tbuckley/cabot-search huggingface dataset:
General Principles of the Laboratory Diagnosis of Viral Infections
Authors: F. S. Cheever
Journal: New England Journal of Medicine (1947)

VIRUSES may be defined as ultramicroscopic agents, usually filterable, that are unable to propagate themselves in the absence of living cells and that are frequently the cause of clinical disease in man. This definition does not set off viruses sharply from certain bacteria; in fact, the current view is that "viruses represent the degenerate descendants of larger pathogenic micro-organisms."1 Laboratory procedures for the specific diagnosis of disease due to bacterial agents are well known and standardized, and can usually be handled satisfactorily by the average hospital laboratory. The identification of virus agents, which is carried out along the same general . . .
Effect of low-load eccentric training before high-intensity eccentric exercise on delayed onset muscle soreness, revealed by c-fos expression in the spinal dorsal horn in rats
Authors: T Munehiro, K Kitaoka, H Tsuchiya
Journal: British Journal of Sports Medicine (2011)

Background Delayed onset muscle soreness (DOMS) occurs after unaccustomed exercise and is particularly associated with high-intensity eccentric exercise. Eccentric exercise is reported to have a protective effect against DOMS caused by subsequent eccentric exercise. Since objective assessment of pain is difficult, only limited experimental studies on DOMS and a few studies on pain prevention in DOMS have been performed. Objective To examine the hypothesis that performing a low-load eccentric exercise before the high-intensity exercise could reduce the pain associated with DOMS. Design Experimental study. Interventions 36 male Wistar rats were divided into five groups: rats that received muscular compression only (Comp); those that performed high-intensity eccentric exercise only (HE); those that received muscular compression 3, 24, 48, and 96 h after high-intensity eccentric exercise (HE+Comp/3, 24, 48, and 96 h); those that received muscular compression 48 h after a single low-load eccentric exercise (LE); and those that underwent a week of low-load eccentric training before starting high-intensity eccentric exercise, which was followed by muscular compression 48 h later (LET). Main outcome measurements Immunohistochemistry was used to determine c-fos expression in the spinal dorsal horn, and change in the tenderness of the exercised muscle was determined from c-fos expression. Results In the HE+Comp/48 h rats, the total number of c-fos-positive neurons at the L2 segment was significantly greater than that at the L2 segment in the Comp and HE rats. A week of low-load eccentric training resulted in a decreased number of c-fos-positive neurons compared with the HE+Comp/48 h rats. Conclusions The increase in c-fos-positive neurons in the dorsal horn indicated the presence of muscle tenderness. Our data suggest that muscle tenderness occurs in muscles for which high-intensity eccentric exercise has been applied 48 h ago; this tenderness is reduced when low-load eccentric training is performed before high-intensity eccentric exercise.
Deploying Ibrutinib to Lung Cancer: Another Step in the Quest Towards Drug Repurposing
Authors: E. B. Haura, U. Rix
Journal: JNCI Journal of the National Cancer Institute (2014)

Exploiting the inherent promiscuity of drugs can enable recognition of important “off-target” effects that can be leveraged to repurpose drugs toward medical conditions not originally intended. Perhaps the classic example is the repurposing of imatinib, originally intended for breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL)-driven chronic myelogenous leukemia (CML), toward mast/stem cell growth factor receptor (KIT)-driven gastrointestinal stromal tumor (GIST) tumors (1). Compounds that have already demonstrated safety and utility in one disease can be rapidly redirected toward another disease entity, thereby quickening the pace of clinical trial development and proof of benefit from compounds. It is under this context that the report by Gao and colleagues (2) is important. This group took advantage of the recent US Food and Drug Administration (FDA) approval of ibrutinib, a small molecule tyrosine kinase inhibitor with activity against the Bruton tyrosine kinase and efficacy in mantle cell lymphoma (3). Previous studies had demonstrated that other tyrosine kinases,
Predictive Impact of Urokinase-Type Plasminogen Activator
Authors: Peggy Manders, Vivianne C. G. Tjan-Heijnen, Paul N. Span, Nicolai Grebenchtchikov, John A. Foekens, Louk V. A. M. Beex, C. G. J. (Fred) Sweep
Journal: Cancer Research (2004)

One of the most thoroughly studied systems in relation to its prognostic relevance in patients with breast cancer, is the plasminogen activation system. This system comprises of, among others, the urokinase-type plasminogen activator (uPA) and its main inhibitor (PAI-1). In this study we investigated whether the uPA:PAI-1 complex is associated with the responsiveness of patients with primary breast cancer to adjuvant systemic therapy. Quantitative enzyme-linked immunosorbent assays were used to assess the levels of uPA, PAI-1, and uPA:PAI-1 complex in 1119 tumors of patients with primary invasive breast cancer. These patients were followed for a median follow-up time of 59 months (range, 2-267 months) after the primary diagnosis. Correlations with well-known clinicopathological factors, and univariate and multivariate survival analyses were performed. High uPA:PAI-1 complex levels were correlated with an adverse histological grade, and inversely associated with negative estrogen and progesterone receptor status. High tumor levels of uPA:PAI-1 complex predicted an early relapse in the univariate relapse-free survival analysis (P < 0.001). The multivariate analysis showed that high uPA:PAI-1 complex levels were associated with a decreased relapse-free survival time (P = 0.033), independently of age, tumor size, number of lymph nodes affected, progesterone receptor status, uPA, adjuvant endocrine, and chemotherapy. More important, it was demonstrated that there is a larger benefit from adjuvant chemotherapy for patients with higher versus lower tumor levels of uPA:PAI-1 complex. The results of this study imply that the expression of uPA:PAI-1 complex independently predicts the efficacy of adjuvant chemotherapy in patients with primary breast cancer.
Resting Amygdala and Medial Prefrontal Metabolism Predicts Functional Activation of the Fear Extinction Circuit
Authors: Clas Linnman, Mohamed A. Zeidan, Sharon C. Furtak, Roger K. Pitman, Gregory J. Quirk, Mohammed R. Milad
Journal: American Journal of Psychiatry (2012)

Objective: Individual differences in a person's ability to control fear have been linked to activation in the dorsal anterior cingulate cortex, the ventromedial prefrontal cortex, and the amygdala. This study investigated whether functional variance in this network can be predicted by resting metabolism in these same regions. Method: The authors measured resting brain metabolism in healthy volunteers with positron emission tomography using [18F]fluorodeoxyglucose. This was followed by a 2-day fear conditioning and extinction training paradigm using functional MRI to measure brain activation during fear extinction and recall. The authors used skin conductance response to index conditioned responding, and they used resting metabolism in the amygdala, the dorsal anterior cingulate cortex, and the ventromedial prefrontal cortex to predict responses during fear extinction and extinction recall. Results: During extinction training, resting amygdala metabolism positively predicted activation in the ventromedial prefrontal cortex and negatively predicted activation in the dorsal anterior cingulate cortex. In contrast, during extinction recall, resting amygdala metabolism negatively predicted activation in the ventromedial prefrontal cortex and positively predicted activation in the dorsal anterior cingulate cortex. In addition, resting metabolism in the dorsal anterior cingulate cortex predicted fear expression (as measured by skin conductance response) during extinction recall. Conclusions: Resting brain metabolism predicted neuronal reactivity and skin conductance changes associated with the recall of the fear extinction memory.
Qualitative and Quantitative Assessment of Taste and Smell Changes in Patients Undergoing Chemotherapy for Breast Cancer or Gynecologic Malignancies
Authors: Silke Steinbach, Thomas Hummel, Christina Böhner, Sabina Berktold, Walter Hundt, Monika Kriner, Petra Heinrich, Harald Sommer, Claus Hanusch, Anita Prechtl, Burghart Schmidt, Ingo Bauerfeind, Katharina Seck, Volker R. Jacobs, Barbara Schmalfeldt, Nadia Harbeck
Journal: Journal of Clinical Oncology (2009)

Purpose Smell and taste changes during chemotherapy are significant complaints of cancer patients. Loss of olfactory/gustatory function can lead to malnutrition, weight loss, and possibly a prolonged morbidity of chemotherapy-induced adverse effects, decreased quality of life, poor compliance, and even decreased therapy response. This prospective study comprehensively investigated, to our knowledge for the first time, smell and taste changes in a cohort of 87 patients undergoing chemotherapy for breast cancer or gynecologic malignancies. Patients and Methods Olfactory function was tested using Sniffin' Sticks (Burghart; Wedel, Germany) and gustatory function was tested using taste strips before, during, and immediately and 3 months after chemotherapy. Results Olfactory and gustatory function significantly decreased during chemotherapy and recovered almost completely 3 months after chemotherapy. Scores of odor thresholds were affected more than those of discrimination or identification. The olfactory function of older patients was affected more than that of younger patients. There was no difference in the olfactory function during chemotherapy with respect to the chemotherapeutic agent or initial diagnosis (breast or ovarian cancer). Regarding taste, scores of salty taste were affected more than scores of sweet, sour, or bitter taste. The gustatory function did not differ significantly during chemotherapy with respect to age or diagnosis but did differ with respect to the chemotherapeutic agent. Taxane-based chemotherapy caused the most severe disorders. Conclusion Chemotherapy has a significant but transient effect on olfactory and gustatory function, possibly causing reduced appetite, a low energy intake, and weight loss. Additional spices and flavoring may compensate for this diminished chemosensory function, enhancing patient compliance and quality of life.
The Risk of Dying in Alcohol-Related Automobile Crashes among Habitual Drunk Drivers
Authors: Robert D. Brewer, Peter D. Morris, Thomas B. Cole, Stephanie Watkins, Michael J. Patetta, Carol Popkin
Journal: New England Journal of Medicine (1994)

Reports suggest that people who drive while intoxicated by alcohol may do so repeatedly. We hypothesized that persons arrested for driving while impaired might be at increased risk for death in an alcohol-related motor vehicle crash. To evaluate this possibility, we studied the deaths of drivers in alcohol-related motor vehicle accidents in North Carolina over a 10-year period.We compared drivers who died in motor vehicle crashes from 1980 through 1989 and who had blood alcohol concentrations of at least 20 mg per deciliter (4.3 mmol per liter), referred to as the case drivers, with those who died in crashes but had blood alcohol concentrations below 20 mg per deciliter, referred to as the control drivers. We identified case drivers and control drivers through the state Medical Examiner System. We then searched North Carolina driver-history files for the five years before each death to identify arrests for driving while impaired.We linked a total of 1646 case drivers and 1474 control drivers to their driver-history files. Case drivers were more likely than control drivers to have been arrested for driving while impaired (26 percent vs. 3 percent). After we controlled for potential confounding variables, case drivers 21 to 34 years of age were 4.3 times more likely (95 percent confidence interval, 2.7 to 6.8) than control drivers to have been arrested for driving while impaired; case drivers 35 years of age or older were 11.7 times more likely (95 percent confidence interval, 6.8 to 20.1). The strength of the association appeared to increase with the number of prior arrests. Case drivers were also more likely than the general population of currently licensed drivers to have been arrested.Arrests for driving while impaired substantially increase the risk of eventual death in an alcohol-related crash. Aggressive intervention in the cases of people arrested for driving while impaired may decrease the likelihood of a future fatal alcohol-related crash.
Increased T Helper Type 17 Response To Pathogen Stimulation in Patients With Primary Sclerosing Cholangitis
Authors: Janosch Katt, Dorothee Schwinge, Tanja Schoknecht, Alexander Quaas, Ingo Sobottka, Eike Burandt, Christoph Becker, Markus F. Neurath, Ansgar W. Lohse, Johannes Herkel, Christoph Schramm
Journal: Hepatology (2013)

T helper (Th)17 cells are important for host defense against bacteria and fungi, but are also involved in the pathogenesis of autoimmune diseases. In primary sclerosing cholangitis (PSC), bile fluid is frequently colonized with pathogens and its strong association with inflammatory bowel disease suggests the contribution of pathogen responses to disease pathogenesis. Interleukin (IL)-17A, the signature cytokine of Th17 cells, was recently described to promote inflammation and fibrosis within the liver. Therefore, we investigated Th17 immune response to pathogens in patients with PSC. Bile fluid was obtained by endoscopic retrograde cholangiography, and bacterial and fungal species grew in the majority of samples. In addition, bacterial RNA was stained in liver sections using 16sRNA fluorescence in situ hybridization and was detected in the portal tracts in 12 of 13 tested PSC patients. Bacteria grown from patients' bile fluid were then used to stimulate peripheral blood mononuclear cells (PBMCs) and to assess their Th17 response. Compared to healthy controls or primary biliary cirrhosis patients, PBMCs from PSC patients manifested significantly higher frequencies of Th17 and Th1/Th17 cells after pathogen stimulation. The highest frequencies of Th17 cells were detected after stimulation with Candida albicans , a pathogen that has been linked to disease progression. Immunohistochemically, IL-17A-expressing lymphocytes were detected within the periductal areas of PSC patients. Th17 induction was also noted after stimulation of Toll-like receptor 5 or 7, but not of other pattern recognition receptors tested, pointing to signaling pathways potentially involved in Th17 induction in PSC. Conclusion : We demonstrate an increased Th17 response to microbial stimulation in patients with PSC. These data should prompt further studies investigating the link between pathogen responses, inflammation, and fibrosis in patients with PSC. (Hepatology 2013;53:1084–1093)
Evidence for In Vivo Breakdown of β1C-Globulin in Hypocomplementemic Glomerulonephritis *
Authors: Clark D. West, Sara Winter, Judith Forristal, Janice M. McConville, Neil C. Davis
Journal: Journal of Clinical Investigation (1967)

Evidence has been obtained for the presence in vivo of alpha(2D)-globulin, a breakdown product of serum beta(1C)-globulin, in patients with acute and persistent hypocomplementemic glomerulonephritis. The protein has been identified by immunoelectrophoretic analysis, and the amounts present have been determined by direct measurement of specific antigenic determinants present on alpha(2D). beta(1A)-Globulin, another breakdown product of beta(1C)-globulin, may also be present in vivo in severely hypocomplementemic patients, but its levels are much lower than those of alpha(2D)-globulin.Alpha(2D)-globulin has been identified by immunoelectrophoretic analysis of fresh EDTA plasma from patients with hypocomplementemic nephritis as an arc in the alpha(2) region that shows a reaction of identity with the arc representing alpha(2D)-globulin produced by aged normal serum. beta(1A)-Globulin was not seen in these patterns. Measurement of specific antigenic determinants has been carried out in both fresh EDTA plasma and aged serum. In the fresh plasma, the concentration of D antigen, found on both beta(1C)- and alpha(2D)-globulins, has been related to that of B antigen, found only on beta(1C) and taken as a measure of the concentration of this protein. In the hypocomplementemic patients, the concentration of D antigen, in comparison to that of B, was greater than in the normal subjects. Similarly, in aged serum, the level of alpha(2D) was greater than would be expected from the amount of beta(1C) that had been broken down in vitro, measured by the concentration of beta(1A). Calculations indicated that the in vivo alpha(2D) level in severely hypocomplementemic patients ranged from 7.5 to 18% of that which would be found in a pool of aged normal serum in which beta(1C) is completely broken down. The levels tended to be lower in less severely hypocomplementemic patients, and none could be detected in normal plasma. Only small quantities of A and D antigens are detectable in the urine of patients with hypocomplementemic nephritis. The rate of excretion is about equal to that of the normal subject. The study indicates that the low serum levels of beta(1C)-globulin that may be present over long periods in patients with persistent hypocomplementemic glomerulonephritis can be ascribed, in part, to in vivo breakdown of this protein as a result of reaction with immune complexes. The contribution of beta(1C) deposition on immune complexes and of diminished synthesis to the depressed serum levels cannot be assessed by the present study.
Using big data to predict collective behavior in the real world
Authors: Helen Susannah Moat, Tobias Preis, Christopher Y. Olivola, Chengwei Liu, Nick Chater
Journal: Behavioral and Brain Sciences (2014)

Abstract Recent studies provide convincing evidence that data on online information gathering, alongside massive real-world datasets, can give new insights into real-world collective decision making and can even anticipate future actions. We argue that Bentley et al.’s timely account should consider the full breadth, and, above all, the predictive power of big data.
Depression and Cardiovascular Disease
Authors: Mary A. Whooley
Journal: JAMA (2006)

Major depressive disorder is a risk factor for the development of incident coronary heart disease events in healthy patients and for adverse cardiovascular outcomes in patients with established heart disease. Depression is present in 1 of 5 outpatients with coronary heart disease and in 1 of 3 outpatients with congestive heart failure, yet the majority of cases are not recognized or appropriately treated. It is not known whether treating depression improves cardiovascular outcomes, but antidepressant treatment with selective serotonin reuptake inhibitors is generally safe, alleviates depression, and improves quality of life. This article evaluates the importance of major depression in patients with cardiovascular disease, and provides practical guidance for identifying and treating this disorder.
P87 The needs and experiences of progressive idiopathic fibrotic interstitial lung disease patients, informal caregivers and health professionals: a qualitative study
Authors: S. Bajwah, J. Koffman, I. J. Higginson, J. R. Ross, A. U. Wells, S. S. Birring, A. Patel, J. Riley
Journal: Thorax (2011)

While there have been some studies looking at the needs of patients with idiopathic pulmonary fibrosis, to date no qualitative research has been conducted in the UK. This novel study aimed to assess the needs and experiences of people living with end stage progressive idiopathic fibrotic interstitial lung disease (PIF-ILD) and their informal caregivers. We also interviewed health professionals to examine views of current services, communication between health professionals and end of life planning. 18 qualitative semi-structured in-depth interviews were conducted with patients, their informal caregivers, and health professionals across two specialists ILD centres in London and in the community. Many participants reported that their main symptoms were shortness of breath and cough which impacted on every part of both theirs and the informal caregivers9 lives. Psychologically, patients were frustrated and angry at the way in which their illness severely limited their ability to engage in activities of daily living and compromised their independence. Further, both patients and informal caregivers also reported that the disease seriously affected family relationships especially spousal relationships where strain was pronounced. Patients and their informal caregivers reported a good understanding of the progressive nature of their illness but held unrealistic expectations about prognosis. Health professionals expressed that there was a poor understanding of the palliative care needs of these patients, reluctance to recognise the terminal phase and poor end of life planning. All participants expressed that communication was often poor between health professionals and there was a lack of clarity about where primary responsibility for the care of the patient lay. This Phase I study has provided valuable insight into the overwhelming experiences of patients with PIF-ILD and their informal caregivers. It is clear that the disease affects the patients physically and also impacts greatly psychosocially. The palliative care needs of these patients are not being met and better co-ordination of care with improved communication is needed.
Pulmonary infection with Mycobacterium kansasii in Wales, 1970-9: review of treatment and response.
Authors: J Banks, A M Hunter, I A Campbell, P A Jenkins, A P Smith
Journal: Thorax (1983)

Thirty-five patients (88% male) with pulmonary infection caused by Mycobacterium kansasii have been reviewed. Sixty-six per cent had pre-existing lung disease, chronic bronchitis and emphysema accounting for half of the disorders. Unilateral lesions were present in 69% of patients whose chest radiographs were reviewed and 90% had cavitating disease. The development of unilateral or bilateral disease appeared to be independent of any delay in starting treatment. Five patients died while receiving treatment, but none of these deaths was due to M kansasii infection. The remaining 30 patients were successfully treated with drug regimens, all of which included rifampicin and 86% of which included ethambutol. There was 100% sputum conversion, with no relapses after a mean follow-up period of five-and-a-half years. Rifampicin and ethambutol given for a mean period of 15 months appeared to be a non-toxic, effective combination.
Mixed Response in Interim Positron Emission Tomography/Computed Tomography Leads to Detection of a Gastrointestinal Stromal Tumor in a Patient With Mediastinal Diffuse Large B-Cell Lymphoma
Authors: Cord Rehmsmeier, Torsten Kessler, Steffen Koschmieder, Matthias Ross, Matthias Weckesser, Johannes Wessling, Gabriele Koehler, Wolfgang E. Berdel
Journal: Journal of Clinical Oncology (2010)
Advisory group sets out measures to boost career prospects of women doctors
Authors: A. O'Dowd
Journal: BMJ (2009)

A government group has recommended several changes that will help England’s increasingly high proportion of women doctors to develop their careers.

Proposals such as improving access to child care, introducing part time training, and improving career guidance are given in a report published on 12 October by the National Working Group on Women in Medicine.

The group, set up by the Department of Health, is keen to see wide ranging changes implemented that would help improve the career prospects of women doctors.

Its report says that the female intake into medical schools had risen from just 492 (24% of …