tbuckley/cabot-search huggingface dataset:
Abstract B35: Enhanced antitumor efficacy by combining oncolytic herpes simplex virus and Aurora A kinase inhibition in models of neuroblastoma and malignant peripheral nerve sheath tumor
Authors: Mark Currier, Tilat Rizvi, Brooke Nartker, Duo Chen, Chun-Yu Chen, Pin-Yi Wang, Les Sprague, Meghan Franczek, Ami Patel, Katherine Chaney, Keri Streby, Jeff Ecsedy, Joe Conner, Nancy Ratner, Timothy Cripe
Journal: Cancer Research (2016)

Abstract We previously reported xenograft models of neuroblastoma and malignant peripheral nerve sheath tumor (MPNST) are responsive to direct intratumoral injection of oncolytic Herpes Simplex Viruses (Parikh et al., Ped Blood Can 44:469, 2005; Mahller et al., Ped Blood Can 46:745, 2006; Mahller et al., Can Res 68:1170, 2008). We have confirmed these findings using an oncolytic HSV, Seprehvir (HSV1716), which is in clinical trials that include pediatric patients (NCT00931931, NCT02031965). The models showed wide variability, however, with some models having maintained complete responses and others showing only delayed growth. Because DNA viruses are highly dependent on normal nuclear machinery for DNA synthesis/replication and virus packaging/assembly, we postulated that increased transit time in mitosis may be beneficial to an oncolytic DNA virus. Aurora A Kinase is an enzyme critical for formation of centrioles and mitotic spindles during mitosis and is often dysregulated in cancer. The selective AAK inhibitor, Alisertib (MLN8237), arrests cells in G2/M and has significant activity in models of neuroblastoma (data from the Pediatric Preclinical Testing Program) and in MPNST (data from our prior study: Patel et al., Clin Can Res 18:5020, 2012). We found tumor responses in xenograft models using the combination of Seprehvir and Alisertib was more than additive. Immunohistochemical staining for HSV antigens revealed a marked difference in the extent and spread of virus as early as 24 hrs after virus injection. Our preliminary data assessing kinetics of virus infection suggest that Alisertib pretreatment enhances virus uptake and spread, accounting for the combinatorial effects. These data strongly suggest alisertib pretreatment “primes” tumor cells, making them highly susceptible to virus infection and spread and greatly accelerates the virolytic effects. Overall, our findings support clinical testing of Alisertib combined with Seprehvir in patients with refractory neurogenic tumors such as neuroblastoma and MPNST. Citation Format: Mark Currier, Tilat Rizvi, Brooke Nartker, Duo Chen, Chun-Yu Chen, Pin-Yi Wang, Les Sprague, Meghan Franczek, Ami Patel, Katherine Chaney, Keri Streby, Jeff Ecsedy, Joe Conner, Nancy Ratner, Timothy Cripe. Enhanced antitumor efficacy by combining oncolytic herpes simplex virus and Aurora A kinase inhibition in models of neuroblastoma and malignant peripheral nerve sheath tumor. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr B35.
Tobacco Use Among Middle and High School Students — United States, 2011–2015
Authors: Tushar Singh, René A. Arrazola, Catherine G. Corey, Corinne G. Husten, Linda J. Neff, David M. Homa, Brian A. King
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Tobacco use is the leading cause of preventable disease and death in the United States; if current smoking rates continue, 5.6 million Americans aged <18 years who are alive today are projected to die prematurely from smoking-related disease. Tobacco use and addiction mostly begin during youth and young adulthood. CDC and the Food and Drug Administration (FDA) analyzed data from the 2011-2015 National Youth Tobacco Surveys (NYTS) to determine the prevalence and trends of current (past 30-day) use of seven tobacco product types (cigarettes, cigars, smokeless tobacco, electronic cigarettes [e-cigarettes], hookahs [water pipes used to smoke tobacco], pipe tobacco, and bidis [small imported cigarettes wrapped in a tendu leaf]) among U.S. middle (grades 6-8) and high (grades 9-12) school students. In 2015, e-cigarettes were the most commonly used tobacco product among middle (5.3%) and high (16.0%) school students. During 2011-2015, significant increases in current use of e-cigarettes and hookahs occurred among middle and high school students, whereas current use of conventional tobacco products, such as cigarettes and cigars decreased, resulting in no change in overall tobacco product use. During 2014-2015, current use of e-cigarettes increased among middle school students, whereas current use of hookahs decreased among high school students; in contrast, no change was observed in use of hookahs among middle school students, use of e-cigarettes among high school students, or use of cigarettes, cigars, smokeless tobacco, pipe tobacco, or bidis among middle and high school students. In 2015, an estimated 4.7 million middle and high school students were current tobacco product users, and, therefore, continue to be exposed to harmful tobacco product constituents, including nicotine. Nicotine exposure during adolescence, a critical period for brain development, can cause addiction, might harm brain development, and could lead to sustained tobacco product use among youths. Comprehensive and sustained strategies are warranted to prevent and reduce the use of all tobacco products among U.S. youths.
Treatment of Adenosine Deaminase Deficiency with Polyethylene Glycol–Modified Adenosine Deaminase
Authors: Michael S. Hershfield, Rebecca H. Buckley, Michael L. Greenberg, Alton L. Melton, Richard Schiff, Christine Hatem, Joanne Kurtzberg, M. Louise Markert, Roger H. Kobayashi, Ai Lan Kobayashi, Abraham Abuchowski
Journal: New England Journal of Medicine (1987)

We treated two children who had adenosine deaminase deficiency and severe combined immunodeficiency disease by injecting bovine adenosine deaminase modified by conjugation with polyethylene glycol. The modified enzyme was rapidly absorbed after intramuscular injection and had a half-life in plasma of 48 to 72 hours. Weekly doses of approximately 15 U per kilogram of body weight maintained plasma adenosine deaminase activity at two to three times the level of erythrocyte adenosine deaminase activity in normal subjects. The principal biochemical consequences of adenosine deaminase deficiency were almost completely reversed. In erythrocytes, adenosine nucleotides increased and deoxyadenosine nucleotides decreased to less than 0.5 percent of total adenine nucleotides. The activity of S-adenosylhomocysteine hydrolase, which is inactivated by deoxyadenosine, increased to normal in red cells and nucleated marrow cells. Neither toxic effects nor hypersensitivity reactions were observed. In vitro tests of the cellular immune function of each patient showed marked improvement, along with an increase in circulating T lymphocytes. Clinical improvement was indicated by absence of infection and resumption of weight gain. We conclude that from the standpoints of efficacy, convenience, and safety, polyethylene glycol-modified adenosine deaminase is preferable to red-cell transfusion as a treatment for adenosine deaminase deficiency. Patients with other inherited metabolic diseases in which accumulated metabolites equilibrate with plasma could benefit from treatment with the appropriate polyethylene glycol-modified enzyme.
Abstract 17809: In Vivo High Resolution Isotropic 3D MRI of Coronary Atherosclerosis in Hypertensive Hypercholesterolemic Minipigs
Authors: Rozh H Al-Mashhadi, Esben S Hansen, Lars ø Bloch, Ahmed H Al-Mashhadi, Steffen Ringgaard, René M Botnar, Won Y Kim, Jacob F Bentzon
Journal: Circulation (2014)

Introduction: Accurate non-invasive visualization and quantification of coronary atherosclerosis may greatly facilitate clinical research and practice, but the lack of suitable human-sized atherosclerosis models with progressive coronary lesions has hampered development and validation of reliable imaging techniques. Methods: D374Y-PCSK9 transgenic minipigs with (n=7) or without (n=8) hypertension, induced by suprarenal aortic banding, were placed on a cholesterol-rich diet for 16 months. Wildtype minipigs (n=4) on normal diet served as disease-free controls. A T1-weighted inversion recovery fast gradient echo magnetic resonance imaging (MRI) sequence was used to acquire 1x1x1mm images of the coronary arteries. MRI scans were conducted following injection of a gadolinium labeled elastin specific contrast agent (LMI1174). Pigs were subsequently euthanized and the coronary arteries were processed for pathological analysis. LMI1174 was provided by Lantheus Medical Imaging under a material transfer agreement Results: Hypertension significantly augmented coronary fibroatheromas by more than 5-fold compared to normotensive transgenic pigs. No signal enhancement was observed in lesion-free coronaries of wildtype pigs. In hypertensive pigs, there was a strong correlation between plaque area measured by MRI and plaque area measured postmortem r2=0.84, p=0.02 (Fig 1). Conclusions: Hypertensive transgenic minipigs with accelerated coronary atherosclerosis provide a useful model for coronary imaging. Using this model we were able to develop a high-resolution isotropic LMI1174-enhanced scanning technique that accurately depicts coronary atherosclerotic lesion size and distribution. Figure 1: A) Digitally unfolded and color coded MRI of the LAD (left) and corresponding sudan IV stained segment opened and viewed en face (right). B) Cross-sectional MRI of another LAD and corresponding histological sections showing fibroatheromas.
Genetic Variation in the β<sub>3</sub>-Adrenergic Receptor and an Increased Capacity to Gain Weight in Patients with Morbid Obesity
Authors: Karine Clément, Christian Vaisse, Brian St. J. Manning, Arnaud Basdevant, Bernard Guy-Grand, Juan Ruiz, Kristi D. Silver, Alan R. Shuldiner, Philippe Froguel, A. Donny Strosberg
Journal: New England Journal of Medicine (1995)

The β3-adrenergic receptor, located mainly in adipose tissue, is involved in the regulation of lipolysis and thermogenesis. The potential relevance of this receptor to obesity in humans led us to screen obese French patients for a recently identified mutation in the gene for the receptor.
Amelioration of Diabetes and Striking Rarity of Acidosis in Patients with Kimmelstiel-Wilson Lesions
Authors: Charles G. Zubrod, Stanton L. Eversole, George W. Dana
Journal: New England Journal of Medicine (1951)

A REMARKABLE reduction in insulin requirement in a patient (Case 1 — H. R.) with diabetes, who died in uremia, focused attention on the general subject of occasional spontaneous amelioration in diabetes mellitus. Improvement in diabetes has been described as coincident with the following: limitation of diet and consequent loss of weight,1 cirrhosis,2 myxedema,3 extirpation of pheochromocytoma,4 radiation of the pituitary gland in acromegaly,5 onset of Addison's disease,5 relief of Cushing's syndrome,6 senescence,7 and also, most dramatically, in anterior-pituitary-artery thrombosis. None of these mechanisms seemed to be operative in Patient H. R., in whom the dominant feature of her later . . .
Effect of peretinoin on recurrence of hepatocellular carcinoma (HCC): Results of a phase II/III randomized placebo-controlled trial.
Authors: K. Okita, O. Matsui, H. Kumada, K. Tanaka, S. Kaneko, H. Moriwaki, N. Izumi, T. Okusaka, Y. Ohashi, M. Makuuchi
Journal: Journal of Clinical Oncology (2010)

4024 Background: HCC is a poor prognosis cancer leading to death, with high rate of recurrence after curative therapy. No effective therapy for HCC recurrences has been established. Peretinoin (Per) is an acyclic retinoid suggested the efficacy for HCC (Muto et al. 1996). However, the early results require confirmation due to the small sample size. We conducted a phase II/III trial under GCP to evaluate its efficacy and dose-response relationship. Methods: Eligible patients (n = 401) were HCV (+), underwent curative therapy (resection or ablation) for initial HCC or first recurrence, and were Child-Pugh A or B, were randomized to 600 mg (H; n = 124), 300 mg (L; n = 126), or placebo (P; n = 127) in a multicenter, double-blind trial. Cures and recurrences of HCC were confirmed by d-CT every 12 wks by the blinded centralized image committee. Primary endpoint was recurrence free survival (RFS). Assuming a recurrence rate of 30%/yr and hazard ratio (HR) of 0.60-0.65, 180-200 events were required. Dosing period was up to 96 wks. Primary analysis: Efficacy for RFS in H + L vs P was analyzed by the stratified log-rank test. Secondary analysis: Dose-response was examined by a set of contrasts: (H, L, P) = (1, 0, -1), (2, -1, -1), (1, 1, -2). Results: Median follow-up time was 2.5 yrs. Events (H, L, P) = (53, 80, 77) were observed. Cumulative RFS rates were calculated (H, L, P) = (1 yr; 28%, 36%, 34%, 3 yrs; 56%, 75%, 70%). While the predefined primary analysis failed to show a statistically significant effect, a significant dose-response relationship was shown with (2, -1, -1) (P=0.023, multiplicity-adjusted P=0.048). This contrast means a difference between H and combination of L and P. HR (H vs P) more than 2 yrs after assignment was notably low (see table). Common adverse drug reactions were albuminuria, hypertension, and headache, and were tolerated. Conclusions: A significant dose-response relationship was shown with (2, -1, -1). Per 600 mg was tolerated and had a strong effect on the HR after 2 yrs. These findings confirm Per as a novel first-line therapy to reduce recurrences of HCC. HR (95% CI) < 1 yr ≥ 1 yr - < 2 yrs ≥ 2 yrs H vs. P 0.72 (0.45-1.17) 0.93 (0.52-1.66) 0.27 (0.07-0.96) L vs. P 1.11 (0.73-1.70) 0.89 (0.50-1.60) 1.19 (0.55-2.60) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration KOWA Co. Ltd. KOWA Co. Ltd. KOWA Co. Ltd.
The Medical Treatment of Dissecting Aortic Aneurysms
Authors: James McFarland, James T. Willerson, Robert E. Dinsmore, W. Gerald Austen, Mortimer J. Buckley, Charles A. Sanders, Roman W. DeSanctis
Journal: New England Journal of Medicine (1972)

Abstract Medical treatment of a group of 33 patients with dissecting aortic aneurysms resulted in 17 survivors (52 per cent) with a mean follow-up period of 43 months. In-hospital survival was influenced favorably by the presence of a subacute or chronic dissection (onset of symptoms 14 days or longer before presentation for treatment) although long-term survival was similar to that of patients with acute dissections. Patients who failed to show communication between the true and false lumens at the time of their initial angiograms had significantly better survival than those with such a communication (p less than 0.05) and also showed no tendency for late expansion of the aorta at the site of the dissection.
Flexor Tendon Grafts in the Hand
Authors: J. Edward Flynn
Journal: New England Journal of Medicine (1949)

IN CIVILIAN life, acute suppurative tenosynovitis and trauma to the joint phalanges are the most common causes of loss of flexor function in the hand. Loss of flexor function means loss of the "hook and pinch" mechanism, inability to grasp and hold objects and weakness of grasp. Improper treatment of the complications of acute suppurative tenosynovitis and trauma to flexor tendons in the hands have too often resulted in amputation of the fingers. In selected cases the grafting of tendons may restore function to the involved parts if there is normal joint function, good circulation and normal sensation. The following . . .
On the Phrygian Cap
Authors: William B. Ober, Ralph N. Wharton
Journal: New England Journal of Medicine (1956)

AMONG the odd features of medical terminology is the occasional selection of objects of antique or historical association to describe either normal or pathologic configurations or observations. The Phrygian cap, a former symbol of liberty, has been so honored by anatomists and roentgenologists, and to a lesser extent by pathologists. Apparently, Bartel1 , 2 was the first to apply the term, phrygische Mütze, to the appearance of a persistent notch in the gall bladder, a configuration in which the fundus "is bent down to the breaking point (abgeknickte). . . now smaller, now larger segments of the top appear sharply . . .
Physician-Payment Reform — Unfinished Business
Authors: David Blumenthal, Arnold M. Epstein
Journal: New England Journal of Medicine (1992)

WITH the final implementation of the Medicare fee schedule in January of this year, the renegotiation of a political bargain first struck more than 25 years ago was successfully concluded. To secure a reluctant profession's cooperation with Medicare, Congress promised in 1965 that it would refrain from exercising  supervision or control over the practice of medicine or the manner in which medical services are provided, or over the selection, tenure or compensation of any officer or employee of any institution, agency or person providing health services.1 During the past decade, this laissez-faire posture proved economically untenable. It was abandoned . . .
Restoring Ikaros Function in Leukemia : Casein Kinase II ( CK2) Inhibition Restores Ikaros Tumor Supressor Function and Shows Theraputic Efficacy in Preclinical Models of High Risk Pediatric Leukemia
Authors: Chandrika S. Gowda, Chunhua Song, Sunil Muthusami, Yali Ding, Mansi Sachdev, Kimberly Payne, Sinisa Dovat
Journal: Blood (2014)
Familial Nature of Congenital Absence and Severe Dysgenesis of Both Kidneys
Authors: Ann Marie Roodhooft, Jason C. Birnholz, Lewis B. Holmes
Journal: New England Journal of Medicine (1984)

Seventy-one parents and 40 siblings of 41 index patients with bilateral renal agenesis, bilateral severe dysgenesis, or agenesis of one kidney and dysgenesis of the other were evaluated by gray-scale ultrasonography for genitourinary malformations. Nine per cent (10 of 111) had asymptomatic renal malformations, most often unilateral renal agenesis (4.5 per cent--a frequency that was significantly higher than the frequency of 0.3 per cent among 682 adults [P less than 0.004]). We recommend ultrasonographic screening for parents and siblings of infants born with agenesis or dysgenesis of both kidneys or with agenesis of one kidney and dysgenesis of the other, since renal malformations may have medical implications even for asymptomatic patients.
Gastric Inhibitory Polypeptide–Dependent Cortisol Hypersecretion — A New Cause of Cushing's Syndrome
Authors: André Lacroix, Edouard Bolté, Johanne Tremblay, John Dupré, Pierre Poitras, Hélène Fournier, Jean Garon, Dominique Garrel, Francis Bayard, Raymond Taillefer, Richard J. Flanagan, Pavel Hamet
Journal: New England Journal of Medicine (1992)

Corticotropin-independent nodular adrenal hyperplasia is a rare cause of Cushing's syndrome, and the factors responsible for the adrenal hyperplasia are not known.
The Management of Perforative Carcinoma of the Colon
Authors: Gordon A. Donaldson
Journal: New England Journal of Medicine (1958)

FOR many years the general principles of surgical procedure in the management of carcinoma of the colon have been recognized and practiced. The results of treatment are now available, and the significance of various prognostic factors is known. These operative methods have been based on an intimate knowledge of the blood supply and lymphatic drainage of the various segments of the bowel, and more recently on control of operative dissemination of malignant cells through veins and through the bowel lumen itself. The matter of spread by direct extension, with resulting perforation of the carcinoma into free peritoneum or local adjacent . . .
CSF neurotensin concentrations and antipsychotic treatment in schizophrenia and schizoaffective disorder
Authors: R P Sharma, P G Janicak, G Bissette, C B Nemeroff
Journal: American Journal of Psychiatry (1997)

The relationship between CSF neurotensin concentrations and measures of psychopathology in patients with schizophrenia or schizoaffective disorder was examined before and after treatment with antipsychotic drugs.CSF neurotensin concentrations were measured in 42 drug-free patients with schizophrenia or schizoaffective disorder. For 18 of these patients, CSF neurotensin was measure again after 4 weeks of antipsychotic treatment.Significantly higher levels of pretreatment psychopathology were observed in the patients with the lowest CSF neurotensin concentrations. Furthermore, improvements in overall psychopathology and, particularly, negative symptoms were correlated with increases in CSF neurotensin concentrations during treatment.These findings provide further evidence for a role of neurotensin the pathophysiology of psychosis and in the mechanism of action of antipsychotic drugs.
Chronic kidney disease, hypertension, diabetes, and obesity in the adult population of Morocco: how to avoid “over”- and “under”-diagnosis of CKD
Authors: Mohammed Benghanem Gharbi, Monique Elseviers, Mohamed Zamd, Abdelali Belghiti Alaoui, Naïma Benahadi, El Hassane Trabelssi, Rabia Bayahia, Benyounès Ramdani, Marc E. De Broe
Journal: Kidney International (2016)
Substance P (subP) Suppresses Induction of Specific Memory IgE Responses By PBMC of Ragweed Sensitized IgE+ Humans, but NOT CD4+IL4+ or CD8+CD60+IL-4+ T CELLS or IL-4
Authors: Bryan McCarthy, Charles J. Kim, Seto M. Chice, Isabella DeGregorio, Vahe Amassian, Mark Stewart, Maja Nowakowski, Yitzchok M. Norowitz, Tamar A. Smith-Norowitz, Rauno Joks, Helen G. Durkin
Journal: Journal of Allergy and Clinical Immunology (2016)
S74 Assessing the diagnostic accuracy of the British Thoracic Society algorithm for investigation of solid pulmonary nodules
Authors: A Al-Ameri, P Malhotra, H Thygesen, S Vaidyanathan, S Karthik, A Scarsbrook, M Callister
Journal: Thorax (2015)

<h3>Background</h3> The British Thoracic Society guidelines (2015) on the investigation and management of pulmonary nodules recommend the use of two risk prediction tools to assess the likelihood of malignancy in solid pulmonary nodules (Brock model following initial CT and the model described by Herder <i>et al</i>. following PET-CT). Management strategies are suggested on the basis of these risk assessments. The aim of this study was to assess the performance of this algorithm in patients with solid pulmonary nodules recruited from a UK teaching hospital. <h3>Method</h3> Patients with solid pulmonary nodules (4–30 mm) were retrospectively identified from the lung cancer MDT and a nodule follow-up clinic (n = 221). All patients had a final diagnosis confirmed by histology or radiological stability on 2-year follow up. <h3>Results</h3> The median age was 69 years. The prevalence of malignancy was 37.1% (29.9% primary lung cancer, 7.2% metastatic disease). 25 patients where PET-CT was recommended by the guideline but did not occur were excluded from subsequent analysis. Ten patients had nodules &lt;5 mm and therefore would have been immediately discharged. All these nodules were benign. CT surveillance was recommended for 106 patients (37 with nodule &lt;8 mm, 45 with malignant risk of &lt;10% following initial CT, and 24 with malignant risk of &lt;10% following PET-CT). 94% of these 106 patients had benign disease, 2% had primary lung cancer and 4% had metastatic disease. Surgical/non-surgical treatment was recommended for 58 patients where the malignant risk was &gt;70% following PET-CT. 81% of these patients had primary lung cancer, 10% had metastatic disease and 9% were benign. For nodules with a malignant risk of between 10 and 70% following PET-CT, the guidelines recommend consideration of biopsy with alternatives of CT surveillance or surgical resection depending on patient preference and fitness. Of the 22 patients with nodules in this range, 36% were benign, 55% primary lung cancer and 9% metastatic disease. <h3>Conclusion</h3> The solid nodule algorithm from the BTS guidelines shows good accuracy in discriminating benign from malignant nodules, recommending appropriate management in a high proportion of cases. Further studies should evaluate this and the other management algorithms with prospectively collected data.