tbuckley/cabot-search huggingface dataset:
Outcomes of Prognostic Disclosure: Associations With Prognostic Understanding, Distress, and Relationship With Physician Among Patients With Advanced Cancer
Authors: Andrea C. Enzinger, Baohui Zhang, Deborah Schrag, Holly G. Prigerson
Journal: Journal of Clinical Oncology (2015)

To determine how prognostic conversations influence perceptions of life expectancy (LE), distress, and the patient-physician relationship among patients with advanced cancer.This was a multicenter observational study of 590 patients with metastatic solid malignancies with progressive disease after ≥ one line of palliative chemotherapy, undergoing follow-up to death. At baseline, patients were asked whether their oncologist had disclosed an estimate of prognosis. Patients also estimated their own LE and completed assessments of the patient-physician relationship, distress, advance directives, and end-of-life care preferences.Among this cohort of 590 patients with advanced cancer (median survival, 5.4 months), 71% wanted to be told their LE, but only 17.6% recalled a prognostic disclosure by their physician. Among the 299 (51%) of 590 patients willing to estimate their LE, those who recalled prognostic disclosure offered more realistic estimates as compared with patients who did not (median, 12 months; interquartile range, 6 to 36 months v 48 months; interquartile range, 12 to 180 months; P < .001), and their estimates were less likely to differ from their actual survival by > 2 (30.2% v 49.2%; odds ratio [OR], 0.45; 95% CI, 0.14 to 0.82) or 5 years (9.5% v 35.5%; OR, 0.19; 95% CI, 0.08 to 0.47). In adjusted analyses, recall of prognostic disclosure was associated with a 17.2-month decrease (95% CI, 6.2 to 28.2 months) in patients' LE self-estimates. Longer LE self-estimates were associated with lower likelihood of do-not-resuscitate order (adjusted OR, 0.439; 95% CI, 0.296 to 0.630 per 12-month increase in estimate) and preference for life-prolonging over comfort-oriented care (adjusted OR, 1.493; 95% CI, 1.091 to 1.939). Prognostic disclosure was not associated with worse patient-physician relationship ratings, sadness, or anxiety in adjusted analyses.Prognostic disclosures are associated with more realistic patient expectations of LE, without decrements to their emotional well-being or the patient-physician relationship.
THE LINKAGE OF GENES FOR THE HUMAN INTERFERON-INDUCED ANTIVIRAL PROTEIN AND INDOPHENOL OXIDASE-B TRAITS TO CHROMOSOME G-21
Authors: Y. H. Tan, J. Tischfield, F. H. Ruddle
Journal: The Journal of Experimental Medicine (1973)

13 independent mouse-human somatic cell hybrid clones derived from beta-propiolactone-inactivated Sendai stimulated cell fusion of human cells with mouse cells were tested for their sensitivities to human and mouse interferon. All of them were protected by mouse interferon and only six of the clones were protected by both human and mouse interferon. Only the six that were protected by human interferon were shown to express the human dimeric form of indophenol oxidase. Complete chromosomal analysis of the clones indicated human chromosome G-21 to be the only human chromosome in common for the six clones which had both phenotypes present. Nine subclones were derived from one of the clones expressing both phenotypes. Eight of the nine subclones were shown to retain both phenotypes, whereas one subclone lost both. Chromosomal analysis of the subclones indicated the loss of chromosome G-21 from the subclone which lost both phenotypes. It is apparent from these findings that the gene(s) for indophenol oxidase (IPO-B) and the gene(s) for the antiviral protein are syntenic and that they are linked to human chromosome G-21.
Prospective seroepidemiologic study of human papillomavirus infection as a risk factor for invasive cervical cancer
Authors: J. Dillner, M. Lehtinen, T. Bjorge, T. Luostarinen, L. Youngman, E. Jellum, P. Koskela, R. E. Gislefoss, G. Hallmans, J. Paavonen, M. Sapp, J. T. Schiller, T. Hakulinen, S. Thoresen, M. Hakama
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: Major risk factors for invasive cervical cancer include infection with human papillomavirus (HPV), infection with other sexually transmitted pathogens (e.g., Chlamydia trachomatis ), and smoking. Since exposures to these risk factors can be related, the contribution of any single factor to cervical carcinogenesis has been difficult to assess. We conducted a prospective study to define the role of HPV infection in cervical carcinogenesis, with invasive cancer as an end point. Methods: A nested case-control study within a joint cohort of 700 000 Nordic subjects was performed. The 182 women who developed invasive cervical cancer during a mean follow-up of 5 years were matched with 538 control women on the basis of age and time of enrollment. Serum samples taken at enrollment were analyzed for evidence of tobacco use (i.e., cotinine levels); for antibodies against HPV types 16, 18, and 33; and for antibodies against C. trachomatis . Relative risks (RRs) were estimated by use of conditional logistic regression. Results: Presence of antibodies against HPV in serum (seropositivity) was associated with an increased risk of cervical cancer, and adjustment for smoking and for C. trachomatis seropositivity did not affect this finding (RR = 2.4; 95% confidence interval [CI] = 1.6-3.7). HPV16 seropositivity was associated primarily with an increased risk of squamous cell carcinoma (RR = 3.2; 95% CI = 1.7-6.2). In contrast, risk associated with HPV18 seropositivity tended to be higher for cervical adenocarcinoma (RR = 3.4; 95% CI = 0.8-14.9). In populations with a low prevalence of antibodies against C. trachomatis , the HPV16- associated risk of cervical cancer was very high (RR = 11.8; 95% CI = 3.7-37.0); in contrast, in populations with a high prevalence of antibodies against C. trachomatis , no excess risk was found. Conclusion: Past infection with HPV16 increases the risk of invasive cervical squamous cell carcinoma, most clearly seen in populations with a low prevalence of sexually transmitted diseases.
Serum cytidine deaminase levels after withdrawal of non-steroidal anti-inflammatory treatment in rheumatoid arthritis.
Authors: P W Thompson, J R Kirwan, D D Jones, H L Currey
Journal: Annals of the Rheumatic Diseases (1988)

Increases in joint inflammation in nine patients with rheumatoid arthritis were provoked by withdrawal of their non-steroidal anti-inflammatory drugs. Pain score, duration of morning stiffness, Ritchie articular index score, and the number of analgesic tablets consumed reached peaks after five, three, five, and five days respectively compared with values during six days of normal treatment. Changes in serum cytidine deaminase (believed to reflect polymorph turnover in inflamed joints) showed a different pattern, with a sharp peak after two days and a subsequent trough. Possible mechanisms for these differences are discussed.
Evaluation of Mitral Insufficiency in Dogs by Electronic Analog Simulation of Radioisotope Dilution Data
Authors: DANIEL T. HAYDEN, WAYNE GARRETT, P. JORDAN
Journal: Circulation Research (1958)

Left atrial and left ventricular volumes, regurgitant flows and systolic efficiencies have been calculated for dogs with and without mitral valve insufficiency, using a technic of electric analog simulation of radioisotope dilution data. Amounts of blood between the valve of the pulmonary artery and the left atrium were calculated by use of mean transit time and flow, and compared to those of the analog. It is concluded that the analog technic is practical and will be more useful when data is available on flow patterns in the pulmonary bed.
Risk factors associated with exertional medial tibial pain: a 12 month prospective clinical study
Authors: S G Burne, K M Khan, P B Boudville, R J Mallet, P M Newman, L J Steinman, E Thornton
Journal: British Journal of Sports Medicine (2004)

To investigate in a military setting the potential role of intrinsic biomechanical and anthropometric risk factors for, and the incidence of, exertional medial tibial pain (EMTP).A prospective clinical outcome study in a cohort of 122 men and 36 women at the Australian Defence Force Academy. Each cadet underwent measurements of seven intrinsic variables: hip range of motion, leg length discrepancy, lean calf girth, maximum ankle dorsiflexion range, foot type, rear foot alignment, and tibial alignment. Test-retest reliability was undertaken on each variable. A physician recorded any cadet presenting with diagnostic criteria of EMTP. Records were analysed at 12 months for EMTP presentation and for military fitness test results.23 cadets (12 men, 11 women) met the criteria for EMTP after 12 months, with a cross gender (F/M) odds ratio of 3.1. In men, both internal and external range of hip motion was greater in those with EMTP: left internal (12 degrees, p = 0.000), right internal (8 degrees, p = 0.014), left external (8 degrees, p = 0.042), right external (9 degrees, p = 0.026). Lean calf girth was lower by 4.2% for the right leg (p = 0.040) but by only 2.9% for the left leg (p = 0.141). No intrinsic risk factor was associated with EMTP in women. EMTP was the major cause for non-completion of the run component of the ADFA fitness test in both men and women.Greater internal and external hip range of motion and lower lean calf girth were associated with EMTP in male military cadets. Women had high rates of injury, although no intrinsic factor was identified. Reasons for this sex difference need to be identified.
Differential exoprotease activities confer tumor-specific serum peptidome patterns
Authors: J. Villanueva
Journal: Journal of Clinical Investigation (2005)

Recent studies have established distinctive serum polypeptide patterns through mass spectrometry (MS) that reportedly correlate with clinically relevant outcomes. Wider acceptance of these signatures as valid biomarkers for disease may follow sequence characterization of the components and elucidation of the mechanisms by which they are generated. Using a highly optimized peptide extraction and matrix-assisted laser desorption/ionization–time-of-flight (MALDI-TOF) MS–based approach, we now show that a limited subset of serum peptides (a signature) provides accurate class discrimination between patients with 3 types of solid tumors and controls without cancer. Targeted sequence identification of 61 signature peptides revealed that they fall into several tight clusters and that most are generated by exopeptidase activities that confer cancer type–specific differences superimposed on the proteolytic events of the ex vivo coagulation and complement degradation pathways. This small but robust set of marker peptides then enabled highly accurate class prediction for an external validation set of prostate cancer samples. In sum, this study provides a direct link between peptide marker profiles of disease and differential protease activity, and the patterns we describe may have clinical utility as surrogate markers for detection and classification of cancer. Our findings also have important implications for future peptide biomarker discovery efforts.
DREAMING SLEEP IN AUTISTIC AND SCHIZOPHRENIC CHILDREN
Authors: EDWARD M. ORNITZ, EDWARD R. RITVO, RICHARD D. WALTER
Journal: American Journal of Psychiatry (1965)

Seven psychotic children in the diagnostic categories of early infantile autism or childhood schizophrenia and six nonpsychotic children were studied during total nights of spontaneous sleep. The electroencephalogram, eye movements, heart rate, heart rate irregularity and submandibular muscle potential were recorded. The autistic and schizophrenic children showed a similar patterning and percentage of sleep time spent in dreaming to the nonpsychotic subjects and to that reported for normal children of the same age. They also showed the concurrence of several components of the dreaming sleep state, particularly decreased submandibular muscle tone and increased heart rate and heart rate irregularity in conjunction with conjugate rapid eye movements during a stage I EEG. No EEG abnormalities indicative of cerebral dysrhythmia were observed during the seven nights of recording.
IN-HOSPITAL SWITCHING OF P2Y12 INHIBITOR IN REAL-LIFE PATIENTS WITH ACUTE CORONARY SYNDROME: INSIGHTS FROM THE GREEK ANTIPLATELET (GRAPE) REGISTRY
Authors: Dimitrios Alexopoulos, Ioanna Xanthopoulou, Evropi Tsoni, Ioannis Ntalas, Spyridon Deftereos, George Sitafidis, Periklis Davlouros, Vlassis Pyrgakis, Ioannis Goudevenos, Filippos Triposkiadis
Journal: Journal of the American College of Cardiology (2013)
Avian Influenza A (H5N1) Infection in Eastern Turkey in 2006
Authors: Ahmet Faik Oner, Ali Bay, Sukru Arslan, Hayrettin Akdeniz, Huseyin Avni Sahin, Yasar Cesur, Serdar Epcacan, Neziha Yilmaz, Ibrahim Deger, Baran Kizilyildiz, Hasan Karsen, Mehmet Ceyhan
Journal: New England Journal of Medicine (2006)

An outbreak of highly pathogenic avian influenza A (H5N1) that had previously been detected throughout Asia, with major economic and health repercussions, extended to eastern Turkey in late December 2005 and early January 2006.We documented the epidemiologic, clinical, and radiologic features of all cases of confirmed H5N1 virus infection in patients who were admitted to Yuzuncu Yil University Hospital in Van, Turkey, between December 31, 2005, and January 10, 2006.H5N1 virus infection was diagnosed in eight patients. The patients were 5 to 15 years of age, and all eight had a history of close contact with diseased or dead chickens. The mean (+/-SD) time between exposure and the onset of illness was 5.0+/-1.3 days. All the patients had fever, and seven had clinical and radiologic evidence of pneumonia at presentation; four patients died. Results of enzyme-linked immunosorbent assay and rapid influenza tests were negative in all patients, and the diagnosis was made by means of a polymerase-chain-reaction assay.H5N1, which causes a spectrum of illnesses in humans, including severe and fatal respiratory disease, can be difficult to diagnose.
Accelerated atherosclerosis in patients with Wegener's granulomatosis
Authors: K de Leeuw
Journal: Annals of the Rheumatic Diseases (2004)

Several autoimmune disorders are complicated by excess cardiovascular disease. In addition to traditional risk factors, non-traditional risk factors such as endothelial activation and excessive vascular remodelling might be determinants of the progression of atherosclerosis in patients with an autoimmune disease.To evaluate whether patients with Wegener's granulomatosis (WG) have an increased prevalence of atherosclerosis and to determine predisposing factors.29 WG patients (19 men; mean (SD) age, 53 (14) years) with inactive disease and 26 controls (16 men; age 53 (15) years) were studied. Common carotid intima-media thickness (IMT) was measured by ultrasound. In all individuals traditional risk factors for cardiovascular disease were determined. High sensitivity C reactive protein (hsCRP) was measured. Endothelial activation was assessed by measuring thrombomodulin, vascular cell adhesion molecule-1, and von Willebrand factor. As a marker of vascular remodelling matrix metalloproteinases (MMP-3 and MMP-9) and TIMP-1 were measured.IMT was increased in WG patients compared with controls (p<0.05). No differences in traditional risk factors and endothelial activation markers between patients and controls were found. Levels of hsCRP, MMPs, and TIMP-1 were increased in WG patients (p<0.05).Increased IMT found in WG patients cannot be explained by an increased prevalence of traditional risk factors. Although endothelial activation markers in WG patients with inactive disease were not increased, the raised levels of hsCRP, MMPs, and TIMP-1 suggest that enhanced inflammation and excessive vascular remodelling are contributing factors in the development of accelerated atherosclerosis in WG.
Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies
Authors: Rachel Huxley, Federica Barzi, Mark Woodward
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To estimate the relative risk for fatal coronary heart disease associated with diabetes in men and women. <b>Design</b> Meta-analysis of prospective cohort studies. <b>Data sources</b> Studies published between 1966 and March 2005, identified through Embase and Medline, using a combined text word and MESH heading search strategy, in addition to studies from the Asia Pacific Cohort Studies Collaboration. <b>Review methods</b> Studies were eligible if they had reported estimates of the relative risk for fatal coronary heart disease comparing men and women with and without diabetes. Studies were excluded if the estimates were not adjusted at least for age. <b>Results</b> 37 studies of type 2 diabetes and fatal coronary heart disease among a total of 447 064 patients were identified. The rate of fatal coronary heart disease was higher in patients with diabetes than in those without (5.4 <i>v</i> 1.6%). The overall summary relative risk for fatal coronary heart disease in patients with diabetes compared with no diabetes was significantly greater among women than it was among men: 3.50, 95% confidence interval 2.70 to 4.53 <i>v</i> 2.06, 1.81 to 2.34. After exclusion of the eight studies that had adjusted only for age, the difference in risk between the sexes was substantially reduced but still highly significant. The pooled ratio of the relative risks (women: men) from the 29 studies with multiple adjusted estimates was 1.46 (1.14 to 1.88). <b>Conclusions</b> The relative risk for fatal coronary heart disease associated with diabetes is 50% higher in women than it is in men. This greater excess coronary risk may be explained by more adverse cardiovascular risk profiles among women with diabetes, combined with possible disparities in treatment that favour men.
ANNUAL LIPID CYCLES IN HIBERNATORS: Integration of Physiology and Behavior
Authors: Dark John
Journal: Annual Review of Nutrition (2005)

▪ Abstract Mammalian hibernation is a temporary suspension of euthermia allowing endotherms to undergo reversible hypothermia and generate a marked savings in energy expenditure. In most fat-storing hibernator species, seasonal changes in food intake, triacylglycerol deposition, metabolism, and reproductive development are controlled by a circannual clock. In ground-dwelling sciurid rodents (ground squirrels and marmots), for example, energy intake increases during a summer body mass gain phase, and toward the end of this phase metabolic rate also begins to decrease, resulting in a profound increase in lipid deposition as fat. Increased activity of lipogenic hormones and enzymes correspond with this increase. The hibernation mass loss phase begins after the body mass peak in the fall and ends in spring. During this phase, stored lipids are slowly utilized in a programmed manner by undergoing deep torpor or hibernation during which the hypothalamic setpoint for body temperature is typically reduced to just above 0°C. Throughout the hibernation season, bouts of deep torpor are punctuated by periodic arousals in which brown adipose tissue thermogenesis plays a critical role. Lipid oxidation nearly exclusively fuels deep torpor and most of the rewarming process. The fatty acid composition of stored lipids can affect the depth and duration of deep torpor, and saturated fatty acids may be preferentially used during hibernation, whereas polyunsaturated fatty acids may be preferentially retained. Female and underweight male hibernators terminate hibernation in spring when aboveground food becomes available; in contrast, heavier males with sufficient lipid reserves spontaneously terminate hibernation several weeks before females and independent of food availability. Mating occurs shortly after emergence from hibernation, and the lipid cycle begins again with the completion of reproduction. Lipid deposition and mobilization, temperature regulation, reproduction, and circannual timing are intimately interdependent. The unique manner in which they are controlled during the annual cycle, especially lipid reserves, makes hibernators valuable and promising models for research into the mechanisms underlying these processes in all mammals.
Regular Feeding Plays an Important Role in Cholesterol Homeostasis Through the Liver Circadian Clock
Authors: Daisuke Yamajuku, Shingo Okubo, Tomonori Haruma, Takahiko Inagaki, Yuji Okuda, Tomoko Kojima, Keiji Noutomi, Seiichi Hashimoto, Hiroaki Oda
Journal: Circulation Research (2009)

Peripheral clock control and the relevance of the circadian rhythm to physiology and disease are major questions in mammalian circadian biology.We examined the physiological functions of the liver clock.We established a suppressed feeding schedule regimen constituting a high-cholesterol diet delivered every 6 hours without changes in energy and cholesterol intake. We found that rats exposed to this regimen developed hypercholesteremia. In the liver, the rhythmicity of expression of several clock genes was disrupted. Furthermore, the nocturnal expression of the CYP7A1 gene, which encodes the rate-limiting enzyme for the conversion of cholesterol to bile acids, was shifted to a diurnal pattern. Indeed, suppression of a regular feeding rhythm increased the secretion rate of very-low-density lipoprotein cholesterol from the liver and decreased the excretion of fecal bile acids.Our results demonstrated that not only the amount and quality of food but also the timing of meals has crucial health implications.
Inhibition of Breast Cancer Metastases by a Novel Inhibitor of TGFβ Receptor 1
Authors: Yuanzhang Fang, Yihua Chen, Linxi Yu, Cong Zheng, Ya Qi, Zhenxi Li, Zhengfeng Yang, Yong Zhang, Tieliu Shi, Jian Luo, Mingyao Liu
Journal: JNCI Journal of the National Cancer Institute (2012)

Transforming growth factor beta (TGFβ), which is implicated in metastasis to various organs in breast cancer, is a potential target for new antitumor metastasis drugs.To identify specific inhibitors of TGFβ receptor 1 (TGFβR1) in breast cancer metastasis, a virtual library of more than 400000 different compounds was screened by molecular docking modeling and confirmed with Smad-binding element luciferase and TGFβR1 kinase assays. Affymetrix GeneChip expression analysis of mRNA levels and real-time polymerase chain reaction were performed to determine expression changes of TGFβ-mediated, metastasis-associated genes in breast cancer cells after treatment with the small-molecule inhibitor YR-290. YR-290 was also examined for its effects on breast cancer migration, invasion, and metastasis using transwell and epithelial-to-mesenchymal transition (EMT) assays in vitro and three different mouse (BALB/c and NU/NU nude) models (n = 10 per group). Kaplan-Meier analyses were used to assess survival. All statistical tests were two-sided.YR-290 interacted with the kinase domain of TGFβR1, abrogated kinase activity (half maximal inhibitory concentration = 137nM, 95% confidence interval = 126.4 to 147.6nM) and inhibited the TGFβ-mediated downstream signaling pathway and metastasis-associated genes in breast cancer cells. YR-290 inhibited TGFβ-modulated breast cancer cell migration and invasion. In tumor metastasis mouse models, YR-290 almost completely blocked cancer metastasis. Numbers of lung tumor nodules of mice treated with 1mg/kg and 5mg/kg YR-290 were reduced by 74.93% (95% confidence interval = 61.45% to 88.41%) and 94.93% (95% confidence interval = 82.13% to 100%), respectively, compared with control mice. Treatment with YR-290 also statistically significantly prolonged the survival of tumor-bearing mice.YR-290 is a novel inhibitor of tumor metastasis that works by blocking TGFβ signaling pathways.