2010)

Men with penile squamous cell carcinoma and regional lymph node involvement have a low probability of survival with lymphadenectomy alone. A multimodal approach to treatment is desirable for such patients. We performed a phase II study of neoadjuvant chemotherapy with the objective of determining the response rate, time to progression (TTP), and overall survival (OS) among patients with bulky adenopathy.Eligible patients had stage N2 or N3 (stage III or stage IV) penile cancer without distant metastases. Neoadjuvant treatment (four courses every 3-4 weeks) consisted of paclitaxel 175 mg/m(2) administered over 3 hours on day 1; ifosfamide 1,200 mg/m(2) on days 1 to 3; and cisplatin 25 mg/m(2) on days 1 to 3. Clinical and pathologic responses were assessed, and patient groups were compared for TTP and OS.Thirty men received chemotherapy of whom 15 (50.0%) had an objective response and 22 (73.3%) subsequently underwent surgery. Three patients had no remaining tumor on histopathology. Nine patients (30.0%) remained alive and free of recurrence (median follow-up, 34 months; range, 14-59 months), and two patients died of other causes without recurrence. Improved TTP and OS were significantly associated with a response to chemotherapy (P < .001 and P = .001, respectively), absence of bilateral residual tumor (P = .002 and P = .017, respectively), and absence of extranodal extension (P = .001 and P = .004, respectively) or skin involvement (P = .009 and P = .012, respectively).The neoadjuvant regimen of paclitaxel, ifosfamide, and cisplatin induced clinically meaningful responses in patients with bulky regional lymph node metastases from penile cancer.
Reporting of Conflicts of Interest in Meta-analyses of Trials of Pharmacological Treatments
Authors: Michelle Roseman
Journal: JAMA (2011)

<h3>Context</h3>Disclosure of conflicts of interest (COIs) from pharmaceutical industry study funding and author-industry financial relationships is sometimes recommended for randomized controlled trials (RCTs) published in biomedical journals. Authors of meta-analyses, however, are not required to report COIs disclosed in original reports of included RCTs.<h3>Objective</h3>To investigate whether meta-analyses of pharmacological treatments published in high-impact biomedical journals report COIs disclosed in included RCTs.<h3>Data Sources and Study Selection</h3>We selected the 3 most recent meta-analyses of patented pharmacological treatments published January 2009 through October 2009 in each general medicine journal with an impact factor of at least 10; in high-impact journals in each of the 5 specialty medicine areas with the greatest 2008 global therapeutic sales (oncology, cardiology, respiratory medicine, endocrinology, and gastroenterology); and in the Cochrane Database of Systematic Reviews.<h3>Data Extraction</h3>Two investigators independently extracted data on disclosed study funding, author-industry financial ties, and author employment from each meta-analysis, from RCTs included in each meta-analysis, and on whether meta-analyses reported disclosed COIs of included RCTs.<h3>Results</h3>Of 29 meta-analyses reviewed, which included 509 RCTs, only 2 meta-analyses (7%) reported RCT funding sources; and 0 reported RCT author-industry ties or employment by the pharmaceutical industry. Of 318 meta-analyzed RCTs that reported funding sources, 219 (69%) were industry funded; and 91 of 132 (69%) that reported author financial disclosures had 1 or more authors with pharmaceutical industry financial ties. In 7 of the 29 meta-analyses reviewed, 100% of included RCTs had at least 1 form of disclosed COI (pharmaceutical industry funding, author-industry financial ties, or employment), yet only 1 of these 7 meta-analyses reported RCT funding sources, and 0 reported RCT author-industry ties or employment.<h3>Conclusion</h3>Among a group of meta-analyses of pharmacological treatments published in high-impact biomedical journals, information concerning primary study funding and author COIs for the included RCTs were only rarely reported.