tbuckley/cabot-search huggingface dataset:
Lymph node metastases develop through a wider evolutionary bottleneck than distant metastases
Authors: Johannes G. Reiter, Wei-Ting Hung, I-Hsiu Lee, Shriya Nagpal, Peter Giunta, Sebastian Degner, Gang Liu, Emma C. E. Wassenaar, William R. Jeck, Martin S. Taylor, Alexander A. Farahani, Hetal D. Marble, Simon Knott, Onno Kranenburg, Jochen K. Lennerz, Kamila Naxerova
Journal: Nature Genetics (2020)
Marihuana Psychosis Revisited
Authors: Isaac Persyko
Journal: JAMA (1971)

<h3>To the Editor.—</h3> In my case report of "Marihuana Psychosis" (<b>212:</b>1527, 1970), I emphasized the following medically important features of psychiatric acute adverse reactions to marihuana: (1) the relative mildness of their course, (2) their transient nature, and (3) infrequency of their occurrence. Perna (<b>214:</b>760, 1970) claims that my views do not represent a "statement of fact" and are "dangerously misleading." A review of recent reports on the subject clarifies some points. Comparison of the effects of marihuana and alcoholic intoxication is valid as both produce similar effects of relaxation, tension-reduction, and sense of well being.<sup>1</sup> 2. The frequency of psychiatric acute adverse reactions to marihuana in<i>non-psychiatric</i>populations was recorded by Pillard.<sup>2</sup>An "informal survey of the Boston University Student Health Service, which cares for a student population of 20,000, revealed that only 5-7 marihuanaassociated anxiety reactions are being seen yearly." He also refers
Abstract 11144: Demographics of Study Participants in Clinical Trials for Cardiovascular Drugs Approved at FDA CDER From 2013 to 2014
Authors: Emmanuel O Fadiran, Hawi Itana, Merina Elahi, Ayomide Igun, Greg Soon, Alice Chen, Anne Pariser
Journal: Circulation (2015)

Introduction: Cardiovascular disease (CVD) is the leading cause of death for women in the United States. To assess the safety and efficacy of CVD drugs in the diverse population of patients who will use them post-approval, the US FDA has implemented guidance and regulation to encourage the inclusion of women and racial/ethnic minorities in drug clinical trials (CTs). This study assessed the participation of women and minorities in CTs for CVD indications for New Drug Applications (NDAs) approved at FDA CDER from 2013-2014. Methods: The sex, race/ethnicity, and age of subjects who participated in CVD drug CTs were assessed from final clinical study reports accessed via internal FDA databases, and were evaluated for the presence of data analysis by sex. The ratio of the percent of women in the CT population was also compared to those in the disease population. Results: Four novel CVD drugs were approved in this time frame, including 2 drugs indicated for pulmonary hypertension (PH) (riociguat, total CT population n=2691; macitentan, n=1884), and 1 drug each for prevention of thrombotic acute CV events (vorapaxar, n=41972) and treatment of neurogenic orthostatic hypotension (NOH) (droxidopa, n=1125). Demographic subgroup analysis indicated that percent female participation was 26% for thrombotic CV events, 40% for NOH, and 47% for PH. Female participation in pivotal trials only (in which benefit-risk was demonstrated) was 24% for thrombotic CV events, 33% for NOH, and 75% for PH. The majority of the trial participants were White (85%), and mean ages were 48 years (PH), 61 years (thrombotic CV events), and 64 years (NOH). Sex-based analysis for both efficacy and safety was presented for all drugs. Three of the NDAs with available disease prevalence data had a ratio of percent female participation to disease prevalence that was between 0.80 and 1.2. Conclusions: Percent female participation varied substantially by disease indication, with PH (a female predominant disease) having the highest female participation. Female participation in the prevention of thrombotic CV events was lower than anticipated based upon disease prevalence in the population. Further exploration of demographic subgroup participation in CTs for CVD drugs in a larger sample size is ongoing.
Polygenic risk scores: from research tools to clinical instruments
Authors: Cathryn M. Lewis, Evangelos Vassos
Journal: Genome Medicine (2020)

Abstract Genome-wide association studies have shown unequivocally that common complex disorders have a polygenic genetic architecture and have enabled researchers to identify genetic variants associated with diseases. These variants can be combined into a polygenic risk score that captures part of an individual’s susceptibility to diseases. Polygenic risk scores have been widely applied in research studies, confirming the association between the scores and disease status, but their clinical utility has yet to be established. Polygenic risk scores may be used to estimate an individual’s lifetime genetic risk of disease, but the current discriminative ability is low in the general population. Clinical implementation of polygenic risk score (PRS) may be useful in cohorts where there is a higher prior probability of disease, for example, in early stages of diseases to assist in diagnosis or to inform treatment choices. Important considerations are the weaker evidence base in application to non-European ancestry and the challenges in translating an individual’s PRS from a percentile of a normal distribution to a lifetime disease risk. In this review, we consider how PRS may be informative at different points in the disease trajectory giving examples of progress in the field and discussing obstacles that need to be addressed before clinical implementation.
Abstract 18068: mRNA Degradation of Mitochondrial Electron Transport Chain Proteins by Trsitetraprolin Protects the Heart Against Iron Deficiency
Authors: Tatsuya Sato, Hsiang-Chun Chang, María T Martínez-Pastor, Konrad T Sawicki, Marina Bayeva, Sergi Puig, Perry J Blackshear, Lisa D Wilsbacher, Hossein Ardehali
Journal: Circulation (2017)

Introduction: Iron deficiency is the most common nutrient deficiency in the world, and cells respond to iron deficiency by activating iron regulatory proteins (IRP) to increase cellular iron uptake...
Management of patients with multiple myeloma in the era of COVID-19 pandemic: a consensus paper from the European Myeloma Network (EMN)
Authors: Evangelos Terpos, Monika Engelhardt, Gordon Cook, Francesca Gay, Maria-Victoria Mateos, Ioannis Ntanasis-Stathopoulos, Niels W. C. J. van de Donk, Hervé Avet-Loiseau, Roman Hajek, Annette Juul Vangsted, Heinz Ludwig, Sonja Zweegman, Philippe Moreau, Hermann Einsele, Mario Boccadoro, Jesus San Miguel, Meletios A. Dimopoulos, Pieter Sonneveld
Journal: Leukemia (2020)
Quest for Clinically Effective RAF Dimer Inhibitors
Authors: Jenny Y. Xue, Piro Lito
Journal: Journal of Clinical Oncology (2020)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Phase I, Open-Label, Dose-Escalation/Dose-Expansion Study of Lifirafenib (BGB-283), an RAF Family Kinase Inhibitor, in Patients With Solid Tumors. March 17, 2020 ARTICLE CITATION DOI: 10.1200/JCO.20.00401 Journal of Clinical Oncology - published online before print May 20, 2020 PMID: 32432945 Quest for Clinically Effective RAF Dimer Inhibitors Jenny Y. Xue, BS1,2xJenny Y. XueSearch for articles by this author and Piro Lito, MD, PhD1,3,4xPiro LitoSearch for articles by this author Show More 1Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY2Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, NY3Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY4Department of Medicine, Weill Cornell Medical College, New York, NY https://doi.org/10.1200/JCO.20.00401 First Page Full Text PDF Figures and Tables © 2020 by American Society of Clinical Oncology Companion Phase I, Open-Label, Dose-Escalation/Dose-Expansion Study of Lifirafenib (BGB-283), an RAF Family Kinase Inhibitor, in Patients With Solid Tumors
A study of apolipoproteins E and A-I in cutaneous amyloids
Authors: Y.T. Chang, S.F. Tsai, W.J. Wang, C.J. Hong, C.Y. Huang, C.K. Wong
Journal: British Journal of Dermatology (2008)

Background Apolipoprotein E (apoE) is present in a variety of biochemically different amyloid deposits, including Alzheimer's disease, systemic amyloidosis and primary cutaneous amyloidosis (PCA). Among the three closely related alleleic forms of apoE, the ε4 allele is linked to Alzheimer's disease. Apolipoprotein A‐I (apoA‐I), another apolipoprotein, is also found in senile plaques of Alzheimer's disease and in amyloid of aortic atherosclerotic plaques. Furthermore, apoA‐I has recently been found to be associated with hereditary cutaneous and cardiac amyloidosis. Objectives To determine whether the apoE ε4 allele is associated with increased risk of PCA and whether apoE and apoA‐I are present in PCA and common secondary cutaneous amyloidosis (SCA) (i.e. basal cell carcinoma, Bowen's disease and seborrhoeic keratosis). Methods We examined the apoE genotype in 57 Chinese patients with PCA and 58 normal healthy control subjects of similar age. In addition, immunohistochemical staining was performed to determine the localization of apoE and apoA‐I in skin tissues from 15 patients with SCA and 15 with PCA. Results The frequency of the ε4 allele in the PCA group was not significantly higher than that in the control group (8·8% vs. 6·9%, P > 0·05). ApoE was present in amyloid deposits in both PCA and SCA, but apoA‐I was not detected in these cutaneous amyloid deposits. Conclusions ApoE is also a component of amyloid deposits in SCA. Although the genetic susceptibility of certain apoE isoforms may not be a crucial factor in the development of PCA and, although apoA‐I is not associated with amyloid deposits of PCA and SCA, the role of apolipoproteins in amyloidogenesis deserves further scrutiny.
SMART and as-needed therapies in mild-to-severe asthma: a network meta-analysis
Authors: Paola Rogliani, Beatrice Ludovica Ritondo, Josuel Ora, Mario Cazzola, Luigino Calzetta
Journal: European Respiratory Journal (2020)

To date, there are no network meta-analyses comparing the impact of as-needed treatments in asthma, including the single maintenance and reliever therapy (known as "SMART" or "MART"; for simplicity, SMART will be used hereafter) and the use of inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) combination exclusively on an as-needed basis. Therefore, we performed a systematic review and network meta-analysis concerning the efficacy and safety of SMART and as-needed therapies in asthma. Data from 32 096 asthmatic patients were extracted from 21 studies, lasting from 6 to 12 months. In adult mild-to-moderate asthmatic patients low-dose SMART and as-needed low-dose ICS/LABA combination were significantly (relative effect <0.78; p<0.05) more effective than the other as-needed therapies in reducing the risk of exacerbation, and both were ranked as the first treatment option reaching the first quartile of the surface under the cumulative ranking curve analysis (SUCRA). In adult moderate-to-severe asthmatic patients, low-dose to medium-dose SMART and high-dose ICS/LABA+as-needed short-acting β2-agonist were equally effective in reducing the risk of severe asthma exacerbation (p>0.05), although only low- to medium-dose SMART was ranked as the first treatment option (first SUCRA quartile). Overall, these treatments were well tolerated, and effective also on lung function and disease control. This study supports SMART and as-needed therapies as a suitable therapeutic option for asthma, by providing the most effective positioning of each specific treatment according to the disease severity.
Repression of LKB1 by miR-17∼92 Sensitizes MYC-Dependent Lymphoma to Biguanide Treatment
Authors: Said Izreig, Alexandra Gariepy, Irem Kaymak, Hannah R. Bridges, Ariel O. Donayo, Gaëlle Bridon, Lisa M. DeCamp, Susan M. Kitchen-Goosen, Daina Avizonis, Ryan D. Sheldon, Rob C. Laister, Mark D. Minden, Nathalie A. Johnson, Thomas F. Duchaine, Marc S. Rudoltz, Sanghee Yoo, Michael N. Pollak, Kelsey S. Williams, Russell G. Jones
Journal: Cell Reports Medicine (2020)

Cancer cells display metabolic plasticity to survive stresses in the tumor microenvironment. Cellular adaptation to energetic stress is coordinated in part by signaling through the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) pathway. Here, we demonstrate that miRNA-mediated silencing of LKB1 confers sensitivity of lymphoma cells to mitochondrial inhibition by biguanides. Using both classic (phenformin) and newly developed (IM156) biguanides, we demonstrate that elevated miR-17∼92 expression in Myc+ lymphoma cells promotes increased apoptosis to biguanide treatment in vitro and in vivo. This effect is driven by the miR-17-dependent silencing of LKB1, which reduces AMPK activation in response to complex I inhibition. Mechanistically, biguanide treatment induces metabolic stress in Myc+ lymphoma cells by inhibiting TCA cycle metabolism and mitochondrial respiration, exposing metabolic vulnerability. Finally, we demonstrate a direct correlation between miR-17∼92 expression and biguanide sensitivity in human cancer cells. Our results identify miR-17∼92 expression as a potential biomarker for biguanide sensitivity in malignancies.
72P Non-mass like enhancement patterns on MR mammography and their pathological correlation
Authors: A. Parashar, A. Jajodia, A. Chaturvedi, A. Rao, A. Mehta, D.C. Doval, A. Bp, P. Medisetty, V.P.B. Koyyala, S. Pasricha, M. la Mantia, M.K. Chllamma, D. Leithner, M.E. Mayerhoefer, A. Russo, H. Prosch
Journal: Annals of Oncology (2020)
Effect of intensive lifestyle intervention on bodyweight and glycaemia in early type 2 diabetes (DIADEM-I): an open-label, parallel-group, randomised controlled trial
Authors: Shahrad Taheri, Hadeel Zaghloul, Odette Chagoury, Sara Elhadad, Salma Hayder Ahmed, Neda El Khatib, Rasha Abou Amona, Katie El Nahas, Noor Suleiman, Abdulla Alnaama, Abdulla Al-Hamaq, Mary Charlson, Martin T Wells, Samya Al-Abdulla, Abdul Badi Abou-Samra
Journal: The Lancet Diabetes & Endocrinology (2020)
Current Studies on the Effect of Antimetabolites in Nephrosis, Other Non-Neoplastic Diseases, and Experimental Animals
Journal: JAMA (1963)

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
The Medical Malpractice System
Authors: Mark I. Taragin
Journal: Annals of Internal Medicine (1993)

Letters1 June 1993The Medical Malpractice SystemMark I. Taragin, MD, Laura R. Willett, MD, and Jeffrey L. Carson, MDMark I. Taragin, MDSearch for more papers by this author, Laura R. Willett, MDSearch for more papers by this author, and Jeffrey L. Carson, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-11-199306010-00028 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:These letters highlight the fact that medical malpractice is a complex process where simplistic descriptions or solutions always fall short. Dr. Yaes' concern that the number of claims is too many depends on one's perspective [1]. Malpractice claims vary greatly among specialties [2]. We agree with Dr. Oppenheimer that the fear of malpractice is a powerful force in U.S. medicine. The prevalence of medical prostitution and the possible deterrent effect of filing countersuits are unknown.One aim of our study was to contrast malpractice perceptions with reality based on the experience of a physician-owned insurance company in New ...References1. Brennan TA, Leape LL, Laird NM, Hebert L, Localio AR, Lawthers AG, et al. Incidence of adverse events and negligence in hospitalized patients. Results of the Harvard Medical Practice Study I. N Engl J Med. 1991; 324:370-6. Google Scholar2. Taragin MI, Wilczek AP, Karns ME, Trout R, Carson JL. Physician demographics and the risk of medical malpractice. Am J Med. 1992; 93:537-42. Google Scholar3. Schroeder SA, Kabcenell AI. Do bad outcomes mean substandard care? JAMA. 1991; 265:1995. Google Scholar4. US General Accounting Office. Medical malpractice: characteristics of claims closed in 1984. Washington D.C.: General Accounting Office; 1987; publication no GAO/HRD 87-55. Google Scholar5. Vidmar N. The unfair criticism of medical malpractice juries. Judicature. 1992; 76:118-24. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1993Volume 118, Issue 11Page: 908-909KeywordsEmotionsFallsFearPeer reviewPerception ePublished: 15 August 2000 Issue Published: 1 June 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Erratum: Differential expression of a basic helix-loop-helix phosphoprotein gene, GOS8, in acute leukemia and localization to human chromosome 1q31 (Leukemia (1995) 9 (1291-1298))
Authors: H. K. Wu, H. H.Q. Heng, X. M. Shi, D. R. Forsdyke, L. C. Tsui, M. D. Minden, D. P. Siderovski, T. W. Mak
Journal: Leukemia (1995)
Editorial: Geophagia-induced hyperkalemia
Authors: H. H. Hussey
Journal: JAMA (1975)

Geophagia, melodious word that it may sound to some, is nevertheless a "dirty" word. It means the ingestion of dirt (soil) or clay by persons whose perverted appetites lead them to eat "dirt" instead of nutritious food. In their article on this subject in this issue ofThe Journal(p 738), Gelfand et al delve briefly into the history of geophagia, but their search for the origins of the perversion is by no means complete. They note that geophagia-induced illness that resembled beriberi occurred among black slaves in Louisiana and that geophagia, as a cause of anemia, is still prevalent among blacks living in New York City. For their own part, Gelfand et al report five cases in which geophagia led to life-threatening hyperkalemia in the presence of chronic renal failure. The mechanism appeared to be absorption of large amounts of potassium from ingested clay. One patient, a 45-year-old black
Joyce Lilian Dunlop
Authors: Douglas Dunlop
Journal: BMJ (2020)

Joyce Lilian Dunlop was a general adult consultant psychiatrist practicing in the mixed urban and rural area of Kingston upon Hull and East Riding of Yorkshire. She was born in Dublin, Ireland, where she enjoyed a privileged early life as the only daughter of a textile mill owner. She was sent to Glengara Park School in Dun Laoghaire, Dublin, where she excelled in tennis, representing her school. She also excelled at science, indeed when her niece followed her to Glengara Park some years later, Joyce’s picture was still up in the entrance hall and the science teacher, Miss O’Dowd, used to periodically call her “Joyce.”

When her schooling was completed, Joyce crossed the Irish Sea to Winkfield Place finishing school near Windsor. This was Constance Spry’s school for young ladies, where they learnt the latest techniques of cordon bleu cookery, laundry, flower arranging, and secretarial and needlework. Much to her parents’ surprise, on her return she announced that she wished to study medicine and had their full support.

Joyce went to Trinity College Dublin to study medicine in 1954, where she …
Pathophysiology, Clinical Presentation, and Treatment of Psoriasis
Authors: April W. Armstrong, Charlotte Read
Journal: JAMA (2020)

Importance Approximately 125 million people worldwide have psoriasis. Patients with psoriasis experience substantial morbidity and increased rates of inflammatory arthritis, cardiometabolic diseases, and mental health disorders. Observations Plaque psoriasis is the most common variant of psoriasis. The most rapid advancements addressing plaque psoriasis have been in its pathogenesis, genetics, comorbidities, and biologic treatments. Plaque psoriasis is associated with a number of comorbidities including psoriatic arthritis, cardiometabolic diseases, and depression. For patients with mild psoriasis, topical agents remain the mainstay of treatment, and they include topical corticosteroids, vitamin D analogues, calcineurin inhibitors, and keratolytics. The American Academy of Dermatology-National Psoriasis Foundation guidelines recommend biologics as an option for first-line treatment of moderate to severe plaque psoriasis because of their efficacy in treating it and acceptable safety profiles. Specifically, inhibitors to tumor necrosis factor α (TNF-α) include etanercept, adalimumab, certolizumab, and infliximab. Other biologics inhibit cytokines such as the p40 subunit of the cytokines IL-12 and IL-23 (ustekinumab), IL-17 (secukinumab, ixekizumab, bimekizumab, and brodalumab), and the p19 subunit of IL-23 (guselkumab, tildrakizumab, risankizumab, and mirikizumab). Biologics that inhibit TNF-α, p40IL-12/23, and IL-17 are also approved for the treatment of psoriatic arthritis. Oral treatments include traditional agents such as methotrexate, acitretin, cyclosporine, and the advanced small molecule apremilast, which is a phosphodiesterase 4 inhibitor. The most commonly prescribed light therapy used to treat plaque psoriasis is narrowband UV-B phototherapy. Conclusions and Relevance Psoriasis is an inflammatory skin disease that is associated with multiple comorbidities and substantially diminishes patients’ quality of life. Topical therapies remain the cornerstone for treating mild psoriasis. Therapeutic advancements for moderate to severe plaque psoriasis include biologics that inhibit TNF-α, p40IL-12/23, IL-17, and p19IL-23, as well as an oral phosphodiesterase 4 inhibitor.
Representation without Taxation
Authors: A N Johnson
Journal: New England Journal of Medicine (1967)

grained in human nature, being based upon the hoary and time-honored notion that riches can be acquired only through extortion, that therefore the possession of wealth indicates wickedness and that its owner ought to be punished.Taxation of property practically discourages thrift and puts a premium on poverty.Would it not be better to encourage the accumulation of wealth and frame the laws in such a way as to induce the wage-earner to become a capitalist and thus develop into a responsible share-holder of our general prosperity ?
Antibiotic Use Associated With Risk of Colorectal Polyps in a Nationwide Study
Authors: Mingyang Song, Long H. Nguyen, Louise Emilsson, Andrew T. Chan, Jonas F. Ludvigsson
Journal: Clinical Gastroenterology and Hepatology (2020)

Use of antibiotics affects the composition of the microbiome and might affect development of colorectal polyps, which are precursors to colorectal cancer.