tbuckley/cabot-search huggingface dataset:
Connectivity-based risk score for hepatocellular carcinoma prognosis
Authors: Hua Ye, Wei Liu
Journal: Hepatology (2013)

Kim et al.1 proposed a 65-gene-based risk score classifier of overall survival in hepatocellular carcinoma (HCC). The risk score, derived by multiplying the expression level of a gene by its Cox coefficient, could robustly predict overall survival of HCC patients. Its clinical usefulness was further confirmed in a second test cohort. There were some minor defects in Fig. 1A and Table 2. The article adopted a previous method2 by simply using Cox's coefficient from univariate regression analysis, ignoring the inherent correlation between genes. However, as mentioned in the literature,2 nonlinear relationships may exist between genes, that is, the potential interaction between signature genes. Furthermore, although three cohorts are used for survival analysis in the study, none of the survival data are publicly available. It is worth noting that the microarray data analyzed were from different platforms, including single- and double-channel arrays, but no details about data manipulation were provided, which further complicated the prediction model. To examine whether these signature genes plus univariate coefficients can consistently stratify patients into low- or high-risk groups, chip data GSE10141,3 the gene-expression data set of an HCC cohort with survival data, was reanalyzed. The original expression-matrix data of intensity was utilized directly. Patients were similarly dichotomized into groups at high or low risk using the risk-score classifier, but the two groups of patients showed indistinguishable prognostic outcome (P = 0.13). To test whether the correlation between signature genes accounts for prediction power, the sum of Pearson's correlation (connectivity) with other signature genes was used, instead of the univariate Cox coefficient. Patients were regrouped, and the low-risk group had a better prognosis (P = 0.025). The different stratification result was possibly because of having taken gene interaction into consideration. However, it should be noted that most of the samples from Kim et al.'s study were frozen specimens, whereas samples from Hoshida et al.'s study3 were formalin-fixed paraffin-embedded tissues. Moreover, only 52 of the 65 signature genes were analyzed because of platform differences. Further large-scale evaluation of the two risk-score methods as HCC overall survival prediction in prospective studies among multicenters are needed. HUA YE, M.D.1 WEI LIU, PH.D.2 1Department of Gastroenterology, Lihuili Hospital, Ningbo, China 2Department of Pathology, Human Centrifuge Medical Training Center, Institute of Aviation Medicine of Chinese People's Liberation Army Air Force, Beijing, China
Phase II Study of Yttrium-90–Ibritumomab Tiuxetan in Patients With Relapsed or Refractory Mantle Cell Lymphoma
Authors: Michael Wang, Yasuhiro Oki, Barbara Pro, Jorge Enrique Romaguera, Maria Alma Rodriguez, Felipe Samaniego, Peter McLaughlin, Frederick Hagemeister, Sattva Neelapu, Amanda Copeland, Barry I. Samuels, Evelyne M. Loyer, Yuan Ji, Anas Younes
Journal: Journal of Clinical Oncology (2009)

This phase II trial evaluated the safety and efficacy of yttrium-90 ((90)Y)-ibritumomab tiuxetan in patients with relapsed or refractory mantle cell lymphoma (MCL).Patients with relapsed or refractory MCL were eligible for the study if they had adequate major organ function and performance status. Those with CNS disease, pleural effusion, circulating lymphoma cells > or = 5,000/microL, or history of stem-cell transplant were ineligible. Patients with a platelet count > or = 150,000/microL received a dose of 0.4 mCi/kg of (90)Y-ibritumomab tiuxetan, whereas those with a platelet count less than 150,000/microL received a dose of 0.3 mCi/kg.Thirty-four patients with a median age of 68 years (range, 52 to 79 years) received the therapeutic dose. The patients had received a median of three prior treatment regimens (range, one to six treatment regimens), including those that contained rituximab (n = 32) and bortezomib (n = 7). Of the 32 patients with measurable disease, 10 (31%) achieved complete or partial remission. After a median follow-up of 22 months (range, 2 to 72+ months), an intent-to-treat analysis revealed a median event-free survival (EFS) duration of 6 months and an overall survival duration of 21 months. The median EFS for those who achieved partial or complete remission was 28 months, while it was 3 months for those whose disease did not respond (P < .0001); it was 9 months for patients whose tumor measured less than 5 cm in the largest diameter before treatment and 3 months for those whose tumor measured > or = 5 cm (P = .015).The single-agent activity of (90)Y-ibritumomab tiuxetan and its favorable safety profile warrant its further development for the treatment of MCL.
Two Patterns of Genome Organization in Mammals: the Chromosomal Distribution of Duplicate Genes in Human and Mouse
Authors: R. Friedman
Journal: Molecular Biology and Evolution (2004)

Gene duplication occurs repeatedly in the evolution of genomes, and the rearrangement of genomic segments has also occurred repeatedly over the evolution of eukaryotes. We studied the interaction of these two factors in mammalian evolution by comparing the chromosomal distribution of multigene families in human and mouse. In both species, gene families tended to be confined to a single chromosome to a greater extent than expected by chance. The average number of families shared between chromosomes was nearly 60% higher in mouse than in human, and human chromosomes rarely shared large numbers of gene families with more than one or two other chromosomes, whereas mouse chromosomes frequently did so. A higher proportion of duplicate gene pairs on the same chromosome originated from recent duplications in human than in mouse, whereas a higher proportion of duplicate gene pairs on separate chromosomes arose from ancient duplications in human than in mouse. These observations are most easily explained by the hypotheses that (1) most gene duplications arise in tandem and are subsequently separated by segmental rearrangement events, and (2) that the process of segmental rearrangement has occurred at a higher rate in the lineage of mouse than in that of human.
Once-Only Sigmoidoscopy in Colorectal Cancer Screening: Follow-up Findings of the Italian Randomized Controlled Trial--SCORE
Authors: N. Segnan, P. Armaroli, L. Bonelli, M. Risio, S. Sciallero, M. Zappa, B. Andreoni, A. Arrigoni, L. Bisanti, C. Casella, C. Crosta, F. Falcini, F. Ferrero, A. Giacomin, O. Giuliani, A. Santarelli, C. B. Visioli, R. Zanetti, W. S. Atkin, C. Senore
Journal: JNCI Journal of the National Cancer Institute (2011)

A single flexible sigmoidoscopy at around the age of 60 years has been proposed as an effective strategy for colorectal cancer (CRC) screening.We conducted a randomized controlled trial to evaluate the effect of flexible sigmoidoscopy screening on CRC incidence and mortality. A questionnaire to assess the eligibility and interest in screening was mailed to 236,568 men and women, aged 55-64 years, who were randomly selected from six trial centers in Italy. Of the 56,532 respondents, interested and eligible subjects were randomly assigned to the intervention group (invitation for flexible sigmoidoscopy; n = 17,148) or the control group (no further contact; n = 17,144), between June 14, 1995, and May 10, 1999. Flexible sigmoidoscopy was performed on 9911 subjects. Intention-to-treat and per-protocol analyses were performed to compare the CRC incidence and mortality rates in the intervention and control groups. Per-protocol analysis was adjusted for noncompliance.A total of 34,272 subjects (17,136 in each group) were included in the follow-up analysis. The median follow-up period was 10.5 years for incidence and 11.4 years for mortality; 251 subjects were diagnosed with CRC in the intervention group and 306 in the control group. Overall incidence rates in the intervention and control groups were 144.11 and 176.43, respectively, per 100,000 person-years. CRC-related death was noted in 65 subjects in the intervention group and 83 subjects in the control group. Mortality rates in the intervention and control groups were 34.66 and 44.45, respectively, per 100,000 person-years. In the intention-to-treat analysis, the rate of CRC incidence was statistically significantly reduced in the intervention group by 18% (rate ratio [RR] = 0.82, 95% confidence interval [CI] = 0.69 to 0.96), and the mortality rate was non-statistically significantly reduced by 22% (RR = 0.78; 95% CI = 0.56 to 1.08) compared with the control group. In the per-protocol analysis, both CRC incidence and mortality rates were statistically significantly reduced among the screened subjects; CRC incidence was reduced by 31% (RR = 0.69; 95% CI = 0.56 to 0.86) and mortality was reduced by 38% (RR = 0.62; 95% CI = 0.40 to 0.96) compared with the control group.A single flexible sigmoidoscopy screening between ages 55 and 64 years was associated with a substantial reduction of CRC incidence and mortality.
Effect of Intravenous FX06 as an Adjunct to Primary Percutaneous Coronary Intervention for Acute ST-Segment Elevation Myocardial Infarction
Authors: Dan Atar, Peter Petzelbauer, Jürg Schwitter, Kurt Huber, Benno Rensing, Jaroslaw D. Kasprzak, Christian Butter, Lars Grip, Peter R. Hansen, Tim Süselbeck, Peter M. Clemmensen, Marcos Marin-Galiano, Bernard Geudelin, Peter T. Buser
Journal: Journal of the American College of Cardiology (2009)
Recombinant Human Erythropoietin in the Treatment of Anemia Associated with Human Immunodeficiency Virus (HIV) Infection and Zidovudine Therapy
Authors: David H. Henry, Gildon N. Beall, Constance A. Benson, John Carey, Lawrence A. Cone, Lawrence J. Eron, Milan Fiala, Margaret A. Fischl, Stephen J. Gabin, Michael S. Gottlieb, Jeffrey E. Galpin, Jerome E. Groopman, Thomas M. Hooton, Joseph G. Jemsek, Randy L. Levine, Steven A. Miles, John J. Rinehart, Adan Rios, William J. Robbins, John C. Ruckdeschel, Jean A. Smith, Spotswood L. Spruance, Barbara Starrett, John Toney, Ralph Zalusky, Robert I. Abels, Edward C. Bryant, Kay M. Larholt, Allan R. Sampson, Seth A. Rudnick
Journal: Annals of Internal Medicine (1992)

To assess the effect of recombinant human erythropoietin (r-HuEPO) on anemia in patients with the acquired immunodeficiency syndrome (AIDS) who are receiving zidovudine therapy.Combined analysis of four 12-week, randomized, double-blind, controlled clinical trials.Multiple centers in the United States.Two hundred and ninety-seven anemic (hematocrit < 30%) patients with AIDS who were receiving zidovudine therapy. Of the 297 patients, 255 were evaluable for efficacy, but all patients were included in analysis of safety.Patients were randomly assigned to receive either r-HuEPO (100 to 200 U/kg body weight) or placebo, intravenously or subcutaneously, three times per week for up to 12 weeks.Changes in mean hematocrit, transfusion requirement, and quality of life.Sixty-nine percent of patients had endogenous serum erythropoietin levels less than or equal to 500 IU/L, and 31% had erythropoietin levels greater than 500 IU/L. In patients with low erythropoietin levels (< or equal to 500 IU/l), r-HuEPO therapy decreased the mean number of units of blood transfused per patient when compared with placebo (3.2 units and 5.3 units, respectively; P = 0.003) and increased the mean hematocrit from the baseline level (4.6 percentage points and 0.5 percentage points, respectively; P <0.001). Overall quality of life improved in patients on r-HuEPO therapy (P = 0.13). Patients with erythropoietin levels greater than 500 IU/L showed no benefit from r-HuEPO in any outcome variable. Placebo and r-HuEPO recipients did not differ in the incidence of adverse effects or opportunistic infections.Therapy with r-HuEPO can increase the mean hematocrit and decrease the mean transfusion requirement in anemic patients with AIDS who are receiving zidovudine and have endogenous low erythropoietin levels (< or equal to 500 IU/L). Such therapy is of no apparent benefit in patients whose endogenous erythropoietin levels are higher than 500 IU/L.
Concomitant exposure to nicotine and endotoxin in vitro induces murine airway hyperreactivity possibly via nicotine-induced upregulation of toll-like receptors
Authors: Yuan Xu, Yaping Zhang, Lars-Olaf Cardell
Journal: European Respiratory Journal (2011)

Introduction:  Nicotine and endotoxin are important components of cigarette smoke, known to cause asthma and trigger exacerbations. The present study examined whether concomitant exposure to nicotine and endotoxin in vitro can cause airway hyperreactivity (AHR) in murine tracheal segments, and explored the involvement of Toll-like receptors (TLR) and MAPK signalling pathways in this process.   Methods:  Isolated murine tracheal segments were exposed to nicotine (10 μM) and/or endotoxin (10 μg/ml) in organ culture for 4 days. Contractile responses to carbachol were recorded by myograph. In parallel, mRNA and protein expressions of the cell surface TLRs and several inflammatory mediators were semi-quantified by real-time PCR and confocal microscopy-based immunohistochemistry after exposure to only nicotine with/without specific inhibitors for MAPK pathways JNK, ERK1/2 or p38.   Results:  Nicotine or endotoxin alone failed to affect contractile responses to carbachol, whereas AHR appeared after concomitant exposure. Incubation with nicotine increased expression of TLR2, 4 and 6, decreased TLR5, while TLR1 and 11 expressions remained unchanged. In parallel, MCP-1 and COX-2 expressions also increased. Inhibition of JNK, but not ERK1/2 or p38, attenuated nicotine9s effects.   Conclusion:  Long-term nicotine exposure induces local inflammation and derrangement of the airway cell surface TLR expression pattern via the MAPK JNK signaling dependent pathways. It is therefore tempting to suggest that the nicotine-induced up-regulation of TLR is responsible for the AHR observed after concomitant incubation with nicotine and endotoxin.
The Decision Not to Drive During Hypoglycemia in Patients With Type 1 and Type 2 Diabetes According to Hypoglycemia Awareness
Authors: Alexander D.M. Stork, Timon W. van Haeften, Thiemo F. Veneman
Journal: Diabetes Care (2007)

In recent years, there has been an ongoing discussion on the relationship between diabetes and driving. As driving performance will inevitably decline at lower levels of glycemia, patients' decisions concerning driving or taking corrective action when hypoglycemia occurs immediately before or during driving seems paramount.Twenty-four type 1 diabetic patients with normal awareness of hypoglycemia (T1Norm group), 21 type 1 diabetic patients with impaired awareness of hypoglycemia (T1Imp group), and 20 type 2 diabetic patients with normal awareness of hypoglycemia (T2 group) were studied. They were asked whether they felt hypoglycemic and whether they would currently drive during experimental euglycemia (5.0 mmol/l) and hypoglycemia (2.7 mmol/l).In the T1Norm group, 1 patient (4.2%) decided to drive during hypoglycemia. In the T1Imp group, 9 patients (42.9%) said they would drive in the hypoglycemic condition. In the T2 group, 5 patients (25%) would drive. This was more frequently the case for patients on oral hypoglycemic agents (chi2 = 4.44; P = 0.04). No effect of sex (chi2 = 0.78; P = 0.38) or age (chi2 = 0.22; P = 0.64) was noted.Patients with type 1 diabetes and impaired awareness of hypoglycemia frequently decided to drive while hypoglycemic, whereas patients with type 1 diabetes and normal awareness of hypoglycemia appeared to make safe decisions concerning hypoglycemia and driving. Strikingly, patients with type 2 diabetes and normal hypoglycemia awareness frequently made potentially dangerous decisions as well, particularly when using oral hypoglycemic agents. Therefore, early, clear, and consistent education is imperative.
Sequential Magnetic Resonance Monitoring of Pulmonary Flow With Endovascular Stents Placed Across the Pulmonary Valve in Growing Swine
Authors: Titus Kuehne, Maythem Saeed, Gautham Reddy, Haydar Akbari, Kelly Gleason, Daniel Turner, David Teitel, Phillip Moore, Charles B. Higgins
Journal: Circulation (2001)

Background Patients with endovascular stent implantation for the treatment of right ventricular outflow tract obstruction are often left with incomplete relief of the obstruction and significant pulmonary regurgitation. A noninvasive and reproducible method for monitoring such patients is desirable. MRI in the presence of a stent, however, has to overcome the problem of potential metallic artifacts. Methods and Results Under x-ray fluoroscopic guidance, endovascular nitinol stents were placed across the pulmonary valve in 6 young pigs to induce pulmonary regurgitation. Five additional pigs served as controls. Initial MRI was performed after 2 days (13.5±1.8 kg) and follow-up after 3 months (32±2.9 kg). Pulmonary flow volumes and regurgitant fraction were quantified by velocity-encoded cine (VEC) MRI through (VEC-TS) and distal to (VEC-DS) the stent. VEC-TS was compared with VEC-DS and volumetric measurements of left and right ventricular stroke volumes provided by cine MRI (“gold standard”). Antegrade and retrograde pulmonary flow volumes by VEC-TS were slightly but significantly less than those with VEC-DS and cine MRI. Excellent correlations ( r &gt;0.97) for phasic pulmonary flow volumes as measured by VEC-TS and VEC-DS were shown. Pulmonary regurgitant fraction increased from 32.8±15% to 49.6±17% ( P &lt;0.05) over the course of 3 months with VEC-TS. Conclusions MRI demonstrates the progression of pulmonary regurgitation in growing swine. VEC MRI has the ability to quantify pulmonary blood flow inside the lumen of nitinol stents. MRI appears to be ideally suited for monitoring patients with endovascular nitinol stents in the pulmonary artery or pulmonary valve position.
Hepatitis B virus, hepatitis non-A, non-B virus and hepatitis delta virus in lyophilized antihemophilic factor: Relative sensitivity to heat
Authors: Robert H. Purcell, John L. Gerin, Hans Popper, William T. London, John Cicmanec, Jorg W. Eichberg, Jack Newman, Michael E. Hrinda
Journal: Hepatology (1985)

Lyophilized plasma derivatives are more stable to heat than when they are in the liquid state. Commercial Factor VIII (antihemophilic factor) was seeded with a measured quantity of hepatitis B virus. The contaminated material was then lyophilized and subjected to heat of 60 degrees C for 30 hr. Chimpanzees were inoculated with the heat-treated antihemophilic factor or sham-treated antihemophilic factor that had been held at 4 degrees C. Surprisingly, hepatitis B virus survived the heating procedure with no apparent loss in titer: the incubation period to appearance of HBsAg was that expected for the challenge dose of virus. Even more surprising, one chimpanzee (the recipient of the unheated antihemophilic factor) also developed non-A, non-B hepatitis and two chimpanzees (recipients of the heated antihemophilic factor) also developed delta hepatitis. Neither of these agents was a contaminant of the hepatitis B virus challenge pool, since the purity of this hepatitis B virus pool was established previously in chimpanzees. Thus, both a non-A, non-B agent and the delta agent apparently contaminated the commercial antihemophilic factor. This is the first direct evidence for contamination of antihemophilic factor with the delta agent and confirms previous seroepidemiologic evidence for its presence in pooled plasma derivatives. Subsequent inactivation studies were performed with antihemophilic factor experimentally contaminated with the Hutchinson strain of non-A, non-B hepatitis virus. In these studies, heating at 60 degrees C for 30 hr in the dry state rendered antihemophilic factor free of detectable non-A, non-B hepatitis virus.
Enhanced Photocarcinogenesis in Interleukin-12–Deficient Mice
Authors: Akira Maeda, Stefan W. Schneider, Motohiro Kojima, Stefan Beissert, Thomas Schwarz, Agatha Schwarz
Journal: Cancer Research (2006)

Abstract UV-induced DNA damage is the basis for the development of UV-mediated skin cancer because reduction of DNA damage lowers the risk for photocarcinogenesis. The cytokine interleukin (IL)-12 was shown to exhibit the capacity to reduce UV-induced DNA damage presumably via induction of nucleotide excision repair. Because IL-12 is also produced in the skin, we wondered whether endogenous IL-12 protects from photocarcinogenesis. Therefore, we used knockout mice that lack the IL-12p40 chain and thus do not secrete biologically active IL-12. IL-12p40 knockout (IL-12p40−/−) and wild-type (wt) mice were exposed thrice weekly to UV. Skin biopsies obtained after 6 weeks revealed significantly increased numbers of sunburn cells in IL-12p40−/− mice. Additionally, a higher load of UV-induced pyrimidine dimers could be detected in the skin of UV-exposed IL-12p40−/− mice. Staining of epidermal sheets with an antibody against the tumor suppressor gene p53 revealed a higher number of p53 patches in the skin of IL-12p40−/− mice. After ∼200 days, first skin tumors developed. Kaplan-Meier analysis indicated a significantly increased probability of tumor development in the IL-12p40−/− mice. In addition, the number of tumors developing in the individual mice was significantly higher in IL-12p40−/− mice than in wt mice. Tumors obtained in IL-12p40−/− mice grew faster than those obtained from wt mice on inoculation into nu/nu mice. This was confirmed in an electrophysiologic assay evaluating the intrinsic invasive potency of tumor cells. Together, these data indicate that IL-12 deficiency is associated with an increased risk to develop UV-induced skin cancer, implying that endogenous IL-12 may protect from photocarcinogenesis. (Cancer Res 2006; 66(6): 2962-9)
Physical therapy is as effective as surgery for lumbar spinal stenosis, study finds
Authors: J. Wise
Journal: BMJ (2015)

Surgical decompression treatment for lumbar spinal stenosis is no better than physical therapy in improving symptoms and function, a randomised controlled trial has shown.

The study, published in the Annals of Internal Medicine ,1 showed that both groups of patients began to show improvement at 10 weeks and continued to improve through 26 weeks. Improvements were maintained in both groups at the …