tbuckley/cabot-search huggingface dataset:
Heritable and Nonheritable Pathways to Early Callous-Unemotional Behaviors
Authors: Luke W. Hyde, Rebecca Waller, Christopher J. Trentacosta, Daniel S. Shaw, Jenae M. Neiderhiser, Jody M. Ganiban, David Reiss, Leslie D. Leve
Journal: American Journal of Psychiatry (2016)

Callous-unemotional behaviors in early childhood signal higher risk for trajectories of antisocial behavior and callous-unemotional traits that culminate in later diagnoses of conduct disorder, antisocial personality disorder, and psychopathy. Studies demonstrate high heritability of callous-unemotional traits, but little research has examined specific heritable pathways to early callous-unemotional behaviors. Studies also indicate that positive parenting protects against the development of callous-unemotional traits, but genetically informed designs have not been used to confirm that these relationships are not the product of gene-environment correlations. In a sample of adopted children and their biological and adoptive mothers, the authors tested novel heritable and nonheritable pathways to preschool callous-unemotional behaviors.In an adoption cohort of 561 families, history of severe antisocial behavior assessed in biological mothers and observations of adoptive mother positive reinforcement at 18 months were examined as predictors of callous-unemotional behaviors at 27 months.Despite limited or no contact with offspring, biological mother antisocial behavior predicted early callous-unemotional behaviors. Adoptive mother positive reinforcement protected against early callous-unemotional behaviors. High levels of adoptive mother positive reinforcement buffered the effects of heritable risk for callous-unemotional behaviors posed by biological mother antisocial behavior.The findings elucidate heritable and nonheritable pathways to early callous-unemotional behaviors. The results provide a specific heritable pathway to callous-unemotional behaviors and compelling evidence that parenting is an important nonheritable factor in the development of callous-unemotional behaviors. The finding that positive reinforcement buffered heritable risk for callous-unemotional behaviors has important translational implications for the prevention of trajectories to serious antisocial behavior.
IMPACT OF WALL SHEAR STRESS AND AXIAL PLAQUE STRESS ON CORONARY PLAQUE INITIATION AND PROGRESSION
Authors: Takayoshi Toba, Gilwoo Choi, Hyun Jin Kim, Arjun Roy, Tran Nguyen, Michiel Schaap, Leo Grady, Kenzo Uzu, Shumpei Mori, Tomofumi Takaya, Toshiro Shinke, Bon-Kwon Koo, Charles Taylor, Hiromasa Otake
Journal: Journal of the American College of Cardiology (2016)
Renal Filtration and Catabolism of Complement Protein D
Authors: John E. Volanakis, Scott R. Barnum, Margaret Giddens, John H. Galla
Journal: New England Journal of Medicine (1985)

Complement protein D, a serine protease participating in the formation of the C3 convertase of the alternative complement pathway, has the lowest molecular weight (23,750) and serum concentration of all complement proteins. In normal serum, D is the rate-limiting protease of the alternative pathway of complement activation. We report that the serum concentrations of D in 20 patients with chronic renal failure (mean +/- S.D., 0.42 +/- 0.28 mg per deciliter) and in 16 patients on long-term dialysis (1.53 +/- 0.39 mg per deciliter) were significantly higher (P less than 0.001) than in 22 healthy adults (0.18 +/- 0.04 mg per deciliter). In chronic renal failure the serum concentration of D correlated with that of creatinine (r = 0.75, P less than 0.001). The serum concentrations of D found in patients with renal failure reached and in some cases exceeded those at which the protease is no longer rate-limiting. Thus, enhanced activity of the alternative pathway of complement should be expected in patients with advanced renal failure. Urinary D was undetectable (less than 0.2 micrograms per deciliter) in 17 normal adults and either undetectable or below the concentration expected from the degree of proteinuria in 10 patients with nephrotic syndrome. However, in a patient with Fanconi's syndrome the urinary concentration of D (1.3 mg per deciliter) was an order of magnitude higher than the serum concentration, representing 0.5 per cent of the total protein. The urinary D in this patient had normal hemolytic activity, antigenicity, and size. These results indicate that D is filtered through the glomerular membrane and is probably catabolized in the proximal renal tubules.
Abstract 4342: Multimodal contrast agent development using imprint lithography based techniques: New tools for examining biodistribution
Authors: Kevin P. Herlihy, Timothy Merkel, Joseph M. DeSimone
Journal: Cancer Research (2010)

Abstract Modern medicine stands to benefit greatly from recent advances in polymer science. Many state of the art therapeutics suffer from a poor therapeutic index because of poor biodistribution characteristics. To solve this problem, researchers are turning to new methods for therapeutic delivery. Herein we employ a top-down particle fabrication technique called Particle Replication In Non-wetting Templates (PRINT®) to fabricate unique biocompatible particles with distinct therapeutic properties based on their composition, size and shape. The particles are easily tagged with a variety of imaging beacons and radioisotopes making them effective as contrast agents for magnetic resonance imaging, positron emission tomography and fluorescence imaging and as radiotherapeutics. We employ this technique to design particles that will target or de-target specific organs and tissues as a function of their size and shape and therefore more effectively deliver their cargo. To our knowledge this work represents the first example of imprint lithography-based multimodal contrast agents and the first in-depth study of biodistribution of nanometer scale shape and size specific particles. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4342.
AB0603 The effects of technetium [99TC] methylenediphosphonate on peripheral gammadelta T cells and regulatory T cells in patients with rheumatoid arthritis
Authors: D. Su, X. Li, L. Sun
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Regulatory T-cells (Tregs) are the guardians of peripheral tolerance acting to prevent autoimmune diseases such as rheumatoid arthritis (RA). Defects in Tregs have been reported in RA, and the application of therapeutic drugs may cause enhancement of Treg numbers, which is positively correlated with clinical remission of disease. γδT cells display characteristics of both innate and adaptive immunity and play important roles in infectious diseases and tumor, but exert pro- or anti-inflammatory effects depending on various local milieu. Studies have shown that γδT cells could exert immuno-regulatory effect by secreting IL-10 and TGF-β, participating in the pathogenesis of autoimmune diseases. <h3>Objectives</h3> To investigate the changes of γδT cell and Treg percentage as well as secretion of associated inflammatory cytokines in RA patients after the treatment with Technetium [99Tc] methylenediphosphonate injection(99Tc-MDP) <h3>Methods</h3> Active RA patients were treated with 99Tc-MDP for 14 days. Before and after treatment, the percentages of peripheral blood γδT cells and Treg were detected by flow cytometry (FACS), and serum levels of IL-10, IFN-γ, TNF-α were measured using enzyme-linked immunosorbent assay (ELISA). DAS28 scores before and after treatment were also recorded and correlation analysis was performed. <h3>Results</h3> The percentages of peripheral blood γδT cells and Treg in RA patients presented no significant difference with healthy controls. After treatment with 99Tc-MDP, the frequency of γδT cells and Treg in the peripheral blood of RA patients were significantly elevated, meanwhile with markedly increased serum level of IL-10 and significantly decreased serum levels of INF-γ and TNF-α levels. The changes of γδT cells and Treg percentages and serum levels of cytokines were positively correlated with DAS28 score. <h3>Conclusions</h3> The bisphosphonate 99Tc-MDP may exert its anti-inflammatory effect on RA patients by up-regulation of the frequency of peripheral γδT cells and Treg as well as increased secretion of IL-10. <h3>Disclosure of Interest</h3> None Declared
Pevonedistat, a NEDD8-activating enzyme inhibitor, is active in mantle cell lymphoma and enhances rituximab activity in vivo
Authors: Natalie M. Czuczman, Matthew J. Barth, Juan Gu, Vishala Neppalli, Cory Mavis, Sarah E. Frys, Qiang Hu, Song Liu, Pavel Klener, Petra Vockova, Myron S. Czuczman, Francisco J. Hernandez-Ilizaliturri
Journal: Blood (2015)
Does The Diagnostic Accuracy Of EUS for Vascular Invasion Depend On The Experience of The Endosonographer: A Retrospective Single Center Experience
Authors: S Puli, J Talapaneni, S Singh, M Oropeza-vail, M Olyaee
Journal: Endoscopy (2006)

Introduction: Endoscopic Ultrasound (EUS) has emerged as an accurate tool to diagnose and stage pancreatic cancer. The accuracy for vascular invasion might depend on operator's experience. Goal: To evaluate the difference in accuracy of EUS to diagnose vascular invasion during the first and second year of an endosonographer's practice. Methods: Patients with pancreatic cancer who underwent pre-operative EUS by a trained endosonographer and surgery at one hospital were identified in a retrospective manner. These patients were stratified into either having the EUS during the first or the second year of practice of the physician. Vascular involvement was defined as loss of echoplane or tumor in the lumen or abnormal vessel contour or the presence of collateral vessels in the absence of a main vascular structure. Surgical definition for vascular invasion was tumor encasing the vessel or vascular unresectability. Results: 17 patients during the first year and 16 patients during the second year of the endosonographer's practice were included in the analysis. EUS showed vascular involvement in 13 patients and no involvement in 22 patients. The accuracy of EUS for vascular invasion during the first and second year of practice is shown in table 1. Conclusion: EUS is a sonographic diagnostic tool and requires training. In this analysis we did not find a significant difference in the accuracy to diagnose vascular involvement during the second year of practice as compared to the first year of practice. Larger studies are needed to confirm this find.
Abstract 323: High grade serous ovarian cancer cells spontaneously self-organize in vitro into multicellular irregular aggregates and highly organized spheroids.
Authors: Alicia A. Goyeneche
Journal: Cancer Research (2013)

Abstract Ovarian cancer (OvCa) has the worst prognosis among gynecologic cancers because it is typically detected at an advanced stage. Accumulation of fluid inside the peritoneal cavity, and multicellular clusters featured within ascites are common manifestations of the disease. Patients undergo aggressive cytoreductive surgery followed by platinum-taxane therapy; yet in most cases, patients will relapse and die due to tumor progression. OvCa recurs as it presents, with growths within the peritoneal cavity, accumulation of ascites, but with a chemotherapy-resistant phenotype. Thus, understanding the dynamics of peritoneal metastases is of clear significance. This work provides evidences that OvCa cells derived from serous, treatment-resistant relapsed disease spontaneously develop multicellular anchorage-independent OvCa aggregates in vitro. The human serous ovarian adenocarcinoma PEO6 cells, while growing as adherent monolayer, spontaneously self-assemble into multicellular foci that float away off the adherent component of the culture. The floating phenotype is comprised of irregular cellular clusters and more organized spheroids with blastocyst-like morphology. Within each multicellular structure cells gather differently as evidenced by the distribution pattern of the cell junction adhesion molecule E-cadherin. Both types of non-adherent multicellular aggregates have live cells with no morphological features of apoptosis indicating their resistance to anoikis. Anchorage independent OvCa spheroids have the capacity to recreate the entire culture phenotype when placed in a new dish; the spheroids adhere upon transference and develop foci that grow upright irregular aggregates and more organized spheroids, ultimately leading to the generation of new non-adherent components. The floating PEO6 structures include clusters of cells expressing the cancer initiating antigen CD133 supporting their plasticity to perpetuate the anchorage-independent component of the culture. In summary, this study led to the characterization of an in vitro model of recurrent, treatment-resistant serous OvCa cells with intrinsic ability to gather in two types of clusters that survive in an anchorage-independent manner-a hallmark of transformation and critical factor in metastasis. The spontaneous in vitro development of OvCa multicellular irregular aggregates and spheroids at recurrence may represent a preclinical model to study the biology of selection and adaptation of disease malignancy and ways to interrupt its progression. Citation Format: Alicia A. Goyeneche. High grade serous ovarian cancer cells spontaneously self-organize in vitro into multicellular irregular aggregates and highly organized spheroids. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 323. doi:10.1158/1538-7445.AM2013-323
250 EVALUATION OF HAEMOSTASIS IN ACUTE LIVER FAILURE: A COMPREHENSIVE STUDY USING TRADITIONAL PLASMATIC TESTS AND WHOLE BLOOD THROMBOELASTOGRAPHY
Authors: G.A.K. Wright, V.M. Vemala, A.K. Burroughs, A. Gatt, A. Riddell, A. Davenport, S. Mallett, P. Chowdary, S. Shaw, R. Jalan, B. Agarwal
Journal: Journal of Hepatology (2012)
Xenoestrogens alter mammary gland differentiation and cell proliferation in the rat.
Authors: N M Brown, C A Lamartiniere
Journal: Environmental Health Perspectives (1995)

We investigated mammary gland differentiation and cell proliferation in rats after acute exposure to xenoestrogens. Pubertal female Sprague-Dawley rats (six/group) were treated for 1 week with diethylstilbestrol (DES), genistein, o,p'-DDT, Aroclor 1221, Aroclor 1254, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), or the vehicle, sesame oil. Animals were killed 18 hr after the last treatment. Analysis of mammary whole-mounts revealed that exposure to DES, genistein, and o,p'-DDT resulted in enhanced gland differentiation and increased epithelial cell proliferation as measured by proliferating cell nuclear antigen immunohistochemistry, TCDD treatment inhibited cell proliferation and gland development. Aroclor 1221 and Aroclor 1254 treatments had slight but not statistically significant effects on cell proliferation and mammary gland development. We conclude that DES, genistein, and o,p'-DDT given to pubertal rats act as morphogens; i.e., they increase cell proliferation, which promotes maturation of the undifferentiated terminal end buds to more differentiated lobular terminal ductal structures.
Bone SPECT of the Back After Lumbar Surgery
Authors: GARY F. GATES, ROBERT J. McDONALD
Journal: Clinical Nuclear Medicine (1999)

Purpose: It may be difficult to evaluate back pain in patients who have undergone spinal surgery, because symptoms may be secondary to all the possible abnormalities in patients who have not had surgery plus postoperative complications, including infection, unstable fusion sites, or transfer of biomechanical stresses to other regions. Materials and Methods: Sixty-three patients with back pain and a history of lumbar spinal surgery had bone SPECT examinations. Twenty-eight patients had laminectomies, 10 had laminectomies with fusion, 10 had laminectomies with fusion and metallic stabilization devices (3 of which were removed), 7 had fusion without laminectomy, 7 had discectomies, and 1 had a fusion with metallic stabilization but no laminectomy. Eighty-seven percent of the fusions were posterior. The results of SPECT scanning were correlated with surgery, clinical information, and diagnostic radiologic studies. Results: Patients with fusions tended to be scanned further out from the time of surgery than were patients with laminectomy alone or especially discectomy. Bone SPECT excluded bony abnormalities in the operative site in 7 of 63 patients. One hundred thirty-two lesions were uncovered, with facet abnormalities (n = 51) the most common followed by disc space-centered conditions (n = 29), pseudarthrosis (n = 20), sacroiliac joint (n = 18), vertebral body lesions (n = 9), and miscellaneous sites (n = 5). Sixty percent of the abnormalities located in the facets, disc spaces, and vertebral bodies were located in the operative field, whereas 29% were above and 11% were below it. Conclusion: Bone SPECT was useful in evaluating these patients to exclude bony lesions or to identify pseudarthrosis, abnormal facets, disc space-centered lesions, and sacroilitis.
Translumenal applications of a novel EUS-guided lumen apposition stent
Authors: KF Binmoeller
Journal: Endoscopy (2011)

Introduction: Tubular stents designed for ductal drainage have been used for endoscopic translumenal drainage of the gallbladder, pseudocysts, and extraintestinal fluid collections. Limitations are the potential for leakage, migration, and trauma to the surrounding tissue. Purpose: To evaluate a novel lumen apposition stent (LAS) for the following translumenal applications: 1) gallbladder drainage; 2) gastro-enteric bypass; 3) creation of a NOTES port. Methods: LAS devices were implanted in acute and survival animals (swine) under general anesthesia. The LAS is made of braided nitinol wire and fully coated to prevent tissue ingrowth, leakage, and enable removability. Dual-flanged anchors provide lumen-to-lumen apposition. Fully expanded, the flange & body diameters measure 20mm and 10mm, respectively. The LAS is constrained onto a 10.5Fr delivery catheter and deployed with a proprietary handle that luer-locks onto the inlet port of a 3.7mm channel echoendoscope. A standardized 4-step technique was used: 1) Lumen access with 19G needle; 2) Tract dilation with 4mm balloon; 3) LAS deployment across the tract; 4) LAS lumen dilation with a 10mm balloon. Translumenal endoscopy using an ultraslim 5.9mm gastroscope was performed across the deployed LAS. Survival animals underwent endoscopy at weekly intervals. Results: Devices were successfully deployed under EUS-guidance from the stomach lumen into each of the following target lumens: 1) gallbladder; 2) colon; 3) peritoneum. After dilation, the gastroscope could be easily advanced through the LAS into the target lumen. The LAS stabilized the endoscope for translumenal interventions. Gallbladder: mucosa inspected, cystic duct identified. Bowel: mucosa inspected, advancement into afferent and efferent limbs, retroflexion view of LAS possible. NOTES port: biopsies obtained from organ surfaces, small bowel grasped with forceps and pulled into the stomach through the LAS. Follow-up for 5 weeks: the LAS remained stable, patent, and the covering intact without tissue ingrowth or overgrowth. One device was removed with a snare at 4 weeks. Gross necropsy showed the devices were well-tolerated by the surrounding tissue. Conclusion: 1. EUS-guided deployment of the LAS is feasible and safe. 2. The LAS enables a robust, reliable, and removable lumen approximating conduit for translumenal endoscopic procedures.
Abstract 247: Effect of Post Resuscitation Care Frequency on Outcome After Cardiac Arrest
Authors: Andreas Schober, Helene Hochrieser, Martin Posch, Rene Schmutz, Philipp Metnitz, Michael Holzer
Journal: Circulation (2013)

Determination of the impact of the treatment frequency, hospital size and capability on mortality of patients admitted after cardiac arrest for post resuscitation care to different intensive care units in Austria. Methods: Prospectively recorded data from 242,588 adults consecutively admitted to 87 Austrian intensive care units over a period of 13 years (1998-2010) were analyzed retrospectively. Results: In total 5,857 patients had suffered cardiac arrest and were admitted to an intensive care unit for post resuscitation care. Observed hospital mortality was 15% in the non cardiac arrest cohort (36,460 non survivors) and 56% in the cardiac arrest cohort (3302 non survivors; p&lt;0.0001). Patients treated in intensive care units with a high frequency of post resuscitation care generally had higher severity of illness. Intensive care units with a higher frequency of post resuscitation care showed improved risk adjusted mortality. The SAPS II adjusted, observed to expected mortality ratios (O/E-Ratios) in the three strata (less than &lt;18; 18 to 26; more than 26 resuscitations per ICU per year) were 0.869 (95-%-confidence interval: 0.844 - 894), 0.876 (0.850 - 0.902) and 0.808 (0.784 - 0.833). Conclusions: Intensive care units, providing post resuscitation care at a high frequency, were associated with improved outcome. Establishing cardiac arrest care centers might be a reasonable step to improve outcome after cardiac arrest.
Teratogenicity of High Vitamin A Intake
Authors: Kenneth J. Rothman, Lynn L. Moore, Martha R. Singer, Uyen-Sa D.T. Nguyen, Salvatore Mannino, Aubrey Milunsky
Journal: New England Journal of Medicine (1995)

Studies in animals indicate that natural forms of vitamin A are teratogenic. Synthetic retinoids chemically similar to vitamin A cause birth defects in humans; as in animals, the defects appear to affect tissues derived from the cranial neural crest.Between October 1984 and June 1987, we identified 22,748 pregnant women when they underwent screening either by measurement of maternal serum alpha-fetoprotein or by amniocentesis. Nurse interviewers obtained information on the women's diet, medications, and illnesses during the first trimester of pregnancy, as well as information on their family and medical history and exposure to environmental agents. We obtained information on the outcomes of pregnancy from the obstetricians who delivered the babies or from the women themselves. Of the 22,748 women, 339 had babies with birth defects; 121 of these babies had defects occurring in sites that originated in the cranial neural crest.For defects associated with cranial-neural-crest tissue, the ratio of the prevalence among the babies born to women who consumed more than 15,000 IU of preformed vitamin A per day from food and supplements to the prevalence among the babies whose mothers consumed 5000 IU or less per day was 3.5 (95 percent confidence interval, 1.7 to 7.3). For vitamin A from supplements alone, the ratio of the prevalence among the babies born to women who consumed more than 10,000 IU per day to that among the babies whose mothers consumed 5000 IU or less per day was 4.8 (95 percent confidence interval, 2.2 to 10.5). Using a smoothed regression curve, we found an apparent threshold near 10,000 IU per day of supplemental vitamin A. The increased frequency of defects was concentrated among the babies born to women who had consumed high levels of vitamin A before the seventh week of gestation.High dietary intake of preformed vitamin A appears to be teratogenic. Among the babies born to women who took more than 10,000 IU of preformed vitamin A per day in the form of supplements, we estimate that about 1 infant in 57 had a malformation attributable to the supplement.