tbuckley/cabot-search huggingface dataset:
NHS England pulls funding from 25 cancer treatments
Authors: Z. Kmietowicz
Journal: BMJ (2015)

<h3>Abstract</h3> The study of viral communities has revealed the enormous diversity and impact these biological entities have on a range of different ecosystems. These observations have sparked widespread interest in developing computational strategies that support the comprehensive characterization of viral communities based on sequencing data. Here we introduce VIRify, a new computational pipeline designed to provide a user-friendly and accurate functional and taxonomic characterization of viral communities. VIRify identifies viral contigs and prophages from metagenomic assemblies and annotates them using a collection of viral profile hidden Markov models (HMMs). These include our manually-curated profile HMMs, which serve as specific taxonomic markers for a wide range of prokaryotic and eukaryotic viral taxa and are thus used to reliably classify viral contigs. We tested VIRify on assemblies from two microbial mock communities and a large metagenomics study. The results showed that VIRify was able to identify sequences from both prokaryotic and eukaryotic viruses, and provided taxonomic classifications from the genus to the family rank with an accuracy of at least 95.5%. In addition, VIRify allowed the detection and taxonomic classification of a range of prokaryotic and eukaryotic viruses present in 243 marine metagenomic assemblies. Overall, we demonstrate that VIRify is a novel and powerful resource that offers an enhanced capability to detect a broad range of viral contigs and taxonomically classify them.
Chemical induction of oncogene mutations and growth factor activity in mouse skin carcinogenesis.
Authors: B Bailleul, K Brown, M Ramsden, R J Akhurst, F Fee, A Balmain
Journal: Environmental Health Perspectives (1989)

The goal of understanding the molecular basis of human tumor development has been greatly facilitated by the use of animal model systems in which the etiology of tumor development can be carefully controlled. Environmental chemicals, either naturally occurring or artificially produced, are thought to make a major contribution to the human tumor burden. Many of the concepts of multistage carcinogenesis have been developed and refined using the mouse skin model system and the work described in this article has been carried out in an attempt to analyze the molecular changes that are associated with the initiation of tumor development, the selection of initiated cells to form papillomas, or the progression of premalignant tumors to carcinoma. We have analyzed a number of skin tumors induced in mice by a two-stage initiation and promotion protocol and have detected a high frequency of c-ras oncogene mutations in this system. The mutation found in each case correlates well with the known reactivity of the carcinogens used. It has also been shown that where ras activation occurs this represents an early event in the tumor model system. Transforming growth factor beta is induced in mouse skin by tumor promoter treatment and may therefore play a role in the selection of initiated cells to form papillomas. Additional events, some of which involve the loss of normal ras alleles and possibly tumor suppressor genes, appear to take place at a later stage of carcinogenesis.
The novel synthetic immune response modifier R-848 (Resiquimod) shifts human allergen-specific CD4+ TH2 lymphocytes into IFN-γ–producing cells
Authors: Francesca Brugnolo, Salvatore Sampognaro, Francesco Liotta, Lorenzo Cosmi, Francesco Annunziato, Cinzia Manuelli, Paolo Campi, Enrico Maggi, Sergio Romagnani, Paola Parronchi
Journal: Journal of Allergy and Clinical Immunology (2003)
BROWN ADIPOSE TISSUE, β3-ADRENERGIC RECEPTORS, AND OBESITY
Authors: B. B. Lowell, MD, PhD, J. S. Flier, MD
Journal: Annual Review of Medicine (1997)

Brown adipose tissue is distinguished by its unique capacity for uncoupled mitochondrial respiration, which is highly regulated by sympathetic nerve activity. Because of this, energy expenditure in brown fat is capable of ranging over many orders of magnitude. The fact that the function of brown adipose tissue is impaired in obese rodents and that transgenic mice with decreased brown fat develop obesity demonstrates the importance of brown fat in maintaining nutritional homeostasis. However, the role of brown fat in humans is less clear. beta 3-Adrenergic receptors are found on brown adipocytes, and treatment with beta 3-selective agonists markedly increases energy expenditure and decreases obesity in rodents. Whether beta 3-selective agonists will be effective anti-obesity agents in humans is presently under investigation.
Serum Creatine Kinase Screening for Susceptibility to Malignant Hyperthermia
Authors: E. H. Flewellen
Journal: JAMA (1986)

<h3>To the Editor.—</h3> In the Feb 14 issue, Paasuke and Brownell<sup>1</sup>reported that serum creatine kinase levels routinely determined before muscle biopsy for caffeine contracture testing for susceptibility to malignant hyperthermia (MH) had no diagnostic value. Creatine kinase values were uniformly within the normal range unless the patient had a diagnosed clinical myopathy. I wish to report a different result. While I was associated with the University of Texas Medical Branch, Galveston, my colleague, T. E. Nelson, and I established a diagnostic laboratory offering halothane-caffeine contracture testing for MH susceptibility.<sup>2</sup>A review of my records indicates that 113 patients had determination of their creatine kinase level prior to biopsy. The results are shown in the Table. My experience disagrees with that of Paasuke and Brownell. Patients who are MH susceptible frequently have an elevated serum creatine kinase level before biopsy. A serum creatine kinase screen of the MH
How Do We Continue Treatment in Patients With Type 2 Diabetes When Therapeutic Goals Are Not Reached With Oral Antidiabetes Agents and Lifestyle? Incretin versus insulin treatment
Authors: Baptist Gallwitz, Reinhard G. Bretzel
Journal: Diabetes Care (2013)

The pandemic of type 2 diabetes necessitates early and effective treatment to delay or prevent micro- and macrovascular complications associated with diabetes (1–3). However, the majority of patients with type 2 diabetes do not reach their therapeutic goals as a result of insufficient treatment. The cardiovascular mortality risk is increased, and 75% of patients with type 2 diabetes die of cardiovascular events. Type 2 diabetes is the main cause of end-stage renal disease and dialysis in many countries (4). The vascular complication risk can be lowered by improved metabolic control (2,3). However, further important treatment goals such as body weight reduction or the prevention of hypoglycemia are seldom accomplished.

In type 2 diabetes, a stepwise escalation of therapy is suggested along the course and progression of the disease. Metformin is widely accepted as the first-line therapy, but owing to partly lacking evidence, with regard to further therapeutic steps there is room for various individual treatment choices. Recently, a Position Statement by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) tried to value and position second- and third-line therapies according to their efficacy, side effects, hypoglycemia incidence, body weight development, and costs (5).

Adding another oral agent to metformin in order to escalate therapy when necessary presently gives the choice of sulfonylureas, glinides, dipeptidyl peptidase (DPP)-4 inhibitors, pioglitazone, and α-glucosidase inhibitors. The efficacy of these agents as add-on medication to metformin is only modest, and on average an additional HbA1c reduction of ~0.5–1% can be expected. Furthermore, the treatment with sulfonylureas, glinides, and pioglitazone is associated with body weight gain. Sulfonylurea and glinide therapy is also associated with a risk of hypoglycemia. α-Glucosidase inhibitors predominantly lower postprandial hyperglycemia and therefore show less HbA1c reduction in most studies. …
Detection of a Platelet-Agglutinating Factor in Thrombotic Thrombocytopenic Purpura
Authors: JOHN G. KELTON
Journal: Annals of Internal Medicine (1984)

A sensitive and specific test was used to identify a platelet-agglutinating factor in sera from patients with thrombotic thrombocytopenic purpura. Serum from patients plus a preparation rich in large multimers of factor VIII: von Willebrand factor were added to target platelets, and agglutination occurred in 41 of 48 samples. Edetic acid, heparin, or heating, but not aspirin, monomeric IgG, or dansylarginine N-(3-ethyl-1,5-pentanediyl)amide inhibited the platelet-agglutinating factor. In-vitro agglutination requires the presence of a platelet-agglutinating factor and large multimers of von Willebrand factor. High concentrations of either component lowers the amount of the other required for platelet agglutination. Some patients may be more susceptible to the agglutinating factor because of a congenital or acquired abnormality in processing unusually large multimers of von Willebrand factor or because of infections or inflammatory disorders that lead to increased synthesis of large multimers of von Willebrand factor.
Smoking and prognosis after acute myocardial infarction in the thrombolytic era (Israeli thrombolytic national survey)
Authors: Shmuel Gottlieb, Valentina Boyko, Doron Zahger, Jonathan Balkin, Hanoch Hod, Benyamin Pelled, Shlomo Stern, Solomon Behar
Journal: Journal of the American College of Cardiology (1996)
ON EXALTATION OF BACTERIAL VIRULENCE BY PASSAGE IN VITRO
Authors: E. A. Shaw
Journal: BMJ (1903)

BACTERIAL VIRULENCE.[MAY 9, * 9 0 3 .followed in the case where the inoculation is successful by the maintenance of a higher base line of immunity.2. We have seen that the inoculation of an excessive dose may involve a risk, in particular, the risk of an undue pro- longation of the negative phase.3. We have seen that the inoculation of a series of doses of a vaccine will, in the case where the inoculations -are un-
A phase I dose escalation study of oral c-MET inhibitor tivantinib (ARQ 197) in combination with gemcitabine in patients with solid tumors
Authors: S. Pant, M. Saleh, J. Bendell, J.R. Infante, S. Jones, C.D. Kurkjian, K.M. Moore, J. Kazakin, G. Abbadessa, Y. Wang, Y. Chen, B. Schwartz, L.H. Camacho
Journal: Annals of Oncology (2014)
Care for people with learning disabilities is to be audited
Authors: Madeleine Brettingham
Journal: BMJ (2006)

England's Healthcare Commission is to investigate the standards of all NHS trusts that provide services for people with learning disabilities, after a scathing report into the standard of services in Cornwall was published.

The Healthcare Commission's head of investigations, Nigel Ellis, said that every trust in England would need to prove that its care homes and accommodation met acceptable standards or would face a full scale investigation.

“I can say with certainty that learning disabilities services do not have the priority given to them that they need,” Mr Ellis said. “We will be carrying out an audit to give us a clearer picture. There's a risk that …
The Essential Book of Traditional Chinese Medicine
Authors: Steven H. Fox
Journal: JAMA (1989)

These two volumes present for a Western audience an orthodox Chinese formulation of the basis of traditional Chinese medicine. They are the product of an international collaborative effort begun in 1980 by the People's Medical Publishing House of the Ministry of Public Health (Beijing) and the United States—China Educational Institute (San Francisco, Calif), with the financial support of the Educational Foundation of America (Westport, Conn). The book reflects a great deal of work not only by the author Liu Yanchi, of the faculty of the Beijing College of Traditional Chinese Medicine, but also by a group of about 10 highly proficient translators and editors on both sides of the Pacific who did a wonderful job of rendering the Chinese original into readable English. Their success in translating and presenting the material is a mixed blessing. In other, less careful English-language works on traditional Chinese medicine, the imprecision and impenetrability of
Training Primary Care Physicians for the 21st Century
Authors: John P. Geyman
Journal: JAMA (1986)

THE TITLE of this article could well be "The Primary Care Problem Revisited." We are still struggling with the predictable sequelae of an oversupply of specialists and a shortage of primary care physicians despite serious attempts to address the problem. It is now 20 years since the publication of three major national reports that together served as the impetus for the development of family practice: the Millis, Willard, and Folsom reports.<sup>1-3</sup> Each chronicled the increasing deficit of generalist physicians trained and committed to the practice of continuing, comprehensive, and personal health care. They called for redirection of the nation's medical education system to train larger numbers of generalist physicians. It is 16 years since the formation of the American Board of Family Practice in 1969 and more than ten years since the initiation of federal grants to encourage the training of increased numbers of family physicians, general internists, and
Elevated Serum Inhibin Concentrations in Postmenopausal Women with Ovarian Tumors
Authors: David L. Healy, Henry G. Burger, Pamela Mamers, Tom Jobling, Mohan Bangah, Michael Quinn, Peter Grant, Arthur J. Day, Robert Rome, James J. Campbell
Journal: New England Journal of Medicine (1993)

Inhibin is an ovarian hormone that inhibits the secretion of follicle-stimulating hormone (FSH) by the anterior pituitary gland. Women with granulosa-cell tumors of the ovary have elevated serum inhibin concentrations, but whether the concentrations are increased in women with other ovarian tumors is unknown.
Italian police investigate GSK Italy for bribery
Authors: F. Turone
Journal: BMJ (2003)

The top management of the Italian branch of GlaxoSmithKline (GSK) is under investigation together with more than 2900 physicians, most of whom are general practitioners.

Based on the preliminary conclusions of an inquiry by police, who collected more than 13000 hours of phone conversations in 15 Italian regions and seized several computers, 72 people have been charged with corruption (37 employees of GSK Italy and 35 physicians and health service managers).

In addition, 80 sales representatives and managers are accused of illicitly compensating doctors for agreeing to prescribe or recommend to colleagues the …
Association of Diagnostic Coding With Trends in Hospitalizations and Mortality of Patients With Pneumonia, 2003-2009
Authors: Peter K. Lindenauer, Tara Lagu, Meng-Shiou Shieh, Penelope S. Pekow, Michael B. Rothberg
Journal: JAMA (2012)

A LEADING CAUSE of morbidity and mortality among US adults, resulting in more than 1 million annual hospital admissions and accounting for more than $10.5 billion in aggregate costs. 1,2Given its public health significance, pneumonia has been the target of quality improvement activities for nearly 2 decades.This began with the publication of clinical practice guidelines in the early 1990s, 3 was followed by a series of statewide and national quality improvement initiatives, 4 and more recently has included public reporting and pay-for-performance programs led by the Joint Commission and the Centers for Medicare & Medicaid Services (CMS) and other payers. 5,6hese efforts have been associated with favorable trends in adherence to recommended processes of care, 7-10 including the choice and timely administration of antibiotics.At the same time, several epidemiologic analyses have reported that survival among pneumonia patients appears to be improving, suggesting that clinical advances, improvements in health care quality, or both are having beneficial effects. 11-14Although the decline in pneumonia mortality may reflect real improvements in clinical outcomes, in the absence of any
Neonatal mortality almost halved in India between 1990 and 2012
Authors: C. Travasso
Journal: BMJ (2014)

<h3>Abstract</h3> The global battle against the Covid-19 pandemic relies strongly on the human defence of antibody, which is assumed to bind the antigen’s Receptor Binding Domain with its Hypervariable Region. Due to the similarity to other viruses such as SARS, however, our understanding of the antibody-virus interaction has been largely limited to the genomic sequencing, which poses serious challenges to the containment, vaccine exploration and rapid serum testing. Based on the physical/chemical nature of the interaction, infrared spectroscopy was employed to reveal the binding disparity, when unusual temperature dependence was discovered from the 1550cm<sup>-1</sup> absorption band, attributed to the hydrogen bonds by carboxyl/amino groups, binding the SARS-CoV-2 spike protein and closely resembled SARS-CoV-2 or SARS-CoV-1 antibodies. The infrared absorption intensity, associated with the number of hydrogen bonds, was found to increase sharply between 27°C and 31°C, with the relative absorbance matches at 37°C the hydrogen bonding numbers of the two antibody types (19 vs 12). Meanwhile the ratio of bonds at 27°C, calculated by thermodynamic exponentials rather than by the layman’s guess, produces at least 5% inaccuracy. As a result, the specificity of the SARS-CoV-2 antibody will be more conclusive beyond 31°C, instead of at the usual room temperature of 20°C - 25°C, when the vaccine research and antibody diagnosis would likely be undermined. Beyond genomic sequencing, the temperature dependence, as well as the bond number match at 37°C between relative absorbance and the hydrogen bonding numbers of the two antibody types, are not only of clinical significance in particular, but also of a sample for the physical/chemical understanding of the vaccine-antibody interactions in general.
Splenic Scintiscanning in the Preoperative Diagnosis of Subcapsular Hematoma
Authors: Louis Wener, C. D. Boyle
Journal: New England Journal of Medicine (1967)

AFTER splenic trauma a hematoma may reabsorb if it is small and may also undergo liquefaction, with subsequent cyst formation.1 In a certain number of cases it may slowly enlarge and subsequently rupture through the capsule, provoking the catastrophic abdominal picture of a ruptured spleen.Since the hematoma displaces the normal splenic pulp, the presence of such a lesion should produce a filling defect on the splenic scintiscan – even when other diagnostic criteria are lacking. A case recently seen at this Hospital afforded an ideal opportunity to test this thesis.Case ReportA 27-year-old man fell from a 7 . . .
Abstract 703: Verification of a novel approach to identify disease mechanisms in breast cancer patient subsets and application of this approach to indicating and characterizing tamoxifen resistance
Authors: David A. Drubin, Ty M. Thomson, Jennifer S. Park, Michael Macoritto, David de Graaf, Renee D. Kenney
Journal: Cancer Research (2012)

Abstract Breast cancer is a heterogeneous disease that can be divided into distinct clinical and molecular subtypes. Key biomarkers such as the expression of HER2 or ER serve as a basis for subdividing the disease into distinct clinical entities and to distinguish patients who will most likely respond to specific targeted therapies, such as Herceptin and tamoxifen, respectively. Further understanding the molecular mechanistic differences among and within the breast cancer subtypes can facilitate the identification of treatment regimens that can be even more tailored to an individual's disease. If such a strategy is implemented, efficacy rates for cancer treatments can be improved, and more importantly, patients will be spared from any collateral effects of those treatments that will not combat their specific disease. We have taken a systems biology approach to segregate breast cancer patients into subgroups by semi-quantitatively evaluating the literature-derived molecular gene expression footprints of over 2100 mechanisms in our Knowledgebase. This approach effectively enables the stratification of breast cancer patients by their individual levels of signaling amplitude for these mechanisms. Using publicly available breast cancer data sets from GEO, we validated the stratification capability of these inferred mechanism activities against immunohistochemical staining for ER and HER2, and sequencing-based identification of TP53 mutation. In addition, applying this semi-quantitative evaluation of mechanism molecular footprints based on gene expression data from ER+ breast cancer patients before tamoxifen treatment (GSE17705), we developed a tamoxifen-sensitivity classifier a priori of knowledge of clinical outcome. This classifier enabled prediction of 16 of the 19 patients from an independent test set (GSE6532) who had gone on to develop distant metastases. Beyond identifying specific breast cancer sub-groups, which has been well established by clustering sets of genes, the systems biology-based approach presented here enables us to identify the specific mechanisms defining the separation of patient groups, and offers a means of either selecting the right patient population for a drug candidate or indicating additional/alternative disease pathways that could be targeted for clinical efficacy. This strategy is universal and can be applied to a variety of other cancers and diseases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 703. doi:1538-7445.AM2012-703
Epidemic intelligence thrives on mystery
Authors: Bruce B. Dan
Journal: JAMA (1983)

When they race around Emory University's presidential estate, they are perhaps the most select group of cross-country runners in the world. Hailing from as far away as the jungles of Jakarta, the valleys of Ouagadougou, Upper Volta, and the streets of São Paulo, 150 entrants compete over the course. But the runner who crosses the finish line first is not the winner. Instead, in keeping with the group's precision in predicting epidemics around the world, the winner is the person who can most accurately predict his or her time over the meticulously measured 3,218.688-meter "EIS Prediction Run." EIS stands for Epidemic Intelligence Service, and the runners are all present or former members of this elite investigative corps of the Centers for Disease Control (CDC) in Atlanta (<i>JAMA</i>MEDICAL NEWS 1979;241:2776-2782). In the last few years, EIS officers have been responsible for large parts of such major achievements as determining the