tbuckley/cabot-search huggingface dataset:
Inhibition of Restenosis With β-Emitting Radiotherapy
Authors: Albert E. Raizner, Stephen N. Oesterle, Ron Waksman, Patrick W. Serruys, Antonio Colombo, Yean-Leng Lim, Alan C. Yeung, Wim J. van der Giessen, Lynn Vandertie, Joseph K. Chiu, Larry R. White, Peter J. Fitzgerald, Grzegorz L. Kałuża, Nadir M. Ali
Journal: Circulation (2000)

Background —Intracoronary γ- and β-radiation have reduced restenosis in animal models. In the clinical setting, the effectiveness of β-emitters has not been studied in a broad spectrum of patients, particularly those receiving stents. Methods and Results —A prospective, randomized, sham-controlled study of intracoronary radiotherapy with the β-emitting 32 P source wire, using a centering catheter and automated source delivery unit, was conducted. A total of 105 patients with de novo (70%) or restenotic (30%) lesions who were treated by stenting (61%) or balloon angioplasty (39%) received 0 (control), 16, 20, or 24 Gy to a depth of 1 mm in the artery wall. Angiography at 6 months showed a target site late loss index of 11±36% in radiotherapy patients versus 55±30% in controls ( P &lt;0.0001). A low late loss index was seen in stented and balloon-treated patients and was similar across the 16, 20, and 24 Gy radiotherapy groups. Restenosis (≥50%) rates were significantly lower in radiotherapy patients at the target site (8% versus 39%; P =0.012) and at target site plus adjacent segments (22% versus 50%; P =0.018). Target lesion revascularization was needed in 5 radiotherapy patients (6%) and 6 controls (24%; P &lt;0.05). Stenosis adjacent to the target site and late thrombotic events reduced the overall clinical benefit of radiotherapy. Conclusions —β-radiotherapy with a centered 32 P source is safe and highly effective in inhibiting restenosis at the target site after stent or balloon angioplasty. However, minimizing edge narrowing and late thrombotic events must be accomplished to maximize the clinical benefit of this modality.
Emergence of Zaire Ebola Virus Disease in Guinea
Authors: Sylvain Baize, Delphine Pannetier, Lisa Oestereich, Toni Rieger, Lamine Koivogui, N'Faly Magassouba, Barrè Soropogui, Mamadou Saliou Sow, Sakoba Keïta, Hilde de Clerck, Amanda Tiffany, Gemma Dominguez, Mathieu Loua, Alexis Traoré, Moussa Kolié, Emmanuel Roland Malano, Emmanuel Heleze, Anne Bocquin, Stephane Mély, Hervé Raoul, Valérie Caro, Dániel Cadar, Martin Gabriel, Meike Pahlmann, Dennis Tappe, Jonas Schmidt-Chanasit, Benido Impouma, Abdoul Karim Diallo, Pierre Formenty, Michel van Herp, Stephan Günther
Journal: New England Journal of Medicine (2014)

In March 2014, the World Health Organization was notified of an outbreak of a communicable disease characterized by fever, severe diarrhea, vomiting, and a high fatality rate in Guinea. Virologic investigation identified Zaire ebolavirus (EBOV) as the causative agent. Full-length genome sequencing and phylogenetic analysis showed that EBOV from Guinea forms a separate clade in relationship to the known EBOV strains from the Democratic Republic of Congo and Gabon. Epidemiologic investigation linked the laboratory-confirmed cases with the presumed first fatality of the outbreak in December 2013. This study demonstrates the emergence of a new EBOV strain in Guinea.
Reversal of Cardiac Hypertrophy by Medical Treatment
Authors: R C Tarazi, F M Fouad
Journal: Annual Review of Medicine (1985)

Reversal of left ventricular hypertrophy in hypertensive patients has been proven to follow effective blood pressure control by some antihypertensive drugs. This reversal does not depend solely on the degree of pressure reduction but is also modulated by other factors including, among others, stability of blood pressure control, degree of cardioadrenergic stimulation, and individual variations due to genetic background and possible age. Regression of left ventricular hypertrophy is most likely to occur when the reduction in arterial pressure and peripheral resistance can be maintained without induced reflex cardiac stimulation. Left ventricular performance at rest was not depressed by the reduction in cardiac mass but remained normal both in absolute terms and in relation to changes in LV end-systolic stress.
Induction of Glucagon Synthesis in Diabetic CBA Mice Bearing Mammary Aplastic Carcinomas
Authors: K Pavelić
Journal: JNCI Journal of the National Cancer Institute (1979)

Passaging of the mammary aplastic carcinoma several times in diabetic CBA mice induced an extrapancreatic secretion of glucagon. Consequently, the concentration of immunoreactive glucagon was higher in plasma and the tumor tissue extract. After the injection of alloxan, attempts to reduce the level of this hormone in the diabetic mice were unsuccessful. The tumor cells could have been responsible for the secretion of glucagon.
THE ROLE OF IMMUNITY IN THE PATHOGENESIS OF EXPERIMENTAL RETROGRADE PYELONEPHRITIS
Authors: Betty W. Hunter, Lona L. Akins, Jay P. Sanford
Journal: The Journal of Experimental Medicine (1964)

Retrograde pyelonephritis was produced in rats by the intravesical injection of Proteus mirabilis. When animals were preimmunized against Proteus mirabilis by (a) prior infection, (b) administration of antigen, or (c) passively transferred antiserum, they were resistant to infection by proteus when challenged by the retrograde route. The protective effect of specific preimmunization in retrograde pyelonephritis indicates that a major site of action is retardation of bacterial growth within the parenchyma of the kidney.
Psychological monitoring of overtraining and staleness.
Authors: W P Morgan, D R Brown, J S Raglin, P J O'Connor, K A Ellickson
Journal: British Journal of Sports Medicine (1987)

It is widely agreed that overtraining should be employed in order to achieve peak performance but it is also recognised that overtraining can actually produce decrements in performance. The challenge appears to be one of monitoring stress indicators in the athlete in order to titrate the training stimulus and prevent the onset of staleness. The present paper summarises a ten-year research effort in which the mood states of competitive swimmers have been monitored at intervals ranging from 2-4 weeks during individual seasons for the period 1975-1986. The training cycle has always involved the indoor season which extends from September to March and the athletes who served as subjects were 200 female and 200 male competitive swimmers. The results indicate that mood state disturbances increased in a dose-response manner as the training stimulus increased and that these mood disturbances fell to baseline levels with reduction of the training load. Whilst these results have been obtained in a realistic setting devoid of experimental manipulation, it is apparent that monitoring of mood state provides a potential method of preventing staleness.
Pericardial and Ventricular Pressure
Authors: J. P. HOLT, E. A. RHODE, HELGA KINES, Hawkins Ruth
Journal: Circulation Research (1960)

In anesthetized open-chest and closed-chest dogs subjected to plethora and hemorrhage, pressures were measured simultaneously in the right atrium, right and left ventricles, and the pleural and pericardial spaces. It was found that an increase in ventricular end-diastolic pressure above approximately 1 mm. Hg was associated with a rise in pericardial pressure of nearly the same amount. Thus, the practice of defining "effective" ventricular end-diastolic pressure as the difference between the ventricular and intrapleural pressure gives erroneous values when ventricular end-diastolic pressure is greater than a few mm. Hg. The true ventricular transmural pressure is the difference between ventricular end-diastolic and pericardial end-diastolic pressure and has a value of no more than 2 or 3 mm. Hg under all except the most abnormal circumstances. When ventricular end-diastolic pressure is greater than a few mm. Hg, the pericardial pressure at the end of systole is likewise elevated, but to a lesser degree. Thus, when ventricular end-diastolic pressure is elevated, the measured ventricular end-systolic pressure is greater than the pressure developed by ventricular muscular contraction because end-systolic pressure is the algebraic sum of the pressure developed by ventricular muscular contraction and the pressure in the pericardial space. This error in ventricular systolic pressure may be relatively large for the right and small for the left ventricle. Pericardial pressure decreases during ventricular systole, lowers the pressure on the outside of the atria, and thus, tends to draw blood into the right atrium during ventricular systole.
An operant analysis of problem solving
Authors: B. F. Skinner
Journal: Behavioral and Brain Sciences (1984)

Abstract Behavior that solves a problem is distinguished by the fact that it changes another part of the solver's behavior and is strengthened when it does so. Problem solving typically involves the construction of discriminative stimuli. Verbal responses produce especially useful stimuli, because they affect other people. As a culture formulates maxims, laws, grammar, and science, its members behave more effectively without direct or prolonged contact with the contingencies thus formulated. The culture solves problems for its members, and does so by transmitting the verbal discriminative stimuli called rules. Induction, deduction, and the construction of models are ways of producing rules. Behavior that solves a problem may result from direct shaping by contingencies or from rules constructed either by the problem solver or by others. Because different controlling variables are involved, contingency-shaped behavior is never exactly like rule-governed behavior. The distinction must take account of (1) a system which establishes certain contingencies of reinforcement, such as some part of the natural environment, a piece of equipment, or a verbal community; (2) the behavior shaped and maintained by these contingencies; (3) rules, derived from the contingencies, which specify discriminative stimuli, responses, and consequences, and (4) the behavior occasioned by the rules.
Cuts in NHS waiting lists cannot be attributed to private sector
Authors: Rebecca Coombes
Journal: BMJ (2005)

Private sector involvement in the NHS is making a difference only “at the margins,” a senior civil servant admitted last week. The NHS's group director of health and social care services delivery, John Bacon, made the comments to MPs on the health select committee, which is inquiring into health spending.

The independent sector has been credited with reducing waiting lists, but MPs heard that the proportion of procedures done privately remained low. For example, the number of cataract operations carried out by …
Determinants of the bronchial response to high molecular weight occupational agents in a dry aerosol form
Authors: B Nguyen, K Weytjens, Y Cloutier, H Ghezzo, JL Malo
Journal: European Respiratory Journal (1998)

In occupational challenge tests with isocyanate vapours, bronchial responsiveness is determined by the total dose rather than the concentration or duration of exposure. Whether the same applies for high molecular weight (HMW) agents in powder form is unknown. The aim of this study was to determine whether the total dose of HMW agents in powder form is responsible for the immediate reaction documented in specific challenge tests. Included in the study were nine subjects (seven males and two females) with a diagnosis of occupational asthma proved by specific challenge tests carried out on a preliminary visit. Two challenge tests (using a closed-circuit exposure chamber) were performed at an interval of 2 weeks; the concentrations administered in a random order on these two visits were half and double the one that had caused a 20% fall in forced expiratory volume in one second (FEV1) on a preliminary visit. The duration of exposure was adjusted until a significant fall in FEV1 (target of 20%) occurred. The two concentrations obtained were significantly different, by 2.07+/-0.36-fold (SD). The observed durations of exposure leading to a 20% fall in FEV1 on the two visits also differed significantly by 0.46+/-0.32-fold. Consequently, the cumulative efficient doses were not significantly different between the two visits: 12+/-5.4 and 9+/-5 mg x mL(-1) x min(-1), respectively. The corresponding cumulative dose ratio was 0.96+/-0.61. The expected duration of exposure (10.8+/-24 min) was not significantly different from the observed duration (5.4+/-9 min). The mean and 95% confidence interval for the difference in concentration between the two visits was 1.83-fold (1.48-2.21). In conclusion, the total dose rather than the concentration or duration of exposure per se determines bronchial responsiveness to high molecular weight agents in powder form.
Human Papillomavirus Type 16 Infections and 2-Year Absolute Risk of Cervical Precancer in Women With Equivocal or Mild Cytologic Abnormalities
Authors: Philip E. Castle, Diane Solomon, Mark Schiffman, Cosette M. Wheeler
Journal: JNCI Journal of the National Cancer Institute (2005)

The 2-year absolute risk for cervical precancer attributable to infection by human papillomavirus type 16 (HPV16), the most common and oncogenic HPV type, in the millions of women diagnosed annually with equivocal or mildly abnormal cytology has not been definitively evaluated.Baseline cervical specimens of 5060 women with equivocal (atypical squamous cells of undetermined significance [ASCUS]) or mildly abnormal (low-grade squamous intraepithelial lesion [LSIL]) cytology were tested for HPV DNA using Hybrid Capture 2 (HC2) and type-specific L1 consensus primer polymerase chain reaction. We calculated absolute risks with 95% confidence intervals (CIs) for cumulative diagnosis, during the 2-year study period, of cervical intraepithelial neoplasia grade 3 (CIN3) (n = 535) or cancer (n = 7) (collectively referred to as > or = CIN3) and compared risk by HPV16 status and by other oncogenic HPV types using logistic regression. All statistical tests were two-sided.The baseline prevalences of HPV16 in women with ASCUS or LSIL cytology were 14.9% and 21.1%, respectively. Women with ASCUS or LSIL cytology who were HPV16 DNA positive at baseline had 2-year cumulative absolute risks for > or = CIN3 of 32.5% (95% CI = 28.4% to 36.8%) and 39.1% (95% CI = 33.8% to 44.7%), respectively. By comparison, women with ASCUS who were positive by HC2 for other oncogenic HPV types combined had an 8.4% (95% CI = 6.9% to 10.4%) risk for > or = CIN3, which was similar to the risk posed by having ASCUS (risk = 8.8%, 95% CI = 7.9% to 9.8%) without knowledge of the oncogenic HPV DNA status. Women with LSILs who were positive by HC2 for other oncogenic HPV types combined had a 9.9% (95% CI = 8.0% to 12.0%) 2-year risk for > or = CIN3, which was less than the risk posed by having LSILs (risk = 15.0%, 95% CI = 13.3% to 16.9%) without knowledge of the oncogenic HPV DNA status. Together, women with ASCUS or LSILs who were HPV16-positive had the highest 2-year risk for > or = CIN3 compared with women who were HPV-negative (odds ratio [OR] = 38, 95% CI = 22 to 68; P < .001 ), fivefold greater than the increased risk in women who were positive for other oncogenic HPV types (OR = 7.2, 95%CI = 4.2 to 13, P < .001).Distinguishing the high absolute risk for cervical precancer in HPV16-positive women from the lower risk posed by other oncogenic HPV types might have clinical implications.
Molecular Causes for BUBR1 Dysfunction in the Human Cancer Predisposition Syndrome Mosaic Variegated Aneuploidy
Authors: Saskia J.E. Suijkerbuijk, Maria H.J. van Osch, Frank L. Bos, Sandra Hanks, Nazneen Rahman, Geert J.P.L. Kops
Journal: Cancer Research (2010)

Genetic mutations in the mitotic regulatory kinase BUBR1 are associated with the cancer-susceptible disorder mosaic variegated aneuploidy (MVA). In patients with biallelic mutations, a missense mutation pairs with a truncating mutation. Here, we show that cell lines derived from MVA patients with biallelic mutations have an impaired mitotic checkpoint, chromosome alignment defects, and low overall BUBR1 abundance. Ectopic expression of BUBR1 restored mitotic checkpoint activity, proving that BUBR1 dysfunction causes chromosome segregation errors in the patients. Combined analysis of patient cells and functional protein replacement shows that all MVA mutations fall in two distinct classes: those that impose specific defects in checkpoint activity or microtubule attachment and those that lower BUBR1 protein abundance. Low protein abundance is the direct result of the absence of transcripts from truncating mutants combined with high protein turnover of missense mutants. In this group of missense mutants, the amino acid change consistently occurs in or near the BUBR1 kinase domain. Our findings provide a molecular explanation for chromosomal instability in patients with biallelic genetic mutations in BUBR1.
Gene Expression Signature–Based Prognostic Risk Score in Patients with Primary Central Nervous System Lymphoma
Authors: Atsushi Kawaguchi, Yasuo Iwadate, Yoshihiro Komohara, Masakazu Sano, Koji Kajiwara, Naoki Yajima, Naoto Tsuchiya, Jumpei Homma, Hiroshi Aoki, Tsutomu Kobayashi, Yuko Sakai, Hiroaki Hondoh, Yukihiko Fujii, Tatsuyuki Kakuma, Ryuya Yamanaka
Journal: Clinical Cancer Research (2012)

Better understanding of the underlying biology of primary central nervous system lymphomas (PCNSL) is critical for the development of early detection strategies, molecular markers, and new therapeutics. This study aimed to define genes associated with survival of patients with PCNSL.Expression profiling was conducted on 32 PCNSLs. A gene classifier was developed using the random survival forests model. On the basis of this, prognosis prediction score (PPS) using immunohistochemical analysis is also developed and validated in another data set with 43 PCNSLs.We identified 23 genes in which expressions were strongly and consistently related to patient survival. A PPS was developed for overall survival (OS) using a univariate Cox model. Survival analyses using the selected 23-gene classifiers revealed a prognostic value for high-dose methotrexate (HD-MTX) and HD-MTX-containing polychemotherapy regimen-treated patients. Patients predicted to have good outcomes by the PPS showed significantly longer survival than those with poor predicted outcomes (P < 0.0001). PPS using immunohistochemical analysis is also significant in test (P = 0.0004) and validation data set (P = 0.0281). The gene-based predictor was an independent prognostic factor in a multivariate model that included clinical risk stratification (P < 0.0001). Among the genes, BRCA1 protein expressions were most strongly associated with patient survival.We have identified gene expression signatures that can accurately predict survival in patients with PCNSL. These predictive genes should be useful as molecular biomarkers and they could provide novel targets for therapeutic interventions.
A Contact Energy Function Considering Residue Hydrophobic Environment and Its Application in Protein Fold Recognition
Authors: Mo-Jie Duan, Yan-Hong Zhou
Journal: Genomics Proteomics & Bioinformatics (2005)

Abstract The three-dimensional (3D) structure prediction of proteins is an important task in bioinformatics. Finding energy functions that can better represent residue-residue and residue-solvent interactions is a crucial way to improve the prediction accuracy. The widely used contact energy functions mostly only consider the contact frequency between different types of residues; however, we find that the contact frequency also relates to the residue hydrophobic environment. Accordingly, we present an improved contact energy function to integrate the two factors, which can reflect the influence of hydrophobic interaction on the stabilization of protein 3D structure more effectively. Furthermore, a fold recognition (threading) approach based on this energy function is developed. The testing results obtained with 20 randomly selected proteins demonstrate that, compared with common contact energy functions, the proposed energy function can improve the accuracy of the fold template prediction from 20% to 50%, and can also improve the accuracy of the sequence-template alignment from 35% to 65%.
EZH2 Protein Expression Associates with the Early Pathogenesis, Tumor Progression, and Prognosis of Non–Small Cell Lung Carcinoma
Authors: Carmen Behrens, Luisa M. Solis, Heather Lin, Ping Yuan, Ximing Tang, Humam Kadara, Erick Riquelme, Hector Galindo, Cesar A. Moran, Neda Kalhor, Stephen G. Swisher, George R. Simon, David J. Stewart, J. Jack Lee, Ignacio I. Wistuba
Journal: Clinical Cancer Research (2013)

Enhancer of zeste homolog 2 (EZH2) promotes carcinogenesis by epigenetically silencing tumor suppressor genes. We studied EZH2 expression by immunohistochemistry in a large series of non-small cell lung carcinomas (NSCLC) in association with tumor characteristics and patient outcomes.EZH2 immunohistochemistry expression was analyzed in 265 normal and premalignant bronchial epithelia, 541 primary NSCLCs [221 squamous cell carcinomas (SCC) and 320 adenocarcinomas] and 36 NSCLCs with paired brain metastases. An independent set of 91 adenocarcinomas was also examined. EZH2 expression was statistically correlated with clinico-pathological information, and EGFR/KRAS mutation status.EZH2 expression was significantly (P < 0.0001) higher in SCCs compared with adenocarcinomas and in brain metastasis relative to matched primary tumors (P = 0.0013). EZH2 expression was significantly (P < 0.0001) elevated in bronchial preneoplastic lesions with increasing severity. In adenocarcinomas, higher EZH2 expression significantly correlated with younger age, cigarette smoking, and higher TNM stage (P = 0.02 to P < 0.0001). Higher EZH2 expression in adenocarcinoma was associated with worse recurrence-free survival (RFS; P = 0.025; HR = 1.54) and overall survival (OS; P = 0.0002; HR = 1.96). Furthermore, lung adenocarcinomas with low EZH2 levels and high expression of the lineage-specific transcription factor, TTF-1, exhibited significantly improved RFS (P = 0.009; HR = 0.51) and OS (P = 0.0011; HR = 0.45), which was confirmed in the independent set of 91 adenocarcinomas.In lung, EZH2 expression is involved in early pathogenesis of SCC and correlates with a more aggressive tumor behavior of adenocarcinoma. When EZH2 and TTF-1 expressions are considered together, they serve as a prognostic marker in patients with surgically resected lung adenocarcinomas.