tbuckley/cabot-search huggingface dataset:
Survival after IBTR in NSABP Node Negative Protocols B-13, B-14, B-19, B-20 and B-23
Authors: I. Wapnir, S. Anderson, E. Mamounas, C. Geyer, J. Hyeon-Jeong, J. Costantino, B. Fisher, N. Wolmark
Journal: Journal of Clinical Oncology (2005)

517 Breast irradiation and adjuvant therapies decrease ipsilateral breast tumor recurrences (IBTR) after breast conserving surgery. We have previously reported poor outcomes in women experiencing IBTR in NSABP node positive protocols. The overall survival in the first five years following IBTR is approximately 60%. We postulated that the risk of mortality after IBTR in node negative breast cancers would be similar. Methods: IBTR events were calculated in patients randomized on recent NSABP node negative prospective randomized trials. Women with estrogen-receptor negative tumors were entered into B-13, B-19, B-23 while those with estrogen-receptor positive tumors into B-14 and B-20. Only randomized eligible patients with follow-up were considered. Breast conserving surgery was performed in 3799 of these women, constituting our population at risk. Results: As of December 31, 2003, the median time on study for this cohort was 166.2 months (Table 1). Ten-year cumulative incidence of IBTR across all protocols was 6.0%. Rates were highest in the placebo arms of protocols B-13 and B-14. The overall survival in the first five years after IBTR was 75.7%. Five year survival after IBTR in ER- protocols was 68.6% versus 80.0% in ER+ trials. Conclusion: The cumulative risk of death after IBTR in patients with node-negative breast cancer is considerable but somewhat lower than that in patients with positive nodes. These results lend further support to the concept that IBTR is a powerful predictive marker of risk for metastatic disease and death.
Astrogenomics: big data, old problems, old solutions?
Authors: Aaron Golden, S George Djorgovski, John M Greally
Journal: Genome biology (2013)

The ominous warnings of a data deluge in the life sciences from high-throughput DNA sequencing data are being supplanted by a second deluge, of cliches bemoaning our collective scientific fate unless we address the genomic data tsunami. It is imperative that we explore the many facets of the genome, not just sequence but also transcriptional and epigenetic variability, integrating these observations in order to attain a genuine understanding of how genes function, towards a goal of genomics-based personalized medicine. Determining any individual's genomic properties requires comparison to many others, sifting out the specific from the trends, requiring access to the many in order to yield information relevant to the few. This is the central big data challenge in genomics that still requires some sort of resolution. Is there a practical, feasible way of directly connecting the scientific community to this data universe?
Carcinogenic Effects of Combined Treatment of Inbred Mice With 3-Methylcholanthrene and 1,2-Dimethylhydrazine2
Authors: B. A. Diwan, K. E. Blackman
Journal: JNCI Journal of the National Cancer Institute (1980)

Inbred mice of strains C57BL/6J (B6) (Ahb/-Ahb) and DBA/2J (D2) (Ahd/Ahd) were administered 3-methylcholanthrene (MCA) alone, 1,2-dimethylhydrazine (DMH) alone, and MCA and DMH together. Colorectal tumors were observed in 32% of the DMH-treated B6 mice, but no such tumors occurred in similarly treated D2 mice. Of the MCA-treated D2 mice, 46% were susceptible to leukemia, whereas in similarly treated B6 mice, 19% developed only lung tumors. The combined application of MCA and DMH resulted in an increased incidence of colorectal (52%) and lung (44%) tumors in B6 mice and, to some extent, of leukemia (63%) in D2 mice. The role of genetic background on the carcinogenic effects of combined application of MCA and DMH in inbred mice is discussed.
Miniature Chest Radiograph Screening for Tuberculosis in Jails
Authors: TIMOTHY F. JONES, WILLIAM SCHAFFNER
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Jails are an important reservoir of tuberculosis infection in the United States. Screening for active disease in these high-risk settings is difficult. We used decision analysis to assess the cost effectiveness of routine miniature chest radiography for screening for tuberculosis on admission to jail. Infection rates, probabilities, and costs associated with detecting and treating tuberculosis were derived from published studies. We calculated an average total cost of $6.60 per inmate for routine radiograph screening on admission to jail. The cost of screening for active tuberculosis with miniature chest radiography was estimated to be $9,600 per case identified, compared with $32,100 per case with tuberculin skin testing and $54,100 per case with symptom screening. Chest radiography would also identify substantially more cases than other methods of screening. Screening for tuberculosis with miniature chest radiography is cost effective even under a wide range of assumptions regarding risk factors and prevalence of disease. Miniature chest radiography should be strongly considered as an important tool in the fight to eliminate tuberculosis from the high-risk populations that may be reached through screening in jails.
Health-related effects of smoking on patients with bronchial asthma participating in a disease management program. Results from the DMP asthma in the north Rhine Region, Germany
Authors: Arne Weber, Sabine Groos, Bernd Hagen, Jens Kretschmann, Lutz Altenhofen
Journal: European Respiratory Journal (2012)

Background and objective  Asthma is one of the most common chronic disorders. In Germany in 2006 a disease management program (DMP) for asthma started, focussing on patient education, standardised documentation and optimisation of quality of care. Smoking is known as a negative risk factor on pathogenesis for asthma. We want to check whether there is also an effect of smoking on selected outcome parameters.  Methods and population  In 2010 there were 85.586 patients and 4.166 physicians, who participated. We conducted descriptive cross-sectional analyses and a logistic regression for all DMP participants. We used standardised medical records providing information on pharmacotherapy, frequency of symptoms and non-medical interventions. A three-step severity scale has been developed, which is based on different parameters (e.g. Peak Flow Value).  Results  Smokers have a three times lower chance to avoid asthma-related emergency department visits (OR 0.32; CI 95 %: 0.11 – 0.92). Further they suffer more often from daily symptoms (17 vs. 12 %) and show less current absence of asthma symptoms (31 vs. 25 %). The severity scale show that smokers suffer more often from more severe asthma (Group 1 15%, Group 2 18%, Group 3: 24 %). Hence smokers get more often controller medication than non-smokers (67 vs. 64 %).  Conclusions  There were worse results for smokers relating health-related parameters, e.g. they suffer more often on asthma symptoms. Therefore efforts on smoke prevention for asthma patients need further improvement. Limitations due to potential selection bias in the DMP population have to be considered.
Revisiting the September asthma epidemic
Authors: Conrad Capili, Robert Jacobson, Xujian Li, Young Juhn
Journal: European Respiratory Journal (2011)

Background:  September asthma epidemic has been well documented. Whether a similar pattern of asthma exacerbation is observed in children returning to school from winter and spring break is unknown.   Objective:  To assess whether the September asthma epidemic occurs in Olmsted County, Minnesota and determine whether similar asthma epidemics occur after winter and spring break.   Methods:  The study included all asthmatic children ages 5-18 who had received medical care at our institution as of March 12, 2008 (n=3092). Asthma status was defined by physician diagnosis in the medical records. We compared the frequency of all asthma-related hospitalizations, ED visits, outpatient visits, and corticosteroid therapies for acute asthma symptoms between August and September of 2008 and 2009. Similarly we compared the frequency of all asthma-related visits or treatments between during and after spring break and between during and after winter break.   Results:  The frequency of asthma-related visits and treatments in September of 2008 and 2009 was 2.1% per person-month, which was significantly greater than that in August of 2008 and 2009 (1.1% per person-month) (p=0.003). Similarly, the frequency of asthma-related visits and therapies during the period after spring break of 2008 and 2009 (1.89% per person-month) tended to be greater than that during spring break (0.75% per person-month) (p = 0.063). There was no difference in asthma-related visits or therapies during and after winter break (p=0.59).   Conclusions:  The September asthma epidemic does occur in our study setting, but this may not be a September-specific concern. Clinicians should consider a step-up therapy and reinforce medication compliance for asthma exacerbation-prone children returning to school.
Susceptibility of <i>Helicobacter Pylori</i> to the Antibacterial Activity of Manuka Honey
Authors: N Al Somal, K E Coley, P C Molan, B M Hancock
Journal: Journal of the Royal Society of Medicine (1994)

Honey is a traditional remedy for dyspepsia, and is still used for this by some medical practitioners although there is no rational basis for its use. The finding that Helicobacter pylori is probably the causative agent in many cases of dyspepsia has raised the possibility that the therapeutic action of honey may be due to its antibacterial properties. Consequently, the sensitivity of Helicobacter pylori to honey was tested, using isolates from biopsies of gastric ulcers. It was found that all five isolates tested were sensitive to a 20% (v/v) solution of manuka honey in an agar well diffusion assay, but none showed sensitivity to a 40% solution of a honey in which the antibacterial activity was due primarily to its content of hydrogen peroxide. Assessment of the minimum inhibitory concentration by inclusion of manuka honey in the agar showed that all seven isolates tested had visible growth over the incubation period of 72 h prevented completely by the presence of 5% (v/v) honey.
Suggested Method for Closed Treatment of Fractures of the Carpal Scaphoid: Hypothesis Supported by Dissection and Clinical Practice
Authors: Richard J King, Robert P Mackenney, Salah Elnur
Journal: Journal of the Royal Society of Medicine (1982)

The anatomy and kinetics of the carpus with special reference to the fractured scaphoid are described. Clinical, radiological and post-mortem studies of the wrist show that the scaphoid can be immobilized and compressed in its long axis, with the wrist held in full supination, mid-dorsiflexion and full ulnar deviation. Immobilization of the upper limb in this position for four weeks has achieved union of those fractures of the scaphoid which are often problematical, i.e. the displaced fracture, fractures of the proximal pole, and those exhibiting delay in union of many months. The method of manipulation and immobilization in a plaster of Paris cast is described, and some clinical examples are presented. The indications for the complications of the method of treatment are discussed and briefly compared with other methods of treatment.
Prospective Randomized Trial of the Treatment of Patients With Metastatic Melanoma Using Chemotherapy With Cisplatin, Dacarbazine, and Tamoxifen Alone or in Combination With Interleukin-2 and Interferon Alfa-2b
Authors: Steven A. Rosenberg, James C. Yang, Douglas J. Schwartzentruber, Patrick Hwu, Francesco M. Marincola, Suzanne L. Topalian, Claudia A. Seipp, Jan H. Einhorn, Donald E. White, Seth M. Steinberg
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The combination of chemotherapy with immunotherapeutic agents such as interleukin-2 and interferon alfa-2b has been reported to provide improved treatment results in patients with metastatic melanoma, compared with the use of chemotherapy alone. We have performed a prospective randomized trial in patients with metastatic melanoma, comparing treatment with chemotherapy to treatment with chemoimmunotherapy. PATIENTS AND METHODS: One hundred two patients with metastatic melanoma were prospectively randomized to receive chemotherapy composed of tamoxifen, cisplatin, and dacarbazine or this same chemotherapy followed by interferon alfa-2b and interleukin-2. Objective responses, survival, and toxicity in the two groups were evaluated at a median potential follow-up of 42 months. RESULTS: In 52 patients randomized to receive chemotherapy, there were 14 objective responses (27%), including four complete responses. In 50 patients randomized to receive chemoimmunotherapy, there were 22 objective responses (44%) (P 2 = .071), including three complete responses. In both treatment groups, the duration of partial responses was often short, and there was a trend toward a survival advantage for patients receiving chemotherapy alone (P 2 = .052; median survival of 15.8 months compared with 10.7 months). Treatment-related toxicities were greater in patients receiving chemoimmunotherapy. CONCLUSION: With the treatment regimens used in this study, the addition of immunotherapy to combination chemotherapy increased toxicity but did not increase survival. The use of combination chemoimmunotherapy regimens is not recommended in the absence of well-designed, prospective, randomized protocols showing the benefit of this treatment strategy.
Continuous harvest of stem cells via partial detachment from thermoresponsive nanobrush surfaces
Authors: I-Chia Peng, Chin-Chen Yeh, Yi-Tung Lu, Saradaprasan Muduli, Qing-Dong Ling, Abdullah A. Alarfaj, Murugan A. Munusamy, S. Suresh Kumar, Kadarkarai Murugan, Hsin-chung Lee, Yung Chang, Akon Higuchi
Journal: Biomaterials (2015)
The devil's triangle of steatosis, obesity, and liver stiffness
Authors: Horia Stefanescu, Monica Lupsor‐Platon, Radu I. Badea
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. This work was partially funded by European Social Fund, Romanian Human Resources Development Operational Programme 2007–2013, project no. POSDRU/159/1.5/S/138776. [This sentence was added on September 29, 2015, after original online publication.] Author names in bold designate shared co‐first authorship. To the Editor: We read with enthusiasm the study of Petta et al.1 demonstrating the influence of severe steatosis on liver stiffness measurement (LSM). We totally agree with the conclusion, although the results cannot be extrapolated to other etiologies of chronic liver disease except nonalcoholic fatty liver disease. The finding is important for everyday practice because LSM is the most utilized method to estimate liver fibrosis and the prevalence of steatosis is high. Despite a well‐characterized aspect on imaging, an accurate noninvasive method for steatosis quantification was lacking until recently, when the controlled attenuation parameter (CAP) became available.2 Therefore, we checked if CAP could stratify the risk of liver fibrosis overestimation. From a cohort of pluri‐etiologic chronic liver disease patients in which we recently validated CAP for grading steatosis,3 we selected 31 patients with moderate fibrosis (F2‐METAVIR) and mild/moderate activity (A1/A2‐METAVIR) and further divided based on a CAP value < or ≥280 dB/m (arbitrary value, pooled from a previously published meta‐analysis4 and our own study3 for prediction of at least moderate steatosis [>34% fatty infiltration]). They were mainly women (54.8%) with a mean age of 48.87 (±11.79) years. Figure 1 demonstrates that LSM and body mass index (BMI, highly associated with ultrasound attenuation) were significantly higher in patients with CAP ≥280. In order to escape from this “devil's triangle” of steatosis, obesity, and stiffness, we looked for predictors of LSM overestimation (>9.5 kPa, the generally accepted threshold for F3), but neither CAP nor BMI was independently associated with out‐of‐range LSM values in multivariate analysis.Figure 1: Box‐plots representing the higher LSM and BMI in patients with higher (≥280 dB/m) CAP values, but having the same histologically proved fibrosis stage and activity grade.Our data confirm that liver stiffness is a physical parameter influenced also by moderate/severe steatosis as suggested by CAP values. Furthermore, intrahepatic fat accumulation appears not to overestimate the actual fibrosis grade, despite higher stiffness values in patients with elevated CAP. Because the latter is well correlated with BMI (r = 0.732, P < 0.0001), further elaboration of BMI‐based nomograms for CAP interpretation appears useful, as well as larger prospective studies to investigate CAP's role in the misinterpretation of LSM.
The Efficacy of Drugs and Psychotherapy in the Treatment of Acute Depressive Episodes
Authors: Myrna M. Weissman, Brigitte A. Prusoff, Alberto Dimascio, Carlos Neu, Mahesh Goklaney, Gerald L. Klerman
Journal: American Journal of Psychiatry (1979)

The efficacy of tricyclic antidepressants and various psychotherapies, in comparison with one another or in combination, has not been fully established in randomized clinical trials. The authors present a randomized controlled trial comparing the combination of amitriptyline and short-term interpersonal psychotherapy, either treatment alone, and nonscheduled supportive psychotherapy in ambulatory patients with acute depression. They found that pharmacotherapy and psychotherapy alone were equally efficacious and better than nonscheduled treatment. The combination treatment of psychotherapy and pharmacotherapy was more effective than either treatment alone and delayed the onset of symptomatic failure.
PET imaging of tumor glycolysis downstream of hexokinase through noninvasive measurement of pyruvate kinase M2
Authors: Timothy H. Witney, Michelle L. James, Bin Shen, Edwin Chang, Christoph Pohling, Natasha Arksey, Aileen Hoehne, Adam Shuhendler, Jun-Hyung Park, Deepika Bodapati, Judith Weber, Gayatri Gowrishankar, Jianghong Rao, Frederick T. Chin, Sanjiv Sam Gambhir
Journal: Science Translational Medicine (2015)

Cancer cells reprogram their metabolism to meet increased biosynthetic demands, commensurate with elevated rates of replication. Pyruvate kinase M2 (PKM2) catalyzes the final and rate-limiting step in tumor glycolysis, controlling the balance between energy production and the synthesis of metabolic precursors. We report here the synthesis and evaluation of a positron emission tomography (PET) radiotracer, [(11)C]DASA-23, that provides a direct noninvasive measure of PKM2 expression in preclinical models of glioblastoma multiforme (GBM). In vivo, orthotopic U87 and GBM39 patient-derived tumors were clearly delineated from the surrounding normal brain tissue by PET imaging, corresponding to exclusive tumor-associated PKM2 expression. In addition, systemic treatment of mice with the PKM2 activator TEPP-46 resulted in complete abrogation of the PET signal in intracranial GBM39 tumors. Together, these data provide the basis for the clinical evaluation of imaging agents that target this important gatekeeper of tumor glycolysis.
Screening for Lung Cancer
Authors: K Moghissi, J A C Thorpe
Journal: Journal of the Royal Society of Medicine (2001)

Mr Dalrymple-Hay and Dr Drury (January 2001 JRSM, pp. 2-5) rightly highlight the deficiencies which have been associated with lung cancer screening programmes and the fact that thus far none of the `tools' have measured up to expectations. One should hardly be surprised that this is the case when many of the investigators have been looking for a single test which has `high sensitivity, specificity and positive predictive value'. Is this not the search for Nirvana?

Regarding the low-dose helical computed tomography (CT) being evaluated by the Early Lung Cancer Action Group, it should be noted that some 50% of lung cancer cases develop within the bronchial tree. It is unlikely such a tumour would be identified by low-dose CT at an early stage; some other methods would be needed to diagnose such tumours. I was therefore surprised that no reference is made in the article to fluorescence bronchoscopy which, when combined with proper sampling and the use of histological and molecular methods, has been shown to have great potential in the screening of high-risk individuals1, particularly when combined with sputum cytology. Whilst this method does not fulfil the criteria for an ideal screening test, it does offer a way forward. Several pilot studies are already in progress throughout the world, including one at the Yorkshire Laser Centre.
Patient Outcomes after Acute Pulmonary Embolism
Authors: Frederikus A. Klok, Wendy Zondag, Klaas W. van Kralingen, Arie P. J. van Dijk, Jouke T. Tamsma, Fenna H. Heyning, Hubert W. Vliegen, Menno V. Huisman
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

There is a lack of information on the long-term prognosis of patients with acute pulmonary embolism (PE).To assess the long-term risk for adverse events after PE.Consecutive patients diagnosed with PE between January 2001 and July 2007, and patients in whom PE was ruled out from a previous study were followed until July 2008 for the occurrence of adverse clinical events: mortality, symptomatic recurrent venous thromboembolism, cancer, arterial cardiovascular events and chronic thromboembolic pulmonary hypertension. Hazard ratios (HR) for all endpoints and a combined endpoint were calculated and adjusted for potential confounders.Three hundred eight patients with unprovoked, 558 with provoked, and 334 without PE were studied with a median follow-up period of 3.3 years. Patients with unprovoked PE had a lower overall risk for mortality than patients with provoked PE (HR, 0.59; 95% confidence interval [CI], 0.43-0.82), but a higher risk for nonmalignancy-related mortality (HR, 1.8; 95% CI, 1.3-2.5), recurrent venous thromboembolism (HR, 2.1; 95% CI, 1.3-3.1), cancer (HR, 4.4; 95% CI, 2.0-10), cardiovascular events (HR, 2.6; 95% CI, 1.5-3.8) and chronic thromboembolic pulmonary hypertension (1.5 vs. 0%). The risk for the combined endpoint did not differ between both groups (HR, 0.98; 95% CI, 0.82-1.1). Patients without PE had similar risks for malignancy and cardiovascular events than patients with provoked PE, but lower risks for the remaining outcomes. The fraction of both patients with provoked and unprovoked PE without events after 1 year was only 70% and decreased to fewer than 60% after 2 years and fewer than 50% after 4 years, whereas this latter was 84% for the control patients.The clinical course of acute PE is complicated by high rates of serious adverse events, which occur in half of the patients within 4 years.
Essential role of class II PI3K-C2α in platelet membrane morphology
Authors: Colin Valet, Gaëtan Chicanne, Childerick Severac, Claire Chaussade, Maria A. Whitehead, Cendrine Cabou, Marie-Pierre Gratacap, Frederique Gaits-Iacovoni, Bart Vanhaesebroeck, Bernard Payrastre, Sonia Severin
Journal: Blood (2015)