tbuckley/cabot-search huggingface dataset:
MicroRNA-30e* promotes human glioma cell invasiveness in an orthotopic xenotransplantation model by disrupting the NF-κB/IκBα negative feedback loop
Authors: Lili Jiang, Chuyong Lin, Libing Song, Jueheng Wu, Baixue Chen, Zhe Ying, Lishan Fang, Xiao Yan, Mian He, Jun Li, Mengfeng Li
Journal: Journal of Clinical Investigation (2011)

Constitutive activation of NF-κB is a frequent event in human cancers, playing important roles in cancer development and progression. In nontransformed cells, NF-κB activation is tightly controlled by IκBs. IκBs bind NF-κB in the cytoplasm, preventing it from translocating to the nucleus to modulate gene expression. Stimuli that activate NF-κB signaling trigger IκB degradation, enabling nuclear translocation of NF-κB. Among the genes regulated by NF-κB are those encoding the IκBs, providing a negative feedback loop that limits NF-κB activity. How transformed cells override this NF-κB/IκB negative feedback loop remains unclear. Here, we report in human glioma cell lines that microRNA-30e* (miR-30e*) directly targets the IκBα 3ι-UTR and suppresses IκBα expression. Overexpression of miR-30e* in human glioma cell lines led to hyperactivation of NF-κB and enhanced expression of NF-κB-regulated genes, which promoted glioma cell invasiveness in in vitro assays and in an orthotopic xenotransplantation model. These effects of miR-30e* were shown to be clinically relevant, as miR-30e* was found to be upregulated in primary human glioma cells and correlated with malignant progression and poor survival. Hence, miR-30e* provides an epigenetic mechanism that disrupts the NF-κB/IκBα loop and may represent a new therapeutic target and prognostic marker.
Evolution of GluN2A/B cytoplasmic domains diversified vertebrate synaptic plasticity and behavior
Authors: Tomás J Ryan, Maksym V Kopanitsa, Tim Indersmitten, Jess Nithianantharajah, Nurudeen O Afinowi, Charles Pettit, Lianne E Stanford, Rolf Sprengel, Lisa M Saksida, Timothy J Bussey, Thomas J O'Dell, Seth G N Grant, Noboru H Komiyama
Journal: Nature Neuroscience (2012)
Imprinting of the COPD airway epithelium for dedifferentiation and mesenchymal transition
Authors: Sophie T. Gohy, Cloé Hupin, Chantal Fregimilicka, Bruno R. Detry, Caroline Bouzin, Héloïse Gaide Chevronay, Marylène Lecocq, Birgit Weynand, Maha Z. Ladjemi, Christophe E. Pierreux, Philippe Birembaut, Myriam Polette, Charles Pilette
Journal: European Respiratory Journal (2015)

In chronic obstructive pulmonary disease (COPD), epithelial changes and subepithelial fibrosis are salient features in conducting airways. Epithelial-to-mesenchymal transition (EMT) has been recently suggested in COPD, but the mechanisms and relationship to peribronchial fibrosis remain unclear. We hypothesised that de-differentiation of the COPD respiratory epithelium through EMT could participate in airway fibrosis and thereby, in airway obstruction. Surgical lung tissue and primary broncho-epithelial cultures (in air-liquid interface (ALI)) from 104 patients were assessed for EMT markers. Cell cultures were also assayed for mesenchymal features and for the role of transforming growth factor (TGF)-β1. The bronchial epithelium from COPD patients showed increased vimentin and decreased ZO-1 and E-cadherin expression. Increased vimentin expression correlated with basement membrane thickening and airflow limitation. ALI broncho-epithelial cells from COPD patients also displayed EMT phenotype in up to 2 weeks of culture, were more spindle shaped and released more fibronectin. Targeting TGF-β1 during ALI differentiation prevented vimentin induction and fibronectin release. In COPD, the airway epithelium displays features of de-differentiation towards mesenchymal cells, which correlate with peribronchial fibrosis and airflow limitation, and which are partly due to a TGF-β1-driven epithelial reprogramming.
Pancreatic pseudocyst causing portal vein thrombosis and pancreatico-pleural fistula.
Authors: P A McCormick, N Chronos, A K Burroughs, N McIntyre, J E McLaughlin
Journal: Gut (1990)

Portal vein thrombosis and pancreatico-pleural fistula are unusual complications of chronic pancreatitis. We describe a patient with chronic alcoholic pancreatitis in whom erosion of the splenic vein led to portal vein thrombosis and to the development of a pancreatico-pleural fistula. We suggest that fistula formation may occur over a considerable time period as the portal vein thrombosis was diagnosed three years before the amylase-rich pleural effusions.
641 PPARALPHA LIVER GENE EXPRESSION IS RELATED WITH NASH FEATURES IN HCV PATIENTS AND WITH TREATMENT RESPONSE
Authors: F. Sanchez-Munoz, M.S. Sixtos-Alonso, R.M. Munoz-Fuentes, S. Rodriguez-Aparicio, R. Avalos-Martinez, J. Hernandez-Calleros, J.F. Sanchez-Avila, A. Dominguez-Lopez, M. Uribe
Journal: Journal of Hepatology (2009)
Gene Expression Levels Are Correlated with Synonymous Codon Usage, Amino Acid Composition, and Gene Architecture in the Red Flour Beetle, Tribolium castaneum
Authors: Anna Williford, Jeffery P. Demuth
Journal: Molecular Biology and Evolution (2012)

Gene expression levels correlate with multiple aspects of gene sequence and gene structure in phylogenetically diverse taxa, suggesting an important role of gene expression levels in the evolution of protein-coding genes. Here we present results of a genome-wide study of the influence of gene expression on synonymous codon usage, amino acid composition, and gene structure in the red flour beetle, Tribolium castaneum. Consistent with the action of translational selection, we find that synonymous codon usage bias increases with gene expression. However, the correspondence between tRNA gene copy number and optimal codons is weak. At the amino acid level, translational selection is suggested by the positive correlation between tRNA gene numbers and amino acid usage, which is stronger for highly expressed genes. In addition, there is a clear trend for increased use of metabolically cheaper, less complex amino acids as gene expression increases. tRNA gene numbers also correlate negatively with amino acid size/complexity (S/C) score indicating the coupling between translational selection and selection to minimize the use of large/complex amino acids. Interestingly, the analysis of 10 additional genomes suggests that the correlation between tRNA gene numbers and amino acid S/C score is widespread and might be explained by selection against negative consequences of protein misfolding. At the level of gene structure, three major trends are detected: 1) complete coding region length increases across low and intermediate expression levels but decreases in highly expressed genes; 2) the average intron size shows the opposite trend, first decreasing with expression, followed by a slight increase in highly expressed genes; and 3) intron density remains nearly constant across all expression levels. These changes in gene architecture are only in partial agreement with selection favoring reduced cost of biosynthesis.
Gold induced enterocolitis complicated by cytomegalovirus infection: a previously unrecognised association.
Authors: V Wong, J Wyatt, F Lewis, P Howdle
Journal: Gut (1993)

Enterocolitis is a rare complication of treatment with gold salts.It was first described in 1935 by Goldhammer2 and since then only 21 cases have been described.>"7118The mechanism is unclear.An appreciable proportion of these cases was associated with high morbidity and mortality.4 781' Different treatment regimes including intensive supportive care with a combination of antibiotics, steroids, dimer- caprol, and disodium cromoglycate have pro- duced variable success.5 713 '5 No other concomi- tant infective agents have been implicated in the course of the disease to date.We report a case of gold induced enterocolitis complicated by cyto- megalovirus (CMV) infection that responded to treatment with intravenous gangcyclovir.-namely, oral 20 mg prednisolone daily in a reducing dose and ampicillin.There was a reduction in her stool frequency, an improvement in her abdominal pain, and a less productive cough.She was discharged after one week but four weeks later, she relapsed with symp- toms of watery diarrhoea and fresh blood, abdominal pain, and a further weight loss of 6 3 kg.Also, her productive cough had persisted.Her only medication was dihydrocodeine.On examination she was moribund and dehydrated.She was apyrexial and a maculopapular rash was present on her arms.Chest examination showed left basal crepitations and her abdomen was diffusely tender but bowel sounds were present.Moderate peripheral leg oedema was also noted.
Inbreeding Affects Gene Expression Differently in Two Self-Incompatible<i>Arabidopsis lyrata</i>Populations with Similar Levels of Inbreeding Depression
Authors: Mandy Menzel, Nina Sletvold, Jon Ågren, Bengt Hansson
Journal: Molecular Biology and Evolution (2015)

Knowledge of which genes and pathways are affected by inbreeding may help understanding the genetic basis of inbreeding depression, the potential for purging (selection against deleterious recessive alleles), and the transition from outcrossing to selfing. Arabidopsis lyrata is a predominantly self-incompatible perennial plant, closely related to the selfing model species A. thaliana. To examine how inbreeding affects gene expression, we compared the transcriptome of experimentally selfed and outcrossed A. lyrata originating from two Scandinavian populations that express similar inbreeding depression for fitness (∂ ≈ 0.80). The number of genes significantly differentially expressed between selfed and outcrossed individuals were 2.5 times higher in the Norwegian population (≈ 500 genes) than in the Swedish population (≈ 200 genes). In both populations, a majority of genes were upregulated on selfing (≈ 80%). Functional annotation analysis of the differentially expressed genes showed that selfed offspring were characterized by 1) upregulation of stress-related genes in both populations and 2) upregulation of photosynthesis-related genes in Sweden but downregulation in Norway. Moreover, we found that reproduction- and pollination-related genes were affected by inbreeding only in Norway. We conclude that inbreeding causes both general and population-specific effects. The observed common effects suggest that inbreeding generally upregulates rather than downregulates gene expression and affects genes associated with stress response and general metabolic activity. Population differences in the number of affected genes and in effects on the expression of photosynthesis-related genes show that the genetic basis of inbreeding depression can differ between populations with very similar levels of inbreeding depression.
How much do you need: a randomised experiment of whether readers can understand the key messages from summaries of Cochrane Reviews without reading the full review
Authors: Lisa K Maguire, Mike Clarke
Journal: Journal of the Royal Society of Medicine (2014)

Objective We explored whether readers can understand key messages without having to read the full review, and if there were differences in understanding between various types of summary. Design A randomised experiment of review summaries which compared understanding of a key outcome. Participants Members of university staff ( n = 36). Setting Universities on the island of Ireland. Method The Cochrane Review chosen examines the health impacts of the use of electric fans during heat waves. Participants were asked their expectation of the effect these would have on mortality. They were then randomly assigned a summary of the review (i.e. abstract, plain language summary, podcast or podcast transcription) and asked to spend a short time reading/listening to the summary. After this they were again asked about the effects of electric fans on mortality and to indicate if they would want to read the full Review. Main outcome measure Correct identification of a key review outcome. Results Just over half (53%) of the participants identified its key message on mortality after engaging with their summary. The figures were 33% for the abstract group, 50% for both the plain language and transcript groups and 78% for the podcast group. Conclusions The differences between the groups were not statistically significant but suggest that the audio summary might improve knowledge transfer compared to written summaries. These findings should be explored further using a larger sample size and with other reviews.
Transient down-modulation of CD20 by rituximab in patients with chronic lymphocytic leukemia
Authors: Iman Jilani, Susan O'Brien, Taghi Manshuri, Deborah A. Thomas, Vilmos A. Thomazy, Maha Imam, Sana Naeem, Srdan Verstovsek, Hagop Kantarjian, Francis Giles, Michael Keating, Maher Albitar
Journal: Blood (2003)
Depletion of Zebrafish Titin Reduces Cardiac Contractility by Disrupting the Assembly of Z-Discs and A-Bands
Authors: Michael Seeley, Wei Huang, Zhenyue Chen, William Oscar Wolff, Xueying Lin, Xiaolei Xu
Journal: Circulation Research (2006)

The genetic study of titin has been notoriously difficult because of its size and complicated alternative splicing routes. Here, we have used zebrafish as an animal model to investigate the functions of individual titin isoforms. We identified 2 titin orthologs in zebrafish, ttna and ttnb, and annotated the full-length genomic sequences for both genes. We found that ttna, but not ttnb, is required for sarcomere assembly in the heart as well as the subsequent establishment of cardiac contractility. In fact, ttna is the earliest sarcomeric mRNA that is expressed in the heart, which makes it an early molecular marker for cardiomyocyte differentiation. Surprisingly, ttna is required for later steps of sarcomere assembly, including the assembly of Z-discs and A-bands, but not for early steps such as the assembly of Z-bodies and nonstriated myosin filaments. Reduction of individual titin isoforms in vivo using morpholino-modified antisense oligonucleotides indicated that (1) both N2B exon-containing and N2A exon-containing isoforms of ttna are required for sarcomere assembly in the heart; (2) N2A exon-containing isoforms of both ttna and ttnb are required for sarcomere assembly in the somites; and (3) the N2B exon-containing isoforms of ttnb are expressed later than other titin isoforms and are probably involved in modulating their expression; however, these isoforms of ttnb are not required for sarcomere assembly. Collectively, our results reveal distinct functions of different titin isoforms and suggest that various phenotypes in "titinopathies" may be attributable to the disruption of different titin isoforms.
Immunity against Tumor Angiogenesis Induced by a Fusion Vaccine with Murine β-Defensin 2 and mFlk-1
Authors: Yong-sheng Wang, Guo-qing Wang, Yan-jun Wen, Lian Wang, Xian-cheng Chen, Ping Chen, Bin Kan, Jiong Li, Canhua Huang, You Lu, Qin Zhou, Ning Xu, Dan Li, Ling-yu Fan, Tao Yi, Hong-bo Wu, Yu-quan Wei
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Previous studies indicated that humoral or cellular immunity against murine vascular endothelial growth factor 2 (mFlk-1) was elicited to inhibit tumor growth. Here we describe a genetic fusion vaccine, pMBD2-mFlk-1, based on the targeting of a modified mFlk-1 to antigen-presenting cells by a murine β-defensin 2 (MBD2) protein to induce both humoral and cellular immunity against mFlk-1, with the targeting especially focused on immature dendritic cells. Experimental Design: The protective and therapeutic antitumor immunity of the fusion vaccine was investigated in mouse models. Antiangiogenesis effect was detected by immunohistochemical staining and alginate-encapsulate tumor cell assay. The mechanisms of the fusion vaccine were primarily explored by detection of autoantibodies and CTL activity and confirmed by the deletion of immune cell subsets. Results: The fusion vaccine elicited a strong protective and therapeutic antitumor immunity through antiangiogenesis in mouse models, and this worked through stimulation of an antigen-specific CD8+ T-cell response as well as a specific B-cell response against mFlk-1. The findings were confirmed by depletion of immune cell subsets and in knockout mice. Conclusion: Our study showed that a fusion vaccine based on self immune peptide (MBD2) and self antigen (mFlk-1) induced autoimmunity against endothelial cells, resulting in inhibition of tumor growth, and could be further exploited in clinical applications of cancer immunotherapy.
Dose-dense temozolomide regimen for the treatment of brain metastases from melanoma, breast cancer, or lung cancer not amenable to surgery or radiosurgery: a multicenter phase II study
Authors: S. Siena, L. Crinò, M. Danova, S. Del Prete, S. Cascinu, S. Salvagni, I. Schiavetto, M. Vitali, E. Bajetta
Journal: Annals of Oncology (2009)

BackgroundBrain metastases reduce survival because therapeutic options are limited. This phase II study evaluated the efficacy of single-agent therapy with alternating weekly, dose-dense temozolomide in pretreated patients with brain metastases prospectively stratified by primary tumor type.MethodsEligible patients had bidimensionally measurable brain metastases from histologically/cytologically confirmed melanoma, breast cancer (BC), or non-small-cell lung cancer (NSCLC). Prior chemotherapy, radiotherapy, and whole-brain radiotherapy (WBRT) were allowed. Patients received temozolomide 150 mg/m2/day (days 1–7 and 15–21 every 28- or 35-day cycle).ResultsIn the intent-to-treat population (N = 157; 53 melanoma, 51 BC, and 53 NSCLC), one patient had complete response, nine (6%) had partial responses, and 31 (20%) had stable disease in the brain. Median progression-free survival was 56, 58, and 66 days for melanoma, BC, and NSCLC, respectively. Median overall survival was 100 days for melanoma, 172 days for NSCLC, and not evaluable in the BC group. Thrombocytopenia was the most common adverse event causing dose modification or treatment discontinuation. Grade 4 toxic effects were rare.ConclusionsThis alternating weekly, dose-dense temozolomide regimen was well tolerated and clinically active in heavily pretreated patients with brain metastases, particularly in patients with melanoma. Combining temozolomide with WBRT or other agents may improve clinical outcomes.
Diabetes and Driving Mishaps
Authors: Daniel J. Cox, Jennifer Kim Penberthy, John Zrebiec, Katie Weinger, James E. Aikens, Brian Frier, Barbara Stetson, Mary DeGroot, Paula Trief, Hartmut Schaechinger, Norbert Hermanns, Linda Gonder-Frederick, William Clarke
Journal: Diabetes Care (2003)

OBJECTIVE—The intensive treatment of diabetes to achieve strict glycemic control is a common clinical goal, but it is associated with an increased incidence of hypoglycemia. Becoming hypoglycemic while driving is a hazardous condition and may lead to a greater incidence of driving mishaps. This study investigated whether diabetes is associated with increased risk of driving mishaps and correlates of such a relationship. RESEARCH DESIGN AND METHODS—During routine visits to diabetes specialty clinics in seven U.S. and four European cities, consecutive adults with type 1 diabetes, type 2 diabetes, and nondiabetic spouse control subjects (n = 341, 332, and 363, respectively) completed an anonymous questionnaire concerning diabetes and driving. RESULTS—Type 1 diabetic drivers reported significantly more crashes, moving violations, episodes of hypoglycemic stupor, required assistance, and mild hypoglycemia while driving as compared with type 2 diabetic drivers or spouse control subjects (P &amp;lt; 0.01–0.001). Type 2 diabetic drivers had driving mishap rates similar to nondiabetic spouses, and the use of insulin or oral agents for treatment had no effect on the occurrence of driving mishaps. Crashes among type 1 diabetic drivers were associated with more frequent episodes of hypoglycemic stupor while driving, less frequent blood glucose monitoring before driving, and the use of insulin injection therapy as compared with pump therapy. One-half of the type 1 diabetic drivers and three-quarters of the type 2 diabetic drivers had never discussed hypoglycemia and driving with their physicians. CONCLUSIONS—Type 1 diabetic drivers are at increased risk for driving mishaps, but type 2 diabetic drivers, even on insulin, appear not to be at a higher risk than nondiabetic individuals. Clinical and treatment factors appear to increase risk, e.g., more frequent hypoglycemia while driving, method of insulin delivery, and infrequent self-testing before driving. Physicians are encouraged to talk to their type 1 diabetic patients about hypoglycemia and driving.
Preoperative Thallium Scanning, Selective Coronary Revascularization, and Long-Term Survival After Major Vascular Surgery
Authors: Giora Landesberg, Morris Mosseri, Yehuda G. Wolf, Moshe Bocher, Alon Basevitch, Ehud Rudis, Uzi Izhar, Haim Anner, Charles Weissman, Yacov Berlatzky
Journal: Circulation (2003)

Ischemia on thallium scanning is a strong predictor of long-term mortality in CAD patients. Whether coronary revascularization (CR) in patients with significant ischemia on preoperative thallium scanning (PTS) improves long-term survival after major vascular surgery has not been determined.The perioperative data, including PTS and subsequent CR in patients with moderate to severe reversible ischemia on PTS, and long-term survival of 502 consecutive patients who underwent 578 major vascular procedures were analyzed retrospectively. Patients with PTS who ultimately did not undergo the planned vascular operation were also studied. Cox regression and propensity score analyses were used to analyze survival. A total of 407 patients (81.1%) had PTS: 221 (54.3%) had no or mild defects (group I); 50 (12.3%) had moderate-severe fixed defects (group II); 62 (15.2%) had moderate-severe reversible ischemia yet did not undergo CR (group III); and 74 (18.2%) had moderate-severe reversible ischemia and subsequent CR by CABG (36) or PTCA (38; group IV). Patients who sustained major complications as a result of the preoperative cardiac workup were included in group IV. By multivariate analysis, age, type of vascular surgery, presence of diabetes, previous myocardial infarction, and moderate-severe ischemia on PTS independently predicted mortality (P=0.001, 0.009, 0.039, 0.006, and 0.029, respectively), and preoperative CR predicted improved survival (OR 0.52, P=0.018). Group IV had better survival than group III even when subdivided according to normal and reduced left ventricular function (OR 0.40 and 0.41, P=0.035 and 0.021, respectively).Long-term survival after major vascular surgery is significantly improved if patients with moderate-severe ischemia on PTS undergo selective CR.
Psychosocial aspects of the Tsunami
Authors: M. Carballo
Journal: Journal of the Royal Society of Medicine (2005)

Humanitarian relief has traditionally concentrated on visibly pressing issues such as the need for clean water and sanitation, emergency feeding and shelter, primary care, management of injuries and death, and the prevention of communicable diseases. Such interventions were the main focus of relief operations after the Tsunami of 26 December 2004. Since the war in the former Yugoslavia, however, there has been increasing interest in the psychosocial dynamics of both natural and man-made disasters,2-7 and in the wake of the Tsunami more than three hundred psychosocial projects of various kinds were initiated.

The way in which people will respond to a disaster cannot be predicted with precision: psychosocial outcomes are influenced by personal, social and cultural factors. Not all people will respond in the same way or even suffer from trauma as conceptualized in Western models.2,5 It is also important to keep in mind that disasters can affect people who do not experience them at first hand.3