tbuckley/cabot-search huggingface dataset:
Routine follow up of breast cancer in primary care: randomised trial
Authors: E. Grunfeld, D. Mant, P. Yudkin, R. Adewuyi-Dalton, D. Cole, J. Stewart, R. Fitzpatrick, M. Vessey
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To assess the effect on time to diagnosis of recurrence and on quality of life of transferring primary responsibility for follow up of women with breast cancer in remission from hospital to general practice. <b>Design</b>: Randomised controlled trial with 18 month follow up in which women received routine follow up either in hospital or in general practice. <b>Subjects and setting</b>: 296 women with breast cancer in remission receiving regular follow up care at district general hospitals in England. <b>Main outcome measures</b>: Time between first presentation of symptoms to confirmation of recurrence; quality of life measured by specific dimensions of the SF-36 schedule, the EORTC symptom scale, and hospital anxiety and depression scale. <b>Results</b>: Most recurrences (18/26, 69%) presented as interval events, and almost half (7/16, 44%) of the recurrences in the hospital group presented first to general practice. The median time to hospital confirmation of recurrence was 21 days in the hospital group (range 1-376 days) and 22 days in the general practice group (range 4-64). The differences between groups in the change in SF-36 mean scores from baseline were small: -1.8 (95% confidence interval -7.2 to 3.5) for social functioning, 0.5 (-4.1 to 5.1) for mental health, and 0.6 (-3.6 to 4.8) for general health perception. The change from baseline in the mean depression score was higher in the general practice group at the mid-trial assessment (difference 0.6, 0.1 to 1.2) but there was no significant difference between groups in the anxiety score or the EORTC scales. <b>Conclusion</b>: General practice follow up of women with breast cancer in remission is not associated with increase in time to diagnosis, increase in anxiety, or deterioration in health related quality of life. Most recurrences are detected by women as interval events and present to the general practitioner, irrespective of continuing hospital follow up. <h3>Key messages</h3> Broadly, the goals of follow up are to detect recurrence, detect new contralateral primaries, and provide psychosocial support For women who are free of disease, general prac- tice follow up was not associated with increased time to diagnosis of recurrence or deterioration in health related quality of life
A Parcellation Scheme for Human Left Lateral Parietal Cortex
Authors: Steven M. Nelson, Alexander L. Cohen, Jonathan D. Power, Gagan S. Wig, Francis M. Miezin, Mark E. Wheeler, Katerina Velanova, David I. Donaldson, Jeffrey S. Phillips, Bradley L. Schlaggar, Steven E. Petersen
Journal: Neuron (2010)
Acupuncture in Patients With Seasonal Allergic Rhinitis
Authors: Benno Brinkhaus, Miriam Ortiz, Claudia M Witt, Stephanie Roll, Klaus Linde, Florian Pfab, Bodo Niggemann, Josef Hummelsberger, András Treszl, Johannes Ring, Torsten Zuberbier, Karl Wegscheider, Stefan N Willich
Journal: Annals of Internal Medicine (2013)

Chinese translation Background: Acupuncture is frequently used to treat seasonal allergic rhinitis (SAR) despite limited scientific evidence. Objective: To evaluate the effects of acupuncture in patients with SAR. Design: Randomized, controlled multicenter trial. (ClinicalTrials.gov: NCT00610584) Setting: 46 specialized physicians in 6 hospital clinics and 32 private outpatient clinics. Patients: 422 persons with SAR and IgE sensitization to birch and grass pollen. Intervention: Acupuncture plus rescue medication (RM) (cetirizine) (n = 212), sham acupuncture plus RM (n = 102), or RM alone (n = 108). Twelve treatments were provided over 8 weeks in the first year. Measurements: Changes in the Rhinitis Quality of Life Questionnaire (RQLQ) overall score and the RM score (RMS) from baseline to weeks 7 and 8 and week 16 in the first year and week 8 in the second year after randomization, with predefined noninferiority margins of −0.5 point (RQLQ) and −1.5 points (RMS). Results: Compared with sham acupuncture and with RM, acupuncture was associated with improvement in RQLQ score (sham vs. acupuncture mean difference, 0.5 point [97.5% CI, 0.2 to 0.8 point; P < 0.001]; RM vs. acupuncture mean difference, 0.7 point [97.5% CI, 0.4 to 1.0 point; P < 0.001]) and RMS (sham vs. acupuncture mean difference, 1.1 points [97.5% CI, 0.4 to 1.9 points; P < 0.001]; RM vs. acupuncture mean difference, 1.5 points [97.5% CI, 0.8 to 2.2 points; P < 0.001]). There were no differences after 16 weeks in the first year. After the 8-week follow-up phase in the second year, small improvements favoring real acupuncture over the sham procedure were noted (RQLQ mean difference, 0.3 point [95% CI, 0.03 to 0.6 point; P = 0.032]; RMS mean difference, 1.0 point [95% CI, 0.2 to 1.9 points; P = 0.018]). Limitation: The study was not powered to detect rare adverse events, and the RQLQ and RMS values were low at baseline. Conclusion: Acupuncture led to statistically significant improvements in disease-specific quality of life and antihistamine use measures after 8 weeks of treatment compared with sham acupuncture and with RM alone, but the improvements may not be clinically significant. Primary Funding Source: German Research Foundation.
Association of Prostate Cancer Risk With Genetic Polymorphisms in Vitamin D Receptor and Androgen Receptor
Authors: S. A. Ingles, R. K. Ross, M. C. Yu, R. W. Haile, R. A. Irvine, G. La Pera, G. A. Coetzee
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: Prostate cancer is an increasingly common disease for which there are few well-established risk factors. Family history data suggest a genetic component; however, the majority of prostate cancer cases cannot be explained by a single-gene model. Prostate cell division is influenced by two steroid hormones, testosterone and vitamin D, the action of each being mediated by its respective receptor. The genes for the two receptors are candidates in a multigenic model for prostate cancer susceptibility. Purpose: We examined genetic polymorphisms in two steroid receptors, the androgen receptor (AR) and the vitamin D receptor (VDR), in a case-control pilot study of prostate cancer. Methods: Fifty-seven non-Hispanic white case patients with prostate cancer and 169 non-Hispanic white control subjects were genotyped for a previously described microsatellite (CAG repeats) in the AR gene and for a newly discovered poly-A microsatellite in the 3′-untranslated region (3′UTR) of the VDR gene. To compare genotypes with respect to prostate cancer risk, we estimated odds ratios (ORs) by using logistic regression. ORs were also estimated separately for advanced and localized cases of disease. All P values resulted from two-sided tests. Results: Both the AR and the VDR polymorphisms were associated, individually and after mutual adjustment, with prostate cancer. Adjusted ORs (95% confidence intervals [CIs]) for prostate cancer were 2.10 (95% CI = 1.11-3.99) for individuals carrying an AR CAG allele with fewer than 20 repeats versus an allele with 20 or more repeats and 4.61 (95% CI = 1.34-15.82) for individuals carrying at least one long (A 18 to A 22 ) VDR poly-A allele versus two short (A 14 to A 17 ) poly-A alleles. For both the AR and VDR genes, the at-risk genotypes were more strongly associated with advanced disease than with localized disease. Conclusions: In this pilot study, genetic variation in both the VDR and the AR genes was associated with prostate cancer, and both genes appear to preferentially confer risk for advanced disease. These two genetic risk factors, if confirmed, are among the strongest risk factors yet identified for prostate cancer. Implications: These results are consistent with a multigenic model of prostate cancer susceptibility. On the basis of the joint effect of several genetic loci, one might ultimately be able to construct a risk profile to predict advanced disease, so that men whose disease is unlikely to progress to an advanced stage can possibly be spared aggressive treatment.
Functional <i>Ex Vivo</i> Assay to Select Homologous Recombination–Deficient Breast Tumors for PARP Inhibitor Treatment
Authors: Kishan A.T. Naipal, Nicole S. Verkaik, Najim Ameziane, Carolien H.M. van Deurzen, Petra ter Brugge, Matty Meijers, Anieta M. Sieuwerts, John W. Martens, Mark J. O'Connor, Harry Vrieling, Jan H.J. Hoeijmakers, Jos Jonkers, Roland Kanaar, Johan P. de Winter, Maaike P. Vreeswijk, Agnes Jager, Dik C. van Gent
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Poly(ADP-ribose) polymerase (PARP) inhibitors are promising targeted treatment options for hereditary breast tumors with a homologous recombination (HR) deficiency caused by BRCA1 or BRCA2 mutations. However, the functional consequence of BRCA gene mutations is not always known and tumors can be HR deficient for other reasons than BRCA gene mutations. Therefore, we aimed to develop a functional test to determine HR activity in tumor samples to facilitate selection of patients eligible for PARP inhibitor treatment. Experimental design: We obtained 54 fresh primary breast tumor samples from patients undergoing surgery. We determined their HR capacity by studying the formation of ionizing radiation induced foci (IRIF) of the HR protein RAD51 after ex vivo irradiation of these organotypic breast tumor samples. Tumors showing impaired RAD51 IRIF formation were subjected to genetic and epigenetic analysis. Results: Five of 45 primary breast tumors with sufficient numbers of proliferating tumor cells were RAD51 IRIF formation deficient (11%, 95% CI, 5%–24%). This HR defect was significantly associated with triple-negative breast cancer (OR, 57; 95% CI, 3.9–825; P = 0.003). Two of five HR-deficient tumors were not caused by mutations in the BRCA genes, but by BRCA1 promoter hypermethylation. Conclusion: The functional RAD51 IRIF assay faithfully identifies HR-deficient tumors and has clear advantages over gene sequencing. It is a relatively easy assay that can be performed on biopsy material, making it a powerful tool to select patients with an HR-deficient cancer for PARP inhibitor treatment in the clinic. Clin Cancer Res; 20(18); 4816–26. ©2014 AACR.
The Cancer Stem Cell Marker Aldehyde Dehydrogenase Is Required to Maintain a Drug-Tolerant Tumor Cell Subpopulation
Authors: Debasish Raha, Timothy R. Wilson, Jing Peng, David Peterson, Peng Yue, Marie Evangelista, Catherine Wilson, Mark Merchant, Jeff Settleman
Journal: Cancer Research (2014)

Abstract Selective kinase inhibitors have emerged as an important class of cancer therapeutics, and several such drugs are now routinely used to treat advanced-stage disease. However, their clinical benefit is typically short-lived because of the relatively rapid acquisition of drug resistance following treatment response. Accumulating preclinical and clinical data point to a role for a heterogeneous response to treatment within a subpopulation of tumor cells that are intrinsically drug-resistant, such as cancer stem cells. We have previously described an epigenetically determined reversibly drug-tolerant subpopulation of cancer cells that share some properties with cancer stem cells. Here, we define a requirement for the previously established cancer stem cell marker ALDH (aldehyde dehydrogenase) in the maintenance of this drug-tolerant subpopulation. We find that ALDH protects the drug-tolerant subpopulation from the potentially toxic effects of elevated levels of reactive oxygen species (ROS) in these cells, and pharmacologic disruption of ALDH activity leads to accumulation of ROS to toxic levels, consequent DNA damage, and apoptosis specifically within the drug-tolerant subpopulation. Combining ALDH inhibition with other kinase-directed treatments delayed treatment relapse in vitro and in vivo, revealing a novel combination treatment strategy for cancers that might otherwise rapidly relapse following single-agent therapy. Cancer Res; 74(13); 3579–90. ©2014 AACR.
Continued benefit of coronary stenting versus balloon angioplasty: five-year clinical follow-up of Benestent-I trial
Authors: Ferdinand Kiemeneij, Patrick W Serruys, Carlos Macaya, Wolfgang Rutsch, Guy Heyndrickx, Per Albertsson, Jean Fajadet, Victor Legrand, Pierre Materne, Jorge Belardi, Ulrich Sigwart, Antonio Colombo, Jean-Jacques Goy, Clemens M.C Disco, Marie-Angèle Morel
Journal: Journal of the American College of Cardiology (2001)
Identification of Susceptibility Loci in a Mouse Model of <i>KRASG12D</i>-Driven Pancreatic Cancer
Authors: Tonia C. Jorgenson, Bret R. Williams, Allyson Wendland, Andrea Bilger, Eric P. Sandgren, Norman R. Drinkwater
Journal: Cancer Research (2010)

Genetic background affects susceptibility to pancreatic ductal adenocarcinoma in the Ela-KRAS(G12D) mouse model. In this model, KRAS oncogene expression is driven by an elastase promoter in acinar cells of the pancreas on an FVB/NTac (FVB) background [FVB-Tg(Ela-KRAS(G12D))] with the transgene carried on the Y chromosome. Through linkage analysis of crosses between the C57BL/6J (B6), BALB/cJ (BALB), and DBA/2J (D2) inbred strains of mice and resistant FVB-Tg(Ela-KRAS(G12D)), we have identified six susceptibility loci that affect mean preinvasive lesion multiplicity. Markers on chromosome 2 segregated with high tumor multiplicity in all three strains; these loci were designated Prsq1-3 (pancreatic ras susceptibility quantitative trait loci 1-3; combined F2 and N2 LOD(W), 6.0, 4.1, and 2.7, respectively). Susceptibility loci on chromosome 4, designated Prsq4 and Prsq5, were identified in crosses between FVB transgenic mice and B6 or BALB mice (combined F2 and N2 LOD(W), 3.6 and 2.9, respectively). A marker on chromosome 12 segregated with tumor multiplicity in a BALB × FVB-Tg(Ela-KRAS(G12D)) cross and was designated Prsq6 (LOD(W), ∼2.5). B6-Chr Y(FVB-Tg(Ela-KRASG12D)) and BALB-Chr Y(FVB-Tg(Ela-KRASG12D)) consomics, which carry the KRAS transgene on the FVB Y chromosome on an otherwise inbred B6 or BALB background, developed ∼4-fold (B6) and ∼10-fold (BALB) more lesions than FVB-Tg(Ela-KRAS(G12D)) mice. By 12 months of age, 10% of BALB-Chr Y(FVB-Tg(Ela-KRASG12D)) mice developed invasive carcinomas. Our findings provide evidence that regions of chromosomes 2, 4, and 12 influence the development and progression of pancreatic neoplasms initiated by an oncogenic allele of KRAS in mice.
Effect of hemodilution on the distribution of renal blood flow.
Authors: S Migdal, E A Alexander, F J Bruns, A L Riley, N G Levinsky
Journal: Circulation Research (1975)

We evaluated the effects of hemodilution, expansion of intravascular volume, and expansion of interstitial volume on the distribution of cortical renal blood flow, utilizing the microsphere technique. Hemodilution without volume expansion (saline exchange) produced an increase in fractional blood flow in zone 1 (outermost zone) of the cortex from 34 plus or minus 1% to 43 plus or minus 2% and a decrease in fractional blood flow in zone 4 (innermost zone) from 16 plus or minus 2% to 13 plus or minus 2%. Hemodilution without volume expansion or a decrease in plasma protein concentration (isoncotic exchange) produced a similar redistribution in blood flow in zone 1 from 34 plus or minus 2% to 41 plus or minus 2% and in zone 4 from 14 plus or minus 2% to 10 plus or minus 1%. Hemodilution with intravascular volume expansion (hyperoncotic albumin infusion) also produced a superficial shift; blood flow in zone 1 increased from 27 plus or minus 1% to 30 plus or minus 1% and that in zone 4 decreased from 19 plus or minus 2% to 15 plus or minus 1%. Previous studies have demonstrated a redistribution to the juxtamedullary area after saline expansion. Our data demonstrate that hemodilution causes flow to redistribute to the superficial rather than the deep cortex. This superficial shift appears to be secondary to decrease hematocrit rather than to dilution of plasma proteins or expansions of intravascular volume. The deep shift in cortical blood flow which occurs during saline loading is presumably a consequence of expansion of interstitial volume.
Intensive combination treatment regimens, including prednisolone, are effective in treating patients with early rheumatoid arthritis regardless of additional etanercept: 1-year results of the COBRA-light open-label, randomised, non-inferiority trial
Authors: Marieke M ter Wee, Debby den Uyl, Maarten Boers, Pit Kerstens, Mike Nurmohamed, Dirkjan van Schaardenburg, Alexandre E Voskuyl, Willem F Lems
Journal: Annals of the Rheumatic Diseases (2014)

Background Recently, we documented the likely non-inferiority of Combinatietherapie Bij Reumatoïde Artritis (COBRA)-light therapy (methotrexate increased to 25 mg/week with initial prednisolone 30 mg/day) compared with the original COBRA therapy (methotrexate 7.5 mg/week, sulfasalazine 2 g/day, with initial prednisolone 60 mg/day) after 26 weeks in patients with early active rheumatoid arthritis (RA). Objective To assess the non-inferiority of COBRA-light versus COBRA after 1 year in terms of disease activity (DAS44), functional outcome (Health Assessment Questionnaire (HAQ)) and radiographic progression (Sharp/van der Heijde score (SHS)), and to assess the effect of adding etanercept. Methods An open-label, randomised controlled, non-inferiority trial of 162 patients with active early RA, following a treat-to-target protocol incorporating the addition of etanercept if DAS44 ≥1.6 at weeks 26 or 39. Results Both groups showed major improvements in DAS44 after 52 weeks: mean (SD) −2.41 (1.2) in the COBRA and −2.02 (1.0) in the COBRA-light group (p=ns). In both groups, functional ability improved and radiological progression of joints was minimal. At least one adverse event was reported in 96% of the patients in both groups. In total, 25 serious adverse events occurred: 9 vs 16 in COBRA and COBRA-light, respectively. Treatment actually instituted was often less intensive than required by the protocol: of the total population, 108 patients (67%) required etanercept (more in the COBRA-light group), but only 67 of these (62%) actually received it. Conclusions Intensive COBRA or COBRA-light therapy has major, comparably favourable effects on disease activity, functional ability and radiological outcome after 1 year in patients with early RA. Protocolised addition of etanercept was often not implemented by treating rheumatologists, and patients receiving it appeared to have limited added benefit, probably because of low disease activity levels at its initiation. Trial registration number: ISRCTN55552928.
Injury current and gradients of diastolic stimulation threshold, TQ potential, and extracellular potassium concentration during acute regional ischemia in the isolated perfused pig heart.
Authors: R Coronel, F J Wilms-Schopman, T Opthof, F J van Capelle, M J Janse
Journal: Circulation Research (1991)

During acute regional myocardial ischemia, a "current of injury" flows between the ischemic and the normal tissue. Its direction and magnitude change during the cardiac cycle. During diastole, the injury current flows intracellularly from the ischemic cells toward the normal cells and tends to depolarize the latter. The gain insight into the possible role of the injury current in arrhythmogenesis, we simultaneously determined diastolic stimulation threshold, [K+]o and TQ potential at multiple sites closely spaced across the cyanotic border in Langendorff-perfused pig hearts during the first 10 minutes after occlusion of the left anterior descending coronary artery. The position of the electrodes relative to the border was validated by their response to 1) regional ischemia and 2) selective perfusion with a high-K+ perfusate of the left anterior descending coronary artery. A temporary decrease of diastolic stimulation threshold preceded a rapid increase in the central ischemic zone; a lasting reduction (by +/- 20%) without a concomitant increase of [K+]o was observed at seven sites (of 39 sites tested), five of which were less than 2 mm outside the electrophysiological border. Moreover, up to 4 mm inside the electrophysiological border, a similar lasting decrease of diastolic stimulation threshold was accompanied by a moderate increase of [K+]o. We conclude that 1) the injury current causes increased excitability in normal tissue close to the "ischemic" border and 2) increased excitability related to a moderately increased [K+]o may persist up to 10 minutes of ischemia at the ischemic side of the border. Both factors may facilitate the induction of life-threatening arrhythmias in acute myocardial ischemia.
Collagen measured in primary cultures of normal rat hepatocytes derives from lipocytes within the monolayer.
Authors: J J Maher, D M Bissell, S L Friedman, F J Roll
Journal: Journal of Clinical Investigation (1988)

The cellular origin of hepatic collagen is under active investigation. Several recent studies using cells in primary culture suggest that hepatocytes are the source of much of the collagen in normal rat liver. In view of other data indicating that lipocytes produce substantial amounts of this protein, we have reexamined collagen biosynthesis in hepatocyte cultures that have been carefully characterized with respect to the presence of lipocytes. We find that routinely prepared hepatocyte isolates contain, by number, approximately 10% lipocytes. Lipocytes in early culture are difficult to visualize by phase-contrast microscopy but after 4 d proliferate and eventually replace the parenchymal cells. The size of the lipocyte subpopulation in these cultures correlates positively with collagen production. Similarly, removal of lipocytes by further processing of the initial hepatocyte isolate significantly reduces collagen production. Moreover, the only cells within hepatocyte cultures that display type I collagen by immunohistochemistry are lipocytes. We conclude that lipocytes are the principal source of collagen in primary hepatocyte cultures. The findings indicate also that these cells are the previously described "fibroblast" that appear in relatively long-term hepatocyte cultures.
Draft genome of the mountain pine beetle, Dendroctonus ponderosae Hopkins, a major forest pest
Authors: Christopher I Keeling, Macaire MS Yuen, Nancy Y Liao, T Roderick Docking, Simon K Chan, Greg A Taylor, Diana L Palmquist, Shaun D Jackman, Anh Nguyen, Maria Li, Hannah Henderson, Jasmine K Janes, Yongjun Zhao, Pawan Pandoh, Richard Moore, Felix AH Sperling, Dezene P W Huber, Inanc Birol, Steven JM Jones, Joerg Bohlmann
Journal: Genome biology (2013)

The mountain pine beetle, Dendroctonus ponderosae Hopkins, is the most serious insect pest of western North American pine forests. A recent outbreak destroyed more than 15 million hectares of pine forests, with major environmental effects on forest health, and economic effects on the forest industry. The outbreak has in part been driven by climate change, and will contribute to increased carbon emissions through decaying forests. We developed a genome sequence resource for the mountain pine beetle to better understand the unique aspects of this insect's biology. A draft de novo genome sequence was assembled from paired-end, short-read sequences from an individual field-collected male pupa, and scaffolded using mate-paired, short-read genomic sequences from pooled field-collected pupae, paired-end short-insert whole-transcriptome shotgun sequencing reads of mRNA from adult beetle tissues, and paired-end Sanger EST sequences from various life stages. We describe the cytochrome P450, glutathione S-transferase, and plant cell wall-degrading enzyme gene families important to the survival of the mountain pine beetle in its harsh and nutrient-poor host environment, and examine genome-wide single-nucleotide polymorphism variation. A horizontally transferred bacterial sucrose-6-phosphate hydrolase was evident in the genome, and its tissue-specific transcription suggests a functional role for this beetle. Despite Coleoptera being the largest insect order with over 400,000 described species, including many agricultural and forest pest species, this is only the second genome sequence reported in Coleoptera, and will provide an important resource for the Curculionoidea and other insects.