tbuckley/cabot-search huggingface dataset:
A Marker of Homologous Recombination Predicts Pathologic Complete Response to Neoadjuvant Chemotherapy in Primary Breast Cancer
Authors: Monika Graeser, Afshan McCarthy, Christopher J. Lord, Kay Savage, Margaret Hills, Janine Salter, Nicholas Orr, Marina Parton, Ian E. Smith, Jorge S. Reis-Filho, Mitch Dowsett, Alan Ashworth, Nicholas C. Turner
Journal: Clinical Cancer Research (2010)

Abstract Purpose: To assess the prevalence of defective homologous recombination (HR)-based DNA repair in sporadic primary breast cancers, examine the clincopathologic features that correlate with defective HR and the relationship with neoadjuvant chemotherapy response. Experimental Design: We examined a cohort of 68 patients with sporadic primary breast cancer who received neoadjuvant anthracylcine-based chemotherapy, with core biopsies taken 24 hours after the first cycle of chemotherapy. We assessed RAD51 focus formation, a marker of HR competence, by immunofluorescence in postchemotherapy biopsies along with geminin as a marker of proliferative cells. We assessed the RAD51 score as the proportion of proliferative cells with RAD51 foci. Results: A low RAD51 score was present in 26% of cases (15/57, 95% CI: 15%–40%). Low RAD51 score correlated with high histologic grade (P = 0.031) and high baseline Ki67 (P = 0.005). Low RAD51 score was more frequent in triple-negative breast cancers than in ER- and/or HER2-positive breast cancer (67% vs. 19% respectively; P = 0.0036). Low RAD51 score was strongly predictive of pathologic complete response (pathCR) to chemotherapy, with 33% low RAD51 score cancers achieving pathCR compared with 3% of other cancers (P = 0.011). Conclusions: Our results suggest that defective HR, as indicated by low RAD51 score, may be one of the factors that underlie sensitivity to anthracycline-based chemotherapy. Defective HR is frequent in triple-negative breast cancer, but it is also present in a subset of other subtypes, identifying breast cancers that may benefit from therapies that target defective HR such as PARP inhibitors. Clin Cancer Res; 16(24); 6159–68. ©2010 AACR.
O 6-Benzylguanine suppression of O6-alkylguanine-DNA alkyltransferase in anaplastic gliomas
Authors: S Clifford Schold, Demetrius M Kokkinakis, Susan M Chang, Mitchel S Berger, Kenneth R Hess, David Schiff, H Ian Robins, Minesh P Mehta, Karen L Fink, R L Davis, Michael D Prados
Journal: Neuro-Oncology (2004)

The purpose of the study was to determine the dose of O6-benzylguanine (BG) that would suppress O6-alkylguanine-DNA alkyltransferase (AGT) activity to undetectable levels in >90% of anaplastic gliomas, as measured 6 h after a 1-h BG infusion. Subjects who were scheduled for surgical resection of a known or presumed anaplastic glioma received a 1-h infusion of BG. Tumor tissue was surgically removed approximately 6 h after the end of the infusion and was analyzed for AGT activity. The BG dose was escalated until at least 11 of 14 subjects had no detectable AGT activity. An additional cohort of patients received the identified effective dose of BG approximately 18 h before tumor resection in order to compare our results with an earlier study using the longer time interval. In the 79 subjects who were enrolled, there was no significant toxicity that was attributed to the BG. A dose-response relationship was determined between the BG dose and the percentage of subjects with undetectable AGT. A dose of 120 mg/m2 suppressed AGT to less than detectable levels in 17 of 18 patients when the drug-resection interval was 6 h. With an 18-h interval, only 5 of 11 subjects had undetectable AGT at the 120-mg/m2 dose. We conclude that a BG dose of 120 mg/m2 given 6 h before an alkylating drug would be effective in suppressing AGT and possibly potentiating the cytotoxic effects of the drug.
Reply to Seidenberg and Elman
Authors: Gary F. Marcus
Journal: Trends in Cognitive Sciences (1999)

We completely agree with Seidenberg and Elman 1 Seidenberg M.S. Elman J.L. Networks are not ‘hidden rules’. Trends Cognit. Sci. 1999; 3: 288-289 Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar that what is important is ‘understanding the behaviour of the network and the principles that govern it’, but are mystified by their discussion of rules. Seidenberg and Elman’s claim that ‘the concept of “rule” has been altered to conform to the behaviour of connectionist networks’ is a clever, ironic twist, but it actually has no substance, and reflects only Seidenberg and Elman’s misunderstanding of our earlier point. As I emphasized in a series of recent articles, only a subset of neural networks implement rules 2 Marcus G.F. Vijayan S. Rao S.B. Vishton P.M. Rule learning in 7-month-old infants. Science. 1999; 283: 77-80 Crossref PubMed Scopus (779) Google Scholar , 3 Marcus G.F. Rethinking eliminative connectionism. Cognit. Psychol. 1998; 37: 243-282 Crossref PubMed Scopus (177) Google Scholar , 4 Marcus G.F. Do infants learn grammar with algebra or statistics? Response to Seidenberg & Elman, Negishi, and Eimas. Science. 1999; 284: 436-437 Google Scholar ; not all of them do. As we stated before 2 Marcus G.F. Vijayan S. Rao S.B. Vishton P.M. Rule learning in 7-month-old infants. Science. 1999; 283: 77-80 Crossref PubMed Scopus (779) Google Scholar , the ones that depend on ‘open-ended abstract relationships for which we can substitute arbitrary items’ are the ones that implement rules. As it turns out, the neural network part of Seidenberg and Elman’s system does not implement a rule. But, crucially, another part of the system that Seidenberg and Elman propose does implement a rule: the external teacher (this is what we meant by a ‘hidden rule’). In particular, the external teacher incorporates a universally open-ended rule of the sort, for all syllables x, y, if x = y then output 1 else output 0. This corresponds exactly to our characterization of rules. Since part of the system contains a rule, it follows that the system as a whole contains a rule.
Impact of Smoking on Clinical and Angiographic Restenosis After Percutaneous Coronary Intervention
Authors: David J. Cohen, Michel Doucet, Donald E. Cutlip, Kalon K.L. Ho, Jeffrey J. Popma, Richard E. Kuntz
Journal: Circulation (2001)

Background Recent studies have suggested that smokers may require less frequent repeated revascularization after percutaneous coronary intervention (PCI) compared with nonsmokers. However, the mechanism of this phenomenon is unknown. Methods and Results We examined the association between smoking and restenosis using pooled data from 8671 patients treated with PCI in 9 multicenter clinical trials. Clinical restenosis was examined in the cohort of 5682 patients who were assigned to clinical follow-up only. Angiographic restenosis was evaluated in the subset of 2989 patients who were assigned to mandatory angiographic restudy. Among those patients assigned to clinical follow-up only, target lesion revascularization (TLR) occurred in 6.6% of smokers and 10.1% of nonsmokers ( P &lt;0.001). After adjustment for baseline clinical and angiographic differences, the rate of TLR remained significantly lower in smokers with an adjusted relative risk of 0.69 (95% CI, 0.54 to 0.88). Among the angiographic cohort, there were no differences in the rates of angiographic restenosis or follow-up diameter stenosis in either univariate or multivariate analyses. This dissociation between clinical and angiographic restenosis was explained in part by reduced sensitivity to restenosis on the part of smokers and by the greater reluctance of smokers to seek medical attention despite recurrent angina. Conclusions In patients undergoing contemporary PCI, cigarette smoking is associated with a lower rate of subsequent TLR without affecting angiographic restenosis. These findings have important implications for the follow-up of smokers after PCI and suggest that cross-study comparisons of rates of clinical restenosis must account for the potential confounding effect of smoking.
Contributions of Genetic Risk and Fetal Hypoxia to Hippocampal Volume in Patients With Schizophrenia or Schizoaffective Disorder, Their Unaffected Siblings, and Healthy Unrelated Volunteers
Authors: Theo G M Van Erp, Peter A Saleh, Isabelle M Rosso, Matti Huttunen, Jouko Lönnqvist, Tiia Pirkola, Oili Salonen, Leena Valanne, Veli-Pekka Poutanen, Carl-Gustav Standertskjöld-Nordenstam, Tyrone D Cannon
Journal: American Journal of Psychiatry (2002)

The authors examined in an epidemiologic sample the contributions of genetic predisposition and history of fetal hypoxia to hippocampal volume in patients with psychosis.High-resolution magnetic resonance imaging was used to measure hippocampal volumes in 72 psychotic probands (60 with schizophrenia and 12 with schizoaffective disorder, ascertained so as to be representative of all such probands in a Helsinki birth cohort), 58 nonpsychotic full siblings of the probands, and 53 demographically similar healthy comparison subjects with no family history of psychosis.Hippocampal volume differences occurred in a stepwise fashion with each increase in genetic load for schizophrenia. The probands had smaller hippocampal volumes than did their full siblings, who in turn had smaller hippocampal volumes than did the healthy comparison subjects. Among the probands, smaller hippocampal volumes were seen in those who experienced fetal hypoxia than in those who did not, a difference not noted within the other two groups. Finally, within the schizophrenic/schizoaffective disorder patients, smaller hippocampal volumes correlated positively with age at onset independent of duration of illness.These findings suggest that in patients with schizophrenia spectrum disorders, hippocampal volume is influenced in part by schizophrenia susceptibility genes and an interaction of these genes with fetal hypoxia. They further suggest that hippocampal volume in schizophrenia or schizoaffective disorder may be linked to time of disease onset.
Infectious arthritis caused by Propionibacterium acnes: a report of two cases.
Authors: M F Kooijmans-Coutinho, H M Markusse, B A Dijkmans
Journal: Annals of the Rheumatic Diseases (1989)

Propionibacterium acnes, a micro-organism with low pathogenicity, rarely causes arthritis in a joint without a prosthesis. This report deals with two cases of P acnes infectious arthritis probably caused by direct penetration of the micro-organism into the joint space during arthrocentesis, despite the use of strict disinfection procedures. P acnes isolated from synovial fluid cannot be dismissed as a bothersome contaminant without due consideration of the clinical status of the individual patient.
Costs and Cost-Effectiveness of a Low-Intensity Patient-Directed Intervention to Promote Colorectal Cancer Screening
Authors: Veena Shankaran, June M. McKoy, Neal Dandade, Narissa Nonzee, Cara A. Tigue, Charles L. Bennett, Tom D. Denberg
Journal: Journal of Clinical Oncology (2007)

Purpose Colorectal cancer (CRC) screening is the most underused evidence-based cancer screening test in the United States. Few studies have reported the cost-effectiveness of CRC screening promotional efforts. In a recent randomized controlled trial, a patient-directed intervention for average-risk patients who had been referred for screening colonoscopy led to a 12% increase in CRC screening rates. The objective of this secondary analysis is to assess the cost-effectiveness of this intervention. Patients and Methods Patients in the intervention arm received a customized mailed brochure that included a reminder to schedule a screening colonoscopy and general information about CRC, the importance of CRC screening, and how to prepare for the procedure. The end point was completion of screening colonoscopy. The costs and incremental cost-effectiveness ratio of this patient-directed intervention were derived. Sensitivity analyses were based on varying the costs of labor and supplies. Results Rates of CRC screening for the intervention (n = 386 patients) versus control (n = 395) arms were 71% and 59%, respectively (P = .001). The total cost of the intervention was $1,927 and the incremental cost-effectiveness ratio was $43 per additional patient screened ($38 to $47 in a sensitivity analysis). Conclusion An intervention based on mailing a customized brochure to patients who were referred for a screening colonoscopy improved CRC screening rates at a university-based general medicine clinic. This intervention was comparable in effectiveness and cost-effectiveness to a similar recently reported low-intensity patient-directed CRC screening intervention, and markedly more affordable and cost-effective than a previously reported physician-directed CRC screening promotion intervention.
Post implantation viability in canine allograft heart valves
Authors: D. J. WHEATLEY, C. G. A. McGREGOR
Journal: Cardiovascular Research (1977)

Known viable allograft canine pulmonary valves were inserted in an isotopic position ensuring normal physiological function and simulating the clinical situation. Valves removed at periods up to eight weeks were assessed for viability using previously established criteria of tissue culture and protein and collagen synthesis. The origin of cells present within the allografted leaflets was investigated by chromosome identification where possible. The results, in association with the histological appearances, indicated that pre-implantation viability was not retained in the leaflets of the allografted valves implanted in this study.
TRANSMISSION EXPERIMENTS WITH HUMAN T-LYMPHOTROPIC RETROVIRUSES AND HUMAN AIDS TISSUE
Authors: D.Carleton Gajdusek, HerbertL. Amyx, ClarenceJ. Gibbs, DavidM. Asher, Richardt. Yanagihara, Pamela Rodgers-Johnson, PaulW. Brown, PremS. Sarin, RobertC. Gallo, Annette Maluish, LarryO. Arthur, RaymondV. Gilden, L. Montagnier, J.-C. Chermann, F. Barre-Sinoussi, Donna Mildvan, Usha Mathur, Richard Leavitt
Journal: The Lancet (1984)
Sympathetic and Parasympathetic Neuropathy Are Frequent in Both Type 1 and Type 2 Diabetic Patients
Authors: Carolin Freccero, Henry Svensson, Siv Bornmyr, Per Wollmer, Göran Sundkvist
Journal: Diabetes Care (2004)

OBJECTIVE—The aim of this study was to evaluate the frequency of sympathetic versus parasympathetic neuropathy among type 1 and type 2 diabetic patients. RESEARCH DESIGN AND METHODS—There were 43 patients with type 1 and 17 with type 2 diabetes who were investigated. Sympathetic nerve function was assessed by measurement of the vasoconstriction (VAC) index by laser Doppler perfusion imaging of a locally heated finger followed by indirect cooling. Parasympathetic nerve function was assessed by R-R interval variation during deep breathing as measured by the expiration/inspiration (E/I) ratio. Results were expressed as age-corrected z scores in SD; VAC index &amp;gt;1.64 SD and E/I ratio &amp;lt;−1.64 SD were considered abnormal. RESULTS—VAC index was abnormal in 40% with type 1 and 41% with type 2 diabetes, whereas the E/I ratio was abnormal in 42% with type 1 and 65% with type 2 diabetes. There was a clear association between VAC index and E/I ratio among type 1 (rs = 0.525; P = 0.0002) but not among type 2 (rs = 0.10) diabetic patients. Among type 2 diabetic patients, the degree of dysfunction was most severe regarding parasympathetic function (P = 0.0167). CONCLUSIONS—Sympathetic and parasympathetic neuropathy were frequent in both type 1 and type 2 diabetic patients. However, there was a difference between the two types of diabetes. Sympathetic and parasympathetic nerve functions correlated in type 1 but not in type 2 diabetic patients. The explanation for this discrepancy might be that parasympathetic nerve function was most severely affected among type 2 diabetic patients.
Effects of adrenergic and muscarinic receptor stimulation on serum potassium concentrations and myocardial electrical stability
Authors: S. H HOHNLOSER, R. L VERRIER, B. LOWN
Journal: Cardiovascular Research (1986)

The influence of adrenergic and muscarinic receptor activation on cardiac electrical stability and on serum potassium concentrations was studied in 23 anaesthetised dogs. The ventricular fibrillation threshold was assessed using the single stimulus technique. Adrenaline (1.0 μg·kg−1·min−1) caused a brief rise and a subsequent prolonged fall in serum potassium concentration, which was accompanied by a decline in ventricular fibrillation threshold when baroreceptor activation was prevented. After pretreatment with the betai adrenoceptor blocking agent metoprolol (0.5 mg·kg−1), adrenaline did not alter vulnerability to ventricular fibrillation but still elicited hypokalaemia. In contrast, selective beta2 adrenoceptor blockade (ICI 118551, 100 μg·kg−1) prevented the adrenaline induced lowering of serum potassium concentration but not of ventricular vulnerability. Muscarinic receptor activation by methacholine (3.0 μg·kg−1·min−1) had no effect on serum potassium concentration but increased the ventricular fibrillation threshold by 30%. When methacholine was administered concomitantly with adrenaline the decline in serum potassium concentration persisted, but the increase in ventricular vulnerability was completely prevented. It is concluded that in the normal canine myocardium adrenaline produces an increase in vulnerability that is mediated through beta1 adrenoceptors and that the beta2 adrenoceptor mediated hypokalaemia is dissociated from electrophysiological effects of adrenaline. Parasympathetic nervous system activation does not influence serum potassium concentrations but opposes the effects of adrenaline on susceptibility to ventricular fibrillation.
Relationship of Periodontal Bacterium Genotypic Variations With Periodontitis in Type 2 Diabetic Patients
Authors: Miki Ojima, Munehiro Takeda, Hideo Yoshioka, Makoto Nomura, Noriaki Tanaka, Takahiro Kato, Satoshi Shizukuishi, Atsuo Amano
Journal: Diabetes Care (2005)

Periodontitis is characterized by gingival inflammation, as well as loss of connective tissue and bone from around the roots of the teeth, which leads to eventual tooth exfoliation. Severe periodontitis often coexists with diabetes and is considered to be the sixth complication of the disease, as both type 1 and type 2 diabetic patients show a three- to fourfold increased risk of periodontitis (1–4). However, the involved factors and mechanisms are still unclear.

Periodontitis is caused by a small subset of periodontal Gram-negative bacteria that attach to the gingival margin, such as Porphyromonas gingivalis , Actinobacillus actinomycetemcomitans , Tannerella forsythia , Treponema denticola , and Prevotella intermedia (5). Among them, P. gingivalis is considered to be a bona fide periodontal pathogen (5–7). P. gingivalis fimbriae are hair-like appendages on the bacterial surface that mediate bacterial interactions with and invasion of host tissues (8). These fimbriae have been classified into six types (I through V and Ib), based on the diversity of the fimA genes encoding FimA (a subunit protein of fimbriae) (9,10). Studies have shown that clones with …
Development and first validation of the COPD Assessment Test
Authors: P. W. Jones, G. Harding, P. Berry, I. Wiklund, W-H. Chen, N. Kline Leidy
Journal: European Respiratory Journal (2009)

There is need for a validated short, simple instrument to quantify chronic obstructive pulmonary disease (COPD) impact in routine practice to aid health status assessment and communication between patient and physician. Current health-related quality of life questionnaires provide valid assessment of COPD, but are complex, which limits routine use. The aim of the present study was to develop a short validated patient-completed questionnaire, the COPD Assessment Test (CAT), assessing the impact of COPD on health status. 21 candidate items identified through qualitative research with COPD patients were used in three prospective international studies (Europe and the USA, n = 1,503). Psychometric and Rasch analyses identified eight items fitting a unidimensional model to form the CAT. Items were tested for differential functioning between countries. Internal consistency was excellent: Cronbach's alpha = 0.88. Test re-test in stable patients (n = 53) was very good (intra-class correlation coefficient 0.8). In the sample from the USA, the correlation with the COPD-specific version of the St George's Respiratory Questionnaire was r = 0.80. The difference between stable (n = 229) and exacerbation patients (n = 67) was five units of the 40-point scale (12%; p<0.0001). The CAT is a short, simple questionnaire for assessing and monitoring COPD. It has good measurement properties, is sensitive to differences in state and should provide a valid, reliable and standardised measure of COPD health status with worldwide relevance.
The Fall and Rise of Parathyroidectomy in U.S. Hemodialysis Patients, 1992 to 2002
Authors: Robert N Foley, Suying Li, Jiannong Liu, David T Gilbertson, Shu-Cheng Chen, Allan J Collins
Journal: Journal of the American Society of Nephrology (2004)

Although the therapeutic approach to managing hyperparathyroidism has changed dramatically, it is unknown whether parathyroidectomy rates continue to decline in the United States. Parathyroidectomy rates were studied in successive annual national cohorts, prevalent on hemodialysis on January 1 of 1992 to 2002, with Medicare as primary payer. Parathyroidectomy was defined as International Classification of Diseases, Ninth Revision, Clinical Modification code 068. The annual incidence of parathyroidectomy was 11.6 per 1000 patient-years in 1992. The incidence declined progressively after 1994, reaching a low of 6.8 per 1000 patient-years in 1998. Rates increased progressively after 1998, reaching 11.8 per 1000 patient-years in 2002. Using proportional hazards modeling, with adjustment for comorbidity and 1992 as the reference group, the lowest adjusted hazards ratio, 0.32 (P < 0.0001), was seen in 1998, followed by hazards ratios of 0.39 (P < 0.0001) in 1999, 0.41 (P < 0.0001) in 2000, 0.52 (P < 0.0001) in 2001, and 0.53 (P < 0.0001) in 2002. Other antecedents of parathyroidectomy in multivariate models included ESRD network, younger age, female gender, white race, absence of diabetes, longer duration of previous hemodialysis, use of intravenous vitamin D, previous renal transplantation, several comorbid conditions, and parathyroid hormone measurement in the preceding year. With a case-control method, parathyroidectomy was associated with higher mortality rates immediately after surgery, followed, subsequently, by lower long-term rates. Parathyroidectomy rates in U.S. hemodialysis patients increased between 1998 and 2002, a period in which the therapeutic armamentarium for preventing severe hyperparathyroidism expanded considerably.
MicroRNA in Prostate, Bladder, and Kidney Cancer: A Systematic Review
Authors: James W.F. Catto, Antonio Alcaraz, Anders S. Bjartell, Ralph De Vere White, Christopher P. Evans, Susanne Fussel, Freddie C. Hamdy, Olli Kallioniemi, Lourdes Mengual, Thorsten Schlomm, Tapio Visakorpi
Journal: European Urology (2011)