tbuckley/cabot-search huggingface dataset:
Yttrium-90 Ibritumomab Tiuxetan Doses Calculated to Deliver up to 15 Gy to Critical Organs May Be Safely Combined With High-Dose BEAM and Autologous Transplantation in Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma
Authors: Jane N. Winter, David J. Inwards, Stewart Spies, Gregory Wiseman, David Patton, William Erwin, Alfred W. Rademaker, Bing Bing Weitner, Stephanie F. Williams, Martin S. Tallman, Ivana Micallef, Jayesh Mehta, Seema Singhal, Andrew M. Evens, Michael Zimmer, Arturo Molina, Christine A. White, Leo I. Gordon
Journal: Journal of Clinical Oncology (2009)

To determine the maximum-tolerated radiation-absorbed dose (RAD) to critical organs delivered by yttrium-90 ((90)Y) ibritumomab tiuxetan in combination with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy with autologous transplantation.Eligible patients had relapsed or refractory CD20+ non-Hodgkin's lymphoma (NHL). Individualized (90)Y activities were based on dosimetry and were calculated to deliver cohort-defined RAD (1 to 17 Gy) to critical organs with three to six patients per cohort. The therapeutic dose of (90)Y ibritumomab tiuxetan was followed by high-dose BEAM and autologous transplantation.Forty-four patients were treated. Thirty percent of patients had achieved less than a partial remission to their most recent therapy and would not have been eligible for autologous transplantation at most centers. The toxicity profile was similar to that associated with high-dose BEAM chemotherapy. Two dose-limiting toxicities occurred at the 17 Gy dose level, which made 15 Gy the recommended maximum-tolerated RAD. Although eight patients received at least twice the conventional dose of 0.4 mCi/kg, a weight-based strategy at 0.8 mCi/kg would have resulted in a wide range of RAD; nearly 25% of patient cases would have received 17 Gy or more, and many would have received less than 10 Gy. With a median follow-up of 33 months for all patients, the estimated 3-year progression-free and overall survivals were 43% and 60%, respectively.Dose-escalated (90)Y ibritumomab tiuxetan may be safely combined with high-dose BEAM with autologous transplantation and has the potential to be more effective than standard-dose radioimmunotherapy. Careful dosimetry is required to avoid toxicity and undertreatment.
National physical education curriculum: motor and cardiovascular health related fitness in Greek adolescents
Authors: Y Koutedakis, C Bouziotas
Journal: British Journal of Sports Medicine (2003)

State school physical education (PE) programmes are common throughout Greece. However, it is not known if the main objectives of the Greek PE curriculum are achieved.To assess the current national PE curriculum in relation to selected motor and cardiovascular health related fitness parameters.A sample of 84 Greek schoolboys (mean (SD) age 13.6 (0.3) years, height 160.7 (8.6) cm, weight 50 (10.8) kg) volunteered. Forty three indicated participation only in school PE classes and habitual free play (PE group). The remaining 41 were involved in extracurricular organised physical activities in addition to school PE and habitual free play (PE+ group). The subjects underwent anthropometric, motor (flexibility, balance, standing broad jump, hand grip, sit ups, and plate tapping), and cardiovascular health related (percentage body fat, aerobic fitness, and physical activity) fitness assessments.Children in the PE group had inferior motor and cardiovascular health related fitness profiles compared with those in the PE+ group. Body fat (20.3 (8.8) v 13.9 (3.5); p<0.001), aerobic fitness (34.7 (3.7) v 43.9 (4.2); p<0.001), and time spent in intensive physical activity (0.2 (0.2) v 0.7 (0.3); p<0.001) showed the greatest differences between the two groups. In the pupils in the PE group, these were lower than the levels proposed to be necessary to combat future health risks. Adjustments for confounding variables showed a decrease in the significance of motor fitness, but not in cardiovascular health related parameters.The national PE curriculum for Greek secondary schools does not achieve the required levels of motor and cardiovascular health related fitness and should be reconsidered.
Neuropsychological Study of Frontal Lobe Function in Psychotropic-Naive Children With Obsessive-Compulsive Disorder
Authors: Sue R. Beers, David R. Rosenberg, Elizabeth L. Dick, Theresa Williams, Kirsten M. O’Hearn, Boris Birmaher, Christopher M. Ryan
Journal: American Journal of Psychiatry (1999)

The authors' goal was to evaluate cognition in children with obsessive-compulsive disorder (OCD) early in their illness.They administered neuropsychological tests to 21 pediatric patients with OCD and 21 healthy children matched for age, sex, socioeconomic status, and intelligence. The children with OCD were not depressed, and none had ever received psychotropic medication. The neuropsychological tests were used to assess the relationship between psychiatric symptoms and cognitive function.The children with OCD performed as well as the healthy children on the neuropsychological tests. Psychiatric symptoms and cognitive performance were not related.Nondepressed children with recently diagnosed OCD who had never received psychotropic medication demonstrated no cognitive impairment according to their performance on neuropsychological tests. The authors conclude that OCD symptoms may not interfere with cognitive abilities early in the illness.
O4.07 * A NOVEL POLYCOMB FEED FORWARD LOOP IN GLIOBLASTOMA MULTIFORME
Authors: S. Marino, D. Ceric, B. Ricci, M. Barnes
Journal: Neuro-Oncology (2014)

Dysregulation of epigenetic mechanisms, together with genetic mutations, is an essential driver in the progression of malignant gliomas. Polycomb group proteins (PcG) are chromatin associated proteins that play an essential role in epigenetic regulation of gene expression. We have recently demonstrated that conditional overexpression of Bmi1 in neural stem cells (NSC) increased their proliferation and self-renewal while overexpression of Bmi1 in intermediate progenitors committed toward the neuronal lineage triggered apoptosis. At the mechanistic level, in Bmi1-overexpressing NSC we observed downregulation of both the p21/Foxg1 and the ink4a/arf pathways, the latter of which coincided with the accumulation of H3K27me3 at the promoter region of the p16ink4a gene, thus indicating the key role of this modification as downstream effector of Bmi1-induced silencing. Moreover, we have shown that a similar mechanism is also responsible for silencing expression of Survivin, a key antiapoptotic factor, in committed neuronal progenitors, thereby leading to their apoptosis. Together, this convergent evidence points to increased trimethylation of H3K27 as a core mechanism mediating the functional outcome of Bmi1 upregulation. Bmi1 is overexpressed in a significant proportion of high grade gliomas and a wealth of suggestive evidence linking perturbations in H3K27 methylation to the development of these tumours exist, although it is still unclear how aberrant H3K27me3 contributes to gliomagenesis. Here, we used genetically engineered mouse models to study overexpression of PcG gene Bmi1 in NSC and GBM initiating cells (GBM-IC). ChIP followed by genome wide screening was carried out and the results analysed in combination with gene expression as assessed by RNASeq. We show that Bmi1-mediated regulation of the expression of Survivin was strikingly similar in GBM-IC as observed in NSC. mGBM-IC isolated from a mouse model of glioblastoma express similar level of Bmi1 as detected in NSC isolated from NestinCre;STOPFloxBmi1 and knock down of Bmi1 significantly hampers proliferation of mGBM-IC. Similar to what observed in non-neoplastic NSC overexpressing Bmi1 a significant reduction of H3K27me3 was seen in these cells upon Bmi1 knockdown. Genome wide ChIPSeq analysis for H3K27me3 and RNASeq performed on NSC overexpressing Bmi1 and GBM-IC expressing similar level of Bmi1 allowed us to set these results in the wider context of the global epigenetic regulation of gene expression mediated by Bmi1. Elucidating the molecular mechanisms of the epigenetic dysregulation observed in high grade gliomas is essential for the identification of novel biomarkers of early stage tumours and also offers an opportunity to identify novel druggable targets or drug repositioning opportunities for more effective therapies.
Knowledge translation in sport injury prevention research: an example in youth ice hockey in Canada
Authors: Sarah A Richmond, Carly D McKay, Carolyn A Emery
Journal: British Journal of Sports Medicine (2013)

There is a critical need for scientists to incorporate a knowledge translation (KT) perspective into research plans to demonstrate the relevance of research findings and evaluate their implications for health practice and policy. Since 2011, the British Journal of Sport Medicine ( BJSM ) has had a focus on implementation and dissemination research.1 This field is consistent with KT, which is the term used by the Canadian Institutes of Health Research (CIHR). As the following research example was conducted in Canada, the terminology KT is used, acknowledging similarities to implementation and dissemination concepts referred to elsewhere in BJSM .

Using an interdisciplinary approach, the knowledge exchange process should influence healthcare professionals, community members and other decision-making groups. On the basis of the original model developed by van Mechelen et al ,2 injury prevention research in sport includes identification of injury burden, examination of risk factors, and development, implementation and evaluation of prevention strategies to reduce injury risk. As sport injury prevention programmes cannot be impactful without acceptance and adoption by targeted individuals, an extension of this model must include real-world implementation contexts and evaluation of their effectiveness in a broader, ecological context (figure 1).3 



Figure 1 
Sport Injury Prevention Research Centre adapted integrated knowledge translation model. The prevention of injuries and their long-term …
Inference for the Initial Stage of Domain Shuffling: Tracing the Evolutionary Fate of the PIPSL Retrogene in Hominoids
Authors: K. Ohshima, K. Igarashi
Journal: Molecular Biology and Evolution (2010)

Domain shuffling has provided extraordinarily diverse functions to proteins. Nevertheless, how newly combined domains are coordinated to create novel functions remains a fundamental question of genetic and phenotypic evolution. Previously, we reported a unique mechanism of gene creation, whereby new combinations of functional domains are assembled from distinct genes at the RNA level, reverse transcribed, and integrated into the genome by the L1 retrotransposon. The novel gene PIPSL, created by the fusion of phosphatidylinositol-4-phosphate 5-kinase (PIP5K1A) and 26S proteasome subunit (S5a/PSMD4) genes, is specifically transcribed in human and chimpanzee testes.
Liver in obesity.
Authors: A Braillon, J P Capron, M A Herve, C Degott, C Quenum
Journal: Gut (1985)

We report on clinical, nutritional, and hepatic histological findings in 50 non-selected obese subjects (mean overweight +74%; range +21-138%). The pathogenesis of the liver damage was assessed with the help of multidimensional analysis of a number of clinical variables. According to the severity of the hepatic lesions, the patients have been ranged in five groups: O (normal liver) 10%; I (fatty liver) 48%; II (fatty hepatitis) 26%; III (fatty fibrosis) 8%; IV (fatty cirrhosis) 8%. The more severe changes (groups III and IV) were constantly associated with excessive alcohol intake. The multidimensional analysis was unable to find a relationship between obesity and the development of fibrosis and cirrhosis whereas it showed that: (a) there was a highly significant correlation between the daily ethanol intake and the degree of overweight, (b) severe fatty metamorphosis was significantly associated with the degree of overweight, the existence of diabetes mellitus, and the amount of alcohol and fat intake, (c) nutritional factors, in particular deficient protein intake, have only an accessory effect in the development of mild inflammation and fibrosis, (d) the consumption of potentially hepatotoxic drugs, very high in the obese (about five drugs per day) could have a role in the development of cirrhosis. In conclusion in our study, there was no evidence that obesity per se could result in severe liver damage.
IL-1β, in contrast to TNFα, is pivotal in blood-induced cartilage damage and is a potential target for therapy
Authors: Lize F. D. van Vulpen, Roger E. G. Schutgens, Katja Coeleveld, Els C. Alsema, Goris Roosendaal, Simon C. Mastbergen, Floris P. J. G. Lafeber
Journal: Blood (2015)
Continuing Trastuzumab Beyond Progression
Authors: Mohammad Jahanzeb
Journal: Journal of Clinical Oncology (2009)

During the last decade, most oncologists empirically adopted the practice of continuing trastuzumab beyond progression of disease in patients with human epidermal growth factor 2 (HER-2) –positive metastatic breast cancer (H2MBC), deviating from the established paradigm of stopping and switching drugs or interventions when patients develop disease progression. With trastuzumab, they simply switched the cytotoxic agent paired with this monoclonal anti–HER-2 antibody. Although a whole host of considerations may have facilitated this trend, ranging from virulence of HER-2–positive disease,
Role of Sphingosine-1-Phosphate Phosphohydrolase 1 in the Regulation of Resistance Artery Tone
Authors: Bernhard Friedrich Peter, Darcy Lidington, Aki Harada, Hanno Jörn Bolz, Lukas Vogel, Scott Heximer, Sarah Spiegel, Ulrich Pohl, Steffen-Sebastian Bolz
Journal: Circulation Research (2008)

Sphingosine-1-phosphate (S1P), which mediates pleiotropic actions within the vascular system, is a prominent regulator of microvascular tone. By virtue of its S1P-degrading function, we hypothesized that S1P-phosphohydrolase 1 (SPP1) is an important regulator of tone in resistance arteries. Hamster gracilis muscle resistance arteries express mRNA encoding SPP1. Overexpression of SPP1 (via transfection of a SPP1(wt)) reduced resting tone, Ca2+ sensitivity, and myogenic vasoconstriction, whereas reduced SPP1 expression (antisense oligonucleotides) yielded the opposite effects. Expression of a phosphatase-dead mutant of SPP1 (SPP1(H208A)) had no effect on any parameter tested, suggesting that catalytic activity of SPP1 is critical. The enhanced myogenic tone that follows overexpression of S1P-generating enzyme sphingosine kinase 1 (Sk1(wt)) was functionally antagonized by coexpression with SPP1(wt) but not SPP1(H208A). SPP1 modulated vasoconstriction in response to 1 to 100 nmol/L exogenous S1P, a concentration range that was characterized as S1P2-dependent, based on the effect of S1P(2) inhibition by antisense oligonucleotides and 1 mumol/L JTE013. Inhibition of the cystic fibrosis transmembrane regulator (CFTR) (1) restored S1P responses that were attenuated by SPP1(wt) overexpression; (2) enhanced myogenic vasoconstriction; but (3) had no effect on noradrenaline responses. We conclude that SPP1 is an endogenous regulator of resistance artery tone that functionally antagonizes the vascular effects of both Sk1(wt) and S1P2 receptor activation. SPP1 accesses extracellular S1P pools in a manner dependent on a functional CFTR transport protein. Our study assigns important roles to both SPP1 and CFTR in the physiological regulation of vascular tone, which influences both tissue perfusion and systemic blood pressure.
Autologous stem cell transplantation leads to a change in proinflammatory plasma cytokine profile of patients with juvenile dermatomyositis correlating with disease activity
Authors: F Bellutti Enders, E M Delemarre, J Kuemmerle-Deschner, P van der Torre, N M Wulffraat, B P Prakken, A van Royen-Kerkhof, F van Wijk
Journal: Annals of the Rheumatic Diseases (2014)

Autologous stem cell transplantation leads to a change in proinflammatory plasma cytokine profile of patients with juvenile dermatomyositis correlating with disease activity Autoantibodies after aSCT ANAWeakly positive Weakly positive + anti-SSA-52, anti-SSA-60, anti-SS-B, anti-Sm, anti-nRNP/Sm
Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations
Authors: Brian J O'Roak, Pelagia Deriziotis, Choli Lee, Laura Vives, Jerrod J Schwartz, Santhosh Girirajan, Emre Karakoc, Alexandra P MacKenzie, Sarah B Ng, Carl Baker, Mark J Rieder, Deborah A Nickerson, Raphael Bernier, Simon E Fisher, Jay Shendure, Evan E Eichler
Journal: Nature Genetics (2011)
Inhibition of astroglial nuclear factor κB reduces inflammation and improves functional recovery after spinal cord injury
Authors: Roberta Brambilla, Valerie Bracchi-Ricard, Wen-Hui Hu, Beata Frydel, Annmarie Bramwell, Shaffiat Karmally, Edward J. Green, John R. Bethea
Journal: The Journal of Experimental Medicine (2005)

In the central nervous system (CNS), the transcription factor nuclear factor (NF)-kappaB is a key regulator of inflammation and secondary injury processes. After trauma or disease, the expression of NF-kappaB-dependent genes is highly activated, leading to both protective and detrimental effects on CNS recovery. We demonstrate that selective inactivation of astroglial NF-kappaB in transgenic mice expressing a dominant negative (dn) form of the inhibitor of kappaB alpha under the control of an astrocyte-specific promoter (glial fibrillary acidic protein [GFAP]-dn mice) leads to a dramatic improvement in functional recovery 8 wk after contusive spinal cord injury (SCI). Histologically, GFAP mice exhibit reduced lesion volume and substantially increased white matter preservation. In parallel, they show reduced expression of proinflammatory chemokines and cytokines, such as CXCL10, CCL2, and transforming growth factor-beta2, and of chondroitin sulfate proteoglycans participating in the formation of the glial scar. We conclude that selective inhibition of NF-kappaB signaling in astrocytes results in protective effects after SCI and propose the NF-kappaB pathway as a possible new target for the development of therapeutic strategies for the treatment of SCI.
Luteal phase support in assisted reproduction cycles
Authors: M. van der Linden, K. Buckingham, C. Farquhar, J.A.M. Kremer, M. Metwally
Journal: Human Reproduction Update (2012)

Luteal phase support in assisted reproduction cycles BackgroundThe luteal phase in in vitro fertilization (IVF) cycles is insufficient and therefore supported with either progesterone, hCG or gonadotrophin-releasing hormone (GnRH) agonists.Luteal phase support improves implantation rates and thus pregnancy rates, but the ideal method is still unclear.Progesterone is most frequently used, hCG is known for the risk of ovarian hyperstimulation syndrome (OHSS), but is also widely used.GnRH agonists is a new method for luteal phase support.This is a summary of a meta-analysis published by the Cochrane Library (van der Linden et al., 2011) investigating luteal support in IVF/ICSI. MethodsThe authors searched electronic databases including the Cochrane Library, MEDLINE and EMBASE and conference abstracts in February 2011.Eligible reports were randomized trials of luteal phase support in IVF or ICSI investigating progesterone, hCG or GnRH agonist supplementation.Quasi-randomized trials and trials using frozen transfers or donor oocytes were excluded.Results were presented as risk differences (RDs) with 95% confidence intervals (CIs).In each comparison live birth rate was the primary outcome, secondary outcomes included clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, OHSS and multiple pregnancy rate per women.
Intermittent Explosive Disorder as a Disorder of Impulsive Aggression for DSM-5
Authors: Emil F. Coccaro
Journal: American Journal of Psychiatry (2012)

Intermittent explosive disorder, first introduced in DSM-III, has now received more intensive research and clinical characterization. The disorder consists of either high intensity outbursts of aggression occurring several times yearly or less intensive outbursts several times monthly, a more treatable form. The disorder begins in adolescence or early adulthood; prevalence is about 5%. It appears to be separate from childhood disruptive behavioral disorders, such as conduct disorder and oppositional defiant disorder. Fluoxetine and cognitive-behavioral therapy together appear to have synergistic treatment effects.
Counterintuition, existential anxiety, and religion as a by-product of the designing mind
Authors: Deborah Kelemen
Journal: Behavioral and Brain Sciences (2004)

In arguing for religion as a side effect of everyday cognition, Atran &amp; Norenzayan (A&amp;N) provide useful analyses of the strengths of the “naturalness-of-religion” position over others; however, experimental shortcomings limit the contributions of their empirical work. A relevant addendum involves considering research on children's orientation to teleological explanations of natural phenomena, which suggests that relatively rich cognitive proclivities might underlie religious thought.
Vital Signs, QT Prolongation, and Newly Diagnosed Cardiovascular Disease During Severe Hypoglycemia in Type 1 and Type 2 Diabetic Patients
Authors: Tetsuro Tsujimoto, Ritsuko Yamamoto-Honda, Hiroshi Kajio, Miyako Kishimoto, Hiroshi Noto, Remi Hachiya, Akio Kimura, Masafumi Kakei, Mitsuhiko Noda
Journal: Diabetes Care (2013)

OBJECTIVE To assess vital signs, QT intervals, and newly diagnosed cardiovascular disease during severe hypoglycemia in diabetic patients. RESEARCH DESIGN AND METHODS From January 2006 to March 2012, we conducted a retrospective cohort study to assess type 1 and type 2 diabetic patients with severe hypoglycemia at a national center in Japan. Severe hypoglycemia was defined as the presence of any hypoglycemic symptoms that could not be resolved by the patients themselves in prehospital settings. RESULTS A total of 59,602 cases that visited the emergency room by ambulance were screened, and 414 cases of severe hypoglycemia were analyzed. The median (interquartile range) blood glucose levels were not significantly different between the type 1 diabetes mellitus (T1DM) (n = 88) and type 2 diabetes mellitus (T2DM) (n = 326) groups (32 [24-42] vs. 31 [24-39] mg/dL, P = 0.59). During severe hypoglycemia, the incidences of severe hypertension (≥180/120 mmHg), hypokalemia (<3.5 mEq/L), and QT prolongation were 19.8 and 38.8% (P = 0.001), 42.4 and 36.3% (P = 0.30), and 50.0 and 59.9% (P = 0.29) in the T1DM and T2DM groups, respectively. Newly diagnosed cardiovascular disease during severe hypoglycemia and death were only observed in the T2DM group (1.5 and 1.8%, respectively). Blood glucose levels between the deceased and surviving patients in the T2DM group were significantly different (18 [14-33] vs. 31 [24-39] mg/dL, P = 0.02). CONCLUSIONS T1DM and T2DM patients with severe hypoglycemia experienced many critical problems that could lead to cardiovascular disease, fatal arrhythmia, and death.