tbuckley/cabot-search huggingface dataset:
Abstract LB-2: Open innovation drug discovery: A study in JQ1.
Authors: Daniel L. Shaw, Charles Y. Lin, Richard P. Oakley, Nicholas P. Semenkovich, Jun Qi, James E. Bradner
Journal: Cancer Research (2013)

Abstract Collaborative research from our laboratory, in 2010, produced a first-in-class inhibitor of BET bromodomain proteins (JQ1). As an effort to promote a more open-innovation model of drug discovery, we endeavored to provide JQ1 without restriction of cost or delay to the scientific community. Toward this objective, we have optimized and completed a facile scaling synthesis capable of producing 100 g quantities of the active (+)-JQ1 stereoisomer. In the past 30 months, JQ1 has been provided to over 350 laboratories in more than a dozen countries. Through this research, BET bromodomain proteins have emerged as pharmacologically validated targets in multiple model systems of cancer including squamous carcinoma of the lung, head and neck, acute myeloid leukemia, multiple myeloma, Burkitt lymphoma, B-cell acute lymphoblastic leukemia, neuroblastoma and non-small cell lung cancer. More than 800 cancer cell lines and 25 murine models of cancer have been systematically screened with JQ1 for sensitivity to bromodomain inhibition, identifying additional therapeutic opportunities. Open availability of JQ1 has also lead to unexpected innovation outside of cancer research through studies identifying opportunities for BET bromodomain inhibition in such diverse fields as male contraception and HIV therapeutics. Since publication of the chemical structure and synthetic route to JQ1, seven new BET bromodomain inhibitors have appeared in the literature each derivatized from and/or benchmarked to the JQ1 molecule. Importantly, BET bromodomain inhibition has already accomplished clinical translation. To more objectively assess the consequence of open-innovation as a model of drug discovery, we have systematically analyzed metadata collected from published research and our ongoing efforts in compound distribution. Here, we present an interim analysis which relates the effect of open-innovation in drug discovery to the scope, productivity, reproducibility and importantly the pace of scientific research in epigenetic reader proteins. These results identify open-innovation in drug discovery as a catalyst for scientific discovery, bridging a gap between fields of research and the basic and clinical sciences. Citation Format: Daniel L. Shaw, Charles Y. Lin, Richard P. Oakley, Nicholas P. Semenkovich, Jun Qi, James E. Bradner. Open innovation drug discovery: A study in JQ1. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-2. doi:10.1158/1538-7445.AM2013-LB-2
Unemployment and mortality in Denmark, 1970-80.
Authors: L Iversen, O Andersen, P K Andersen, K Christoffersen, N Keiding
Journal: BMJ (1987)

Relative mortality in the period 1970-80 was studied among Danish men and women who were unemployed and employed on the day of the 1970 census. The study population consisted of the total labour force in the age range 20-64 on 9 November 1970--that is, about 2 million employed and 22,000 unemployed people. Relative mortality was analysed by a multiplicative hazard regression model (as a natural extension of the standardised mortality ratio) and a multiplicative regression model with extra-Poisson variation. A significantly increased death rate (40-50%) was found among the unemployed after adjusting for occupation, housing category, geographical region, and marital state. Analysis of five main causes of death showed increased mortality from all causes, but especially from suicide or accidents. In areas where the local unemployment rate was comparatively high the relative mortality among the unemployed was lower. The increased mortality among the unemployed was interpreted as a consequence of health related selection as well as increased susceptibility associated with the psychosocial stress of unemployment.
Serum adiponectin level is correlated with the size of HDL and LDL particles determined by high performance liquid chromatography
Authors: Kazumi Tsubakio-Yamamoto, Taizo Sugimoto, Makoto Nishida, Rieko Okano, Yasumasa Monden, Rika Kitazume-Taneike, Taiji Yamashita, Hajime Nakaoka, Ryota Kawase, Miyako Yuasa-Kawase, Miwako Inagaki, Kazuhiro Nakatani, Daisaku Masuda, Tohru Ohama, Akifumi Matsuyama, Yumiko Nakagawa-Toyama, Masato Ishigami, Issei Komuro, Shizuya Yamashita
Journal: Metabolism (2012)
BACTERIA IN THE EYEAND NOTES ON SOME RECENT WORK IN OPHTHALMOLOGIC BACTERIOLOGY.
Authors: BROWN PUSEY
Journal: JAMA (1903)

Such an appropriate opening of a subject as that which is forced on me is seldom given to a man. The natural manner in which to consider my subject is to begin with the bacteria that may infect the human conjunctiva, and of these the bacillus of acute, contagious conjunctivitis must first have attention. In the writings of a celebrated German ophthalmologist we find the sentence : "For the principal work in the investigation of this microörganism and the real demonstration of it as the cause of a particular form of conjunctivitis, we are indebted to him who in 1886 described the first cases, in which he was able to prove this microörganism to be the cause of this disease." I have the pleasure of showing a specimen containing the organisms spoken of in the abve sentence, which bear the name of the investigator referred to—Weeks, the chairman of
General principles of chaotic dynamics
Authors: P.B. Persson, C.D. Wagner
Journal: Cardiovascular Research (1996)

The following survey of the fundamental principles of chaos is intended to provide the reader of our spotlight issue with an overview of some of the most essential facts required for understanding chaotic dynamics. It is a great honour that leading scientists from the field of chaos in the cardiovascular system have agreed to provide focused reviews on several specific topics. The interested reader may also wish to refer to excellent previous reviews dealing with the microvasculature [12,15], heart rate [6,9], renal haemodynamics [17] and chaos in general [3,5,11,13,37,40]. For reviews of chaos theory in the physical literature [ 1,7,8,29] or textbooks on chaos, the reader may refer to various other sources [16,18,20,26,28,30,32, 34,391.
Case 36-1983
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Robert H. Rubin, J. Davis Allan
Journal: New England Journal of Medicine (1983)

Presentation of CaseA 26-year-old man was admitted to the hospital because of fever of unknown origin.The patient was a native of India and was studying in this country during the preceding two years. Three months before admission he returned to his home in Calcutta for a visit. He was well until one month before entry, when he took care of his brother-in-law during a three-day febrile diarrheal illness that subsided on oral medication. A few days later the patient experienced the onset of fever with rise of the temperature to 39.4°C, accompanied by shaking chills, headache, pains in . . .
Fifty Consecutive Cases of Pneumonia Without a Death.
Authors: John J. Coffman
Journal: JAMA (1905)

Scotland, Pa., Feb. 2, 1905. <h3>To the Editor:</h3> —I just read with much interest the article by W. J. Galbraith, M. D., inThe Journal, January 28, page 291, also the article by the same writer inThe Journal, July 9, 1904, page 108. Dr. Galbraith has certainly been most fortunate in his treatment of pneumonia by the heroic use of sulphate of quinin, and he certainly deserves credit for the fearless expression of his convictions. With the march which this disease, "the captain of the men of death," is making annually, it is of the greatest moment that any successful manner of combating the power of the disease be recognized by the profession. With such apparently fortunate results by use of these large doses of sulphate of quinin that Dr. Galbraith reports, one naturally feels an honest desire to know whether this method might be the sheet anchor of
THE 1932 THALLOTOXICOSIS OUTBREAK IN CALIFORNIA
Authors: JAMES C. MUNCH
Journal: JAMA (1933)

Following the exposure of human beings to various products containing thallium, prepared for rodenticidal or clinical use, a number of untoward effects have been reported during the last few years. In addition to alopecia, the principal effects reported have been stomatitis and gastro-enteritis, diarrhea and constipation, peripheral neuritis, retrobulbar neuritis and endocrinologic disturbances.<sup>1</sup>In 1924, an intensive study of the pharmacology of thallium was instituted by the Bureau of Biological Survey on animals which led to the development of an antidote for thallium poisoning and to definite information regarding its physiologic actions. "Thalgrain" was prepared by official agencies to contain 1 per cent of thallium sulphate and distributed in certain areas in ten counties in California for assistance in controlling ground squirrel infestation.<sup>2</sup>Following its use on a small scale in 1925, the amount of such material has been increased annually until 1928, since which time progressively smaller
Vitamin K1 Prophylaxis in the Newborn
Authors: T. J. Vietti
Journal: JAMA (1961)

The prophylactic use of vitamin K in the newborn has been abandoned by some physicians because of conflicting reports as to its efficacy and safety. In the present study vitamin K 1 was given either in doses of 5 mg. by mouth daily to the mother in the last month of pregnancy or in doses of 5 mg. intramuscularly to the infant at birth. A test series of 133 infants was treated prophylactically in this way. The contratest series consisted of 50 untreated infants. Among the 50, postcircumcision bleeding occurred 4 times and abnormal prothrombin values were observed 14 times. In the test group there was no postcircumcision bleeding, and the postnatal increase in prothrombin time was controlled without evidence of increased bilirubinemia or hemolysis.
Peripheral muscle weakness in COPD: where does it come from?
Authors: M I Polkey
Journal: Thorax (2003)

Do patients with frequent exacerbations of COPD have a more rapid rate of decline in quadriceps strength than those with stable disease?

Exertional dyspnoea is usually the main complaint of a patient with chronic obstructive pulmonary disease (COPD). Although this is partly a result of impaired pulmonary mechanics, exercise performance remains substantially reduced even if both lungs are replaced,1 which suggests that the lungs alone cannot explain exertional dyspnoea. Quadriceps myopathy is a feature of COPD. Histological examination of quadriceps biopsy tissues shows a switch towards fatiguable type II fibres2 and reduced oxidative enzymes. This in turn leads to anaerobic metabolism at lower work rates than in normal subjects.3 Lactic acid, generated as a byproduct of anaerobic metabolism, is buffered by bicarbonate with the generation of carbon dioxide. Patients with severe COPD cannot clear carbon dioxide by increasing their ventilation and thus treadmill walking may result in transient hypercapnia and acidosis.4 It is perhaps not surprising therefore that quadriceps weakness is demonstrably related to the utilisation of healthcare resources.5

The magnitude of quadriceps weakness is related to disease severity,6 but there is wide variation for a given forced expiratory volume in 1 second (FEV1) and a number of competing (though not mutually exclusive) theories have been proposed as contributors to quadriceps muscle weakness in COPD. The most …
Mask vs Intubation in Resuscitation
Authors: KENNETH F. MURPHY
Journal: Annals of Internal Medicine (1970)

Letters and Comments1 August 1970Mask vs Intubation in ResuscitationKENNETH F. MURPHYKENNETH F. MURPHYSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-73-2-338 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: The article entitled "Serial Blood Gas Studies During Cardiopulmonary Resuscitation" by Fillmore, Shapiro, and Killip (Ann Intern Med72:465-469, 1970) demonstrates conclusively the efficacy of endotracheal intubation over mouth-to-mouth resuscitation in lowering arterial PCO2and raising oxyhemoglobin saturation. The study is misleading, however, in implying that early intubation should be standard procedure in cardiopulmonary resuscitation. This may be true when the alternative is mouth-to-mouth ventilation, but with the availability of Ambu bags such a situation would rarely present itself. Moreover, in the unskilled hands of most medical house officers the attempt at intubation is generally either time-consuming... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1970Volume 73, Issue 2Page: 338-339KeywordsBloodCardiopulmonary resuscitationIntubationPartial pressure of carbon dioxidePulse oximetryResuscitation Issue Published: 1 August 1970 PDF DownloadLoading ...
BLINDNESS FROM INDUSTRIAL USE OF A 4 PER CENT. ADMIXTURE OF WOOD ALCOHOL
Authors: JOHN M. ROBINSON
Journal: JAMA (1918)

T. P., aged 29, a Greek of good physique, was referred, June 1, 1917, to my ophthalmic service at the Duluth Free Dispensary because of some difficulty which an optician had had in fitting the man with glasses. Complaint was made that objects looked smoky, and that the sight of the left eye had been failing for six weeks. Vision of the right eye was 20/30 and J.2; the color fields were much contracted; the field for white was moderately reduced on the nasal side, and greatly contracted on the temporal side. No definite scotoma could be located. The optic disk showed possibly a slight pallor. Vision of the left eye was reduced to fingers at 1 foot, except in the upper temporal quadrant, where fingers could be counted at 12 feet. The disk on this side was distinctly pink—a capillary congestion. Neither at this time nor later was there
Pancreatic Biopsy under Visual Control in Conjunction with Laparoscopy for Diagnosis of Pancreatic Cancer
Authors: M. Watanabe, Y. Takatori, K. Ueki, Y. Umekawa, H. Yoshida, T. Kobatake, H. Hirakawa, S. Fukumoto, Y. Shimada
Journal: Endoscopy (1989)

Two cases of histologically confirmed pancreatic cancer are reported. Histological diagnosis was obtained after pancreatic biopsy was carried out under visual control in conjunction with laparoscopy using pancreatic biopsy forceps designed by us. In Case 1, localized swelling of the pancreas was observed on abdominal ultrasonography (US) and computer tomography (CT) scan, and interruption of the main pancreatic duct was demonstrated by endoscopic retrograde cholangiopancreatography (ERCP). In Case 2, a pancreatic tumor was detected by abdominal US and CT scan, but ERCP findings were only those of chronic pancreatitis.
Emergency admission arrangements in hospital with inadequate resources.
Authors: S S Tachakra
Journal: BMJ (1980)

discussing the problems of working with the elderly, and the usefulness of bringing in aspects of normal life and using appropriate activities as a means of counteracting the apathy of institutional life.We hope and believe that this form of specific intervention by social workers has made a difference in some small way to the quality of life of the elderly people we worked with, and that there is much more urgent work to be done in this field.
Soft tissue sarcomas.
Authors: J N Davies
Journal: BMJ (1978)

<h3>Abstract</h3> The COVID-19 pandemic has highlighted that new diagnostic technologies are essential for controlling disease transmission. Here, we develop SHINE (SHERLOCK and HUDSON Integration to Navigate Epidemics), a sensitive and specific integrated diagnostic tool that can detect SARS-CoV-2 RNA from unextracted samples. We combine the steps of SHERLOCK into a single-step reaction and optimize HUDSON to accelerate viral inactivation in nasopharyngeal swabs and saliva. SHINE’s results can be visualized with an in-tube fluorescent readout — reducing contamination risk as amplification reaction tubes remain sealed — and interpreted by a companion smartphone application. We validate SHINE on 50 nasopharyngeal patient samples, demonstrating 90% sensitivity and 100% specificity compared to RT-PCR with a sample-to-answer time of 50 minutes. SHINE has the potential to be used outside of hospitals and clinical laboratories, greatly enhancing diagnostic capabilities.
Diagnostic Delays With Bacterial Meningitis-Reply
Authors: Markku J. T. Kallio
Journal: JAMA (1995)

In Reply.  —In our series of 325 children with bacterial meningitis, we found that a prior visit to a physician and thus a possible diagnostic delay did not result in a worse clinical condition on admission to hospital, in a poorer recovery during hospitalization, or an increase in the risk of death or persistent sequelae.  Dr Wenner emphasizes that the number of patents in our study is inadequate for any conclusions. He states that we should not have less than 187 000 patients to be able to say whether or not a difference of 1% exists between groups.  However, our study is not a randomized controlled trial but an observational study. The use of significance testing in observational studies can be and has been questioned. 1 Although we apply statistical tests and give P values, our conclusion is cautious, not straightforward acceptance of the null hypothesis.  While our 325 patients
THE FACTORS IN THE DEHYDRATION FOLLOWING PYLORIC OBSTRUCTION
Authors: James L. Gamble, S. Graham Ross
Journal: Journal of Clinical Investigation (1925)

DEHYDRATION FOLLOWING PYLORIC OBSTRUCTION their average normal concentrations in terms of acid-base equiva- lence.2As may be seen Na constitutes nearly all of the plasma base and Cl' is the chief factor on the acid side.The acid-base balance of this structure is preserved by the immediate and automatic adjust- CC. 0.1 N. per ioo Cc. of pIlama.
Immunosuppressive properties of sera and urine dialysates from kidney-graft recipients treated with azathioprine, prednisolone, and niridazole
Authors: B M Jones, M Bird, P Massey, D Millar, J J Miller, S Reeves, J R Salaman
Journal: BMJ (1977)

Niridazole, an antischistosomal agent, was given to renal transplant recipients in addition to azathioprine and prednisolone, as there is experimental evidence that this combination of drugs is highly immunosuppressive. Sera obtained from kidney-graft recipients during the first two weeks after transplantation were examined for their ability to inhibit the one-way mixed lymphocyte reaction (MLR). Sera from seven patients receiving azathioprine, prednisolone, and niridazole (triple-drug treatment), five patients receiving azathioprine and prednisolone, and two other patients treated with niridazole alone for schistosomiasis produced MLR inhibition by comparison with pretreatment (control) sera.A mean of 78% inhibition was observed with sera taken after one day's treatment with the three-drug combination, whereas this level of in-vitro immunosuppression occurred only after eight days of treatment with azathioprine and prednisolone. Niridazole alone produced an effect similar to azathioprine and prednisolone. Concentrated dialysate of urine from a patient receiving triple-drug treatment not only inhibited the MLR but also significantly prolonged the survival of heterotopic heart allografts in rats, whereas dialysate from the same patient after niridazole had been stopped gave less MLR inhibition and failed to prolong heart allograft survival.Since niridazole thus increased the in-vitro and in-vivo immunosuppressive action of azathioprine and prednisolone, we suggest that this triple-drug combination might be useful for preventing early acute kidney graft rejection.
DEVELOPMENT OF ACUTE EXFOLIATIVE DERMATITIS DURING ADMINISTRATION OF SULFATHIAZOLE
Authors: Mary Weinstein
Journal: JAMA (1941)

The cutaneous manifestations of sulfathiazole intoxication have been recently described by Volini, Levitt and O'Neil.<sup>1</sup>They reported an incidence of 3.9 per cent in a group of 180 cases. Urticarial, erythematous, macular, papular, nodular and purpuric eruptions were encountered; the nodular lesion probably represented the advanced stage of a toxic rash and has been the most serious lesion, having been associated with a fatal outcome in a high percentage of cases. Among 400 pneumonia patients treated with sulfathiazole reported from the Philadelphia General Hospital<sup>2</sup>the incidence of cutaneous rashes was 3.7 per cent. There were no cases of acute exfoliative dermatitis observed and to our knowledge there are no reports in the literature of this condition. It seems worth while that the following case be reported. <h3>REPORT OF CASE</h3><h3>History.—</h3> R. A., a Negro aged 38, admitted March 17, 1941 to the Philadelphia General Hospital in the
LF 15-0195 immunosuppressive agent enhances activation-induced T-cell death by facilitating caspase-8 and caspase-10 activation at the DISC level
Authors: Patrick Ducoroy, Olivier Micheau, Sylvain Perruche, Laurence Dubrez-Daloz, Daniel de Fornel, Patrick Dutartre, Philippe Saas, Eric Solary
Journal: Blood (2002)
A Randomized Trial of a Family Physician Intervention for Smoking Cessation
Authors: Douglas M. Wilson
Journal: JAMA (1988)

We assessed the impact of three conditions on one-year smoking cessation rates. Physicians in 70 community general practices were randomly allocated by practice to one of three groups: In the usual care group, smoking patients were to receive the care they normally would receive. In the gum only group, physicians were asked to speak to patients about smoking cessation and offer nicotine gum. In the gum plus group, physicians were trained in the experimental intervention. This intervention involved advice to stop smoking, the setting of a quit date, the offer of nicotine gum, and four follow-up visits. Smoking cessation was measured by self-report after one year and validated using saliva cotinine measures. Using a criterion of at least three months of abstinence, 8.8% of the patients of the trained physicians had stopped smoking at the one-year follow-up compared with 4.4% and 6.1% of the patients in the usual care and gum only groups, respectively.