tbuckley/cabot-search huggingface dataset:
Risk score would be more helpful
Authors: G. Murray
Journal: BMJ (1995)

<b>Background:</b> Substantial evidence of seatbelt efficacy has been shown by several studies, and it is widely recommended that motor vehicle occupants use properly fitted seat belts. However, some (but a heretofore unknown number of) countries with national seat belt laws permit various exemptions which may lower use rates. The aim of this study was to survey the variety of exemptions to national seat belt laws. <b>Methods:</b> This investigation relied on identifying respondents from national traffic safety agencies, other governmental and non-governmental organizations, Internet searches, personal contacts, and other sources. Questionnaires were deployed through a web based survey supplemented by email and postal versions. <b>Results:</b> Responses were received from 30 countries of which 28 (93.7%) had a national seat belt law. About two thirds (63.7%) of the 28 national laws applied to both front and back seat passengers. The leading exemption types included vehicles made before a certain year (n = 13), antique vehicles (n = 12), military vehicles (n = 11), buses (n = 9), and emergency vehicles (n = 8). Most responding countries reported one or more specific categories of individuals as exempt including those with medical exemptions (n = 20), taxi drivers (n = 11), police (n = 9), emergency medical personnel (n = 8), physically disabled people (n = 6), and pregnant women (n = 6). Out of 26 responses to the question regarding current level of enforcement, 42.3% felt enforcement was “very good or good” and 57.7% characterized it as “fair or poor”. <b>Conclusions:</b> This study represents one of the largest international traffic law surveys reported. Most national seatbelt laws offer perilous exemptions to a broad array of vehicle types and road user groups. These findings, coupled with concern over the level of enforcement in the majority of countries surveyed, suggest that international road safety efforts have a long way to go to improve coverage and enforcement of national seat belt laws.
1142-187 Three-dimensional echocardiographic and magnetic resonance assessment of the effect of telmisartan compared with carvedilol on left ventricular mass: A multicenter, randomized, controlled study
Authors: Domenico Galzerano, Luca Del Viscovo, Paolo Tammaro, Carlo Tedeschi, Roberto Breglio, Diana Lama, Antonio Cerciello, Bernardino Tuccillo, Paolo Capogrosso
Journal: Journal of the American College of Cardiology (2004)
Abstract 4445: Dual ALK and EGFR inhibition targets a mechanism of acquired resistance to the tyrosine kinase inhibitor crizotinib in ALK translocated lung cancer.
Authors: Norihiro Yamaguchi, Sohei Nakayama, Lorena L. de Figueiredo-Pontes, Susumu Kobayashi, Daniel B. Costa
Journal: Cancer Research (2013)

Abstract ABSTRACT Introduction: The multitargeted tyrosine kinase inhibitor (TKI) crizotinib is active against ALK translocated non-small-cell lung cancer (NSCLC); however acquired resistance invariably develops over time. ALK mutations have previously been implicated in only a third of resistant tumors. We sought to evaluate alternative mechanisms of resistance and preclinical strategies to overcome these in a cell line driven by EML4-ALK. Methods: We selected the NSCLC cell line NCI-H3122 (H3122: EML4-ALK E13;A20) and derived resistant variants that were able to grow in the presence of 1μM crizotinib. These were analyzed for ALK mutations, sensitivity to crizotinib in combination to other TKIs (imatinib, sorafenib, erlotinib and afatinib), and for activation of alternative tyrosine kinases. Results: All H3122 crizotinib resistant (CR) clones lacked mutations in the kinase domain of ALK. To evaluate if possible alternative kinases functioned as “bypass” tracks for downstream signaling activation in these resistance cells, we used a functional approach of dual ALK TKI (with crizotinib) with combinatory TKI inhibition to screen for possible targets. Crizotinib + sorafenib (BRAF, RET, PDGFR, VEGFR TKI) and crizotinib + imatinib (ABL, PDGFR, KIT TKI) were ineffective. In contrast, crizotinib + erlotinib (reversible EGFR TKI) and crizotinib + afatinib (irreversible EGFR/ERBB2 TKI) were able to inhibit the growth of H3122 CR clones, indicating potential EGFR activation as a mechanism of resistance. Analyses of phosho-receptor tyrosine kinase arrays demonstrated that CR clones had 5-25 times higher phospho-EGFR signal than H3122 parental cells did after the exposure to 1μM crizotinib, indicating phospho-EGFR was the most predominant phosphorylated signal in crizotinib-resistant cells. Conclusions: Using a functional approach of combining ALK and EGFR TKIs, we identified activation of EGFR as a mechanism of resistance to crizotinib in preclinical models of ALK translocated NSCLC. If EGFR activation is confirmed as a predominant mechanism of crizotinib resistance in patient-derived tumors, the use of crizotinib + EGFR TKIs should be tested in future clinical trials for this important cohort of NSCL Citation Format: Norihiro Yamaguchi, Sohei Nakayama, Lorena L. de Figueiredo-Pontes, Susumu Kobayashi, Daniel B. Costa. Dual ALK and EGFR inhibition targets a mechanism of acquired resistance to the tyrosine kinase inhibitor crizotinib in ALK translocated lung cancer. [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 4445. doi:10.1158/1538-7445.AM2013-4445
Spring Helps Research Integrity Report Resurface
Authors: Charles Marwick
Journal: JAMA (1996)

CORRECTING misconduct in science is the scientists' job. The government's role is to make sure that instances of misconduct, when they occur, are handled promptly and fairly and to step in only if the scientists' investigation fails. This, said Kenneth Ryan, MD, is the guiding principle behind the report by the Commission on Research Integrity. Ryan was chair of the 12-member commission chartered by Congress in 1993 to deal with allegations of fraud in federally supported scientific research. Ryan presented a summary of the commission's report during the annual meeting of the American Association for the Advancement of Science, held in Baltimore, Md. He is Kate Macy Ladd Professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School, Boston, Mass. The report was delivered to the Department of Health and Human Services (DHHS) and to Congress last November, but, Ryan noted, it has attracted little public attention. He credited
Effects of verapamil and propranolol on early afterdepolarizations and ventricular arrhythmias induced by epinephrine in congenital long QT syndrome
Authors: Wataru Shimizu, Tohru Ohe, Takashi Kurita, Mayumi Kawade, Yoshio Arakaki, Naohiko Aihara, Shiro Kamakura, Tetsuro Kamiya, Katsuro Shimomura
Journal: Journal of the American College of Cardiology (1995)
Cutaneous manifestations of Gaucher disease
Authors: J. GOLDBLATT, P. BEIGHTON
Journal: British Journal of Dermatology (1984)

We reviewed the cutaneous manifestations of type I non-neuropathic Gaucher disease in fifty South African patients. Characteristic changes such as diffuse pigmentation, easy tanning and flitting brown macules were found to be useful pointers to the diagnosis. Other cutaneous changes secondary to infiltration of the marrow and liver were common and important findings.
The Future of Research Funding in Academic Medicine
Authors: Eric G. Campbell
Journal: New England Journal of Medicine (2009)

Medical schools and teaching hospitals in the United States are essential producers of basic scientific and clinical knowledge that drives our supply of new medicines, devices, and other health care innovations. Today, the funding for this work is dwindling, rendering the current structure of the biomedical research enterprise unsustainable. Given the economic crisis, the fiscal and operational models of this enterprise must be restructured if the stability of academic institutions is to be maintained and our growing health care needs are to be met.The federal government is the single largest source of financial support for academic life-sciences research in . . .
MORAL ASPECTS OF MEDICAL PRACTICE
Authors: A. E. Clark-Kennedy
Journal: BMJ (1955)

<h3>Abstract</h3> The bulk high-throughput omics data contain signals from a mixture of cell types. Recent developments of deconvolution methods facilitate cell-type-specific inferences from bulk data. Our real data exploration suggests that the differential expression or methylation status are often correlated among cell types. Based on this observation, we develop a novel statistical method named CeDAR to incorporate the cell type hierarchy in cell-type-specific differential analyses in bulk data. Extensive simulation and real data analyses demonstrate that this approach significantly improves the accuracy and power in detecting cell-type-specific differential signals compared with existing methods, especially in low abundance cell types.
Immune Hemolytic Anemia and Renal Failure Due to Teniposide
Authors: Bahman Habibi, Manuel Lopez, Michel Serdaru, Alain Baumelou, Marcel Vonlanthen, René Marteau, Charles Salmon
Journal: New England Journal of Medicine (1982)

TENIPOSIDE (VM 26) is a semisynthetic derivative of podophyllotoxin (molecular weight, 657 daltons) that has been used for a decade in cancer chemotherapy, especially in lymphoma and brain tumors. The drug has been reported to cause anaphylactic reactions of unknown origin.1 This paper describes clinical and immunohematologic features of an antibody to teniposide that causes acute hemolysis and renal failure.Case HistoryTeniposide therapy was initiated in a 47-year-old man who had a relapse a few months after removal of a brain tumor. The drug was given monthly at a dose of 100 mg per day on Days 1 and . . .
A Study OF SOME FACTORS CONTROLLING THE NORMAL SUGAR CONTENT OF THE BLOOD
Authors: P. J. Cammidge, J. A. C. Forsyth, H. A. H. Howard
Journal: BMJ (1921)

n X symptoms to subside, we have to wait also for the recovery of the damaged cardiac muscle and adaptation of the heart to the'valvular lesions wllich are almost invariable in the rheumatic form of pericarditis.Six months spent in niursing the heart back to efficiency is a very small part of a lifetime, and you cannot go far wrong if you make each forward step a test, guided by the pulse, tlle apex beat, the cardiac outline, the temperature, and, above all, the general condition of the child.In conclusion, though I realize you already know much that I have commented upon, this lecture may help to recall to you that in the treatment of pericarditis in child- hood we must be prepared to display all our clinical know- ledge and that balance of judgement which it is so difficult to keep when pressed by urgent illness, complicated conditions.anxious parents, and possibly divergent-opinions op
Do coronary risk factors influence lesion morphology? A report from the 1985–1986 NHLBI PTCA registry
Authors: Stuart J Bresee, Alice K Jacobs, Ann Steenkiste, Seth D Bilazarian, Nicholas A Ruocco, Katherine M Detre, Thomas J Ryan, David P Faxon, None Registry Investigators
Journal: Journal of the American College of Cardiology (1991)
Abstract 1560: Loss-of-function JAK1 mutations reveal a new role of protein tyrosine kinase mutations in human cancer
Authors: Yuan Ren, Yonghong Zhang, Richard Z. Liu, David A. Fenstermacher, Kenneth L. Wright, Jamie K. Teer, Jie Wu
Journal: Cancer Research (2014)

Abstract Protein tyrosine kinases (PTKs) have been perceived mostly as proto-oncogenes. PTK mutations that have been studied in human cancer usually have increased kinase activities to drive malignant phenotypes. Thus, these PTK mutations are gain-of-function (GOF) mutations. By analyzing the targeted exome sequencing data of 3,274 human tumors from 48 different tissues in the Total Cancer Care (TCC) tumor bank, we have found JAK1 truncating mutations in 36 of 635 gynecologic tumors. The highest JAK1 truncating mutation rate (9.5%) was found in endometrial cancer. These truncating mutations result in the loss of the JAK1 PTK domain. Thus, they are loss-of-function (LOF) mutations. JAK1 truncating mutations in the Cancer Cell Line Encyclopedia (CCLE) databank also occur most often in endometrial cancer cell lines. Analysis of mutation sites identified three mutation hot spots. Re-sequencing of cancer cell lines, primary tumors, and matched normal tissues confirmed JAK1 mutations and revealed that these JAK1 mutations are somatic. JAK1 and JAK2 mediate interferon (IFN)-γ-regulated tumor immune surveillance. Recurrent JAK2 LOF mutations were also found in TCC tumors but at lower rates. Similar to JAK1, the highest rate of LOF JAK2 mutations was found in endometrial/uterine cancer. No JAK1 or JAK2 truncating mutation was identified in 130 samples from hematological malignancies. Functional assays show that JAK1-deficient cancer cells are defective in IFN-γ-induced expression of tumor antigen processing machinery proteins LMP2 and TAP1 and cell surface expression of HLA molecules. These data identify recurrent JAK1 deficiency in endometrial cancer that could impair tumor antigen presentation by the MHC class I complex to cytotoxic T lymphocytes. Our findings suggest that JAK1 is a PTK tumor suppressor and reveal a novel mechanism of tumor immune evasion via LOF mutations in a PTK. Citation Format: Yuan Ren, Yonghong Zhang, Richard Z. Liu, David A. Fenstermacher, Kenneth L. Wright, Jamie K. Teer, Jie Wu. Loss-of-function JAK1 mutations reveal a new role of protein tyrosine kinase mutations in human cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1560. doi:10.1158/1538-7445.AM2014-1560
PECULIAR REACTIONS BETWEEN THE FIFTH AND SEVENTH CRANIAL NERVES
Authors: W. T. COUGHLIN
Journal: JAMA (1923)

Paralysis of the muscles of expression of the same side of the face is a not uncommon sequel of section of the root of the fifth cranial nerve, also of ganglionectomy as practiced for the cure of major trigeminal neuralgia, and it has occurred frequently as a sequel of deep alcohol injections. Although sometimes this paralysis is very marked, it fortunately seems to be always temporary; its occurrence, therefore, from a practical standpoint, is a matter not worth much consideration.  Various theories have been put forward to account for the paralysis, but it must be understood that so far they are still theories, as its cause is not definitely known. It is thought by some to be due to an error in technic; that in some way the seventh nerve is injured during the operation. In the days when it was customary to cut the zygoma and pull down the
Whole body irradiation combined with adoptive T cell transfer results in regression of high-grade intraepithelial neoplasia and long-term persistence of tumor-specific CD8+ T cells in TRAMP mice
Authors: Lindsay K Ward-Kavanagh, Timothy K Cooper, Todd D Schell
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Lymphodepleting whole body irradiation (WBI) can enhance adoptive T cell transfer-mediated tumor regression in a variety of experimental models and a subset of patients. We investigated the potential of this approach to impact established prostate cancer using the clinically
Salicylate Intoxication Treated with Intermittent Positive-pressure Respiration
Authors: S. Freier, B. W. Neal, H. I. A. Nisbet, G. J. Rees, F. Wilson
Journal: BMJ (1957)

The returns of the Registrar-General for England and Wales indicate that in this country aspirin and its derivatives remain an important cause. of death from poisoning in children. During te three years 1950-2, 21 children lost their lives in this manner.In the United
SP0154 The IL-1 family in inflammation and human disease
Authors: K. Mills
Journal: Annals of the Rheumatic Diseases (2013)

IL-1 is one of a family of cytokines that include IL-1α, IL-1β, IL-18, IL-33, IL-35, IL-36, IL-37 and the anti-inflammatory cytokines IL-1Ra and IL-136Ra that play a vital role in inflammatory responses during infection and in autoimmune diseases. IL-1 was originally called endogenous pyrogen, through its ability to induce fever and was later assigned additional biological functions, including neutrophil recruitment and lymphocyte activation and is now recognized as major mediator of inflammation. Excessive IL-1β drives the recurrent episodes of fever and systemic inflammation in autoinflammatory diseases, such as gout, familial cold autoinflammatory syndrome and Muckle-Wells syndrome. IL-1β, together with tumor necrosis factor-α (TNF-α) and IL-6, also has a key role in the pathology of many autoimmune diseases, including rheumatoid arthritis and multiple sclerosis, caused by uncontrolled pathogenic T cell and antibody responses to self antigens. IL-1β and IL-18 require cleavage by caspase-1 in the inflammasome to generate the mature active cytokines. IL-1β, IL-1α or IL-18 in combination with IL-23 can induce IL-17 production by γδ T cells without T cell receptor (TCR) engagement. IL-1β and IL-23 can also synergise to induce IL-17 production by iNKT cells and innate lymphoid cells (ILCs). Furthermore, CD4<sup>+</sup>αβ effector memory T cells secrete IL-17 in response to IL-23 in combination with either IL-1β or IL-18, in the absence of any TCR stimulation. The early IL-17 produced by innate cells induces recruitment of neutrophils to the site of infection, stimulates local epithelial cells to secrete anti-microbial proteins and promotes production of matrix metalloproteinases. Caspase-1 processed IL-1 family cytokines therefore play a vital role in the innate immune response and induction of IL-17 from innate immune cells which functions to fight infections and promote autoimmunity. <h3>Disclosure of Interest</h3> K. Mills Shareholder of: Opsona Therapeutics and TriMod Therapeutics
Feasibility and Response to Induction Chemotherapy Intensified With High-Dose Methotrexate for Young Children With Newly Diagnosed High-Risk Disseminated Medulloblastoma
Authors: Susan N. Chi, Sharon L. Gardner, Adam S. Levy, Edmond A. Knopp, Douglas C. Miller, Jeffrey H. Wisoff, Howard L. Weiner, Jonathan L. Finlay
Journal: Journal of Clinical Oncology (2004)

Purpose To evaluate the feasibility of and response rate to an intensified induction chemotherapy regimen for young children with newly diagnosed high-risk or disseminated medulloblastomas. Patients and Methods From January 1997 to March 2003, 21 patients with high-risk or disseminated medulloblastoma were enrolled. After maximal surgical resection, patients were treated with five cycles of vincristine (0.05 mg/kg/wk × three doses per cycle for three cycles), cisplatin (3.5 mg/kg per cycle), etoposide (4 mg/kg/d × 2 days per cycle), cyclophosphamide (65 mg/kg/d × 2 days per cycle) with mesna, and methotrexate (400 mg/kg per cycle) with leucovorin rescue. Following induction chemotherapy, eligible patients underwent a single myeloablative chemotherapy cycle with autologous stem-cell rescue. Results Significant toxicities of this intensified regimen, including gastrointestinal and infectious toxicities, are described. Among the 21 patients enrolled, there were 17 complete responses (81%), two partial responses, one stable disease, and one progressive disease. The 3-year event-free survival and overall survival are 49% (95% CI, 27% to 72%) and 60% (95% CI, 36% to 84%), respectively. Conclusion This intensified induction chemotherapy regimen is feasible and tolerable. With the majority of patients with disseminated medulloblastoma having M2 or M3 disease at diagnosis, the encouraging high response rate of this intensified induction regimen suggests that such an addition of methotrexate should be explored in future studies.
Effects of Obesity on Perceptual and Mechanical Responses to Bronchoconstriction in Asthma
Authors: Athavudh Deesomchok, Thomas Fisher, Katherine A. Webb, Josuel Ora, Yuk-Miu Lam, M. Diane Lougheed, Denis E. O'Donnell
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

The influence of obesity on the perception of respiratory discomfort during acute bronchoconstriction in asthma is unknown.We hypothesized that the respiratory impairment associated with an increased body mass index (BMI) would predispose to greater perceived symptom intensity during acute airway narrowing. We therefore compared relationships between induced changes in dyspnea intensity and lung function during methacholine (MCh) bronchoprovocation in obese (OBA) and normal-weight (NWA) individuals with asthma of mild to moderate severity.High-dose MCh challenge tests to a maximum 50% decrease in FEV(1) were conducted in 51 NWA (BMI, 18.5-24.9 kg/m(2); 29% male) and 45 OBA (BMI, 30.1-51.4 kg/m(2); 33% male) between 20 and 60 years of age. Serial spirometry, inspiratory capacity (IC), plethysmographic end-expiratory lung volume (EELV) and dyspnea intensity using the Borg scale were measured throughout bronchoprovocation.Spirometry and airway sensitivity were similar in both groups; baseline EELV was lower (P < 0.0005) and IC was higher (P = 0.007) in OBA compared with NWA. From baseline to PC(20), EELV increased more in OBA (20% predicted) than NWA (13% predicted) (P = 0.008) with concomitant greater reductions in IC (P < 0.0005). Dyspnea ratings were not different for a given FEV(1) or IC across groups. By mixed effects regression analysis, relationships between induced dyspnea and changes in lung function parameters were not influenced by BMI, sex, or their interaction.Perceptual responses to MCh-induced bronchoconstriction and lung hyperinflation were similar in obese and normal-weight individuals with asthma despite significant group differences in baseline lung volumes.
Nanoparticles-based multi-adjuvant whole cell tumor vaccine for cancer immunotherapy
Authors: Shi-Ying Liu, Wei Wei, Hua Yue, De-Zhi Ni, Zhan-Guo Yue, Shuang Wang, Qiang Fu, Yue-Qi Wang, Guang-Hui Ma, Zhi-Guo Su
Journal: Biomaterials (2013)