tbuckley/cabot-search huggingface dataset:
Prognostically Useful Gene-Expression Profiles in Acute Myeloid Leukemia
Authors: Peter J.M. Valk, Roel G.W. Verhaak, M. Antoinette Beijen, Claudia A.J. Erpelinck, Sahar Barjesteh van Waalwijk van Doorn-Khosrovani, Judith M. Boer, H. Berna Beverloo, Michael J. Moorhouse, Peter J. van der Spek, Bob Löwenberg, Ruud Delwel
Journal: New England Journal of Medicine (2004)

In patients with acute myeloid leukemia (AML) a combination of methods must be used to classify the disease, make therapeutic decisions, and determine the prognosis. However, this combined approach provides correct therapeutic and prognostic information in only 50 percent of cases.We determined the gene-expression profiles in samples of peripheral blood or bone marrow from 285 patients with AML using Affymetrix U133A GeneChips containing approximately 13,000 unique genes or expression-signature tags. Data analyses were carried out with Omniviz, significance analysis of microarrays, and prediction analysis of microarrays software. Statistical analyses were performed to determine the prognostic significance of cases of AML with specific molecular signatures.Unsupervised cluster analyses identified 16 groups of patients with AML on the basis of molecular signatures. We identified the genes that defined these clusters and determined the minimal numbers of genes needed to identify prognostically important clusters with a high degree of accuracy. The clustering was driven by the presence of chromosomal lesions (e.g., t(8;21), t(15;17), and inv(16)), particular genetic mutations (CEBPA), and abnormal oncogene expression (EVI1). We identified several novel clusters, some consisting of specimens with normal karyotypes. A unique cluster with a distinctive gene-expression signature included cases of AML with a poor treatment outcome.Gene-expression profiling allows a comprehensive classification of AML that includes previously identified genetically defined subgroups and a novel cluster with an adverse prognosis.
Prevalence and outcome of pulmonary fibrosis in microscopic polyangiitis
Authors: G.E. Tzelepis, M. Kokosi, A. Tzioufas, S.P. Toya, K.A. Boki, A. Zormpala, H.M. Moutsopoulos
Journal: European Respiratory Journal (2009)

We sought to determine the type of pulmonary involvement in microscopic polyangiitis (MPA), primarily focusing on pulmonary fibrosis (PF), its prevalence, temporal relationship with other disease manifestations and outcome. 33 patients (16 males) with biopsy proven perinuclear anti-neutrophilic cytoplasmic antibody-positive MPA (age 63.5 yrs) participated in the study. Pulmonary involvement was assessed using standard methods, including radiographic imaging (chest radiographs and high-resolution computed tomography), pulmonary function testing, bronchoscopy and bronchoalveolar lavage, and, if indicated, lung biopsy. All-cause mortality was analysed by the Kaplan-Meier method and was compared between MPA patients with and without PF. At the time of diagnosis, renal involvement was detected in all patients, with renal biopsies being consistent with segmental necrotising glomerulonephritis in all patients. The most common respiratory symptom was haemoptysis, which was found in nine (27%) patients. PF was present in 12 (36%) patients at the time of diagnosis, whereas one patient developed PF while on therapy approximately 10 yrs after disease diagnosis. In seven patients with PF, respiratory symptoms related to fibrosis preceded other disease manifestations by a median (range) period of 13 (5-120) months. Patients were followed up for a period of 38+/-30 months. Presence of PF was associated with increased mortality (p = 0.02), with six deaths occurring in the fibrotic group and one in the nonfibrotic group. In the fibrotic group most deaths were related to PF. PF occurs frequently in MPA, may precede other disease manifestations by a variable length of time and has a poor prognosis.
Studies of Mobile Phone Use and Brain Tumor Risk Are Independent of Industry Influence
Authors: Jack T. Rowley, Michael J. Milligan
Journal: Journal of Clinical Oncology (2010)

In their article, Myung et al 1 state "We feel the need to mention the funding sources for each research group because it is possible that these may have influenced the respective study designs and results" and refer to the INTERPHONE group of studies that in some cases received partial funding from the GSM Association and Mobile Manufacturers Forum.We reject the suggestion that there was any influence by our organizations on the scientific conduct of the INTERPHONE studies.As has been made clear by the INTER-PHONE study group, our funding was partial and complemented funds received from noncommercial sources including the European Union and national and local research funding organizations.The funds were provided via the International Union Against Cancer and are governed by agreements that guarantee INTERPHONE'S complete scientific independence in conduct, analysis, and reporting. 2We recognize the perception issues when the mobile industry provides funding for such research and we strive through the use of firewalls and partnerships with governments to make our commitment to independent research visible.Ultimately, our organizations believe that safety standards should be based on the best available evidence and that as a responsible industry we should contribute to knowledge development.In the interest of balance and providing a complete picture, the authors should also have noted the correspondence in regard to possible conflict of interest associated with the Hardell et al studies. 1,3 Myung et al 1 ascribe a higher quality score to the Hardell et al 1 group of studies despite other analyses raising methodologic questions, such as evidence of selection, information, and recall bias, and unusually high reported participation rates for data collected via a self-administered mailed questionnaire (close to 90% for both cases and population-based controls). 4,5In addition, there are no published validation studies of the self-reported indices of phone use that are the basis of exposure assessment in the Hardell et al studies. 1 The meta-analysis included a 2001 study by Stang et al; 6 however, recently that group has published a follow-up study 7 that increased the number of cases (118 to 549) and improved on the incomplete exposure assessment of the original study.In the new study they found no increased risk of uveal melanoma for regular mobile phone use and no trend for cumulative measures of exposure.Finally, we note that in respect of the Myung et al 1 research recommendation, an international prospective cohort study is underway, termed COSMOS, involving Denmark, Finland, Sweden, the Netherlands, and the United Kingdom, which aims to follow the health of approximately 250,000 European mobile phone users.
Reduced perioperative mortality after centralization of lung cancer surgery
Authors: Anders Bugge, Johny Kongerud, Steinar Solberg, May-Brit Lund
Journal: European Respiratory Journal (2013)

Background:  Studies indicate that concentration into higher-volume centers improves survival after lung cancer surgery. Since 2008 all thoracic surgery in southern Norway (population 1.5 mill) has been centralized to one tertiary hospital. We have consecutively registered all lung cancer operations in our hospital (n=881) over the last 10 years. In this study we aim to compare survival in the first and last 5-years period, i.e before and after centralization.   Results:    Conclusions:  The annual number of operations was nearly doubled as a result of centralization. Comparing the two 5-year periods before and after centralization, there was a significant reduction in perioperative mortality in the second period. The patients were comparable with respect to age and gender, and surgical procedures did not differ significantly. The results suggest that concentration of lung cancer surgery into a higher-volume center has improved early survival.
Female Survivors of Childhood Cancer: Preterm Birth and Low Birth Weight Among Their Children
Authors: Lisa B. Signorello, Sarah S. Cohen, Cristina Bosetti, Marilyn Stovall, Catherine E. Kasper, Rita E. Weathers, John A. Whitton, Daniel M. Green, Sarah S. Donaldson, Ann C. Mertens, Leslie L. Robison, John D. Boice
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Improved survival after childhood cancer raises concerns over the possible long-term reproductive health effects of cancer therapies. We investigated whether children of female childhood cancer survivors are at elevated risk of being born preterm or exhibiting restricted fetal growth and evaluated the associations of different cancer treatments on these outcomes. Methods: Using data from the Childhood Cancer Survivor Study, a large multicenter cohort of childhood cancer survivors, we studied the singleton live births of female cohort members from 1968 to 2002. Included were 2201 children of 1264 survivors and 1175 children of a comparison group of 601 female siblings. Data from medical records were used to determine cumulative prepregnancy exposures to chemotherapy and radiotherapy. Logistic regression was used to estimate odds ratios (ORs) for the association between quantitative therapy exposures and preterm (<37 weeks) birth, low birth weight (<2.5 kg), and small-for-gestational-age (SGA) (lowest 10th percentile) births. All statistical tests were two-sided. Results: Survivors' children were more likely to be born preterm than the siblings' children (21.1% versus 12.6%; OR = 1.9, 95% confidence interval [CI] = 1.4 to 2.4; P <.001). Compared with the children of survivors who did not receive any radiotherapy, the children of survivors treated with high-dose radiotherapy to the uterus (>500 cGy) had increased risks of being born preterm (50.0% versus 19.6%; OR = 3.5, 95% CI = 1.5 to 8.0; P = .003), low birth weight (36.2% versus 7.6%; OR = 6.8, 95% CI = 2.1 to 22.2; P = .001), and SGA (18.2% versus 7.8%; OR = 4.0, 95% CI = 1.6 to 9.8; P = .003). Increased risks were also apparent at lower uterine radiotherapy doses (starting at 50 cGy for preterm birth and at 250 cGy for low birth weight). Conclusions: Late effects of treatment for female childhood cancer patients may include restricted fetal growth and early births among their offspring, with risks concentrated among women who receive pelvic irradiation.
Microgravity and the respiratory system
Authors: G. Kim Prisk
Journal: European Respiratory Journal (2014)

The structure of the lung, with its delicate network of airspaces and capillaries, means that gravity has a profound influence on its function. Studies of lung function in the absence of gravity provide valuable insight into how, for we Earth-bound individuals, its unavoidable effects shape our lung function. Gravity causes uneven ventilation in the lung through the deformation of lung tissue (the so-called Slinky effect), and uneven perfusion through a combination of the Slinky effect and the zone model of pulmonary perfusion. Both ventilation and perfusion exhibit persisting heterogeneity in microgravity, indicating important other mechanisms. However, gravity serves to maintain a degree of matching of these two processes, so that the ventilation/perfusion ratio, and thus gas exchange, remains efficient. Therefore, while both ventilation and perfusion are more uniform in spaceflight, gas exchange is seemingly no more efficient than on Earth. Despite the changes in lung function when gravity is removed, the lung continues to function well in weightlessness. Unlike many other organ systems, the lung does not appear to undergo structural adaptive changes when gravity is removed, and so there is no apparent degradation in lung function upon return to earth, even after 6 months in space.
Assessment of the potential for international dissemination of Ebola virus via commercial air travel during the 2014 west African outbreak
Authors: Isaac I Bogoch, Maria I Creatore, Martin S Cetron, John S Brownstein, Nicki Pesik, Jennifer Miniota, Theresa Tam, Wei Hu, Adriano Nicolucci, Saad Ahmed, James W Yoon, Isha Berry, Simon I Hay, Aranka Anema, Andrew J Tatem, Derek MacFadden, Matthew German, Kamran Khan
Journal: The Lancet (2014)
TRANSORBITAL LOBOTOMY VERSUS ELECTROCONVULSIVE THERAPY IN THE TREATMENT OF MENTALLY ILL TUBERCULOUS PATIENTS
Authors: SYLVIA CHENG, H. SINCLAIR TAIT, WALTER FREEMAN
Journal: American Journal of Psychiatry (1956)

Electroconvulsive therapy was found definitely harmful to patients suffering from active pulmonary tuberculosis. Transorbital lobotomy was found to be an effective substitute for shock therapy. The prolonged relief of mental tension, anxiety, and emotional distress was found to be very beneficial to psychotic patients who suffered also from active pulmonary tuberculosis.
Identification of a Homozygous PSTPIP1 Mutation in a Patient With a PAPA-Like Syndrome Responding to Canakinumab Treatment
Authors: Alexandra Geusau, Nadine Mothes-Luksch, Hesam Nahavandi, Winfried F. Pickl, Carol A. Wise, Zahra Pourpak, Elisabeth Ponweiser, Leopold Eckhart, Raute Sunder-Plassmann
Journal: JAMA Dermatology (2013)

Pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome (OMIM 604416) is a rare autosomal dominant inherited autoinflammatory syndrome characterized by pyogenic sterile arthritis and less frequently accompanied by pyoderma gangrenosum and acne. It is associated with dominant missense mutations in the proline-serine-threonine phosphatase-interacting protein 1 gene (PSTPIP1) located on chromosome 15. The patient was diagnosed as having features of a PAPA-like syndrome in which cutaneous manifestations, such as pyoderma gangrenosum and acne fulminans, predominated.Sequencing of the PSTPIP1 gene was performed in the patient and his extended family. The patient's DNA analysis revealed a homozygous nucleotide exchange c.773G>C in the PSTPIP1 gene, leading to the substitution of glycine 258 by alanine (p.Gly258Ala), a previously reported heterozygous polymorphism. Heterozygous changes were identified in both of the patient's parents and in 7 other family members, all of whom were asymptomatic. The patient was treated with canakinumab, a human anti-interleukin 1β monoclonal antibody, which led to rapid remission of the symptoms.To our knowledge, this is the first reported case of the resolution of dermatological symptoms associated with a PAPA-like syndrome using canakinumab treatment. Further study of the p.Gly258Ala variant is warranted to determine whether this mutation has a role in causing an apparently recessive cutaneous syndrome resembling PAPA syndrome.
Psychological stress and the passage of a standard meal through the stomach and small intestine in man
Authors: P A Cann, N W Read, J Cammack, H Childs, S Holden, R Kashman, J Longmore, S Nix, N Simms, K Swallow, J Weller
Journal: Gut (1983)

Gastric emptying half-time and mouth to caecum transit time of a solid meal were measured in eight normal volunteers, once during a period of psychological stress and again during a period of relative calm. No consistent or significant effect on gastric emptying was observed, but mouth to caecum transit times were faster in all subjects and this difference was highly significant (p<0.01).
Triple therapy with ursodeoxycholic acid, prednisone and azathioprine in primary biliary cirrhosis: a 1-year randomized, placebo-controlled study
Authors: Frank H.J. Wolfhagen, Hubert J.F. van Hoogstraten, Henk R.van Buuren, Gerard P. van Berge-Henegouwen, Fiebo J.W. ten Kate, Wim C.J. Hop, Egbert W. van der Hoek, Marjo J. Kerbert, Hans H. van Lijf, Janny W. den Ouden, Adelbert M. Smit, Richard A. de Vries, Rene A.A. van Zanten, Solko W. Schalm
Journal: Journal of Hepatology (1998)
Persistent measles virus infection of the intestine: confirmation by immunogold electron microscopy.
Authors: J Lewin, A P Dhillon, R Sim, G Mazure, R E Pounder, A J Wakefield
Journal: Gut (1995)

This study sought to investigate persistent measles virus infection of the intestine: a novel protocol for immunogold electron microscopy was developed using a polyclonal anti-measles nucleoprotein antibody on reprocessed, formalin fixed paraffin wax embedded tissue sections. Antibody binding was detected using both immunoperoxidase and light microscopy on tissue sections, and 10 nm gold conjugated secondary antibody and electron microscopy on ultrathin sections. The techniques were validated using both measles infected vero cells and human tissues with established measles infection: these included brain affected by subacute sclerosing panencephalitis and acute measles appendicitis. The technique was applied subsequently to six untreated cases of granulomatous Crohn9s disease, and two cases of ileocaecal tuberculosis, a granulomatous control. Mumps primary antibody--applied to both mumps infected vero cells, and measles infected vero cells and tissues studied by immunoperoxidase, and measles antibody on mumps infected cells studied by immunoperoxidase and immunogold--were used as specificity controls: the primary antibodies identified their respective target antigen and there was no antibody cross reactivity. Measles virus nucleocapsids labelled with gold conjugated antibody in both infected cells and tissues, including foci of granulomatous inflammation in five of six cases of Crohn9s disease: in the fifth case, the granuloma could not be identified in ultrathin section. In one of the tuberculosis cases, a low level of signal was noted while the second case was negative. Labelling adopted a characteristic pattern in all infected tissues, strengthening the specificity of these findings. This study provides the first direct confirmation of persistent measles virus infection of the intestine.
Selective Inhibition of HER2-Positive Breast Cancer Cells by the HIV Protease Inhibitor Nelfinavir
Authors: Joong Sup Shim, Rajini Rao, Kristin Beebe, Len Neckers, Inkyu Han, Rita Nahta, Jun O. Liu
Journal: JNCI Journal of the National Cancer Institute (2012)

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is highly aggressive and has higher risk of recurrence than HER2-negative cancer. With few treatment options available, new drug targets specific for HER2-positive breast cancer are needed.We conducted a pharmacological profiling of seven genotypically distinct breast cancer cell lines using a subset of inhibitors of breast cancer cells from a screen of the Johns Hopkins Drug Library. To identify molecular targets of nelfinavir, identified in the screen as a selective inhibitor of HER2-positive cells, we conducted a genome-wide screen of a haploinsufficiency yeast mutant collection. We evaluated antitumor activity of nelfinavir with xenografts in athymic nude mouse models (n = 4-6 per group) of human breast cancer and repeated mixed-effects regression analysis. All statistical tests were two-sided.Pharmacological profiling showed that nelfinavir, an anti-HIV drug, selectively inhibited the growth of HER2-positive breast cancer cells in vitro. A genome-wide screening of haploinsufficiency yeast mutants revealed that nelfinavir inhibited heat shock protein 90 (HSP90) function. Further characterization using proteolytic footprinting experiments indicated that nelfinavir inhibited HSP90 in breast cancer cells through a novel mechanism. In vivo, nelfinavir selectively inhibited the growth of HER2-positive breast cancer cells (tumor volume index of HCC1954 cells on day 29, vehicle vs nelfinavir, mean = 14.42 vs 5.16, difference = 9.25, 95% confidence interval [CI] = 5.93 to 12.56, P < .001; tumor volume index of BT474 cells on day 26, vehicle vs nelfinavir, mean = 2.21 vs 0.90, difference = 1.31, 95% CI = 0.83 to 1.78, P < .001). Moreover, nelfinavir inhibited the growth of trastuzumab- and/or lapatinib-resistant, HER2-positive breast cancer cells in vitro at clinically achievable concentrations.Nelfinavir was found to be a new class of HSP90 inhibitor and can be brought to HER2-breast cancer treatment trials with the same dosage regimen as that used among HIV patients.
Sex Differences in Brain Morphology in Schizophrenia
Authors: Peg Nopoulos, Michael Flaum, Nancy C. Andreasen
Journal: American Journal of Psychiatry (1997)

OBJECTIVE: The current literature on sex differences in schizophrenia with regard to structural brain abnormalities is inconsistent. Several studies have suggested that male and female patients may differ in severity of brain abnormalities. Efforts to explore this issue have been hindered by small study groups, unbalanced groups (i.e., those with many more men than women), or both. The relatively smaller number of female schizophrenic patients in most studies may have made it more difficult to detect differences between patients and comparison subjects. This study was designed to evaluate brain morphology in a carefully selected group of patients with schizophrenia and healthy comparison subjects who were balanced by sex. METHOD: Eighty patients (40 male and 40 female) and 80 healthy volunteers matched by sex and age were studied. Magnetic resonance imaging scans were analyzed with the use of an automated method that yields volumes of major brain regions. RESULTS: There was a significant sex-by-diagnosis interaction for ventricular volume, with male patients having significantly larger ventricles than male comparison subjects but female patients showing no significant enlargement in comparison with healthy female subjects. Although the overall distribution of structural brain differences was very similar in the male and female patients, the male patients had a greater number of significant abnormalities than the female patients. CONCLUSIONS: These findings indicate that male and female patients with schizophrenia have the same pattern of structural brain abnormalities, but male patients appear to manifest greater severity, especially with regard to ventricular enlargement. (Am J Psychiatry 1997; 154:1648–1654)