tbuckley/cabot-search huggingface dataset:
Risk Assessment for Prostate Cancer Metastasis and Mortality at the Time of Diagnosis
Authors: Matthew R. Cooperberg, Jeanette M. Broering, Peter R. Carroll
Journal: JNCI Journal of the National Cancer Institute (2009)

Although many tools for the assessment of prostate cancer risk have been published, most are designed to predict only biochemical recurrence, usually after a single specified treatment. We assessed the accuracy of the Cancer of the Prostate Risk Assessment (CAPRA) score, which was validated previously to predict pathological and biochemical outcomes after radical prostatectomy, to predict metastases, prostate cancer–specific mortality, and all-cause mortality. We studied 10 627 men with clinically localized prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavor registry, who underwent primary radical prostatectomy, radiation therapy (external beam or interstitial), androgen deprivation monotherapy, or watchful waiting/active surveillance, and had at least 6 months of follow-up after treatment. CAPRA scores were calculated at diagnosis from the prostate-specific antigen level, Gleason score, percentage of biopsy cores that were positive for cancer, clinical tumor stage, and age at diagnosis. Survival was studied with Kaplan–Meier analyses. Associations between increasing CAPRA scores and bone metastasis, cancer-specific mortality, and all-cause mortality were examined by use of proportional hazards regression, with adjustment for primary treatment; for all-cause mortality, the analysis also included adjustment for age and comorbidity. Accuracy of the CAPRA score was assessed with the concordance ( c )-index. Among the 10 627 patients, 311 (2.9%) men developed bone metastases, 251 (2.4%) died of prostate cancer, and 1582 (14.9%) died of other causes. Each single-point increase in the CAPRA score was associated with increased bone metastases (hazard ratio [HR] for bone metastases = 1.47, 95% confidence interval [CI] = 1.39 to 1.56), cancer-specific mortality (HR for prostate cancer death = 1.39, 95% CI = 1.31 to 1.48), and all-cause mortality (HR for death = 1.13, 95% CI = 1.10 to 1.16). The CAPRA score was accurate for predicting metastases ( c -index = 0.78), cancer-specific mortality ( c -index = 0.80), and all-cause mortality ( c -index = 0.71). In a large cohort of patients with clinically localized prostate cancer who were managed with one of five primary modalities, the CAPRA score predicted clinical prostate cancer endpoints with good accuracy. These results support the value of the CAPRA score as a risk assessment and stratification tool for both research studies and clinical practice.
VEGF/Neuropilin-2 Regulation of Bmi-1 and Consequent Repression of IGF-IR Define a Novel Mechanism of Aggressive Prostate Cancer
Authors: Hira Lal Goel, Cheng Chang, Bryan Pursell, Irwin Leav, Stephen Lyle, Hualin Simon Xi, Chung-Cheng Hsieh, Helty Adisetiyo, Pradip Roy-Burman, Ilsa M. Coleman, Peter S. Nelson, Robert L. Vessella, Roger J. Davis, Stephen R. Plymate, Arthur M. Mercurio
Journal: Cancer Discovery (2012)

We show that the VEGF receptor neuropilin-2 (NRP2) is associated with high-grade, PTEN-null prostate cancer and that its expression in tumor cells is induced by PTEN loss as a consequence of c-Jun activation. VEGF/NRP2 signaling represses insulin-like growth factor-1 receptor (IGF-IR) expression and signaling, and the mechanism involves Bmi-1-mediated transcriptional repression of the IGF-IR. This mechanism has significant functional and therapeutic implications that were evaluated. IGF-IR expression positively correlates with PTEN and inversely correlates with NRP2 in prostate tumors. NRP2 is a robust biomarker for predicting response to IGF-IR therapy because prostate carcinomas that express NRP2 exhibit low levels of IGF-IR. Conversely, targeting NRP2 is only modestly effective because NRP2 inhibition induces compensatory IGF-IR signaling. Inhibition of both NRP2 and IGF-IR, however, completely blocks tumor growth in vivo.
Long Noncoding RNAs and MicroRNAs in Cardiovascular Pathophysiology
Authors: Thomas Thum, Gianluigi Condorelli
Journal: Circulation Research (2015)

RNAs not encoding proteins have gained prominence over the last couple of decades as fundamental regulators of cellular function. Not surprisingly, their dysregulation is increasingly being linked to pathology. Here, we review recent reports investigating the pathophysiological relevance of this species of RNA for the cardiovascular system, concentrating mainly on recent findings on long noncoding RNAs and microRNAs in cardiac hypertrophy and failure.
Interleukin 10 production correlates with pathology in human Leishmania donovani infections.
Authors: H W Ghalib, M R Piuvezam, Y A Skeiky, M Siddig, F A Hashim, A M el-Hassan, D M Russo, S G Reed
Journal: Journal of Clinical Investigation (1993)

We have found that an important Th2 cytokine, IL-10, is produced by tissues from patients acutely infected with Leishmania donovani. In all individuals tested, IL-10 mRNA production was increased in lymph nodes taken during acute disease over that observed in postacute samples. In contrast, both pre- and posttreatment lymph nodes had readily detected mRNA for IFN-gamma and IL-2. A down-regulating effect of IL-10 on leishmania-induced proliferative responses was demonstrated when Hu rIL-10 was added to cultures of PBMC from clinically cured individuals. PBMC from individuals with acute visceral leishmaniasis responded to stimulation with leishmania lysate by producing IL-10 mRNA. Simultaneously cultured PBMC collected from the same patients after successful chemotherapy produced no detectable IL-10 mRNA after leishmania antigen stimulation. Neutralizing anti-IL-10 mAb added to PBMC from patients with acute visceral leishmaniasis markedly increased the proliferative response to leishmania lysate. Finally, we observed mRNA for IL-10 and IFN-gamma concurrently in a lesion from a patient with post-kala-azar dermal leishmaniasis (PKDL). These results indicate the production of IL-10 during L. donovani infection, and suggest a role for this cytokine in the regulation of immune responsiveness during visceral leishmaniasis.
Detection of apnoeas, hypopnoeas and arousals by the AutoSet in the sleep apnoea/hypopnoea syndrome
Authors: K Rees, PK Wraith, M Berthon-Jones, NJ Douglas
Journal: European Respiratory Journal (1998)

Limited sleep study systems are increasingly being used to diagnose the sleep apnoea/hypopnoea syndrome, but validation is essential and detection of arousal's desirable. One such system (AutoSet) was validated on an event-by-event basis, and the hypothesis that sudden large breaths detected by this system mark arousal from sleep was also examined. Twenty consecutive patients (apnoea/hypopnoea index (AHI) 39+/-6 (SEM)) underwent polysomnography (PSG), which included real-time signals of AutoSet (Version 3.03) scored events. PSG respiratory events were defined using airflow and thoracoabdominal movement and AutoSet events using nasal pressure. All apnoeas were scored by both systems, but 41% more hypopnoeas were scored on PSG and these were clinically significant, with 78% ending in cortical arousal. Twenty per cent of apnoeas and hypopnoeas scored by the AutoSet occurred during wakefulness. Large breaths, defined as a two-thirds increase in ventilation, marked 77% of respiratory-associated but only 9% of spontaneous arousals. Large breaths also marked 48% of "autonomic" arousals following respiratory events without visible electroencephalographic changes. Twenty-seven per cent of large breaths occurred during wakefulness. This study shows that the AutoSet and the standard polysomnographic approach differ in their detection of hypopnoeas. The AutoSet underdetected hypopnoeas during sleep, but also included some hypopnoeas occurring during wakefulness. Detection of large breaths may potentially be useful for identifying respiratory arousals. Detection of periods of wakefulness may improve the accuracy of the system.
ELMO1 and Dock180, a Bipartite Rac1 Guanine Nucleotide Exchange Factor, Promote Human Glioma Cell Invasion
Authors: Michael J. Jarzynka, Bo Hu, Kwok-Min Hui, Ifat Bar-Joseph, Weisong Gu, Takanori Hirose, Lisa B. Haney, Kodi S. Ravichandran, Ryo Nishikawa, Shi-Yuan Cheng
Journal: Cancer Research (2007)

Abstract A distinct feature of malignant gliomas is the intrinsic ability of single tumor cells to disperse throughout the brain, contributing to the failure of existing therapies to alter the progression and recurrence of these deadly brain tumors. Regrettably, the mechanisms underlying the inherent invasiveness of glioma cells are poorly understood. Here, we report for the first time that engulfment and cell motility 1 (ELMO1) and dedicator of cytokinesis 1 (Dock180), a bipartite Rac1 guanine nucleotide exchange factor (GEF), are evidently linked to the invasive phenotype of glioma cells. Immunohistochemical analysis of primary human glioma specimens showed high expression levels of ELMO1 and Dock180 in actively invading tumor cells in the invasive areas, but not in the central regions of these tumors. Elevated expression of ELMO1 and Dock180 was also found in various human glioma cell lines compared with normal human astrocytes. Inhibition of endogenous ELMO1 and Dock180 expression significantly impeded glioma cell invasion in vitro and in brain tissue slices with a concomitant reduction in Rac1 activation. Conversely, exogenous expression of ELMO1 and Dock180 in glioma cells with low level endogenous expression increased their migratory and invasive capacity in vitro and in brain tissue. These data suggest that the bipartite GEF, ELMO1 and Dock180, play an important role in promoting cancer cell invasion and could be potential therapeutic targets for the treatment of diffuse malignant gliomas. [Cancer Res 2007;67(15):7203–11]
Evolution of Invertebrate Deuterostomes and Hox/ParaHox Genes
Authors: Tetsuro Ikuta
Journal: Genomics Proteomics & Bioinformatics (2011)

Abstract Transcription factors encoded by Antennapedia-class homeobox genes play crucial roles in controlling development of animals, and are often found clustered in animal genomes. The Hox and ParaHox gene clusters have been regarded as evolutionary sisters and evolved from a putative common ancestral gene complex, the ProtoHox cluster, prior to the divergence of the Cnidaria and Bilateria (bilaterally symmetrical animals). The Deuterostomia is a monophyletic group of animals that belongs to the Bilateria, and a sister group to the Protostomia. The deuterostomes include the vertebrates (to which we belong), invertebrate chordates, hemichordates, echinoderms and possibly xenoturbellids, as well as acoelomorphs. The studies of Hox and ParaHox genes provide insights into the origin and subsequent evolution of the bilaterian animals. Recently, it becomes apparent that among the Hox and ParaHox genes, there are significant variations in organization on the chromosome, expression pattern, and function. In this review, focusing on invertebrate deuterostomes, I first summarize recent findings about Hox and ParaHox genes. Next, citing unsolved issues, I try to provide clues that might allow us to reconstruct the common ancestor of deuterostomes, as well as understand the roles of Hox and ParaHox genes in the development and evolution of deuterostomes.
<i>Thorax</i>: the Cappuccino years
Authors: Andrew Bush, Ian D Pavord
Journal: Thorax (2012)

We are now about half way through our term of office (unless we are prematurely fired for terminal misbehaviour); here we review where we are, and where we are going, and have the first instalment of the showcase of some of our best articles from last year. We have maintained our second position with an improved impact factor (6.84) over 2011, we continue to attract very high quality manuscripts, and handling times have come down (all good news). We owe these achievements to our associate editors and editorial board, the reviewers, and especially those who have submitted such great manuscripts. An especially large bouquet to the editorial staff, in particular Renuka Patel for her work on Hot Topics and marketing, Bryony Skinner, who has stepped magnificently into the breach, Allison Lang and our unsung heroine Sarah Szatkowski, who keeps us sane when ScholarOne is driving us to Prozac or haloperidol or both. Don't leave us! We acknowledge we need to speed up further, and get the impact factor higher—both are a work in progress. However, average time from submission to first decision for all manuscripts is less than 30 days, and accepted manuscripts appear on-line in an average of 25 days. We have had out first randomised controlled trial protocol to review for consideration for fast-track publication when the study is completed—an offer which does not depend on the result being positive—investigators please note. Hot off the Breath continues to generate controversy—totally drug resistant tuberculosis (TB) and the roaring PANTHER being cases in point. We have had two themed issues (North American, to coincide with American Thoracic Society and cystic fibrosis (CF), to coincide with the US CF Foundation annual meeting). In 2013, we will have a Tuberculosis themed issue for World TB day (March 24th) and plan a Pneumonia themed issue …
The MATRICS Consensus Cognitive Battery, Part 2: Co-Norming and Standardization
Authors: Robert S Kern, Keith H Nuechterlein, Michael F Green, Lyle E Baade, Wayne S Fenton, James M Gold, Richard S E Keefe, Raquelle Mesholam-Gately, Jim Mintz, Larry J Seidman, Ellen Stover, Stephen R Marder
Journal: American Journal of Psychiatry (2008)

Objective: The consensus cognitive battery developed by the National Institute of Mental Health’s (NIMH’s) Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative includes 10 independently developed tests that are recommended as the standard battery for clinical trials of cognition-enhancing interventions for schizophrenia. To facilitate interpretation of results from the MATRICS Consensus Cognitive Battery using a common scaling across tests, normative data were obtained from a single representative U.S. community sample with the battery administered as a unit. Method: The MATRICS Consensus Cognitive Battery was administered to 300 individuals from the general community at five sites in differing geographic regions. For each site, recruitment was stratified by age, gender, and education. A scientific survey sampling method was used to help avoid sampling bias. The battery was administered in a standard order to each participant in a single session lasting approximately 60 minutes. Descriptive data were generated, and age, gender, and education effects on performance were examined. Results: Prominent age and education effects were observed across tests. The results for gender differed by measure, suggesting the need for age and gender corrections in clinical trials. The MATRICS Consensus Cognitive Battery components were co-normed, with allowance for demographic corrections. Conclusions: Co-norming a battery such as the MATRICS Consensus Cognitive Battery, comprising tests from independent test developers each with their own set of norms, facilitates valid interpretation of test scores and communication of findings across studies. These normative data will aid in estimating the magnitude of change during clinical trials of cognition-enhancing agents and make it possible to derive more directly interpretable composite scores.
TCT-778 A Comparison of the Complications and Mortality between the Transapical and Transfemoral Accesses for Transcatheter Aortic Valve Replacement with Edwards SAPIEN valve: PARTNER Trial vs Worldwide Studies and Registries
Authors: Abhijit Ghatak, Chirag Bavishi, Rhanderson N. Cardoso, Conrad Macon, Vikas Singh, Apurva Badheka, Brian O'Neill, Santosh Padala, Carlos Alfonso, Mauricio G. Cohen, Alan W. Heldman, Alexandre Ferreira, Raul Mitrani, Roger G. Carrillo, Donald Williams, William W. O'Neill, Eduardo de Marchena
Journal: Journal of the American College of Cardiology (2014)
Mendelian Disorders of High-Density Lipoprotein Metabolism
Authors: Federico Oldoni, Richard J. Sinke, Jan Albert Kuivenhoven
Journal: Circulation Research (2014)

High-density lipoproteins (HDLs) are a highly heterogeneous and dynamic group of the smallest and densest lipoproteins present in the circulation. This review provides the current molecular insight into HDL metabolism led by articles describing mutations in genes that have a large affect on HDL cholesterol levels through their roles in HDL and triglyceride metabolism. Using this information from both human and animal studies, it is discussed how HDL is produced, remodeled in the circulation, affected by factors that control the metabolism of triglyceride-rich lipoproteins, how it helps maintain cellular cholesterol homeostasis, and, finally, how it is catabolized. It can be concluded that HDL cholesterol as a trait is genetically heterogeneous, with as many as 40 genes involved. In most cases, only heterozygotes of gene variants are known, and HDL cholesterol as a trait is inherited in an autosomal-dominant manner. Only 3 Mendelian disorders of HDL metabolism are currently known, which are inherited in an autosomal-recessive mode.
Influence of anxiety on health outcomes in COPD
Authors: M. D Eisner, P. D Blanc, E. H Yelin, P. P Katz, G. Sanchez, C. Iribarren, T. A Omachi
Journal: Thorax (2010)

<h3>Background</h3> Psychological functioning is an important determinant of health outcomes in chronic lung disease. To better define the role of anxiety in chronic obstructive pulmonary disease (COPD), a study was conducted of the inter-relations between anxiety and COPD in a large cohort of subjects with COPD and a matched control group. <h3>Methods</h3> Data were used from the FLOW (Function, Living, Outcomes, and Work) cohort of patients with COPD (n=1202) and matched controls without COPD (n=302). Anxiety was measured using the Anxiety subscale of the Hospital Anxiety and Depression Scale. <h3>Results</h3> COPD was associated with a greater risk of anxiety in multivariable analysis (OR 1.85; 95% CI 1.072 to 3.18). Among patients with COPD, anxiety was related to poorer health outcomes including worse submaximal exercise performance (less distance walked during the 6-min walk test: −66.3 feet for anxious vs non-anxious groups; 95% CI −127.3 to −5.36) and a greater risk of self-reported functional limitations (OR 2.41; 95% CI 1.71 to 3.41). Subjects with COPD with anxiety had a higher longitudinal risk of COPD exacerbation in Cox proportional hazards analysis after controlling for covariates (HR 1.39; 95% CI 1.007 to 1.90). <h3>Conclusion</h3> COPD is associated with a higher risk of anxiety. Once anxiety develops among patients with COPD, it is related to poorer health outcomes. Further research is needed to determine whether systematic screening and treatment of anxiety in COPD will improve health outcomes and prevent functional decline and disability.
Reappearance of serum hepatitis B viral DNA in patients with hepatitis B surface antigen seroclearance
Authors: Masato Nakamura, Tatsuo Kanda, Shingo Nakamoto, Yuki Haga, Reina Sasaki, Xia Jiang, Shin Yasui, Makoto Arai, Osamu Yokosuka
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. To the Editor: We read with great interest the article by Di Bisceglie et al.1 In this report from the United States, the recommendation that all patients undergoing chemotherapy, immunosuppressive therapy, hematopoietic stem cell transplantation, or solid organ transplantation be screened for active or prior hepatitis B viral (HBV) infection by testing for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen in serum. This problem is also serious in Japan, where no universal vaccination programs against HBV exist and HBV infections are still viewed as important issues.2 The elimination of HBsAg is one of the goals in the treatment of HBV infection. We examined the incidence of the reappearance of HBV DNA in chronic hepatitis B patients. We compared the backgrounds of nine patients who achieved HBsAg seroclearance treated by nucleoside analogues (NAs group) with those of 13 patients in whom natural HBsAg seroclearance occurred (control group). We also evaluated HBV DNA levels at 4‐ to 12‐month intervals after the disappearance of HBsAg. The reappearance of HBV DNA was defined as the detection of serum HBV DNA after the disappearance of both of HBV DNA and HBsAg. Ages at HBsAg seroclearance in the NAs group and in the control group were 62 ± 14 and 59 ± 6.3 years, respectively. In the NAs group, five patients (56%) were treated with immunosuppressive agents (three with antibodies to CD20 [rituximab], one with corticosteroid, and one with tacrolimus; P = 0.011, compared with the control group [0%]). After HBsAg seroclearance, HBV DNA reappeared in three (33%) and two (15%) individuals in the NAs and control groups, respectively (Fig. 1). Of interest, patients in whom HBV DNA reappeared after HBsAg seroclearance did not exhibit any elevation in alanine aminotransferase or the reappearance of HBsAg. There was no significant difference in characteristics between patients with and patients without the reappearance of HBV DNA in either the NAs or the control group.Figure 1: Patients with reappearance of HBV DNA after HBsAg seroclearance. In each patient, upper and lower bars indicate HBV DNA and HBsAg, respectively.The reappearance of HBV DNA was occasionally observed in chronic hepatitis B patients with HBsAg seroclearance, suggesting that reactivation occurs in patients who have recovered from hepatitis B and have antibody to hepatitis B core antigen but no detectable serum HBsAg.1 Measurement of HBV DNA after HBsAg seroclearance may thus also be important in such patients receiving chemotherapy. Our data strongly support their recommendations.1 Further understanding of the mechanism of HBV reactivation with or without immunosuppressant or anticancer drug treatment is needed.1