tbuckley/cabot-search huggingface dataset:
Oxytocin Enhances Social Recognition by Modulating Cortical Control of Early Olfactory Processing
Authors: Lars-Lennart Oettl, Namasivayam Ravi, Miriam Schneider, Max F. Scheller, Peggy Schneider, Mariela Mitre, Miriam da Silva Gouveia, Robert C. Froemke, Moses V. Chao, W. Scott Young, Andreas Meyer-Lindenberg, Valery Grinevich, Roman Shusterman, Wolfgang Kelsch
Journal: Neuron (2016)

Highlights•Oxytocin in the olfactory system is required for social recognition•Oxytocin activates cortical top-down inputs to olfactory bulb interneurons•Top-down inputs generate states of high signal-to-noise in odor codingSummaryOxytocin promotes social interactions and recognition of conspecifics that rely on olfaction in most species. The circuit mechanisms through which oxytocin modifies olfactory processing are incompletely understood. Here, we observed that optogenetically induced oxytocin release enhanced olfactory exploration and same-sex recognition of adult rats. Consistent with oxytocin's function in the anterior olfactory cortex, particularly in social cue processing, region-selective receptor deletion impaired social recognition but left odor discrimination and recognition intact outside a social context. Oxytocin transiently increased the drive of the anterior olfactory cortex projecting to olfactory bulb interneurons. Cortical top-down recruitment of interneurons dynamically enhanced the inhibitory input to olfactory bulb projection neurons and increased the signal-to-noise of their output. In summary, oxytocin generates states for optimized information extraction in an early cortical top-down network that is required for social interactions with potential implications for sensory processing deficits in autism spectrum disorders.
Ibrutinib Significantly Prolonged Survival in a Human Burkitt Lymphoma (BL) Xenograft NSG Mouse Model: Ibrutinib May be a Potential Adjuvant Agent in the Treatment of BL
Authors: Sanghoon Lee, Changhong Yin, Janet Ayello, Erin Morris, Timmy O'Connell, Lauren Harrison, Carmella van de Ven, Matthew J. Barth, Rodney R. Miles, Paul J. Galardy, Stanton Goldman, Megan S Lim, Michelle L. Hermiston, Linda McAllister-Lucas, Lisa Giulino-Roth, Sherrie L. Perkins, Mitchell S. Cairo
Journal: Blood (2015)
Metronidazole-Associated Encephalopathy
Authors: Dimitrios Farmakiotis, Barry Zeluff
Journal: New England Journal of Medicine (2016)

A 58-year-old man with cryptogenic cirrhosis was admitted to the ICU with confusion after a fall. He had been taking metronidazole for C. difficile infection. MRI of the brain showed a fluid-attenuated inversion recovery (FLAIR) signal in the dentate nuclei of the cerebellum.
PP-004 A prospective evaluation of acetic acid enhanced chromoendoscopy in the identification of dysplasia within Barrett's oesophagus: Abstract PP-004
Authors: G R Longcroft-Wheaton, R Mead, M Duku, D Poller, P Bhandari
Journal: Gut (2010)

Introduction The current accepted standard of care in Barrett's surveillance has involved the routine collection of large numbers of non-targeted biopsies (Seattle protocol). This is time consuming, expensive and can miss significant abnormalities. Acetic acid has been demonstrated to be effective in identifying areas of metaplasia, with an increasing number of endoscopists questioning whether it has a role in the identification of dysplasia. We aim to evaluate the use of acetic acid (AA) chromoendocopy in the assessment of Barrett's neoplasia. Methods We prospectively collected data on patients with Barrett's oesophagus who had undergone chromoendoscopy between July 2004 and November 2009. All procedures were performed by a single experienced endoscopist (PB) using fujinon (EG-590) gastroscopes and EPX 4400 processor. The mucosae was examined with white light (WLI) high-resolution endoscopy (HRE) and visible abnormalities recorded. Acetic acid (2.5%) dye spray was then performed, and all additional visible abnormalities were characterised and targeted biopsies taken. Quadrantic biopsies at 2 cm intervals of the remaining Barretts epithelium were then taken in all patients. The chromoendoscopic diagnosis was compared with the histological diagnosis to evaluate the sensitivity and specificity of AA chromoendoscopy. Results We performed a total of 335 procedures on 173 patients. The mean age of the group was 67 years with 75% males. The prevalence of dysplasia or malignancy in this cohort was 46%. The mean length of Barrett's oesophagus was 3.7 cm (range 2–15) Pearson's rank correlation showed a statistically significant correlation between the chromoendoscopic targeted histology and the actual histology (qudrantic+targeted histology) (r=0.9). We applied the Chi2 test to our data and found a significant difference between visible neoplasia seen on WLI vs AA chromoendoscopy (p<0.001) (see [Abstract 004][1]). The sensitivity was 93% with a specificity of 80% for all neoplasia View this table: Abstract PP-004 Conclusion This is the largest world series of acetic acid (AA) chromoendoscopic evaluation of Barrett's oesophagus. It demonstrates that dye spray improves the neoplasia detection rate by 2.4-fold, with an excellent correlation with the overall diagnosis. this questions the validity of current surveillance strategy of multiple random biopsies. [1]: #T1
Molecular Analysis of the Inheritance of Phenylketonuria and Mild Hyperphenylalaninemia in Families with Both Disorders
Authors: Fred D. Ledley, Harvey L. Levy, Savio L.C. Woo
Journal: New England Journal of Medicine (1986)

Clinical phenylketonuria and mild hyperphenylalaninemia represent two different phenotypes of phenylalanine hydroxylase deficiency. To determine the genetic relation between these two phenotypes, we studied two families in which one member had phenylketonuria and other members had mild hyperphenylalaninemia. We identified Restriction-Fragment Length polymorphisms that differentiated the four phenylalanine hydroxylase alleles in each family. Phenylketonuria and mild hyperphenylalaninemia were found to be allelic; certain pairs of alleles induced the more severe phenylketonuria phenotype, and other pairs induced the less severe hyperphenylalaninemia phenotype. Several of the alleles that were identified can contribute to either phenylketonuria or mild hyperphenylalaninemia. These results demonstrate that there are multiple and distinct mutations in the phenylalanine hydroxylase gene, with different levels of severity, and that various combinations of the mutant alleles can result in different phenotypes of the metabolic disorders of hyperphenylalaninemia. (N Engl J Med 1986; 314:1276–80.)
Abstract 3952: Late Outgrowth Endothelial Progenitor Cells From Patients With AMI Improve Left Ventricular Ejection Fraction In Experimental Myocardial Infarction
Authors: Martina Knoedler, Eliane Weidl, Sandra Gawehn, Maren Schurmann, Andreas Stein, Stefan Seidl, Christian Peschel, Robert Oostendorp, Ilka Ott
Journal: Circulation (2008)

Background: Recent studies suggest that endothelial progenitor cells (EPC) from bone marrow or peripheral blood improve myocardial function in experimental myocardial infarction (MI). Since applications for cell therapy are limited by the number of available cells, expansion of EPC may facilitate its therapeutic use in ischemic disease. The aim of this study was to expand late outgrowth EPC from peripheral blood from patients with acute myocardial infarction, characterize them and investigate their therapeutic effect in experimental MI. Methods and Results: Venous blood samples were obtained from patients with acute MI (n=51), stable angina (sAP, n=57) and healthy controls (H,n=47). CD34+ cells were isolated using immunomagnetic beads (Miltenyi Biotec). CD34+ cells cultured on fibronectin in endothelial cell medium formed colonies after 1–2 weeks and were further expanded for up to 3 months to generate late outgrowth EPC (eEPC). Expansion was observed up to 2.9x10′9 (MI), 11x10′9 (sAP) and 7x10′9 cells (H) with a mean culture duration of 61 days. Expanded cells showed an endothelial morphology and expressed endothelial surface markers (CD31, VEGF-R2, CD105). Intramyocardial transplantion of 1x10′6 eEPC in experimental myocardial infarction in athymic nude rats revealed improvement in echocardiographic ejection fraction after 2 weeks. This was associated with enhanced vessel density after 1 week and increased mRNA expression of HGF. No differences in infarct size were observed. Similarly in a chronic model of myocardial infarction (eEPC transplantation 1 week after MI) myocardial function significantly improved after 5 weeks in comparison to the control group. Conclusion: Expansion of eEPC from circulating CD34+ cells in patients with coronary artery disease is feasible and improves myocardial function after local transplantation in acute and chronic myocardial infarction. The large number of generated eEPC may prove benefical for therapeutic use and this advantage may prevail time-consuming expansion procedures.
Relation of Smoking and Age to Emphysema
Authors: Oscar Auerbach, E. Cuyler Hammond, Lawrence Garfinkel, Carmine Benante
Journal: New England Journal of Medicine (1972)

To determine the relation of smoking habits to pulmonary emphysema, whole-lung sections were prepared from lungs removed by autopsy from 1443 men and 388 women, and smoking habits were ascertained by interviews with relatives. Among men with the same smoking habits, degree of emphysema increased with age. Of 176 men who never smoked regularly, 90.0 per cent had no emphysema; 3.8 per cent had minimal, 3.3 per cent slight, 2.9 per cent moderate, and 0 per cent advanced emphysema. Corresponding figures for 181 men who smoked one to 19 cigarettes a day were 13.1 per cent no emphysema; 16.4 per cent minimal; 33.7 per cent slight; 25.1 per cent moderate; and 11.7 per cent advanced to far advanced emphysema. Of 658 men who smoked 20 or more cigarettes, 0.3 per cent had no emphysema; 5.2 per cent had minimal, 42.6 per cent slight, 32.7 per cent moderate, and 19.2 per cent advanced emphysema. Findings in 388 women were similar. The observations once again suggest that chronic cigarette smoking leads to pulmonary emphysema.
P283 Hyperpolarised Gas MRI – a pathway to Clinical Diagnostic Imaging
Authors: JM Wild, G Collier, H Marshall, L Smith, G Norquay, AJ Swift, FC Horn, F Chan, NJ Stewart, LC Hutchison, M Rao, I Sabbroe, R Niven, A Horsley, S Siddiqui, K Ugonna, R Lawson
Journal: Thorax (2015)

<h3>Introduction</h3> Despite the excellent functional sensitivity of hyperpolarised gas MRI to early lung disease, clinical uptake of the technique has to date been hindered by patents, regulatory classification, availability of <sup>3</sup>He and access to polariser technology. However, many of these constraints have been alleviated in recent years, and <sup>129</sup>Xe MRI is now providing high quality lung images at relatively low cost. In January 2015 UK regulatory approval for the manufacture of hyperpolarised gases for routine clinical lung imaging was obtained in Sheffield. Here we present a case series as an overview of the clinical questions that this technology can help resolve in various respiratory indications. <h3>Methods</h3> More than 20 patients (aged 13 to 74) have been clinically referred to date with HP gas MRI in Sheffield to date from NHS hospitals across the UK. Clinical histories include non-CF bronchiectasis (scanned before and after a 2 week course of IV antibiotics), COPD for consideration for LVRS/EB valves, complex asthma (scanned before and after bronchodilator inhalation), CF, patients with poor gas transfer but well-preserved lung parenchyma on CT, IPF overlapping with emphysema. <h3>Results</h3> Figure 1 shows example images from a cross-section of patients scanned, details of the individual cases will be expanded upon. No adverse events related to imaging were reported. In terms of imaging workflow, scan time average was between 30 min and 1 h 30 min. Patients have been referred from clinics within a 100 km radius and we are also active in enabling novice sites further afield with the technology. <h3>Conclusion</h3> Hyperpolarised gas MR provides sensitive, regional images of lung function which can be used to aid in clinical decision making on an individual patient basis. With improvements in gas polarisation, MR hardware and image acquisition techniques routine clinical lung imaging with the cheaper gas isotope <sup>129</sup>Xe is also now possible and large scale clinical evaluation of these methods in patient populations are now underway as part of clinical work up.
Genetic Variants of Chronic Granulomatous Disease: Prevalence of Deficiencies of Two Cytosolic Components of the NADPH Oxidase System
Authors: Robert A. Clark, Harry L. Malech, John Gallin, Hiroyuki Nunoi, Bryan D. Volpp, Doran W. Pearson, William M. Nauseef, John T. Curnutte
Journal: New England Journal of Medicine (1989)

Chronic granulomatous disease, a syndrome of recurrent infections and failure of oxidative microbicidal activity in phagocytes, results from defects in the gene for one of several components of an oxidase system that can undergo activation. To determine the relative prevalence of certain of the genetic variants of this disorder, we used immunoblotting to detect two specific neutrophil cytosolic proteins of 47 and 67 kd recently shown to be required for oxidase activation. Chronic granulomatous disease is usually an X-linked disorder associated with the absence of membrane cytochrome b 558. Of our 94 patients with chronic granulomatous disease, however, 36 had a phenotype characterized by autosomal inheritance, normal membrane oxidase components (including cytochrome b 558),and functionally defective cytosolic activity in a cell-free oxidase system. We studied 25 of these 36 patients and found that 22 lacked the 47-kd cytosolic protein, and the remaining 3 were missing the 67-kd component. Patients with chronic granulomatous disease whose functional defect was localized to the neutrophil membrane (classic X-linked cytochrome b–negative type and two other rare variants) had normal amounts of both cytosolic components. We estimate that approximately 33 percent of all patients with chronic granulomatous disease are missing the 47-kd cytosolic oxidase component and about 5 percent of patients are missing the 67-kd component. Chronic granulomatous disease caused by a defect in any cytosolic factors other than the 47-kd and 67-kd proteins, if it exists, is apparently rare. (N Engl J Med 1989; 321:647–52.)
Systemic Exposure to Mercaptopurine as a Prognostic Factor in Acute Lymphocytic Leukemia in Children
Authors: Gideon Koren, Gianmario Ferrazini, Hassan Sulh, Anne Marie Langevin, Joseph Kapelushnik, Julia Klein, Ester Giesbrecht, Stephen Soldin, Mark Greenberg
Journal: New England Journal of Medicine (1990)

Despite a success rate of more than 90 percent in inducing remission in children with acute lymphocytic leukemia, 30 to 40 percent of such children relapse. Maintenance therapy during remission usually includes oral mercaptopurine and methotrexate. Recently, wide variability in the bioavailability of oral mercaptopurine has been demonstrated, and there is concern that this may affect the risk of relapse.
Khellin in the Treatment of Angina Pectoris
Authors: Harold L. Osher, Kermit H. Katz, Donald J. Wagner
Journal: New England Journal of Medicine (1951)

KHELLIN§ is a pure crystalline derivative of Ammi visnaga, a plant that grows wild in the eastern Mediterranean countries, and that is known in Arabic as "khella." The medicinal properties of this plant have apparently been known since ancient times, and a decoction of its seeds has been used by the native populations for many centuries as an antispasmodic for the treatment of renal colic. However, the first recorded pharmacological study of Ammivisnaga is that of Mustapha,1 who in 1879 isolated the chief active principle, khellin, in impure form. Since that time, an extensive series of investigations2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 has clearly . . .
Final results of a randomized phase III trial comparing induction chemotherapy with cisplatin/5-FU or docetaxel/cisplatin/5-FU follow by chemoradiotherapy (CRT) versus CRT alone as first-line treatment of unresectable locally advanced head and neck cancer (LAHNC)
Authors: R. Hitt, J. J. Grau, A. Lopez-Pousa, A. Berrocal, C. Garcia Giron, A. Irigoyen, J. Sastre, J. Martinez, H. Cortes-Funes, J. Cruz-Hernandez
Journal: Journal of Clinical Oncology (2009)

6009 Background: Induction chemotherapy (IC) with TPF isa standard regimen for patients (pts) with locally advanced head and neck squamous cell carcinoma (N Engl J Med. 2007;357:1705–1715). However, CRT alone is standard treatment for unresectable LAHNC. We designed a trial to compare two different regimens of IC followed by CRT versus CRT alone in pts with unresectable LAHNC. Methods: Pts with unresectable, measurable LAHNC, adequate organ function, and ECOG 0–1 were enrolled and stratified according to primary tumor site. (IC) regimens (3 cycles): PF (cisplatin 100 mg/m 2 day [d] 1, then 5-FU 1,000 mg/m 2 continuous infusion [CI], d1–5, q21d); TPF (docetaxel 75 mg/m 2 d1, cisplatin 75 mg/m 2 d1, 5-FU 750 mg/m 2 CI, d1–5, q21d plus G-CSF and ciprofloxacin). All pts were to receive CRT, consisting of conventional radiotherapy up to 70 Gy plus cisplatin 100 mg/m 2 d 1, 22, 43. The primary end point was time to treatment failure (TTF) for (IC) vs. no (IC); secondary endpoints included locoregional control (LRC) rate and safety; 438 pts were needed to demonstrate a 15% difference in treatment failure (death, progression, surgery, other treatments) with α = 0.05, β = 0.2. Results: From December 2002 to June 2007, 439 pts were enrolled: IC 311 pts (TPF 155, PF 156) and CRT 128 pts. The majority of pts were: ECOG 1 (70%); oropharynx and oral cavity (63%); T4 (75%); N2-N3 (61%). In evaluable pts (at least 1 cycle), the median TTF was 12.5 months with IC/CRT vs. 4.9 months with CRT alone (p &lt; 0.001; HR 0.57; 95%CI 0.44–0.74); LRC rate was 60.9% IC/CRT vs. 44.5% CRT (p = 0.003; OR = 0.52; 95%CI 0.3–0.81). Grade 3–4 adverse events (IC/CRT vs. CRT) occurred in 83% vs. 69% of pts and included febrile neutropenia (10% vs 1%), and stomatitis (43.7% vs 37%). Conclusions: This is the first phase III trial to demonstrate that (IC) followed by CRT significantly increases TTF and LRC compared with CRT alone in pts with unresectable LAHNC. IC/CRT should now be considered standard treatment for these pts. No significant financial relationships to disclose.
Progress Toward Consensus on Breast Cancer Screening Guidelines and Reducing Screening Harms
Authors: Jocelyn A. Rapelyea
Journal: JAMA Internal Medicine (2016)

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Specific IgE and IgG Antibodies to Human Rhinovirus 16 Capsid Protein VP1 Among Asthmatic and Non-Asthmatic Children from Costa Rica: Comparison with Virginia and Northern Sweden
Authors: Thomas A.E. Platts-Mills, Alexander J. Schuyler, Lisa J. Workman, Eva Rönmark, Lydiana Avila, Peter W. Heymann
Journal: Journal of Allergy and Clinical Immunology (2016)
Acceleration of Growth in Two Children Treated with Human Growth Hormone-Releasing Factor
Authors: Michael O. Thorner, Julia Reschke, Jean Chitwood, Alan D. Rogol, Richard Furlanetto, Jean Rivier, Wylie Vale, Robert M. Blizzard
Journal: New England Journal of Medicine (1985)

Two growth hormone–deficient children were treated with growth hormone–releasing factor for six months. The pattern of administration — 1 to 3 μg per kilogram of body weight, given subcutaneously over one minute every three hours by infusion pump — was chosen to simulate growth hormone secretion in normal children. During the first week of therapy, both children had evidence of the metabolic effects of increased growth hormone secretion — i.e., nitrogen retention, demonstrated by decreased nitrogen excretion (P<0.05), and increased urinary calcium excretion (P<0.01). Growth hormone secretion was increased after pulses of growth hormone–releasing factor during the entire six-month period, and growth was accelerated. One child grew at a rate of 7.1 cm per year, as compared with 4.6 cm per year before therapy; the other grew at a rate of 13.7 cm per year, as compared with 2.1 cm per year before therapy, and had increased serum levels of somatomedin C. Growth hormone–releasing factor can restore growth hormone secretion and its biologic effects, including an increase in nitrogen retention, an increase in serum somatomedin C, and acceleration of linear growth in children with growth hormone deficiency. It is premature to speculate how useful this agent will prove to be in the treatment of children with growth hormone deficiency. (N Engl J Med 1985;312:4–9.)
An Association between Collateral Blood Flow and Myocardial Viability in Patients with Recent Myocardial Infarction
Authors: Peter J. Sabia, Eric R. Powers, Michael Ragosta, Ian J. Sarembock, Lawrence R. Burwell, Sanjiv Kaul
Journal: New England Journal of Medicine (1992)

We hypothesized that successful reperfusion of an occluded infarct-related coronary artery even late after acute myocardial infarction would result in improved regional wall motion and that such improvement might be related to the presence of collateral blood flow within the infarct bed.
Bilateral Fetal Mesencephalic Grafting in Two Patients with Parkinsonism Induced by 1-Methyl-4-Phenyl-L,2,3,6-Tetrahydropyridine (MPTP)
Authors: Hakan Widner, James Tetrud, Stig Rehncrona, Barry Snow, Patrik Brundin, Björn Gustavii, Anders Björklund, Olle Lindvall, J. William Langston
Journal: New England Journal of Medicine (1992)

Intracerebral transplantation of fetal dopaminergic neurons is a promising new approach for the treatment of Parkinson's disease. Patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) have a relatively stable lesion limited to the nigrostriatal system, rendering them ideal candidates for transplantation. Improvement of motor function after neural grafting has previously been observed in nonhuman primates with MPTP-induced parkinsonism.
Pharmacokinetics Of a Generic Formulation Of Intravenous Busulfan (BUCELON 60™) In Patients Undergoing Hematopoietic Stem Cell Transplantation
Authors: Ezhilpavai Mohanan, Salamun Desire, Sathya Mani, Gopinath Srinivasan, Biju George, Vikram Mathews, Alok Srivastava, Poonkuzhali Balasubramanian
Journal: Blood (2013)