tbuckley/cabot-search huggingface dataset:
Mediators and Moderators of Long-term Effects of Violent Video Games on Aggressive Behavior
Authors: Douglas A. Gentile, Dongdong Li, Angeline Khoo, Sara Prot, Craig A. Anderson
Journal: JAMA Pediatrics (2014)

<h3>Importance</h3> Although several longitudinal studies have demonstrated an effect of violent video game play on later aggressive behavior, little is known about the psychological mediators and moderators of the effect. <h3>Objective</h3> To determine whether cognitive and/or emotional variables mediate the effect of violent video game play on aggression and whether the effect is moderated by age, sex, prior aggressiveness, or parental monitoring. <h3>Design, Setting, and Participants</h3> Three-year longitudinal panel study. A total of 3034 children and adolescents from 6 primary and 6 secondary schools in Singapore (73% male) were surveyed annually. Children were eligible for inclusion if they attended one of the 12 selected schools, 3 of which were boys' schools. At the beginning of the study, participants were in third, fourth, seventh, and eighth grades, with a mean (SD) age of 11.2 (2.1) years (range, 8-17 years). Study participation was 99% in year 1. <h3>Main Outcomes and Measures</h3> The final outcome measure was aggressive behavior, with aggressive cognitions (normative beliefs about aggression, hostile attribution bias, aggressive fantasizing) and empathy as potential mediators. <h3>Results</h3> Longitudinal latent growth curve modeling demonstrated that the effects of violent video game play are mediated primarily by aggressive cognitions. This effect is not moderated by sex, prior aggressiveness, or parental monitoring and is only slightly moderated by age, as younger children had a larger increase in initial aggressive cognition related to initial violent game play at the beginning of the study than older children. Model fit was excellent for all models. <h3>Conclusions and Relevance</h3> Given that more than 90% of youths play video games, understanding the psychological mechanisms by which they can influence behaviors is important for parents and pediatricians and for designing interventions to enhance or mitigate the effects.
Smaller Anterior Hippocampal Formation Volume in Antipsychotic-Naive Patients With First-Episode Schizophrenia
Authors: Philip R Szeszko, Ethan Goldberg, Handan Gunduz-Bruce, Manzar Ashtari, Delbert Robinson, Anil K Malhotra, Todd Lencz, John Bates, David T Crandall, John M Kane, Robert M Bilder
Journal: American Journal of Psychiatry (2003)

The authors investigated volumetric alterations of the anterior hippocampal formation in patients experiencing a first episode of schizophrenia relative to healthy comparison subjects.From contiguous 1.5-mm coronal magnetic resonance images, the hippocampal formation was divided into posterior and anterior segments, and the anterior hippocampal formation was separated from the amygdala. Volumes of the posterior and anterior hippocampal formation and amygdala were computed in 46 (31 male and 15 female) patients experiencing a first episode of schizophrenia and in 34 (21 male and 13 female) healthy comparison subjects. Twenty-four patients were antipsychotic naive at the time of the scan.Patients had significantly reduced total (right plus left) anterior hippocampal formation volume relative to healthy comparison subjects but did not differ in volumes of either the posterior hippocampal formation or amygdala. Similar findings were obtained when analyses were restricted to the antipsychotic-naive subgroup of patients.These findings suggest that volumetric abnormalities of the hippocampus-amygdala complex may be specific to the anterior hippocampal formation in patients experiencing a first episode of schizophrenia and are consistent with hypotheses regarding abnormal frontolimbic connectivity playing a role in the pathophysiology of the disorder.
CCR5 saves lives
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

![Graphic][1] 

CCR5 +  mononuclear cells (black) infiltrate the brain and help eliminate WNV infection.Although West Nile virus (WNV) infections have made headlines in recent years, little is known about how the virus causes disease or how the immune system fights back. On 

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THROMBOPENIC PURPURA FOLLOWING USE OF DIGITOXIN
Authors: Herbert Berger
Journal: JAMA (1952)

Blood dyscrasias are common complications of the use of numerous medicaments. Recently, severe thrombopenic purpura developed in a patient under my care who had rheumatic carditis. Ultimately this hemorrhagic state was shown to be caused by digitoxin. A thorough survey of the literature and of several papers on digitoxin toxicity<sup>1</sup>failed to reveal a single instance of the association of thrombopenic purpura with use of digitoxin. <h3>REPORT OF A CASE</h3> The patient, a woman, aged 70, was first seen at the clinic on March 18, 1950, with complete congestive heart failure. She had had several attacks of a disease called "inflammatory rheumatism" during her childhood, but careful questioning disclosed that in the attacks several joints were swollen, red, and painful in succession, symptoms indicating typical migrating polyarthritis. She was treated, as was the custom 50 years ago, with poultices and pills and was allowed out of bed as soon
Second Primary Tumors in Neurofibromatosis 1 Patients Treated for Optic Glioma: Substantial Risks After Radiotherapy
Authors: Saba Sharif, Rosalie Ferner, Jillian M. Birch, James E. Gillespie, H. Rao Gattamaneni, Michael E. Baser, D. Gareth R. Evans
Journal: Journal of Clinical Oncology (2006)

Purpose Optic pathway gliomas (OPGs) are the most common CNS tumor in neurofibromatosis 1 (NF1) patients. We evaluated the long-term risk of second tumors in NF1-related OPGs after radiotherapy. Patients and Methods We reviewed 80 NF1 OPG patients from two NF1 clinics to evaluate the long-term risk of developing subsequent nervous system tumors, with or without radiotherapy. Results Fifty-eight patients were assessable for second tumors. Nine (50%) of 18 patients who received radiotherapy after their OPGs developed 12 second tumors in 308 person-years of follow-up after radiotherapy. Eight (20%) of 40 patients who were not treated with radiotherapy developed nine tumors in 721 person-years of follow-up after diagnosis of their OPGs. The relative risk of second nervous system tumor after radiotherapy was 3.04 (95% CI, 1.29 to 7.15). Conclusion There is a significantly increased risk of second nervous system tumors in those NF1 patients who received radiotherapy for their OPGs, especially when treated in childhood. Thus radiotherapy should only be used if absolutely essential in children with NF1.
Resin Hemoperfusion for Treatment of Ethchlorvynol Overdose
Authors: ROBERT I. LYNN
Journal: Annals of Internal Medicine (1979)

Hemoperfusion has been increasingly used to treat drug intoxication. Although efficient extraction rates have been reported with hemoperfusion devices, simultaneous measurements of drug adsorption on the columns and endogenous clearance rates have not been made. We studied three patients who ingested 12 to 22 g of ethchlorvynol (Placidyl). In each patient saline diuresis was induced, and Amberlite XAD-4 resin hemoperfusion was done. Resin extraction of ethchlorvynol was calculated hourly, and the recovery of drugs from each column was measured. Renal clearance of ethchlorvynol was simultaneously measured. The resin removed 100% of perfused ethchlorvynol measured by gas chromatography. Ethchlorvynol recovery from the columns agreed well with calculated extraction. Renal clearance was 1 to 6 mL/min, and estimated metabolic clearance was 16% to 31% of resin extraction rate. Complications included anemia, thrombocytopenia, hypocalcemia, and pancreatitis. Resin hemoperfusion substantially supplements endogenous clearance of ethchlorvynol and is a valuable therapy in ethchlorvynol intoxication.
Reply to J. Lagro et al and G. Lughezzani et al
Authors: Alexander Kutikov, Brian L. Egleston, Yu-Ning Wong, Robert G. Uzzo
Journal: Journal of Clinical Oncology (2010)

We appreciate the comments 1,2 regarding our predictive model for competing risks of death in patients with localized renal cell carcinoma. 3We share the views of Largo et al and believe that in the elderly or those with significant comorbidities, competing risks contend with kidney cancer as the primary cause of death.Furthermore, we concur with their statements regarding the need to incorporate comorbidities in future predictive models.As we discussed in our article, one of the limitations of the Surveillance, Epidemiology, and End Results data set is that it does not include comorbidity data.We hope to include such data in future projects.With regard to the appropriateness of using case-mix adjustments in the context of a competing risks analysis, groups outside of our institution have also raised concerns about this approach. 4Despite its shortcomings, we do believe our model affords a unique quantitative scaffold on which one can base clinical choices. 3e thank Lughezzani et al-renowned leaders in development of predictive models-for performing an additional calibration and external validation of our nomogram.We agree with the authors that the supplementary analysis described in their communication greatly adds to the strength of our initial report.In summary, competing risks of death must be thoughtfully integrated into clinical decision making.Current ubiquitous qualitative approaches must be replaced by quantitative strategies.Although such prognostic tools for elderly/comorbid patients with renal cell carcinoma are starting to emerge, more powerful and more refined models are needed.
Nitric Oxide–Donating Acetylsalicylic Acid Induces Apoptosis in Chronic Lymphocytic Leukemia Cells and Shows Strong Antitumor Efficacy <i>In vivo</i>
Authors: Regina Razavi, Iris Gehrke, Rajesh Kumar Gandhirajan, Simon Jonas Poll-Wolbeck, Michael Hallek, Karl-Anton Kreuzer
Journal: Clinical Cancer Research (2010)

Nitric oxide-donating acetylsalicylic acid (NO-ASA) has been shown to possess an antineoplastic effect in Wnt-/β-catenin-active cancers. As chronic lymphocytic leukemia (CLL) cells exhibit aberrantly active Wnt signaling, we investigated the effect of the para-isomer of NO-ASA on CLL cell survival in vitro and in a CLL-like xenograft mouse model.Apoptosis in primary CLL cells was determined by flow cytometric annexin V-FITC (fluorescein isothiocyanate)/PI (propidium iodide) staining and immunoblotting of caspases, poly(ADP-ribose) polymerase (PARP), and antiapoptotic proteins. Interference of NO-ASA with Wnt/β-catenin signaling was analyzed through immunoblots of different pathway members. Influence of caspase activation was investigated by pretreatment with a pan-caspase inhibitor. CLL-like JVM3 cells were subcutaneously inoculated into irradiated nude mice that were treated with 100 mg of para-NO-ASA/kg of body weight p.o. (by mouth) for 21 days.para-NO-ASA induced apoptosis in CLL cells with an LC(50) (lethal concentration) of 8.72 + 0.04 μmol/L, whereas healthy blood cells were not affected. Furthermore, the compound induced caspase 9, caspase 3, and PARP cleavage. In addition, cleavage of β-catenin and downregulation of β-catenin/lymphoid enhancer factor (Lef)-1 targets was observed. para-NO-ASA demonstrated strong antitumor efficacy in the xenograft mouse model with a tumor inhibtion rate of 83.4%. During therapy, no gross toxicity could be observed.para-NO-ASA selectively induces apoptosis in primary CLL cells and efficiently reduces tumor growth in a CLL-like xenograft model. As NO-ASA is orally available and is generally well tolerated, para-NO-ASA might be a promising new compound for CLL therapy.
Phase I Biodistribution and Pharmacokinetic Study of Lewis Y–Targeting Immunoconjugate CMD-193 in Patients with Advanced Epithelial Cancers
Authors: Rebecca A. Herbertson, Niall C. Tebbutt, Fook-Thean Lee, David J. MacFarlane, Bridget Chappell, Noel Micallef, Sze-Ting Lee, Timothy Saunder, Wendie Hopkins, Fiona E. Smyth, David K. Wyld, John Bellen, Daryl S. Sonnichsen, Martin W. Brechbiel, Carmel Murone, Andrew M. Scott
Journal: Clinical Cancer Research (2009)

This phase I study explored the biodistribution and pharmacokinetics of the immunoconjugate CMD-193 [a humanized anti-Lewis Y (Le(y)) antibody conjugated with calicheamicin in patients with advanced cancers expressing the Le(y) antigen.
Putting genetics in perspective
Authors: R. Zimmern
Journal: BMJ (2001)

How will genetics affect society? Is it a science without clear application, or will it bring important health gains? Should we be hugely excited about its potential or worry about the ethical dilemmas it poses? Unquestionably views are polarised, 1 2 as this special issue of the BMJ reflects.

The impact on health and health care of the sequencing of the human genome has been well rehearsed.3 Our understanding and categorisation of disease will be enhanced. Drug therapy may become safer and more effective as treatments are tailored to take account of individual responses to drugs. Genetic tests will increasingly be used to predict the risk of disease and initiate preventive action. Drug development will become faster and more efficient.

Yet hidden among these simple statements lurks great complexity. Extrapolating from single gene disorders such as Huntington's disease to predict how genetics might affect future health care will mislead. In this disorder the detection of an abnormal variant or mutation in the …
Thoracic oncology in Europe: the ERS action plan by the Thoracic Oncology Assembly
Authors: J-P. Sculier, J. Vansteenkiste, N. Schönfeld, A. Scherpereel
Journal: European Respiratory Journal (2010)

Lung cancer is the leading cause of cancer mortality in Europe and its incidence is rapidly increasing in females 1, 2. In addition, malignant mesothelioma is an emerging neoplasm that is expected to become a frequent disease in the forthcoming decade. Based on these considerations, the European Respiratory Society (ERS), which is the only European medical organisation dealing with respiratory diseases, has founded a new assembly to set up an action plan called “Thoracic Oncology in Europe”.

The decision to create a new assembly dedicated to thoracic oncology was made in 2009. The Thoracic Oncology Assembly (assembly 11) was issued from the thoracic oncology group of the Clinical Assembly and consists of two groups: group 11.1, dealing with lung cancer, and group 11.2, dealing with pleural and thoracic malignancies.

The motivation of the ERS to establish a new assembly is that thoracic oncology has become a strong pillar of the society. Indeed, thoracic malignancies are a menacing health problem, not only on our continent. To meet this challenge, an action plan was designed by the assembly officers during a memorable meeting in Brussels in March 2010 and approved immediately, and was strongly welcomed by the ERS executive committee in April. The action plan intends that the ERS becomes the leading European society in the field, as its members already deal with all aspects of thoracic malignancies, from basic science to patient care. To fulfil this objective, various activities will be developed. European guidelines in the field of thoracic oncology are an important part of the plan, not only to keep up with an accelerating development …
The serum protein α2–Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification
Authors: Cora Schäfer, Alexander Heiss, Anke Schwarz, Ralf Westenfeld, Markus Ketteler, Jürgen Floege, Werner Müller-Esterl, Thorsten Schinke, Willi Jahnen-Dechent
Journal: Journal of Clinical Investigation (2003)

Ectopic calcification is a frequent complication of many degenerative diseases. Here we identify the serum protein alpha2-Heremans-Schmid glycoprotein (Ahsg, also known as fetuin-A) as an important inhibitor of ectopic calcification acting on the systemic level. Ahsg-deficient mice are phenotypically normal, but develop severe calcification of various organs on a mineral and vitamin D-rich diet and on a normal diet when the deficiency is combined with a DBA/2 genetic background. This phenotype is not associated with apparent changes in calcium and phosphate homeostasis, but with a decreased inhibitory activity of the Ahsg-deficient extracellular fluid on mineral formation. The same underlying principle may contribute to many calcifying disorders including calciphylaxis, a syndrome of severe systemic calcification in patients with chronic renal failure. Taken together, our data demonstrate a critical role of Ahsg as an inhibitor of unwanted mineralization and provide a novel therapeutic concept to prevent ectopic calcification accompanying various diseases.
NI-02 * ELEVATED MYOINOSITOL IN DIFFUSE ASTROCYTOMA; A MARKER OF ANAPLASTIC PHENOTYPE, AND NOT ATTRIBUTABLE TO MICROGLIAL INFILTRATION
Authors: A. Waldman, N. Upadhyay, A. Adams, D. Peterson, F. Roncaroli
Journal: Neuro-Oncology (2014)

PURPOSE: Although in vivo MRS has been extensively applied to gliomas, the relevance of myoinositol (Myo) to malignant phenotype and the cell types that contribute signal are poorly understood. Microglial infiltration is associated with Myo elevation in inflammatory and neurodegenerative diseases, and has been implicated in neoangiogenesis in transforming gliomas. The aim of this study was to examine the relationship between Myo and Cho imaging biomarkers and enzymatic tissue markers of Myo synthesis and microglial cell type in grade II and III astrocytomas. SUBJECTS AND METHODS: 28 patients with diffuse astrocytoma (14 diffuse LGG, WHO grade II; 14 anaplastic, WHO grade III; 13 stereotactic biopsies, 15 surgical specimens) underwent multivoxel spectroscopy at 1.5 T or 3T (TE = 30ms, TR = 1500ms, 8x8 grid; Siemens Avanto/Verio, Erlangen, De). Metabolite ratios were estimated using proprietary software. Tissue immunostains with rabbit polyclonal antibodies directed against human inositol monophosphatase (IMPA1; Sigma – dilution 1:400; 25 cases) and Iba1 (Wako – dilution 1:750; 21 cases), were assessed semi-quantitatively. Myo/Cr and Cho/Cr ratios were compared (Kruskal-Wallis) and compared with Iba-1 and IMPA1 levels (Wilcoxon rank-sum), and metabolite ratios with Iba1 (Spearman's rank test). Co-localisation of highest Myo/Cr and Cho/Cr was also measured (Fisher's exact test). RESULTS: Myo/Cr was significantly lower in grade II compared with grade III tumours (p < 0.01). Highest Myo/Cr co-localised with highest Cho/Cr voxels in 72%. IMPA1 scores were significantly higher in grade III compared to grade II lesions (p < 0.01). There was no correlation between semi-quantitative microglial analysis using Iba1 antibody and Myo/Cr or tumour grade. CONCLUSION: Higher Myo in grade III than grade II astrocytomas suggests that it is not a marker of indolent tumour phenotype, as has been previously suggested, and may reflect increased de novo synthesis relating to p53 mutations. Our data do not suggest that microglia account for raised Myo levels in gliomas.
Contractility in mammalian heart muscle; calcium and osmolality.
Authors: M A Goethals, S M Adèle, D L Brutsaert
Journal: Circulation Research (1975)

The influence of osmolality of the external medium on the calcium (Ca) dependency of contractility of isolated electrically excited cat papillary muscle was examined. Maximum unloaded velocity of shortening was directly measured by load clamping the muscle from the preload (at the length, Lmax, at which maximum active tension was developed) to zero load (zero load clamp). Peak velocity of shortening at the Lmax preload, peak total force, peak rate of force development, time to peak force, and time to half relaxation were also recorded. The performance-Ca response curves (Ca concentration between 1.25 nM and 10 nM) for maximum unloaded velocity of shortening, peak shortening velocity at Lmax preload, total force, and peak rate of force development were shifted to the left when osmolality was increased (from 290 mosmoles to 410 mosmoles) with sucrose, and to the right when osmolality was increased with NaCl. The sensitivity for Ca, as determined from the slopes of these response curves, appeared essentially unaltered by either sucrose or NaCl, except for the high Ca concentrations (above 5 mM) at the higher osmolalities (above 370 mosmoles) especially with sucrose.
Sustained Antigen-Specific Antitumor Recall Response Mediated by Gene-Modified CD4+ T Helper-1 and CD8+ T Cells
Authors: Maria Moeller, Michael H. Kershaw, Rachel Cameron, Jennifer A. Westwood, Joseph A. Trapani, Mark J. Smyth, Phillip K. Darcy
Journal: Cancer Research (2007)

Abstract Given that specific subsets of T helper 1 (Th1) and T helper 2 (Th2) CD4+ T cells have been shown to play key roles in tumor rejection models, we wanted to assess the contribution of either Th1 or Th2 CD4+ cell subtypes for redirected T-cell immunotherapy. In this study, we have developed a novel method involving retroviral transduction and in vitro T-cell polarization to generate gene-engineered mouse CD4+ Th1 and Th2 cells or T helper intermediate (Thi) cells expressing an anti–erbB2-CD28-ζ chimeric receptor. Gene-modified Th1 and Th2 polarized CD4+ cells were characterized by the preferential secretion of IFN-γ and interleukin-4, respectively, whereas Thi cells secreted both cytokines following receptor ligation. In adoptive transfer studies using an erbB2+ lung metastasis model, complete survival of mice was observed when transduced Th1, Th2, or Thi CD4+ cells were transferred in combination with an equivalent number of transduced CD8+ T cells. Tumor rejection was consistently associated with transduced T cells at the tumor site and interleukin-2 secretion. However, the surviving mice treated with gene-modified Th1 CD4+ cells were significantly more resistant to a subsequent challenge with a different erbB2+ tumor (4T1.2) implanted s.c. This result correlated with both increased expansion of Th1 CD4+ and CD8+ T cells in the blood and a greater number of these cells localizing to the tumor site following rechallenge. These data support the use of gene-modified CD4+ Th1 and CD8+ T cells for mediating a sustained antitumor response. [Cancer Res 2007;67(23):11428–37]
Essential role of IPS-1 in innate immune responses against RNA viruses
Authors: Himanshu Kumar, Taro Kawai, Hiroki Kato, Shintaro Sato, Ken Takahashi, Cevayir Coban, Masahiro Yamamoto, Satoshi Uematsu, Ken J. Ishii, Osamu Takeuchi, Shizuo Akira
Journal: The Journal of Experimental Medicine (2006)

IFN-β promoter stimulator (IPS)-1 was recently identified as an adapter for retinoic acid–inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (Mda5), which recognize distinct RNA viruses. Here we show the critical role of IPS-1 in antiviral responses in vivo. IPS-1–deficient mice showed severe defects in both RIG-I– and Mda5-mediated induction of type I interferon and inflammatory cytokines and were susceptible to RNA virus infection. RNA virus–induced interferon regulatory factor-3 and nuclear factor κB activation was also impaired in IPS-1–deficient cells. IPS-1, however, was not essential for the responses to either DNA virus or double-stranded B-DNA. Thus, IPS-1 is the sole adapter in both RIG-I and Mda5 signaling that mediates effective responses against a variety of RNA viruses.