tbuckley/cabot-search huggingface dataset:
Association between walking distance and percentiles of body mass index in older and younger men
Authors: P T Williams
Journal: British Journal of Sports Medicine (2008)

Objective: To assess the association of weekly walking distance to body weight and waist circumference in elderly (age ⩾75 years), senior (55⩽ age &lt;75 years), middle-aged (35⩽ age &lt;55 years), and younger men (18⩽ age &lt;35 years old). Design: Cross-sectional analyses of baseline questionnaires from 7082 male participants of the National Walkers’ Health Study. Results: Standard regression analyses showed that body mass index (BMI) was inversely and significantly associated with walking distance (kg/m 2 per km/week) in elderly (slope (SE): −0.032 (0.008)), senior (−0.045 (0.005)) and middle-aged men (−0.037 (0.007)), as were their waist circumferences (−0.090 (0.025), −0.122 (0.012) and −0.091 (0.015) cm per km/week, respectively), and that these slopes remained significant when adjusted statistically for reported weekly servings of meat, fish, fruit and alcohol. However, percentile regression analyses showed that the declines in BMI per km/week walked were greater at the higher than the lower percentiles of the BMI distribution. In men ⩾74 years old the decline per km walked was 4.9-fold greater among the heaviest men (that is, 90th BMI percentile; −0.076 kg/m 2 per km/week) than among the leanest men (that is, 10th BMI percentile; −0.015 kg/m 2 per km/week). The differences in slope at the 90th compared to the 10th BMI percentile were 5.4-fold among men 55–74 years old and sixfold among men 35–54 years old. Per km/week walked, the declines at the 90th percentile of waist circumference were also greater than at its 10th percentile, and intermediate for percentiles in between. Whereas standard regression analyses suggest that the average declines in BMI per km/week walked reported here are consistent with those reported previously per km/week run in male runners 35–54 years old (−0.036 (0.001) kg/m 2 per km/week) and ⩾50 years old (−0.038 (0.001) kg/m 2 per km/week), percentile regression analyses showed that when adjusted to the leaner body weights of the runners the declines per km walked were between 49% and 59% less for walkers than runners. Conclusions: Declines in BMI and waist circumferences with walking distance depend upon the percentile of the BMI distribution, with the decline per km walked being significantly greater among heavier men.
DriverNet: uncovering the impact of somatic driver mutations on transcriptional networks in cancer
Authors: Ali Bashashati, Gholamreza Haffari, Jiarui Ding, Gavin Ha, Kenneth Lui, Jamie Rosner, David G Huntsman, Carlos Caldas, Samuel A Aparicio, Sohrab P Shah
Journal: Genome biology (2012)

Simultaneous interrogation of tumor genomes and transcriptomes is underway in unprecedented global efforts. Yet, despite the essential need to separate driver mutations modulating gene expression networks from transcriptionally inert passenger mutations, robust computational methods to ascertain the impact of individual mutations on transcriptional networks are underdeveloped. We introduce a novel computational framework, DriverNet, to identify likely driver mutations by virtue of their effect on mRNA expression networks. Application to four cancer datasets reveals the prevalence of rare candidate driver mutations associated with disrupted transcriptional networks and a simultaneous modulation of oncogenic and metabolic networks, induced by copy number co-modification of adjacent oncogenic and metabolic drivers. DriverNet is available on Bioconductor or at http://compbio.bccrc.ca/software/drivernet/.
The cost-effectiveness of nCPAP treatment in patients with moderate-to-severe obstructive sleep apnoea
Authors: J. Mar, J.R. Rueda, J. Durán-Cantolla, C. Schechter, J. Chilcott
Journal: European Respiratory Journal (2003)

The demand for diagnostic and therapeutic services for obstructive sleep apnoea syndrome (OSAS) showed marked growth during the 1990s. This paper analyses the long-term cost-effectiveness of nasal continuous positive airway pressure (nCPAP) treatment in comparison to conventional null treatment. A Markov model was used to represent the natural history of OSAS based upon published evidence. Utility values came from a survey of OSAS patients. Data on health costs were collected from hospitals in the Basque Country, Spain. The incremental cost-effectiveness ratio of nCPAP treatment is &lt;6,000 Euros per quality-adjusted life year. On disaggregated analysis, nCPAP treatment accounts for 86% of incremental costs; 84% of incremental effectiveness is attributable to improved quality of life. Treatment of obstructive sleep apnoea syndrome with nasal continuous positive airway pressure has a cost-effectiveness that is in line with that of other commonly funded treatments such as antihypertensive drugs. The key clinical benefit of nasal continuous positive airway pressure treatment is improvement in the quality of life of patients with obstructive sleep apnoea syndrome. This benefit is also precisely the one for which the evidence base is strongest. The remaining uncertainties concerning the impact of nasal continuous positive airway pressure on long-term mortality have only a relatively small impact on the economics of treatment.
Receptor for advanced glycation end product (RAGE)-dependent modulation of early growth response-1 in hepatic ischemia/reperfusion injury
Authors: Shan Zeng, Hao Dun, Nikalesh Ippagunta, Rosa Rosario, Qing Y. Zhang, Jay Lefkowitch, Shi F. Yan, Ann Marie Schmidt, Jean C. Emond
Journal: Journal of Hepatology (2009)
Hypoxia-Inducible Factor Signaling in Pheochromocytoma: Turning the Rudder in the Right Direction
Authors: I. Jochmanova, C. Yang, Z. Zhuang, K. Pacak
Journal: JNCI Journal of the National Cancer Institute (2013)

Many solid tumors, including pheochromocytoma (PHEO) and paraganglioma (PGL), are characterized by a (pseudo)hypoxic signature. (Pseudo)hypoxia has been shown to promote both tumor progression and resistance to therapy. The major mediators of the transcriptional hypoxic response are hypoxia-inducible factors (HIFs). High levels of HIFs lead to transcription of hypoxia-responsive genes, which are involved in tumorigenesis. PHEOs and PGLs are catecholamine-producing tumors arising from sympathetic- or parasympathetic-derived chromaffin tissue. In recent years, substantial progress has been made in understanding the metabolic disturbances present in PHEO and PGL, especially because of the identification of some disease-susceptibility genes. To date, fifteen PHEO and PGL susceptibility genes have been identified. Based on the main transcription signatures of the mutated genes, PHEOs and PGLs have been divided into two clusters, pseudohypoxic cluster 1 and cluster 2, rich in kinase receptor signaling and protein translation pathways. Although these two clusters seem to show distinct signaling pathways, recent data suggest that both clusters are interconnected by HIF signaling as the important driver in their tumorigenesis, and mutations in most PHEO and PGL susceptibility genes seem to affect HIF-α regulation and its downstream signaling pathways. HIF signaling appears to play an important role in the development and growth of PHEOs and PGLs, which could suggest new therapeutic approaches for the treatment of these tumors.
Review of the Validity and Significance of Cannabis Withdrawal Syndrome
Authors: Alan J. Budney, John R. Hughes, Brent A. Moore, Ryan Vandrey
Journal: American Journal of Psychiatry (2004)

The authors review the literature examining the validity and significance of cannabis withdrawal syndrome. Findings from animal laboratory research are briefly reviewed, and human laboratory and clinical studies are surveyed in more detail. Converging evidence from basic laboratory and clinical studies indicates that a withdrawal syndrome reliably follows discontinuation of chronic heavy use of cannabis or tetrahydrocannabinol. Common symptoms are primarily emotional and behavioral, although appetite change, weight loss, and physical discomfort are also frequently reported. The onset and time course of these symptoms appear similar to those of other substance withdrawal syndromes. The magnitude and severity of these symptoms appear substantial, and these findings suggest that the syndrome has clinical importance. Diagnostic criteria for cannabis withdrawal syndrome are proposed.
Respiratory effects of lipopolysaccharide-induced inflammatory lung injury in mice
Authors: DS Faffe, VR Seidl, PS Chagas, VL Goncalves de Moraes, VL Capelozzi, PR Rocco, WA Zin
Journal: European Respiratory Journal (2000)

The pathogenic mechanisms of lipopolysaccharide (LPS)-induced lung injury have not been classified. This study examined the physiological changes after endotoxin inhalation and related those to features of pulmonary inflammation in mice. Pulmonary mechanics, histopathology, and bronchoalveolar lavage fluid (BALF) from BALB/c mice were analysed at different occasions (3, 24, 48 and 72 h) after inhalation of saline or LPS from Escherichia coli (0.3 (L0.3) or 10 mg x mL(-1) (L10)). Mice were sedated, anaesthetized, and ventilated. After chest wall resection static (Est) and dynamic (Edyn) elastances, deltaE (Edyn-Est), resistive (deltaP1) and viscoelastic/inhomogeneous pressures (deltaP2), and deltaP1+deltaP2 (deltaPtot) were obtained by end-inflation occlusion method. Lungs were prepared for histopathology. In parallel groups, tumour necrosis factor (TNF)-alpha, neutrophils, and protein were evaluated in the BALF. L0.3 and L10 showed a time-dependent production of TNF-alpha preceding a massive neutrophil infiltration. In L10 BALF there was an increase in protein level at 24 and 48 h. Est and Edyn increased early in L0.3 (65%, 63%) and L10 (41%, 51%). In L10 deltaE, deltaP2, and deltaPtot showed a gradual rise. At 72 h all groups were similar. L0.3 showed an early increase in cellularity, which returned to normal at 72 h. L10 presented the same pattern with the cell count remaining elevated until 72 h. In conclusion, lipopolysaccharide inhalation led to elastic and viscoelastic pulmonary changes together with tumour necrosis factor-alpha production and neutrophil infiltration in mouse lung.
Combined Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy Imaging in the Diagnosis of Prostate Cancer: A Systematic Review and Meta-analysis
Authors: Martin Umbehr, Lucas M. Bachmann, Ulrike Held, Thomas M. Kessler, Tullio Sulser, Dominik Weishaupt, John Kurhanewicz, Johann Steurer
Journal: European Urology (2008)
Characterization and Expression of CT45 in Hodgkin's Lymphoma
Authors: Hans-Jürgen Heidebrecht, Alexander Claviez, Marie Luise Kruse, Marc Pollmann, Friedrich Buck, Sönke Harder, Markus Tiemann, Wolfgang Dörffel, Reza Parwaresch
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The monoclonal antibody Ki-A10 (IgG1) generated after immunization of mice with Hodgkin's lymphoma cell line L428 detects a nuclear antigen in human tissues with a restricted distribution pattern similar to cancer/testis antigens. The aim of this study was to characterize the antigen and to determine the expression profile in Hodgkin's lymphoma. Experimental Design: The half-life and phosphorylation of the antigen were determined by radiolabeling. The antigen was characterized by immunopurification and sequencing. Demethylation of genes is used to induce cancer/testis antigens. Ki-A10-negative cells were treated with 5-aza-2′-deoxycytidine. The Ki-A10 expression in paraffin-embedded tumors was determined immunohistochemically. Results: Immunopurification of the 25/22-kDa antigen and sequencing revealed a peptide of 14 amino acids corresponding to the gene product of the newly described gene family MGC27005, located on chromosome Xq26.3, now termed CT45. CT45 is significantly phosphorylated and down-regulated during mitosis. Demethylation of CT45-negative HeLa cells and stimulated peripheral blood lymphocytes induced CT45 expression. Except testis, immunohistochemical stainings of normal tissues, reactive lymphoid lesions, and most malignant tumors were negative. In comparison, 54 of 99 (55%) samples from pediatric and adolescent Hodgkin's lymphoma patients enrolled in the multicenter trial HD-95 stained Ki-A10 positive. Ki-A10 expression correlated with histologic subtypes (nodular sclerosis Hodgkin's lymphoma 68% versus mixed cellularity Hodgkin's lymphoma 40% versus nodular lymphocyte predominant Hodgkin's lymphoma 9%; P &amp;lt; 0.001). Conclusions: Ki-A10 is the first monoclonal antibody that detects CT45. As benign lymphoid lesions did not express CT45, the use of Ki-A10 antibody will facilitate the discrimination of Hodgkin's lymphoma from reactive lymphadenopathies.
Predictors of Serum Chlorinated Pesticide Concentrations among Prepubertal Russian Boys
Authors: Thuy Lam, Paige L. Williams, Jane S. Burns, Oleg Sergeyev, Susan A. Korrick, Mary M. Lee, Linda S. Birnbaum, Boris Revich, Larisa M. Altshul, Donald G. Patterson, Wayman E. Turner, Russ Hauser
Journal: Environmental Health Perspectives (2013)

Few studies have evaluated predictors of childhood exposure to organochlorine pesticides (OCPs), a class of lipophilic persistent chemicals.Our goal was to identify predictors of serum OCP concentrations-hexachlorobenzene (HCB), β-hexachlorocyclohexane (β-HCH), and p,p-dichlorodiphenyldichloroethylene (p,p´-DDE)-among boys in Chapaevsk, Russia.Between 2003 and 2005, 499 boys 8-9 years of age were recruited in a prospective cohort. The initial study visit included a physical examination; blood collection; health, lifestyle, and food-frequency questionnaires; and determination of residential distance from a local factory complex that produced HCB and β-HCH. Fasting serum samples were analyzed for OCPs at the U.S. Centers for Disease Control and Prevention. General linear regression models were used to identify predictors of the boys' serum HCB, β-HCH, and p,p´-DDE concentrations.Among 355 boys with OCP measurements, median serum HCB, β-HCH, and p,p´-DDE concentrations were 158, 167, and 284 ng/g lipid, respectively. Lower body mass index, longer breastfeeding duration, and local dairy consumption were associated with higher concentrations of OCPs. Boys who lived < 2 km from the factory complex had 64% (95% CI: 37, 96) and 57% (95% CI: 32, 87) higher mean HCB and β-HCH concentrations, respectively, than boys who lived ≥ 5 km away. Living > 3 years in Chapaevsk predicted higher β-HCH concentrations, and having parents who lacked a high school education predicted higher p,p´-DDE concentrations.Among this cohort of prepubertal Russian boys, predictors of serum OCPs included consumption of local dairy products, longer local residence, and residential proximity to the local factory complex.
Liposome transduction into cells enhanced by haptotactic peptides (Haptides) homologous to fibrinogen C-termini
Authors: Raphael Gorodetsky, Lila Levdansky, Akiva Vexler, Irina Shimeliovich, Ibrahim Kassis, Matti Ben-Moshe, Shlomo Magdassi, Gerard Marx
Journal: Journal of Controlled Release (2004)
Comparison of Three Methods for Estimating Rates of Synonymous and Nonsynonymous Nucleotide Substitutions
Authors: Y.-H. Tzeng
Journal: Molecular Biology and Evolution (2004)

Three frequently used methods for estimating the synonymous and nonsynonymous substitution rates (Ks and Ka) were evaluated and compared for their accuracies; these methods are denoted by LWL85, LPB93, and GY94, respectively. For this purpose, we used a codon-evolution model to obtain the expected Ka and Ks values for the above three methods and compared the values with those obtained by the three methods. We also proposed some modifications of LWL85 and LPB93 to increase their accuracies. Our computer simulations under the codon-evolution model showed that for sequences ≤300 codons, the performance of GY94 may not be reliable. For longer sequences, GY94 is more accurate for estimating the Ka/Ks ratio than the modified LPB93 and LWL85 in the majority of the cases studied. This is particularly so when k ≥ 3, which is the transition/transversion (mutation) rate ratio. However, when k is approximately 2 and when the sequence divergence is relatively large, the modified LWL85 performed better than GY94 and the modified LPB93. The inferiority of LPB93 to LWL85 is surprising because LPB93 was intended to improve LWL85. Also, it has been thought that the codon-based method of GY94 is better than the heuristic method of LWL85, but our simulation results showed that in many cases, the opposite was true, even though our simulation was based on the codon-evolution model.
Requirements for Peptide-induced T Cell Receptor Downregulation on Naive CD8+ T Cells
Authors: Zeling Cai, Hidehiro Kishimoto, Anders Brunmark, Michael R. Jackson, Per A. Peterson, Jonathan Sprent
Journal: The Journal of Experimental Medicine (1997)

The requirements for inducing downregulation of α/β T cell receptor (TCR) molecules on naive major histocompatibility complex class I–restricted T cells was investigated with 2C TCR transgenic mice and defined peptides as antigen. Confirming previous results, activation of 2C T cells in response to specific peptides required CD8 expression on the responder cells and was heavily dependent upon costimulation provided by either B7-1 or ICAM-1 on antigen-presenting cells (APC). These stringent requirements did not apply to TCR downregulation. Thus, TCR downregulation seemed to depend solely on TCR/peptide/interaction and did not require either CD8 or B7-1 expression; ICAM-1 potentiated TCR downregulation, but only with limiting doses of peptides. TCR downregulation was most prominent with high affinity peptides and appeared to be neither obligatory nor sufficient for T cell activation. In marked contrast to T cell activation, TCR downregulation was resistant to various metabolic inhibitors. The biological significance of TCR downregulation is unclear, but could be a device for protecting T cells against excessive signaling.
p53 Alterations Predict Tumor Response to Neoadjuvant Chemotherapy in Head and Neck Squamous Cell Carcinoma: A Prospective Series
Authors: Arnauld Cabelguenne, Hélène Blons, Isabelle de Waziers, Françoise Carnot, Anne-Marie Houllier, Thierry Soussi, Daniel Brasnu, Phillipe Beaune, Ollivier Laccourreye, Pierre Laurent-Puig
Journal: Journal of Clinical Oncology (2000)

PURPOSE: The tumor suppressor gene p53 plays a crucial role in cell cycle control and apoptosis in response to DNA damages. p53 gene mutations and allelic losses at 17p are one of the most common genetic alterations in primary head and neck squamous cell carcinoma (HNSCC). Alterations of the p53 gene have been shown to contribute to carcinogenesis and drug resistance. PATIENTS AND METHODS: In this prospective series, patients with HNSCC were treated with cisplatin-fluorouracil neoadjuvant chemotherapy. p53 status was characterized in 106 patients with HNSCC (p53 mutations, allelic losses at p53 locus, and plasma anti-p53 antibodies) to determine the existence of a relationship between p53 gene status and response to neoadjuvant chemotherapy. RESULTS: Exons 4 to 9 of the p53 gene were analyzed, and mutations were found in 72 of 106 patients with HNSCC. p53 mutations were associated with loss of heterozygosity at chromosome 17p (P &lt; .001). The prevalence of p53-mutated tumors was higher in the group of patients with nonresponse to neoadjuvant chemotherapy than in the group of responders (81% v 61%, respectively; P &lt; .04). When compiling p53 mutations and anti-p53 antibodies in plasma, the correlation between p53 status and response to chemotherapy was significant (87% v 57%, respectively; P = .003). A multivariate analysis showed that p53 status is an independent predictive factor of response to chemotherapy. CONCLUSION: This prospective study suggests that p53 status may be a useful indicator of response to neoadjuvant chemotherapy in HNSCC.
2010 Consensus Statement on the Worldwide Standardization of the Hemoglobin A1C Measurement
Authors: Ragnar Hanas, Garry John
Journal: Diabetes Care (2010)

Glycated hemoglobin concentrations (most commonly hemoglobin A1C; HbA1c) reflect time-averaged blood glucose during the previous 2–3 months and are used as the gold standard for long-term follow-up of glycemic control. Standardization with common calibration was first proposed in 1984 (1). It was only after the publication of the Diabetes Control and Complications Trial (DCCT) study in 1993 (2), however, that the issue of international standardization of HbA1c measurements became an important objective for scientists and clinicians. At that time, the lack of international standardization resulted in several countries developing National standardization programs; most notable of these are: 

A common feature of these national programs is the absence of primary and secondary reference materials. To overcome this lack of reference materials, achieve global standardization, and meet the requirements of the European Union directive on in vitro diagnostic (IVD) medical devices, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) established a Working Group on HbA1c Standardization to develop a reference measurement system within the concept of metrological traceability. Such a system has been developed consisting of incubation with the enzyme endoproteinase Glu-C, cleavage of the NH2-terminal hexapeptide of the β-chain, and separation and …
Mutually Exclusive Cyclin-Dependent Kinase 4/Cyclin D1 and Cyclin-Dependent Kinase 6/Cyclin D2 Pairing Inactivates Retinoblastoma Protein and Promotes Cell Cycle Dysregulation in Multiple Myeloma
Authors: Scott Ely, Maurizio Di Liberto, Ruben Niesvizky, Linda B. Baughn, Hearn J. Cho, Eunice N. Hatada, Daniel M. Knowles, Joseph Lane, Selina Chen-Kiang
Journal: Cancer Research (2005)

Abstract Multiple myeloma, the second most common hematopoietic cancer, ultimately becomes refractory to treatment when self-renewing multiple myeloma cells begin unrestrained proliferation by unknown mechanisms. Here, we show that one, but not more than one, of the three early G1 D cyclins is elevated in each case of multiple myeloma. Cyclin D1 or D3 expression does not vary in the clinical course, but that alone is insufficient to promote cell cycle progression unless cyclin-dependent kinase 4 (cdk4) is also elevated, in the absence of cdk6, to phosphorylate the retinoblastoma protein (Rb). By contrast, cyclin D2 and cdk6 are coordinately increased, thereby overriding the inhibition by cdk inhibitors p18INK4c and p27Kip1 and phosphorylating Rb in conjunction with the existing cdk4. Thus, cyclin D1 pairs exclusively with cdk4 and cdk6 pairs only with cyclin D2, although cyclin D2 can also pair with cdk4 in multiple myeloma cells. The basis for this novel and specific cdk/D cyclin pairing lies in differential transcriptional activation. In addition, cyclin D1– or cyclin D3–expressing multiple myeloma cells are uniformly distributed in the bone marrow, whereas cdk6-specific phosphorylation of Rb occurs in discrete foci of bone marrow multiple myeloma cells before proliferation early in the clinical course and is then heightened with proliferation and disease progression. Mutually exclusive cdk4/cyclin D1 and cdk6/cyclin D2 pairing, therefore, is likely to be a critical determinant for cell cycle reentry and progression and may play a pivotal role in the expansion of self-renewing multiple myeloma cells. (Cancer Res 2005; 65(24): 11345-53)
Evidence for two homologous, but nonidentical, Ia molecules determined by the I-EC subregion.
Authors: T L Delovitch, B H Barber
Journal: The Journal of Experimental Medicine (1979)

Sequential immunoprecipitation, two-dimensional gel electrophoresis and peptide mapping analyses of B10A(3R), 35S-methionine-labeled, I-EC subregion products were performed. Evidence is presented here for the presence of two structurally homologous, but nonidentical, gene products of the I-EC subregion. These two Ia molecules are independently immunoprecipitable, identical in molecular size and charge, but differ by approximately equal to 20% in their peptides obtained by partial digestion with Staphylococcus aureus protease V8.