tbuckley/cabot-search huggingface dataset:
Safety and clinical activity of MK-3475 in previously treated patients (pts) with non-small cell lung cancer (NSCLC).
Authors: Edward B. Garon, Natasha B. Leighl, Naiyer A. Rizvi, George R. Blumenschein, Ani Sarkis Balmanoukian, Joseph Paul Eder, Jonathan Wade Goldman, Rina Hui, Jean-Charles Soria, Tara C. Gangadhar, Jong-Mu Sun, Amita Patnaik, Matthew A. Gubens, Gregory M. Lubiniecki, Jin Zhang, Michelle Niewood, Kenneth Emancipator, Marisa Dolled-Filhart, Mary Elizabeth Hanson, Leena Gandhi
Journal: Journal of Clinical Oncology (2014)

8020 Background: This Phase I study evaluated the safety, tolerability, and clinical activity of MK-3475, a selective anti-PD-1 antibody that blocks the interaction between programmed death-1 (PD-1) on T-cells and PD-L1 and PD-L2 on tumor cells in pts with previously-treated, progressive locally advanced or metastatic NSCLC. Methods: Previously-treated pts with NSCLC whose tumors expressed any detectable PD-L1 using a preliminary immunohistochemical assay were randomized to MK-3475 at 10 mg/kg every 2 weeks (Q2W) or 3 weeks (Q3W). Some pts with tumors without PD-L1 expression who had received ≥2 prior lines of therapy were treated with MK-3475 at 10 mg/kg Q2W. At least 1 measurable tumor lesion, ECOG performance status of 0-1, adequate organ function, and new tumor biopsy ≤60 days prior to study entry were required. Tumor response was assessed every 9 wks until disease progression by investigator review using immune-related response criteria (irRC) and independent central review using RECIST 1.1. Results: 450 pts provided tissue for PD-L1 assessment; 305 were eligible based on PD-L1 tumor staining. 221 pts (n=102, Q2W [including 43 whose tumors did not express PD-L1]; n=119, Q3W) began treatment between Feb 2013 and Oct 2013. 48% of pts experienced drug-related adverse events (AEs), usually grade 1-2 in severity, most commonly fatigue (13%), decreased appetite (6.5%), arthralgia (6.1%), pruritus (5.4%), rash (4.7%), and pyrexia (3.6%). The incidence of grade 3/4 drug-related AEs was 6%. There were 3 cases of drug-related grade 3/4 pneumonitis. The preliminary ORR (confirmed & unconfirmed by irRC/RECIST) in all pts was 15%/21% (16%/24% for pts with PD-L1 expressing tumors [19%/31% 10 mg/kg Q2W, 15%/22% 10 mg/kg Q3W], 10%/8% for pts without PD-L1 tumor expression. 40% of pts had <18 wks of follow-up and 69 pts (33%) remain on treatment. A mature dataset will be available for presentation, including correlation between level of tumor PD-L1 expression and response rates. Conclusions: In this cohort of over 200 pts, treatment with MK-3475 was generally well tolerated and provided robust antitumor activity in previously-treated pts with progressive locally advanced or metastatic NSCLC that expressed PD-L1. Clinical trial information: NCT01295827.
Pituitary thyrotropin response to thyrotropin-releasing hormone in affective illness: relationship to spinal fluid amine metabolites
Authors: P W Gold, F K Goodwin, T Wehr, R Rebar
Journal: American Journal of Psychiatry (1977)

The authors studied pituitary thyrotropin, i.e., thyroid-stimulating hormone (TSH), response to thyrotropin-releasing hormone (TRH) in patients with primary affective disorder. There were no overall differences between either depressed or manic patients and normal controls; however, the TSH response was significantly lower in the unipolar depressed patients than in either bipolar depressed patients or normal subjects. Bipolar patients in the manic phase tended to have a lower response than bipolar depressed patients. In the unipolar group, the TSH response showed a significant negative correlation with the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the CSF. These neuroendocrine responses may constitute markers of specific monoamine dysfunction in subgroups of patients with affective illness.
Treatment of Thrombocytopenia in Chimpanzees Infected With Human Immunodeficiency Virus by Pegylated Recombinant Human Megakaryocyte Growth and Development Factor
Authors: Laurence A. Harker, Ulla M. Marzec, Francis Novembre, I. Birgitta Sundell, Edmund K. Waller, Simon Karpatkin, Harold M. McClure, Andrew B. Kelly, Richard B. Stead
Journal: Blood (1998)
Don't Worry, Be Happy: Endocannabinoids and Cannabis at the Intersection of Stress and Reward
Authors: Nora D. Volkow, Aidan J. Hampson, Ruben D. Baler
Journal: The Annual Review of Pharmacology and Toxicology (2016)

Cannabis enables and enhances the subjective sense of well-being by stimulating the endocannabinoid system (ECS), which plays a key role in modulating the response to stress, reward, and their interactions. However, over time, repeated activation of the ECS by cannabis can trigger neuroadaptations that may impair the sensitivity to stress and reward. This effect, in vulnerable individuals, can lead to addiction and other adverse consequences. The recent shift toward legalization of medical or recreational cannabis has renewed interest in investigating the physiological role of the ECS as well as the potential health effects, both adverse and beneficial, of cannabis. Here we review our current understanding of the ECS and its complex physiological roles. We discuss the implications of this understanding vis-á-vis the ECS's modulation of stress and reward and its relevance to mental disorders in which these processes are disrupted (i.e., addiction, depression, posttraumatic stress disorder, schizophrenia), along with the therapeutic potential of strategies to manipulate the ECS for these conditions.
Notes from The Field: Ebola Virus Disease Cluster — Northern Sierra Leone, January 2016
Authors: Charles Alpren, Michelle Sloan, Karen A. Boegler, Daniel W. Martin, Elizabeth Ervin, Faith Washburn, Regan Rickert, Tushar Singh, John T. Redd, Andrew Bangalie, Micah Bass, Sarah D. Bennett, Isaac Akuamoah Boateng, Deanna Campbell, Cynthia Cassell, Matt Cotton, Nadezhda Duffy, Ian Goodfellow, Sara Hersey, Eddie L. Jackson, Umaru Jah, Augustine S. Jimissa, Ansumana S. Kamara, Fatmata Kamara, Paul Kellam, Rebecca Levine, Luke Meredith, Leigh Ann Miller, Stephanie Moody-Geissler, Robert Musoke, Dhamari Naidoo, John Ndyahikayo, Gibril Njie, My Phan, Andrew Rambaut, Foday Sesay
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

On January 14, 2016, the Sierra Leone Ministry of Health and Sanitation was notified that a buccal swab collected on January 12 from a deceased female aged 22 years (patient A) in Tonkolili District had tested positive for Ebola virus by reverse transcription-polymerase chain reaction (RT-PCR). The most recent case of Ebola virus disease (Ebola) in Sierra Leone had been reported 4 months earlier on September 13, 2015 (1), and the World Health Organization had declared the end of Ebola virus transmission in Sierra Leone on November 7, 2015 (2). The Government of Sierra Leone launched a response to prevent further transmission of Ebola virus by identifying contacts of the decedent and monitoring them for Ebola signs and symptoms, ensuring timely treatment for anyone with Ebola, and conducting an epidemiologic investigation to identify the source of infection.
Fine-Tuning the Treatment of Hodgkin’s Lymphoma
Authors: Nancy L. Bartlett
Journal: New England Journal of Medicine (2016)

In 2007, Gallamini et al. published the dramatic results of a retrospective study describing the independent prognostic significance of an early interim positron-emission tomographic (PET) scan in advanced Hodgkin's lymphoma.1 The 2-year progression-free survival among patients with a persistently positive PET scan after two cycles of chemotherapy was a dismal 12.8%, as compared with 95.0% among those with a negative interim PET scan. Investigators across the world saw this as the way forward, using a "response adapted" approach to eliminate potentially unnecessary treatment in patients with an early negative PET scan and to intensify treatment in those with a positive . . .
THE SUPPLY OF MEDICAL FACULTY: A TIME OF REASSURANCE
Authors: M R ZAVON
Journal: JAMA (1964)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Comprehensive Clinical Staging for Resectable Lung Cancer: Clinicopathological Correlations and the Role of Brain MRI
Authors: Jordyn Vernon, Nicole Andruszkiewicz, Laura Schneider, Colin Schieman, Christian J. Finley, Yaron Shargall, Christine Fahim, Forough Farrokhyar, Waël C. Hanna
Journal: Journal of Thoracic Oncology (2016)
Abstract 150: Color-Coded, Prefilled Syringes Corresponding to the Broselow Tape Decrease Medication Time to Administration and Errors Among Emergency Physicians and Nurses in Simulated Critically Ill Pediatric Patients
Authors: Maria E Moreira, Margaret Sande, Allen Stevens, Seth Jones, Jason Blumen, Katherine Bakes, Jason Haukoos, Caleb Hernandez
Journal: Circulation (2012)

Background: Pediatric resuscitations are inherently stressful and clinicians use various methods of determining drug dosing. The processes of calculation may lead to delay or error in drug administ...
The Polymorphisms Of Base Excision Repair Genes Influence The Cytogenetic Risk Factors In Acute Myeloid Leukemia
Authors: Atsushi Iwasaki, Takayuki Saitoh, Yasuhiro Nitta, Batchimeg Norjimaa, Chiharu Omiya, Akira Kamiya, Nahoko Hatsumi, Hiroaki Shimizu, Takuma Ishizaki, Takumi Hoshino, Satoru Takada, Hiroshi Handa, Toru Sakura, Akihiko Yokohama, Norifumi Tsukamoto, Hirokazu Murakami
Journal: Blood (2013)
Case 38-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, H.H. Funkenstein, D.C. Miller
Journal: New England Journal of Medicine (1985)

Presentation of CaseA 66-year-old right-handed man was admitted to the hospital because of increasing motor dysfunction of the left extremities.He was well until five years earlier, when he began to notice rigidity and discomfort of the right upper extremity that were most pronounced at the shoulder. The rigidity worsened, and a rapid-action tremor developed in the right upper extremity and increased in amplitude with intention. Hypertension was found, and the administration of propranolol was followed by slight improvement in the tremor. During the next three years the rigidity of the right hand progressed to the extent that he . . .
Rôles et fonctions d’un centre européen de santé publique sur les maladies transmissibles et autres menaces pour la santé
Authors: F Van Loock, N Gill, S Wallyn, A Nicoll, J C Desenclos, P Leinikki
Journal: Eurosurveillance (2002)

Un consensus international a ete etabli sur la necessite d’une structure europeenne de coordination technique (TCS, technical coordination structure) pour les maladies transmissibles, afin d’ameliorer la reponse future aux menaces internationales des maladies transmissibles, au sein et au-dela des frontieres de l’Union europeenne. Suite aux attentats du 11 septembre 2001 aux etats-Unis et aux disseminations deliberees du bacille du charbon, l’UE a cree un Comite de securite sanitaire, adopte une decision de protection civile, et mis en place pour 18 mois une equipe pour developper les reponses aux propagations deliberees d’agents biologiques et chimiques. Ces deux initiatives, l’approche du reseau et le travail sur la securite sanitaire, doivent converger en un seul courant traitant de la protection sanitaire des personnes en Europe. Elles pourraient etre assurees par un centre europeen des maladies transmissibles, dont l’ouverture est prevue en 2005.
Case 53-1970
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Alexander Leaf, Benjamin Castleman
Journal: New England Journal of Medicine (1970)

CASE 53–1970Presentation of CaseA 74-year-old woman was admitted to the hospital because of renal failure.She had been well except for mild hypertension, found six years previously, for which no treatment was prescribed. One year before entry she was admitted to another hospital because of epigastric pain and postprandial heartburn; a gastrointestinal series was reported to show a gastric ulcer, and she was discharged on a bland diet and antacid, with relief of symptoms. Two months later peripheral edema developed and progressed in severity, with little response to diuretic medication. During the three months before entry nocturia occurred. . . .
Secondary Consult
Authors: Marion Bishop
Journal: JAMA (2002)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Trehalose upregulates progranulin expression in human and mouse models of GRN haploinsufficiency: a novel therapeutic lead to treat frontotemporal dementia
Authors: Christopher J. Holler, Georgia Taylor, Zachary T. McEachin, Qiudong Deng, William J. Watkins, Kathryn Hudson, Charles A. Easley, William T. Hu, Chadwick M. Hales, Wilfried Rossoll, Gary J. Bassell, Thomas Kukar
Journal: Molecular Neurodegeneration (2016)

Progranulin (PGRN) is a secreted growth factor important for neuronal survival and may do so, in part, by regulating lysosome homeostasis. Mutations in the PGRN gene (GRN) are a common cause of frontotemporal lobar degeneration (FTLD) and lead to disease through PGRN haploinsufficiency. Additionally, complete loss of PGRN in humans leads to neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. Importantly, Grn-/- mouse models recapitulate pathogenic lysosomal features of NCL. Further, GRN variants that decrease PGRN expression increase the risk of developing Alzheimer's disease (AD) and Parkinson's disease (PD). Together these findings demonstrate that insufficient PGRN predisposes neurons to degeneration. Therefore, compounds that increase PGRN levels are potential therapeutics for multiple neurodegenerative diseases.Here, we performed a cell-based screen of a library of known autophagy-lysosome modulators and identified multiple novel activators of a human GRN promoter reporter including several common mTOR inhibitors and an mTOR-independent activator of autophagy, trehalose. Secondary cellular screens identified trehalose, a natural disaccharide, as the most promising lead compound because it increased endogenous PGRN in all cell lines tested and has multiple reported neuroprotective properties. Trehalose dose-dependently increased GRN mRNA as well as intracellular and secreted PGRN in both mouse and human cell lines and this effect was independent of the transcription factor EB (TFEB). Moreover, trehalose rescued PGRN deficiency in human fibroblasts and neurons derived from induced pluripotent stem cells (iPSCs) generated from GRN mutation carriers. Finally, oral administration of trehalose to Grn haploinsufficient mice significantly increased PGRN expression in the brain.This work reports several novel autophagy-lysosome modulators that enhance PGRN expression and identifies trehalose as a promising therapeutic for raising PGRN levels to treat multiple neurodegenerative diseases.
Bendamustine, Bortezomib and Dexamethasone (BVD) in Patients with Relapsed-Refractory Multiple Myeloma (MM): Updated Results of a Multicenter Phase II Study
Authors: Massimo Offidani, Laura Maracci, Laura Corvatta, Liberati Anna Marina, Stelvio Ballanti, Imma Attolico, Patrizia Caraffa, Francesco Alesiani, Tommaso Caravita di Toritto, Silvia Gentili, Patrizia Tosi, Marino Brunori, Daniele Derudas, Antonio Ledda, Alessandro Gozzetti, Claudia Cellini, Lara Malerba, Anna Mele, Stefano Felici, Sara Galimberti, Patrizia Mondello, Stefano Pulini, Ugo Coppetelli, Paolo Fraticelli, Rita Rizzi, Pietro Leoni
Journal: Blood (2014)
Review of the Experimental Background and Implementation of Computational Models of the Ocular Lens Microcirculation
Authors: Ho-Ting D. Wu, Paul J. Donaldson, Ehsan Vaghefi
Journal: IEEE Reviews in Biomedical Engineering (2016)

Our sense of vision is critically dependent on the clarity of the crystalline lens. The most common cause of transparency loss in the lens is age-related nuclear cataract, which is due to accumulative oxidative damage to this tissue. Since the ocular lens is an avascular tissue, it has to maintain its physiological homeostasis and antioxidant levels using a system of water microcirculation. This system has been experimentally imaged in animal lenses using different modalities. Based on these data, computational models have been developed to predict the properties of this system in human lenses and its changes due to aging. Although successful in predicting many aspects of lens fluid dynamics, at least in animal models, these in-silica models still need further improvement to become more accurate and representative of human ocular lens. We have been working on gathering experimental data and simultaneously developing computational models of lens microcirculation for the past decade. This review chronologically looks at the development of data-driven computational foundations of lens microcirculation model, its current state, and future advancement directions. A comprehensive model of lens fluid dynamics is essential to understand the physiological optics of this tissue and ultimately the underlying mechanisms of cataract onset and progression.
High sensitivity for tuberculosis in a national integrated surveillance system in Finland
Authors: M Kokki, P Holmström, P Ruutu
Journal: Eurosurveillance (2005)

Little is known about the sensitivity of surveillance for tuberculosis after integration of formerly dedicated tuberculosis surveillance and control into the general health care system, an integration which took place in Finland in 1987. We compared routine laboratory notifications to the National Infectious Disease Register (NIDR) for Mycobacterium tuberculosis from January 1, 1995, to December 31, 1996, with data collected independently from all laboratories offering M. tuberculosis culture, and with data from patient records. 1059 culture-positive cases were found. The overall sensitivity of the NIDR was 93 % (984/1059). The positive predictive value of a culture-positive case in the NIDR to be a true culture-confirmed case was 99%. For the culture-confirmed cases in the NIDR, one or more physician notification forms had been submitted for 89%. A highly sensitive notification system for culture-positive tuberculosis can be achieved in an integrated national infectious disease surveillance system based on laboratory notification.
Abstract 058: Novel Agonist of Adenosine Receptor Ameliorates Ventricular and Vascular Dysfunction in Monocrotaline-induced Pulmonary Arterial Hypertension in Rats
Authors: Gisele Zapata-Sudo, Allan K Alencar, Sharlene L Pereira, Emanelle Ferraz, José H Nascimento, Roberta Tesch, Rodolfo Maia, Carlos M Sant’Anna, Carlos A Fraga, Eliezer J Barreiro, Roberto T Sudo
Journal: Circulation Research (2013)

Aims: Pulmonary arterial hypertension (PAH) consists of increased pulmonary vascular resistance and remodeling and right ventricular hypertrophy. This work investigated the effects of a new N -acylhydrazone derivative, (E)-N’-(3,4-dimethoxybenzylidene)-4-methoxybenzohydrazide (LASSBio-1386), in rats with monocrotaline (MCT)-induced PAH. Methods and Results: Protocols were approved by Animal Care and Use Committee at Universidade Federal do Rio de Janeiro. Male Wistar rats received a single i.p. injection of MCT (60 mg/kg) for PAH induction. Experimental groups were: control, MCT + vehicle (DMSO), MCT + LASSBio-1386 (50 mg/kg p.o.). The animals were treated with vehicle or LASSBio-1386 for 14 days after the onset of disease (n = 6). Right ventricular systolic pressure (RVSP) and relation between RV weight to body weight (RV/BW) were analyzed. Transthoracic echocardiography was performed to determine pulmonary acceleration time (PAT), pulmonary artery diameter and RV wall thickness. Pulmonary vascular morphometry was analyzed using images of terminal arterioles and wall thickness was measured. The parameters evaluated are shown in table 1. In addition, LASSBio-1386-induced vasorelaxation was mediated partially by the activation of A2A adenosine receptors, with an IC50 of 6.2 ± 1.2 µM. Docking analysis in the A 2A crystal structure was performed using the program GOLD 5.1 and showed the interaction of the compound with A 2A receptor. Conclusions: LASSBio-1386 effectively reversed right ventricular hypertrophy and pulmonary vascular remodeling in rats with MCT-induced PAH through activation of adenosine receptor.
Typical Type-C Virus in Human Leukemia 2
Authors: W. T. Hall, G. Schidlovsky
Journal: JNCI Journal of the National Cancer Institute (1976)

The virus HL-23, recently isolated from a patient with myelogenous leukemia, was compared by electron microscopy with virus-like particles observed in human tissues and with several mammalian type-C virus particles. It closely resembled the typical type-C virus particles of murine, feline, and nonhuman primate species, and differed from all particles previously reported in human tissues, including the atypical human placental particle.