tbuckley/cabot-search huggingface dataset:
Reciprocal Association of C-Reactive Protein With Adiponectin in Blood Stream and Adipose Tissue
Authors: Noriyuki Ouchi, Shinji Kihara, Tohru Funahashi, Tadashi Nakamura, Makoto Nishida, Masahiro Kumada, Yoshihisa Okamoto, Koji Ohashi, Hiroyuki Nagaretani, Ken Kishida, Hitoshi Nishizawa, Norikazu Maeda, Hideki Kobayashi, Hisatoyo Hiraoka, Yuji Matsuzawa
Journal: Circulation (2003)

Background— High-sensitive C-reactive protein (hs-CRP) is a well-known risk factor for coronary artery disease (CAD). Recently, we have demonstrated that adiponectin served as an antiatherogenic plasma protein which was secreted specifically from adipocytes. The present study investigated the association between adiponectin and CRP in the blood stream and adipose tissue. Methods and Results— We studied a total of 101 male patients, 71 of whom had angiographically documented coronary atherosclerosis. As a control group, 30 patients with normal coronary angiogram were included. The plasma hs-CRP levels were negatively correlated with the plasma adiponectin levels ( r =−0.29, P &lt;0.01). The plasma adiponectin concentrations were significantly lower and the hs-CRP levels were significantly higher in the CAD patients compared with control subjects. The mRNA levels of CRP and adiponectin were analyzed by quantitative real-time polymerase chain reaction method. We found that the CRP mRNA was expressed in human adipose tissue. A significant inverse correlation was observed between the CRP and adiponectin mRNA levels in human adipose tissue ( r =−0.89, P &lt;0.01). In addition, the CRP mRNA level of white adipose tissue in adiponectin deficient mice was higher than that of wild-type mice. Conclusions— The reciprocal association of adiponectin and CRP levels in both human plasma and adipose tissue might participate in the development of atherosclerosis.
Objects, please remain composed
Authors: Robert L. Goldstone
Journal: Behavioral and Brain Sciences (1998)

The holistic representation of objects as coordinates in a psychological space should be supplemented with decompositional processes that break objects down into components. There is strong psychological evidence for object decomposition, and structured representations are also needed because of their computational efficiency. Structured and unstructured representations can be unified by a process that extracts regularities at multiple levels of an object.
Inflammatory Myofibroblastic Tumors Harbor Multiple Potentially Actionable Kinase Fusions
Authors: Christine M. Lovly, Abha Gupta, Doron Lipson, Geoff Otto, Tina Brennan, Catherine T. Chung, Scott C. Borinstein, Jeffrey S. Ross, Philip J. Stephens, Vincent A. Miller, Cheryl M. Coffin
Journal: Cancer Discovery (2014)

Inflammatory myofibroblastic tumor (IMT) is a neoplasm that typically occurs in children. The genetic landscape of this tumor is incompletely understood and therapeutic options are limited. Although 50% of IMTs harbor anaplastic lymphoma kinase (ALK) rearrangements, no therapeutic targets have been identified in ALK-negative tumors. We report for the first time that IMTs harbor other actionable targets, including ROS1 and PDGFRβ fusions. We detail the case of an 8-year-old boy with treatment-refractory ALK-negative IMT. Molecular tumor profiling revealed a ROS1 fusion, and he had a dramatic response to the ROS1 inhibitor crizotinib. This case prompted assessment of a larger series of IMTs. Next-generation sequencing revealed that 85% of cases evaluated harbored kinase fusions involving ALK, ROS1, or PDGFRβ. Our study represents the most comprehensive genetic analysis of IMTs to date and also provides a rationale for routine molecular profiling of these tumors to detect therapeutically actionable kinase fusions.Our study describes the most comprehensive genomics-based evaluation of IMT to date. Because there is no "standard-of-care" therapy for IMT, the identification of actionable genomic alterations, in addition to ALK, is expected to redefine management strategies for patients with this disease.
Rises in antibody to enteric gram negative bacilli after open heart surgery: a possible mechanism for postoperative pyrexia.
Authors: R Freeman, F K Gould
Journal: Thorax (1985)

Paired sera, taken before operation and 10-14 days after operation from 64 patients having open heart surgery and 10 having closed heart surgery, were examined for agglutinins to seven common serotypes of Escherichia coli. The results showed that, while 20% of both groups of patients had detectable agglutinins before operation, new antibodies appeared after operation in 69% of patients having open heart surgery compared with only 10% of those having closed heart surgery, a significant difference. Thirty six pairs of sera were also examined for the preoperative presence and postoperative development of antiendotoxin. Of 22 open heart patients shown not to possess antiendotoxin before operation, 18 showed the antibody after operation, whereas none of the eight seronegative patients acquired the antibody after closed heart surgery-again a highly significant difference. These results are consistent with the hypothesis that endotoxin and other products of enteric Gram negative bacilli circulate shortly after cardiopulmonary bypass, possibly arising directly from the gut and perhaps explaining the pyrexia seen commonly at this time.
Bidirectional Relationships Between Sleep Duration and Screen Time in Early Childhood
Authors: Christopher A. Magee, Jeong Kyu Lee, Stewart A. Vella
Journal: JAMA Pediatrics (2014)

<h3>Importance</h3> Sleep duration and media use (ie, computer use and television viewing) have important implications for the health and well-being of children. Population data suggest that shorter sleep duration and excessive screen time are growing problems among children and could be interacting issues. <h3>Objective</h3> To examine whether bidirectional relationships exist between sleep duration and media use among children, and whether these associations are moderated by child- and household-related factors. <h3>Design, Setting, and Participants</h3> Cohort study of a representative sample of 3427 Australian children (4-5 years of age at baseline [51.2% male children]), obtained from the Longitudinal Study of Australian Children. Data were available from 3 waves (2004, 2006, and 2008) when children were 4, 6, and 8 years of age, respectively. <h3>Main Outcomes and Measures</h3> Sleep duration and media use. <h3>Results</h3> Bidirectional relationships were observed between sleep duration and media use; for instance, total media use at 4 years of age was significantly associated with sleep duration at 6 years of age (β = −0.06 [95% CI, −0.10 to −0.02]), with media use at 6 years of age predicting sleep duration at 8 years of age (β = −0.06 [95% CI, −0.11 to −0.02]). Sleep duration at 4 years of age was associated with media use at 6 years of age (β = −0.10 [95% CI, −0.14 to −0.05]), with sleep duration at 6 years of age predicting media use at 8 years of age (β = −0.08 [95% CI, −0.13 to −0.03]). Several of these bidirectional relationships varied by socioeconomic status. <h3>Conclusions and Relevance</h3> The results supported the hypotheses that bidirectional relationships exist between sleep duration and media use among children. These findings are important given recent population trends for increased media use and shorter sleep durations among children.
Effects of the 2011 Duty Hour Reforms on Interns and Their Patients
Authors: Srijan Sen, Henry R. Kranzler, Aashish K. Didwania, Ann C. Schwartz, Sudha Amarnath, Joseph C. Kolars, Gregory W. Dalack, Breck Nichols, Constance Guille
Journal: JAMA Internal Medicine (2013)

<h3>Importance</h3>In 2003, the first phase of duty hour requirements for US residency programs recommended by the Accreditation Council for Graduate Medical Education (ACGME) was implemented. Evidence suggests that this first phase of duty hour requirements resulted in a modest improvement in resident well-being and patient safety. To build on these initial changes, the ACGME recommended a new set of duty hour requirements that took effect in July 2011.<h3>Objective</h3>To determine the effects of the 2011 duty hour reforms on first-year residents (interns) and their patients.<h3>Design</h3>As part of the Intern Health Study, we conducted a longitudinal cohort study comparing interns serving before (2009 and 2010) and interns serving after (2011) the implementation of the new duty hour requirements.<h3>Setting</h3>Fifty-one residency programs at 14 university and community-based GME institutions.<h3>Participants</h3>A total of 2323 medical interns.<h3>Main Outcome Measures</h3>Self-reported duty hours, hours of sleep, depressive symptoms, well-being, and medical errors at 3, 6, 9, and 12 months of the internship year.<h3>Results</h3>Fifty-eight percent of invited interns chose to participate in the study. Reported duty hours decreased from an average of 67.0 hours per week before the new rules to 64.3 hours per week after the new rules were instituted (P &lt; .001). Despite the decrease in duty hours, there were no significant changes in hours slept (6.8 → 7.0; P = .17), depressive symptoms (5.8 → 5.7; P = .55) or well-being score (48.5 → 48.4; P = .86) reported by interns. With the new duty hour rules, the percentage of interns who reported concern about making a serious medical error increased from 19.9% to 23.3% (P = .007).<h3>Conclusions and Relevance</h3>Although interns report working fewer hours under the new duty hour restrictions, this decrease has not been accompanied by an increase in hours of sleep or an improvement in depressive symptoms or well-being but has been accompanied by an unanticipated increase in self-reported medical errors.
CMV-specific T cells generated from naïve T cells recognize atypical epitopes and may be protective in vivo
Authors: Patrick J. Hanley, Jan J. Melenhorst, Sarah Nikiforow, Phillip Scheinberg, James W. Blaney, Gail Demmler-Harrison, C. Russell Cruz, Sharon Lam, Robert A. Krance, Kathryn S. Leung, Caridad A. Martinez, Hao Liu, Daniel C. Douek, Helen E. Heslop, Cliona M. Rooney, Elizabeth J. Shpall, A. John Barrett, John R. Rodgers, Catherine M. Bollard
Journal: Science Translational Medicine (2015)

CMV-specific T cells, derived from the naïve population, recognize different epitopes of CMV than do memory-derived T cells and may be functional and protective in vivo.
Contact angioedema and conjunctivitis caused by <i>Lumbricus terrestris</i>: cross‐reactivity with <i>Anisakis simplex</i>
Authors: F. J. De Castro Martinez, V. Tovar, S. Pérez‐Bustamante, M. L. Baeza, L. Moya, M. De Barrio
Journal: Allergy (2006)
Intratumoral Therapy with IL13-PE38 Results in Effective CTL-Mediated Suppression of IL-13Rα2-Expressing Contralateral Tumors
Authors: Koji Kawakami, Masaki Terabe, Mitomu Kioi, Jay A. Berzofsky, Raj K. Puri
Journal: Clinical Cancer Research (2006)

IL13-PE38, a targeted cytotoxin comprised of interleukin 13 (IL-13) and a mutated form of Pseudomonas exotoxin, induces specific killing of tumor cells expressing abundant levels of the IL-13Ralpha2 chain. We hypothesized that tumor cells killed by the cytotoxin may release antigens and/or apoptotic bodies when cells are dying, which then induce adoptive immunity, and that the PE38 portion of IL13-PE38 may act as a stimulant for the induction of a CTL response.To test this hypothesis, we established D5 melanoma tumors with or without expression of the IL-13Ralpha2 chain in both flanks of C57BL/6 mice, and then IL13-PE38 was injected in the right flank tumors only.When animals with IL-13Ralpha2-expressing D5 tumor (right) were injected with IL13-PE38, right flank tumors expressing the IL-13Ralpha2 chain not only showed dramatic regression but contralateral tumors (left flank) also showed tumor regression. Cell depletion experiments in tumor-bearing animals indicated that both CD8(+) and CD4(+) T cells contribute to the regression of contralateral tumors through CTL activation in the periphery and cellular infiltration into tumors. In addition, intratumoral treatment into s.c. tumors of mice bearing metastatic lung tumors with IL13-PE38 showed not only the reduction of treated s.c. tumor but also the reduction of lung metastasis. Thus, IL13-PE38 mediates an antitumor effect not only directly but also indirectly by inducing a host CD8(+) T cell immune response. Accordingly, targeted cytotoxins may be used to treat local disease even if they cannot be administered systemically, and yet may still induce a reasonable systemic antitumor response.
Can an electronic prescribing system detect doctors who are more likely to make a serious prescribing error?
Authors: Jamie J Coleman, Karla Hemming, Peter G Nightingale, Ian R Clark, Mary Dixon-Woods, Robin E Ferner, Richard J Lilford
Journal: Journal of the Royal Society of Medicine (2011)

Objectives We aimed to assess whether routine data produced by an electronic prescribing system might be useful in identifying doctors at higher risk of making a serious prescribing error. Design Retrospective analysis of prescribing by junior doctors over 12 months using an electronic prescribing information and communication system. The system issues a graded series of prescribing alerts (low-level, intermediate, and high-level), and warnings and prompts to respond to abnormal test results. These may be overridden or heeded, except for high-level prescribing alerts, which are indicative of a potentially serious error and impose a ‘hard stop’. Setting A large teaching hospital. Participants All junior doctors in the study setting. Main outcome measures Rates of prescribing alerts and laboratory warnings and doctors' responses. Results Altogether 848,678 completed prescriptions issued by 381 doctors (median 1538 prescriptions per doctor, interquartile range [IQR] 328–3275) were analysed. We identified 895,029 low-level alerts (median 1033 per 1000 prescriptions per doctor, IQR 903–1205) with a median of 34% (IQR 31–39%) heeded; 172,434 intermediate alerts (median 196 per 1000 prescriptions per doctor, IQR 159–266), with a median of 23% (IQR 16–30%) heeded; and 11,940 high-level ‘hard stop’ alerts. Doctors vary greatly in the extent to which they trigger and respond to alerts of different types. The rate of high-level alerts showed weak correlation with the rate of intermediate prescribing alerts (correlation coefficient, r = 0.40, P = &lt;0.001); very weak correlation with low-level alerts (r = 0.12, P = 0.019); and showed weak (and sometimes negative) correlation with propensity to heed test-related warnings or alarms. The degree of correlation between generation of intermediate and high-level alerts is insufficient to identify doctors at high risk of making serious errors. Conclusions Routine data from an electronic prescribing system should not be used to identify doctors who are at risk of making serious errors. Careful evaluation of the kinds of quality assurance questions for which routine data are suitable will be increasingly valuable.
Improved imputation of common and uncommon SNPs with a new reference set
Authors: Zhaoming Wang, Kevin B Jacobs, Meredith Yeager, Amy Hutchinson, Joshua Sampson, Nilanjan Chatterjee, Demetrius Albanes, Sonja I Berndt, Charles C Chung, W Ryan Diver, Susan M Gapstur, Lauren R Teras, Christopher A Haiman, Brian E Henderson, Daniel Stram, Xiang Deng, Ann W Hsing, Jarmo Virtamo, Michael A Eberle, Jennifer L Stone, Mark P Purdue, Phil Taylor, Margaret Tucker, Stephen J Chanock
Journal: Nature Genetics (2011)
Mutant Epidermal Growth Factor Receptor in Benign, Borderline, and Malignant Ovarian Tumors
Authors: Karina Dahl Steffensen, Marianne Waldstrøm, Dorte Aalund Olsen, Thomas Corydon, Karen Axelgaard Lorentzen, Hans Jørgen Knudsen, Ulla Jeppesen, Ivan Brandslund, Anders Jakobsen
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Dysfunction of the epidermal growth factor (EGF) complex is essential to the growth and development of many human tumors. Overexpression of the EGF receptor (EGFR) is a characteristic finding in a considerable number of solid tumors and often signalizes poor prognosis. There is a major disagreement among researchers about both the frequency and possible clinical importance of EGFR overexpression in ovarian cancer. The type III variant of EGFR (EGFRvIII) is a mutant with a deletion. Contrary to the wild-type, it is constitutively active. EGFRvIII has not been found in normal tissue, and consequently, it is an attractive tumor-specific candidate for molecular targeted treatment. The literature dealing with this mutation in ovarian cancer has been very sparse. Experimental Design: Tissue from 225 patients who underwent surgery for a pelvic mass was collected consecutively. The samples included 99 ovarian/peritoneal/tuba cancers, 17 ovarian borderline tumors, 66 benign ovarian tumors, 15 other cancer types, 24 normal ovarian biopsies, and 4 miscellaneous. The presence of EGFRvIII was investigated both by PCR analyses for EGFRvIII gene expression and with protein analysis by Western blots. Results: None of the tissue samples was positive for the EGFRvIII mutation neither at the mRNA level nor at the protein level. Conclusions: The EGFRvIII mutation seems to be very rare in ovarian tissue. Our data indicate that EGFRvIII is not a part of the malignant phenotype in ovarian cancer and should not be pursued as a therapeutic target for treatment of this disease.
Quantitative Monitoring of Adenocarcinoma Development in Rodents by Magnetic Resonance Imaging
Authors: Joel R. Garbow, Min Wang, Yian Wang, Ronald A. Lubet, Ming You
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Accurately following the time course of tumor progression and response to therapy in animal models of cancer is key to the development of better chemopreventive and chemotherapeutic agents. The goal of this work was to monitor quantitatively the development and progression of adenocarcinoma in a time course study of mice treated with the carcinogen urethane using in vivo small-animal magnetic resonance imaging (MRI). Experimental Design: Mice treated with a single dose of urethane were imaged at four time points beginning 8 months after treatment. High-resolution images of mouse lung were obtained in vivo using respiratory-gated MRI methods. Individual tumors were manually segmented and their volumes calculated. At the end of the study, mice were euthanized and MRI tumor quantification was validated by histology and histopathology. Results: Tumors as small as 0.4 mm in diameter can be detected and quantitatively measured in mice by in vivo MRI. Total tumor burden increased consistently in all mice studied, whereas the growth rate of individual tumors varied widely. The positions and diameters of individual tumors as measured by MRI correlated well with histology results. Histologic study of large, rapidly growing tumors showed that these were adenocarcinomas, whereas small, slowly growing lesions were predominantly adenomas. Conclusions: Longitudinal in vivo MRI is a powerful modality that can be of great aid in elucidating the factors that control the onset of lung tumors and can serve as a platform for the development and preclinical testing of novel therapies having a high likelihood of efficacy in human clinical trials.
Prefrontal Activation Deficits During Episodic Memory in Schizophrenia
Authors: John D. Ragland, Angela R. Laird, Charan Ranganath, Robert S. Blumenfeld, Sabina M. Gonzales, David C. Glahn
Journal: American Journal of Psychiatry (2009)

Objective: Episodic memory impairments represent a core deficit in schizophrenia that severely limits patients’ functional outcome. This quantitative meta-analysis of functional imaging studies of episodic encoding and retrieval tests the prediction that these deficits are most consistently associated with dysfunction in the prefrontal cortex. Method: Activation likelihood estimation (ALE) was used to perform a quantitative meta-analysis of functional imaging studies that contrasted patients with schizophrenia and healthy volunteers during episodic encoding and retrieval. From a pool of 36 potential studies, 18 whole-brain studies in standard space that included a healthy comparison sample and low-level baseline contrast were selected. Results: As predicted, patients showed less prefrontal activation than comparison subjects in the frontal pole, dorsolateral and ventrolateral prefrontal cortex during encoding, and the dorsolateral prefrontal cortex and ventrolateral prefrontal cortex during retrieval. The ventrolateral prefrontal cortex encoding deficits were not present in studies that provided patients with encoding strategies, but dorsolateral prefrontal cortex deficits remained and were not secondary to group performance differences. The only medial temporal lobe finding was relatively greater patient versus comparison subject activation in the parahippocampal gyrus during encoding and retrieval. Conclusions: The finding of prominent prefrontal dysfunction suggests that cognitive control deficits strongly contribute to episodic memory impairment in schizophrenia. Memory rehabilitation approaches developed for patients with frontal lobe lesions and pharmacotherapy approaches designed to improve prefrontal cortex function may therefore hold special promise for remediating memory deficits in patients with schizophrenia.
Intragenic Rearrangement and Altered RNA Splicing of the Androgen Receptor in a Cell-Based Model of Prostate Cancer Progression
Authors: Yingming Li, Majid Alsagabi, Danhua Fan, G. Steven Bova, Ahmed H. Tewfik, Scott M. Dehm
Journal: Cancer Research (2011)

Androgen depletion for advanced prostate cancer (PCa) targets activity of the androgen receptor (AR), a steroid receptor transcription factor required for PCa growth. The emergence of lethal castration-resistant PCa (CRPCa) is marked by aberrant reactivation of the AR despite ongoing androgen depletion. Recently, alternative splicing has been described as a mechanism giving rise to COOH-terminally truncated, constitutively active AR isoforms that can support the CRPCa phenotype. However, the pathologic origin of these truncated AR isoforms is unknown. The goal of this study was to investigate alterations in AR expression arising in a cell-based model of PCa progression driven by truncated AR isoform activity. We show that stable, high-level expression of truncated AR isoforms in 22Rv1 CRPCa cells is associated with intragenic rearrangement of an approximately 35-kb AR genomic segment harboring a cluster of previously described alternative AR exons. Analysis of genomic data from clinical specimens indicated that related AR intragenic copy number alterations occurred in CRPCa in the context of AR amplification. Cloning of the break fusion junction in 22Rv1 cells revealed long interspersed nuclear elements (LINE-1) flanking the rearranged segment and a DNA repair signature consistent with microhomology-mediated, break-induced replication. This rearrangement served as a marker for the emergence of a rare subpopulation of CRPCa cells expressing high levels of truncated AR isoforms during PCa progression in vitro. Together, these data provide the first report of AR intragenic rearrangements in CRPCa and an association with pathologic expression of truncated AR isoforms in a cell-based model of PCa progression.