tbuckley/cabot-search huggingface dataset:
CT screening in current moderate smokers may be justified as study finds similar lung cancer risk to heavier smokers
Authors: Susan Mayor
Journal: BMJ (2015)

Low dose CT (computed tomography) lung cancer screening may be justified in current moderate smokers with a smoking history of 20-29 pack years, says a US study published in the Journal of the National Cancer Institute ,1 which found that they had a similar risk of developing lung cancer to heavier smokers and ex-smokers who were currently eligible for screening.

US guidelines recommend low dose CT screening for current and former smokers aged 55-80 with at least 30 pack years of cigarette smoking, and former smokers must have quit within the previous 15 years. One pack year is equivalent to smoking 20 cigarettes (one pack) …
Comparative performance of psoriatic arthritis screening tools in patients with psoriasis in European/North American dermatology clinics
Authors: Philip J. Mease, Dafna D. Gladman, Philip Helliwell, Majed M. Khraishi, Joanne Fuiman, Eustratios Bananis, Daniel Alvarez
Journal: Journal of the American Academy of Dermatology (2014)
Exon arrays provide accurate assessments of gene expression
Authors: Karen Kapur, Yi Xing, Zhengqing Ouyang, Wing Hung Wong
Journal: Genome biology (2007)

Abstract We have developed a strategy for estimating gene expression on Affymetrix Exon arrays. The method includes a probe-specific background correction and a probe selection strategy in which a subset of probes with highly correlated intensities across multiple samples are chosen to summarize gene expression. Our results demonstrate that the proposed background model offers improvements over the default Affymetrix background correction and that Exon arrays may provide more accurate measurements of gene expression than traditional 3' arrays.
Translating an Antagonist of Chemokine Receptor CXCR4: From Bench to Bedside
Authors: Donald Wong, Walter Korz
Journal: Clinical Cancer Research (2008)

Abstract The majority of current cancer therapies focus on a primary tumor approach. However, it is metastases that cause the majority of cancer deaths. The metastatic process has been shown repeatedly to be greatly influenced by chemokines such as CXCL12 [stromal cell derived factor-1 (SDF-1)] and its receptor CXCR4. The activation of this pathway has been reported to modulate cell migration, survival, proliferation, and gene transcription through G proteins, phosphoinositide-3 kinase, Akt, extracellular signal-regulated kinase, arrestin, and Janus-activated kinase/signal transducers and activators of transcription. A wide variety of strategies, such as peptides, small molecules, antibodies, and small interfering RNA, have been used to target this pathway. Treatments in combination with current therapies seem to be especially promising in preclinical studies. A few compounds are advancing into early stages of clinical development. In this article, we will review the development of CXCR4 antagonists in oncology.
Total Skin Electron Beam and Non-Myeloablative Allogeneic Hematopoietic Stem-Cell Transplantation in Advanced Mycosis Fungoides and Sézary Syndrome
Authors: Madeleine Duvic, Michele Donato, Bouthaina Dabaja, Heather Richmond, Lotika Singh, Wei Wei, Sandra Acholonu, Issa Khouri, Richard Champlin, Chitra Hosing
Journal: Journal of Clinical Oncology (2010)

Transformed mycosis fungoides (MF) and Sézary syndrome (SS) are currently incurable. We studied the safety and efficacy of total skin electron beam with allogeneic hematopoietic stem-cell transplantation (HSCT) in patients with cutaneous T-cell lymphoma (CTCL).Nineteen patients with advanced CTCL (median age, 50 years; four prior therapies) underwent total skin electron beam radiation followed by allogeneic HSCT between July 2001 and July 2008. Sixteen patients were conditioned with fludarabine (125 mg/m(2)) and melphalan (140 mg/m(2)) plus thymoglobulin (for mismatched donors). Graft-versus-host disease (GVHD) prophylaxis was with tacrolimus/mini methotrexate.Eighteen patients experienced engraftment, and one died as a result of sepsis on day 16. Median time to recovery of absolute neutrophil count (ANC) was 12 days. Fifteen achieved full donor chimerism, 12 had acute GVHD, and 12 were treated for chronic GVHD. The overall intent-to-treat response was 68%, and the complete response rate was 58%. Four of six patients died in complete remission as a result of bacterial sepsis (n = 2), chronic GVHD and fungal infection (n = 1), or lung cancer (n = 1); only two died as a result of progressive disease. Eight experienced relapse in skin; five regained complete response with reduced immunosuppression or donor lymphocyte infusions. Eleven of 13 are currently in complete remissions, with median follow-up of 19 months (range, 1.3 to 8.3 years). Median overall survival has not been reached.Total skin electron beam followed by allogeneic stem-cell transplantation merits additional evaluation for a selected group of patients with refractory, advanced, cutaneous T-cell lymphoma with evidence for graft-versus-tumor effect.
RLIP76 Is a Major Determinant of Radiation Sensitivity
Authors: Sanjay Awasthi, Sharad S. Singhal, Sushma Yadav, Jyotsana Singhal, Kenneth Drake, Aalok Nadkar, Ewa Zajac, Dilki Wickramarachchi, Nancy Rowe, Adly Yacoub, Paul Boor, Seema Dwivedi, Paul Dent, Wendy E. Jarman, Berchmans John, Yogesh C. Awasthi
Journal: Cancer Research (2005)

Abstract RLIP76 (RALBP1) is a glutathione-conjugate transporter that is a critical component of clathrin-coated pit–mediated endocytosis, as well as in stress responses. In cultured cells, it provides protection from stressors including heat, oxidant chemicals, chemotherapeutic agents, UV irradiation, and X-irradiation. Here, we show marked reduction in glutathione conjugate transport capacity and stepwise increase in radiation sensitivity associated with heterozygous or homozygous loss of the RLIP76 gene in mice. Survival after radiation in homozygous knockout animals was significantly shorter than either the heterozygous knockouts or the wild type. Delivery of recombinant RLIP76 to mice lacking RLIP76 via a liposomal delivery system rescued radiation sensitivity. Furthermore, treatment of wild-type mice with RLIP76-containing liposomes conferred resistance to radiation. These findings suggest that inhibiting RLIP76 could be used for sensitization to radiation during cancer therapy and that RLIP76 liposomes could be radioprotective agents useful for treatment of iatrogenic or catastrophic radiation poisoning.
Parasympathetic failure does not contribute to ocular dryness in primary Sjogren's syndrome
Authors: P J Barendregt, A H van den Meiracker, H M Markusse, J H M Tulen, F Boomsma, G L van der Heijde, A J M. i.'t Veld
Journal: Annals of the Rheumatic Diseases (1999)

To investigate the sympathetic and parasympathetic cardiovascular function in primary Sjögren's syndrome (SS) and to investigate the possible relation with ocular dryness.41 (40 women) patients with primary SS, mean age 50 years (range 20-80) with a mean disease duration of eight years (range 1-30), were studied. In each patient direct arterial blood pressure (BP), heart rate (HR) and respiration were measured continuously for two hours. The function of the autonomic circulatory regulation was evaluated by measuring the heart rate response to deep breathing (6 cycles/min) and by means of the Valsalva manoeuvre and the responses of BP, HR and plasma noradrenaline (norepinephrine) concentrations to a 10 minute 60 degree head up tilt test. Pupillography was done to evaluate ocular autonomic function.The HR-Valsalva ratio was abnormal in 24% of the patients, and the HR variability during forced respiration was abnormal in 56% of the patients. The HR responses to both the Valsalva manoeuvre and deep breathing, as indicators of parasympathetic function, were abnormally low in 6 of 41 (15%) patients. In only two patients the decrease in systolic BP in response to the head up tilt test, as indicator of sympathetic function, was more than 20 mm Hg. However, increment of plasma noradrenaline concentration during head up tilt test and the overshoot of BP in phase IV of the Valsalva manoeuvre, as indicators of sympathetic function, were normal in both patients. Thus, no evidence for sympathetic dysfunction was found, whereas evidence for parasympathetic failure occurred sometimes. Autonomic pupillary function in patients with primary SS and healthy controls, as well as the Schirmer test in patients with or without evidence for parasympathetic dysfunction as based on the results of the Valsalva and deep breathing tests, were not significantly different.Parasympathetic, but not sympathetic dysfunction seems to occur in a subgroup of primary SS. Results show that this does not necessarily contribute to the typical ocular dryness in this condition.
Detection of rhinovirus in induced sputum at exacerbation of chronic obstructive pulmonary disease
Authors: T.A.R. Seemungal, R. Harper-Owen, A. Bhowmik, D.J Jeffries, J.A Wedzicha
Journal: European Respiratory Journal (2000)

Common colds are associated with exacerbations of chronic obstructive pulmonary disease (COPD). However, the role of the common cold virus (human rhinovirus) in the production of symptoms and lower airway inflammation at COPD exacerbation is unknown. Thirty three patients with moderate-to-severe COPD were seen at baseline, when the number of chest infections in the previous year was noted, and acutely at COPD exacerbation. Within 48 h after the onset of the exacerbation and at baseline, nasal aspirates and induced sputum were taken for rhinovirus reverse transcriptase polymerase chain reaction (RT-PCR) analysis and determination of cytokine levels. Symptoms, recorded on diary cards, were noted and forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) measured. At exacerbation, mean FEV1 and FVC fell significantly from baseline (p&lt;0.001). Ten of 43 exacerbations were associated with rhinovirus infection, detected in induced sputum. In four of these, nasopharyngeal samples contained no detectable rhinovirus. All baseline samples were negative for rhinovirus. The simultaneous presence of increased nasal discharge/nasal congestion (in 26 of the 43 exacerbations) and increased sputum (29 exacerbations) was strongly associated with the presence of rhinovirus (odds ratio 6.15; p=0.036). Total symptom scores were greater for rhinovirus as compared to nonrhinovirus exacerbations (p=0.039). Median baseline sputum interleukin-6 levels rose from 90.2 to 140.3 pg x mL(-1) at exacerbation (p=0.005); the change was greater in the presence of rhinovirus infection (p=0.008). Rhinovirus infection can be detected at chronic obstructive pulmonary disease exacerbation. This is associated with elevation of lower airway interleukin-6 levels, which may mediate lower airway symptom expression during chronic obstructive pulmonary disease exacerbations.
RNA-seq Reveals Transcriptomic Shock Involving Transposable Elements Reactivation in Hybrids of Young Lake Whitefish Species
Authors: Anne-Marie Dion-Côté, Sébastien Renaut, Eric Normandeau, Louis Bernatchez
Journal: Molecular Biology and Evolution (2014)

Identifying the molecular basis of reproductive isolation among diverging lineages represents an essential step toward understanding speciation in natural populations. Postzygotic barriers can lead to hybrid breakdown, a syndrome that has been documented in several systems, potentially involving the reactivation of transposable elements. In northeastern North America, two lake whitefish lineages have repeatedly colonized postglacial lakes ∼12,000 years ago, and a dwarf limnetic species has evolved multiple times from the normal benthic species. Reproductive isolation is incomplete between them; viable hybrids can be generated in the laboratory but significant mortality occurs and is associated with a malformed phenotype in backcross embryos, thus revealing a hybrid breakdown syndrome. By means of RNA-seq analyses, the objective of this study was to determine which genes were misregulated in hybrids and rigorously test the hypothesis of transposable element reactivation. We compared the transcriptomic landscape in pure embryos, F1-hybrids, and healthy and malformed backcrosses at the late embryonic stage. Extensive expression differences consistent with previously documented adaptive divergence between pure normal and dwarf embryos were identified for the first time. Pronounced transcriptome-wide deregulation in malformed backcrosses was observed, with over 15% of transcripts differentially expressed in all comparisons, compared with 1.5% between pure parental forms. Convincing evidence of transposable elements and noncoding transcripts reactivation in malformed backcrosses is presented. We propose that hybrid breakdown likely results from extensive genomic incompatibilities, plausibly encompassing transposable elements. Combined with previous studies, these results reveal synergy among many reproductive barriers, thus maintaining divergence between these two young whitefish species.
Increasing Mammography Utilization: A Controlled Study
Authors: Suzanne W. Fletcher, Russell P. Harris, Jorge J. Gonzalez, Darrah Degnan, Donald R. Lannin, Victor J. Strecher, Carol Pilgrim, Dana Quade, Jo Anne Earp, Richard L. Clark
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Increasing Mammography Utilization: A Controlled Study Get access Suzanne W. Fletcher, Suzanne W. Fletcher Search for other works by this author on: Oxford Academic PubMed Google Scholar Russell P. Harris, Russell P. Harris Search for other works by this author on: Oxford Academic PubMed Google Scholar Jorge J. Gonzalez, Jorge J. Gonzalez Search for other works by this author on: Oxford Academic PubMed Google Scholar Darrah Degnan, Darrah Degnan Search for other works by this author on: Oxford Academic PubMed Google Scholar Donald R. Lannin, Donald R. Lannin Search for other works by this author on: Oxford Academic PubMed Google Scholar Victor J. Strecher, Victor J. Strecher Search for other works by this author on: Oxford Academic PubMed Google Scholar Carol Pilgrim, Carol Pilgrim Search for other works by this author on: Oxford Academic PubMed Google Scholar Dana Quade, Dana Quade Search for other works by this author on: Oxford Academic PubMed Google Scholar Jo Anne Earp, Jo Anne Earp Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard L. Clark Richard L. Clark Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 2, 20 January 1993, Pages 112–120, https://doi.org/10.1093/jnci/85.2.112 Published: 20 January 1993
Refinement and prediction of protein prenylation motifs.
Authors: Sebastian Maurer-Stroh, Frank Eisenhaber
Journal: Genome biology (2005)

Abstract We refined the motifs for carboxy-terminal protein prenylation by analysis of known substrates for farnesyltransferase (FT), geranylgeranyltransferase I (GGT1) and geranylgeranyltransferase II (GGT2). In addition to the CaaX box for the first two enzymes, we identify a preceding linker region that appears constrained in physicochemical properties, requiring small or flexible, preferably hydrophilic, amino acids. Predictors were constructed on the basis of sequence and physical property profiles, including interpositional correlations, and are available as the Prenylation Prediction Suite (PrePS, http://mendel.imp.univie.ac.at/sat/PrePS ) which also allows evaluation of evolutionary motif conservation. PrePS can predict partially overlapping substrate specificities, which is of medical importance in the case of understanding cellular action of FT inhibitors as anticancer and anti-parasite agents.
Contribution of transcriptional regulation to natural variations in Arabidopsis.
Authors: Wenqiong J Chen, Sherman H Chang, Matthew E Hudson, Wai-King Kwan, Jingqiu Li, Bram Estes, Daniel Knoll, Liang Shi, Tong Zhu
Journal: Genome biology (2005)

Abstract Background Genetic control of gene transcription is a key component in genome evolution. To understand the transcriptional basis of natural variation, we have studied genome-wide variations in transcription and characterized the genetic variations in regulatory elements among Arabidopsis accessions. Results Among five accessions (Col-0, C24, L er , WS-2, and NO-0) 7,508 probe sets with no detectable genomic sequence variations were identified on the basis of the comparative genomic hybridization to the Arabidopsis GeneChip microarray, and used for accession-specific transcriptome analysis. Two-way ANOVA analysis has identified 60 genes whose mRNA levels differed in different accession backgrounds in an organ-dependent manner. Most of these genes were involved in stress responses and late stages of plant development, such as seed development. Correlation analysis of expression patterns of these 7,508 genes between pairs of accessions identified a group of 65 highly plastic genes with distinct expression patterns in each accession. Conclusion Genes that show substantial genetic variation in mRNA level are those with functions in signal transduction, transcription and stress response, suggesting the existence of variations in the regulatory mechanisms for these genes among different accessions. This is in contrast to those genes with significant polymorphisms in the coding regions identified by genomic hybridization, which include genes encoding transposon-related proteins, kinases and disease-resistance proteins. While relatively fewer sequence variations were detected on average in the coding regions of these genes, a number of differences were identified from the upstream regions, several of which alter potential cis -regulatory elements. Our results suggest that nucleotide polymorphisms in regulatory elements of genes encoding controlling factors could be primary targets of natural selection and a driving force behind the evolution of Arabidopsis accessions.
Ribavirin and interferon retreatment of HCV chronic patients non responder to interferon
Authors: C De Bac, G Pastore, F Piccinino, MC Badolato, ME Tosti, A Osso, M Milella, T Santantonio, G Calabria, FM Felaco, GB Gaeta, G Stornaiuolo, G Taliani
Journal: Journal of Hepatology (1998)
Subunit Interaction Determines <i>I</i> <sub>Ks</sub> Participation in Cardiac Repolarization and Repolarization Reserve
Authors: Jonathan Silva, Yoram Rudy
Journal: Circulation (2005)

Background— The role of I Ks , the slow delayed rectifier K + current, in cardiac ventricular repolarization has been a subject of debate. Methods and Results— We develop a detailed Markov model of I Ks and its α-subunit KCNQ1 and examine their kinetic properties during the cardiac ventricular action potential at different rates. We observe that interaction between KCNQ1 and KCNE1 (the β-subunit) confers kinetic properties on I Ks that make it suitable for participation in action potential repolarization and its adaptation to rate changes; in particular, the channel develops an available reserve of closed states near the open state that can open rapidly on demand. Conclusions— Because of its ability to form an available reserve, I Ks can function as a repolarization reserve when I Kr , the rapid delayed rectifier, is reduced by disease or drug and can prevent excessive action potential prolongation and development of arrhythmogenic early afterdepolarizations.
Florence Pauline Cowmeadow
Authors: R. C. J. Mounty
Journal: BMJ (2013)

Florence Pauline Cowmeadow was passionate about art and literature. After obtaining a first class honours degree in English and fine art from Leeds University and an MA in History of European Art from the Courtauld Institute of Art, Pauline worked for two years as a nursing assistant at an adolescent psychiatric unit in St Albans. This inspired her to take up a career in medicine and psychiatry.

In 1975 Pauline started her medical training at Guy’s …
Increasing Cardiomyopathy Screening in At-Risk Adult Survivors of Pediatric Malignancies: A Randomized Controlled Trial
Authors: Melissa M. Hudson, Wendy Leisenring, Kayla K. Stratton, Nina Tinner, Brenda D. Steen, Susan Ogg, Linda Barnes, Kevin C. Oeffinger, Leslie L. Robison, Cheryl L. Cox
Journal: Journal of Clinical Oncology (2014)

To determine whether the addition of advanced-practice nurse (APN) telephone counseling to a printed survivorship care plan (SCP) significantly increases the proportion of at-risk survivors who complete cardiomyopathy screening.
Long-Term Stimulation of Adenosine A2b Receptors Begun After Myocardial Infarction Prevents Cardiac Remodeling in Rats
Authors: Masakatsu Wakeno, Tetsuo Minamino, Osamu Seguchi, Hidetoshi Okazaki, Osamu Tsukamoto, Ken-ichiro Okada, Akio Hirata, Masashi Fujita, Hiroshi Asanuma, Jiyoong Kim, Kazuo Komamura, Seiji Takashima, Naoki Mochizuki, Masafumi Kitakaze
Journal: Circulation (2006)

Background— Adenosine inhibits proliferation of cardiac fibroblasts and hypertrophy of cardiomyocytes, both of which may play crucial roles in cardiac remodeling. In the present study, we investigated whether chronic stimulation of adenosine receptors begun after myocardial infarction (MI) prevents cardiac remodeling. Methods and Results— MI was produced in Wistar rats by permanent ligation of the left anterior descending coronary artery. One week after the onset of MI, animals were randomized into 8 groups: vehicle, dipyridamole (DIP; the adenosine uptake inhibitor, 50 mg/kg), 2-chroloadenosine (CADO; the stable analogue of adenosine, 2 mg/kg), and CADO in the presence of the nonselective adenosine receptor antagonist 8-sulfophenyltheophylline (8-SPT) or the selective antagonist for adenosine A1, A2a, A2b, or A3 receptor. Three weeks after treatment, hemodynamic and echocardiographic parameters in the DIP and CADO groups were significantly improved compared with the vehicle group. These hemodynamic and echocardiographic improvements were blunted by either 8-SPT or the selective adenosine A2b antagonist MRS1754 but not by the selective antagonists for other subtypes of adenosine receptors. The collagen volume fraction was smaller, and gene expression of the molecules associated with cardiac remodeling such as matrix metalloproteinase in noninfarcted areas was reduced in the DIP and CADO groups compared with the vehicle group, both of which were attenuated by either 8-SPT or MRS1754. Conclusions— Long-term stimulation of adenosine A2b receptors begun after MI attenuates cardiac fibrosis in the noninfarcted myocardium and improves cardiac function. Drugs that stimulate adenosine A2b receptors or increase adenosine levels are new candidates for preventing cardiac remodeling after MI.