tbuckley/cabot-search huggingface dataset:
Cytological samples for the study of EGFR, KRAS and ALK mutations in non-small cell lung cancer
Authors: Caroline Becker, Enric Carcereny Costa, Felipe Andreo Garcia, Eva Castellá, Mariona Lletjós Sanuy, Teresa Morán, Erika Mijangos Basterra, José Sanz Santos, Carmen Centeno Clemente, Juan Ruiz Manzano
Journal: European Respiratory Journal (2013)

Introduction  Recent progresses in targeted therapy of lung cancer have achieved remarkable results in advanced disease. It was generally considered that cytological samples were less likely to be suitable for molecular studies. To assess the validity of using cytological specimens for conducting molecular tests, we performed this retrospective study of cytology samples from Non-Small-Cell lung cancer (NSCLC) patients to determine the presence of EGFR, KRAS and/or ALK mutations.  Material and methods  From 2007 to 2012,233 samples of patients with NSCLC collected at the Deparment of Pathology of our institution were analyzed for the presence of EGFR, KRAS and/or ALK mutations. Biological fluids, bronchoscopy samples, CT guided transthoracic and endobronchial ultrasound guided fine needle aspiration were used. Samples were processed as cell blocks or membrane extensions. Subsequently, tumor cells were selected by micro dissection and DNA sequencing was performed at our Molecular Biology Laboratory.  Results  EGFR mutations were analyzed in 233 samples,the mutations were found in 16/233 (6.8%) and their determination performance was 90.1% (not assessable in 13 samples,insufficient tissue in 6, no tumor in 4). KRAS mutations were tested in 49 samples with a mutation frequency of 14.3 % (7/49) and a performance of 81.63% (not assessable in 5,insufficient tumor cells in 3, no tumor 1) ALK mutations were analyzed in 8 samples with a performance of 62.5% (insufficient samples 2, pending 1).  Conclusions  These results show that the analysis of EGFR, KRAS and ALK mutations in several cytological samples is feasible with a high performance.Therefore it should be an option to consider in clinical practice.
THE SYNDROME OF INTERNAL FRONTAL HYPEROSTOSIS
Authors: NATHAN ROTH
Journal: American Journal of Psychiatry (1941)

There is a syndrome occurring almost exclusively in females, whose pathognomonic sign is internal frontal hyperostosis, and which is generally accompanied by truncal obesity and frequently by facial hirsutism. Certain other metabolic and physiologic disturbances are more or less commonly observed. Considerable experimental, morphologic and pathophysiologic evidence now exists to point to the etiologic importance in this disease of dysfunction of the anterior lobe of the pituitary gland. Neurologic and mental sequelae, as a consequence of the presence of the hyperostoses, appear to be quite infrequent. In the series of cases here presented it was felt that the neuropsychiatric signs and symptoms were not to be attributed to the effect of the hyperostoses on the underlying brain tissue, but were the result of other factors, such as cerebral arteriosclerosis, hypertension, etc. A theory to account for the formation and localization of the hyperostoses has been advanced.
Maternal Smoking in Pregnancy and Asthma in Preschool Children
Authors: Åsa Neuman, Cynthia Hohmann, Nicola Orsini, Göran Pershagen, Esben Eller, Henrik Fomsgaard Kjaer, Ulrike Gehring, Raquel Granell, John Henderson, Joachim Heinrich, Susanne Lau, Mark Nieuwenhuijsen, Jordi Sunyer, Christina Tischer, Maties Torrent, Ulrich Wahn, Alet H. Wijga, Magnus Wickman, Thomas Keil, Anna Bergström
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Although epidemiological studies suggest that exposure to maternal smoking during fetal and early life increases the risk of childhood wheezing and asthma, previous studies were not able to differentiate the effects of prenatal from postnatal exposure.To assess the effect of exposure to maternal smoking only during pregnancy on wheeze and asthma among preschool-age children.A pooled analysis was performed based on individual participant data from eight European birth cohorts. Cohort-specific effects of maternal smoking during pregnancy, but not during the first year, on wheeze and asthma at 4 to 6 years of age were estimated using logistic regression and then combined using a random effects model. Adjustments were made for sex, parental education, parental asthma, birth weight, and siblings.Among the 21,600 children included in the analysis, 735 children (3.4%) were exposed to maternal smoking exclusively during pregnancy but not in the first year after birth. In the pooled analysis, maternal smoking only during pregnancy was associated with wheeze and asthma at 4 to 6 years of age, with adjusted odds ratios of 1.39 (95% confidence interval, 1.08-1.77) and 1.65 (95% confidence interval, 1.18-2.31), respectively. The likelihood to develop wheeze and asthma increased statistically significantly in a linear dose-dependent manner in relation to maternal daily cigarette consumption during the first trimester of pregnancy.Maternal smoking during pregnancy appears to increase the risk of wheeze and asthma among children who are not exposed to maternal smoking after birth.
1-Antitrypsin deficiency
Authors: J K Stoller
Journal: Thorax (2004)

<h3>Background</h3> Nchelenge district is a holoendemic malaria transmission zone in northern Zambia. The district occurs in a region characterised by a mix of water, marshes, islands and lagoons presenting a uniquely suitable ecology for mosquitoes. Annual indoor residual spraying (IRS) campaigns are carried out between September and December synchronised with other regions in the country with different environmental conditions. Targeted vector control interventions have been applied since 2008 without appreciable impact on disease burden. The timing and targeting of vector control measures are not guided by an informed entomological baseline. This study was aimed at providing entomological information on the seasonal abundance, spatial distribution and <i>Plasmodium falciparum</i> sporozoite infections in the local malaria vector species in order to guide implementation of vector control in the district. <h3>Methods</h3> Entomological studies were conducted intermittently spanning the rainy, cold-dry, and hot-dry seasons from 2015–2016. Mosquitoes were collected by CDC light traps, identified to species both morphologically and by PCR techniques. Circumsporozoite ELISA assay was used to detect <i>P. falciparum</i> in mosquito salivary glands. <h3>Results</h3> A total of 5437 female <i>Anopheles funestus</i> and <i>An. gambiae</i> and over 6000 culicines, mostly <i>Mansonia</i> mosquitoes were collected. The peak number of the <i>An. funestus</i> from all sites occurred in July. Overall <i>P. falciparum</i> infection rates in <i>An. funestus</i> were Kilwa island 2.7% (4/146), Mainland 2.5% (3/122), Chisenga island 0.4% (1/220), Isokwe 5.9% (2/34) and in <i>An. leesoni</i> from Kilwa 33% (1/3). The highest number of <i>An. gambiae</i> was collected from Kilwa and none was found infected with <i>P. falciparum</i> regardless of collection site. <h3>Conclusions</h3> The annual IRS conducted between September and December may be ineffective in controlling malaria as this misses the vector peak abundance and peak transmission season. Two rounds of IRS covering more areas would be needed to control the two vector species with different population peak seasons and malaria transmission.
Communicating Hydrocephalus in the Intellectual Deterioration of Diabetes Mellitus
Authors: D B Jones, J P Hosker, C M Asplin
Journal: Journal of the Royal Society of Medicine (1983)

Atherosclerosis of cerebral vessels (Grunnet 1963) and hypoglycaemia (Bale 1973) are thought to be involved in the premature intellectual deterioration which occurs in some diabetics. Two diabetics are now reported who, in the course of their investigation for intellectual deterioration, were found to have communicating hydrocephalus.
Fluorouracil, doxorubicin, cyclophosphamide, and cisplatin combination chemotherapy in advanced or recurrent salivary gland carcinoma.
Authors: I W Dimery, S S Legha, M Shirinian, W K Hong
Journal: Journal of Clinical Oncology (1990)

Seventeen patients with recurrent or unresectable salivary gland carcinomas were treated with combination fluorouracil (5-FU), doxorubicin, cyclophosphamide, and cisplatin (FACP). Sixteen patients were assessable for response and toxicity. A total of 111 courses of chemotherapy were given, yielding one complete and seven partial responses, for an objective response rate of 50%. Two other patients had stable disease and two had a minor response. The median duration of objective response was 32 weeks (range, 4 to 72); median survival for the 16 patients was 72 weeks. Hematologic toxicity was significant, with 88% developing a nadir granulocyte count of less than 1,000 cells per microliter (median, 300 cells per microliter), and 53% a nadir platelet count of less than 100,000 cells per microliter (median, 68,000 cells per microliter). Seven patients (44%) developed neutropenic fever, and three (18%) developed an increase in serum creatinine greater than 1.5 mg/dL during the course of treatment. This combination of chemotherapy was active; however, an increased response rate was not observed above that reported for other combinations. Response duration, or overall patient survival, on this intensive regimen was similar as compared with other published therapeutic trials of this disease entity.
Th2 responses induce humorally mediated injury in experimental anti-glomerular basement membrane glomerulonephritis.
Authors: X R Huang, S R Holdsworth, P G Tipping
Journal: Journal of the American Society of Nephrology (1997)

Acute autologous phase anti-glomerular basement membrane glomerulonephritis was compared in Th1-prone (C57BL/6) and Th2-prone (BALB/c) mice. Sensitized BALB/c mice, given a subnephritogenic intravenous dose of anti-mouse glomerular basement membrane globulin, developed acute glomerulonephritis characterized by marked proteinuria and glomerular deposition of mouse immunoglobulin and complement. A significant glomerular neutrophil influx was observed, but few T cells and macrophages were present. C57BL/6 mice, given the same dose of disease-inducing globulin, also developed acute glomerulonephritis, although their proteinuria was significantly less. Glomerular deposition of mouse immunoglobulin and complement and the influx of neutrophils were also significantly less than in BALB/c mice. However, their glomerular accumulation of macrophages and T cells was significantly greater. Complement depletion attenuated neutrophil influx and proteinuria in BALB/c mice but did not affect T cell or macrophage accumulation or proteinuria in C57BL/6 mice. CD4+ T cell depletion significantly reduced glomerular macrophage, T cell influx, and proteinuria in C57BL/6 mice, but had no effect on proteinuria or neutrophil influx in BALB/c mice. Thus, immune responses to planted glomerular antigens in Th2-prone mice induce acute injury as a result of antibody deposition, complement activation, and neutrophil influx, whereas immune responses to the same antigen in Th1-prone mice induce delayed-type hypersensitivity-like lesions in affected glomeruli.
The influence of obstructive sleep apnoea and obesity on adiponectin, leptin, IGFBP-1 and HOMA-IR
Authors: Kallirroi Lamprou, Ioannis Koutsourelakis, Agathoklis Tsatsoulis, Anna Challa, Stavros Konstantopoulos, George Daskalopoulos
Journal: European Respiratory Journal (2013)

Obstructive sleep apnea (OSA) is associated with hormonal alterations that increase the risk for insulin resistance (IR). The pathophsyiologic mechanisms that link OSA and IR are unclear and are frequently confounded by obesity. The aim of this study was to investigate the independent role of apneas and obesity on plasma adiponectin, leptin, insulin-like growth factor binding protein 1 (IGFBP-1), and homeostasis model assessment-IR (HOMA-IR).  We studied 111 untreated OSA patients (95 males; mean age 55.0±13.2 years). Patients were divided into two groups according to apnea-hypopnea index (AHI). Patients with AHI 20 (second group; n=71; 19 non-obese and 52 obese patients). Plasma adiponectin, leptin, IGFBP-1, and HOMA-IR were determined by ELISA kit.  Patients of the first group had increased leptin (p=0.009) and IGFBP-1 (p=0.009) and decreased HOMA-IR (p=0.03) in comparison with the patients of the second group. In the first group, non-obese patients had decreased leptin (p=0.02) and increased IGFBP-1 (p=0.01) in comparison with obese patients. In the second group, non-obese patients had decreased leptin (p=0.008) in comparison with obese patients.  Between non-obese patients of the two groups only IGFBP-1 was different (p  Obesity is associated with increased leptin and decreased IGFBP-1. OSAS is associated with decreased IGFBP-1.
Serum la Levels During Tumor Growth in Mice and Humans&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: M S Sandrin, M M Henning, H A Vaughan, I F McKenzie, C R Parish
Journal: JNCI Journal of the National Cancer Institute (1981)

Antigen stimulation in mice such as occurs with the rejection of an allogeneic tumor graft caused a substantial rise in serum glycolipid Ia levels. However, mice bearing a measurable syngeneic tumor had no detectable Ia antigens in their sera; this observation was made in several different strains of inbred mice with 5 different tumors. In each instance the serum Ia level fell as the tumor grew progressively, reached zero at about the time the tumor was visible, and remained at this zero level until the mouse died. Similar results were found in humans: Tumor-bearing patients had markedly suppressed serum Ia levels. The mechanism of the fall in serum Ia glycolipid levels is not known, but the measurement of the serum Ia glycolipid content appears to reflect the level of activation of the immune system, and the suppression of serum glycolipid Ia levels found in tumor-bearing mice and patients may have important clinical implications.
Progressive Flow-to-Volume Dysanapsis in Cystic Fibrosis
Authors: Daphna Vilozni, Moran Lavie, Ifat Sarouk, Ori Efrati
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Airways obstruction and lung volume restriction, major features of lung disease in cystic fibrosis (CF), may regress independently, causing dysanapsis between these parameters.To explore the significance of dysanapsis (FEF(25-75)/FVC) ratio in CF.Yearly best spirometry data, collected during 8.6 ± 1 year per patient, was determined from 93 patients with CF. Three groups were formed according to initial FEV(1). Group-N (n = 35; control, FEV(1) above 80%predicted); Group-B (n = 38; FEV(1) below 80% predicted); and Group-LT (n = 20; data collected before lung transplantation). The yearly decline in spirometry indices was defined in relation to the preceding year. Decline exceeding -2 z scores from Group-N in each index was considered "rapid decline."Group-N's yearly decline of FEV(1), FEF(25-75), and FEF(25-75)/FVC were similar and reached -1.88 ± 2.93%, -1.41 ± 3.37%, and -1.81 ± 4.48%, respectively. Rapid decline was equal to -6.5%, -10.8%, and -8.1%, respectively. Group-B's indices declined faster than that of Group-N, but did not exceed 1 z score. Group-LT showed a rapid decline solely in FEF(25-75)/FVC (mean z score = -6.4 ± 2.5; P < 0.0001), which sprouted abruptly from the regular course of regression 4 ± 1.3 years before transplantation. The rapid decline in FEF(25-75)/FVC was found in 19 of 20 patients from Group-LT and five patients from other groups (now waiting for transplantation). The phenomenon did not correlate with initial FEV(1) (%predicted) or age. Having airway hyperreactivity increased the risk of rapid decline in FEF(25-75)/FVC.Roughly 4 years before lung transplantation and independent of FEV(1) (%predicted), FEV(1) decline rate, or age, an abrupt rapid dysanapsis occurs. Findings imply insufficient ventilation/lung volume unit and insinuate a powerful marker for estimating lung translation time in CF.
Genetic Cell Ablation Reveals Clusters of Local Self-Renewing Microglia in the Mammalian Central Nervous System
Authors: Julia Bruttger, Khalad Karram, Simone Wörtge, Tommy Regen, Federico Marini, Nicola Hoppmann, Matthias Klein, Thomas Blank, Simon Yona, Yochai Wolf, Matthias Mack, Emmanuel Pinteaux, Werner Müller, Frauke Zipp, Harald Binder, Tobias Bopp, Marco Prinz, Steffen Jung, Ari Waisman
Journal: Immunity (2015)
Intensity-modulated radiation therapy (IMRT) with concurrent taxane-based chemotherapy for locally-advanced head and neck cancer(LAHNC): Feasibility, technique, and toxicities
Authors: D. Duggan, B. A. Murphy, M. Beach, M. Teng, D. Hallahan, B. Burkey, J. Netterville, C. H. Chung, L. Butler, A. J. Cmelak
Journal: Journal of Clinical Oncology (2005)

5536 Background: Chemotherapy given concurrently with radiation is proven to improve tumor survival in LAHNC at the expense of higher toxicity. IMRT for LAHNC provides a means to minimize dose to sensitive organs. Our initial experience with concurrent IMRT and taxane-based chemotherapy in 83 LAHNC patients is presented. Methods: In order to simplify IMRT planning, a differential IMRT dose plan is developed for all head and neck structures. Daily fractions of 2.1Gy are delivered to gross disease with +/-5% homogeneity (69.3Gy in 33 fxs), simultaneously with 1.7Gy to prophylactic nodes (56.1Gy, homo +8 to -5%). 50% of the volume of sensitive tissue (oral cavity, parotids, back of neck, and larynx/trachea) are limited to ≤25Gy. Weekly paclitaxel 30mg/m2 and carboplatin AUC 1 were given concurrently to all 83 patients, and 40 with N2 or N3 disease also received weekly induction chemotherapy with paclitaxel 60mg/m2 and carboplatin AUC2. Chemo was held for ANC<1000, plts<100k, or gr4 mucositis Results: All 83 patients had AJCC III or IV nonmetastic disease: sinus-5, NPC-9, OP-44, OC-6, larynx-13, hypo-6. This regimen is highly feasible. 2 patients discontinued treatment early into treatment for non-toxicity related reasons (progression in lungs). Only 2 patients required a radiation break greater than 1 week. 28% required temporary PEG (none long-term). Only one patient (T4N0 hypopharynx) is still trach-dependent but has good swallowing function. Grade 3 mucositis occurred in 57% (2%Gr4) and gr3 dermatitis in 37%. There were no pts with nadir sepsis nor sig nephropathy or GI toxicity. One patient with a large base of skull tumor died 1 month after completion from carotid rupture. Xerostomia is ≤gr1 in all patients. Conclusions: IMRT with paclitaxel and carbo for LAHNC is extremely feasible using differential IMRT target dosing. Doses to sensitive non-target structures (oral cavity, trachea/larynx, back of neck, parotids) can be minimized (≤25Gy) and dose homogeneity to gross tumor held within +/-5% to avoid long-term morbidity. Early toxicities are low. Tumor control and survival data will also be presented. No significant financial relationships to disclose.
Dietary Fat and Carbohydrates Are Independently Associated With Circulating Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor–Binding Protein 3 Concentrations in Healthy Adults
Authors: Virginia G. Kaklamani, Athena Linos, Evangelia Kaklamani, Ioanna Markaki, Yvonni Koumantaki, Christos S. Mantzoros
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To evaluate and quantify the association between consumption of specific food groups/macronutrients and concentrations of serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor–binding protein 3 (IGFBP-3). SUBJECTS AND METHODS: Data from a comprehensive food-frequency questionnaire administered to 115 healthy subjects were used to study cross-sectionally the relationship between nutritional factors and circulating IGF-1 and IGFBP-3 concentrations. Adjustment for the effect of total energy intake and a series of epidemiologic parameters (age, sex, height, body mass index, smoking, alcohol consumption, and coffee drinking) was implemented through multivariate linear regression. RESULTS: We observed that serum levels of IGF-1 are positively associated with consumption of redmeats, fats, and oils. In addition, serum levels of IGF-1 are independently and positively associated with energy intake from lipids and negatively associated with energy intake from carbohydrates. Finally, serum levels of IGFBP-3 are independently and negatively associated with energy intake from saturated fat. CONCLUSION: Serum IGF-1 and/or IGFBP-3 concentrations are associated with red meat, carbohydrate intake, and fat intake and, thus, may mediate the effect of these dietary factors on the pathogenesis of several disease states. Additional studies are needed to further quantify these associations and elucidate the underlying mechanisms.
The Proto-Oncogene ERG in Megakaryoblastic Leukemias
Authors: Liat Rainis, Tsutomu Toki, John E. Pimanda, Ester Rosenthal, Keren Machol, Sabine Strehl, Berthold Göttgens, Etsuro Ito, Shai Izraeli
Journal: Cancer Research (2005)

Abstract Aneuploidy is one of the hallmarks of cancer. Acquired additions of chromosome 21 are a common finding in leukemias, suggesting a contributory role to leukemogenesis. About 10% of patients with a germ line trisomy 21 (Down syndrome) are born with transient megakaryoblastic leukemia. We and others have shown acquired mutations in the X chromosome gene GATA1 in all these cases. The gene or genes on chromosome 21 whose overexpression promote the megakaryoblastic phenotype are presently unknown. We propose that ERG, an Ets transcription factor situated on chromosome 21, is one such candidate. We show that ERG is expressed in hematopoietic stem cells, megakaryoblastic cell lines, and in primary leukemic cells from Down syndrome patients. ERG expression is induced upon megakaryocytic differentiation of the erythroleukemia cell lines K562 and UT-7, and forced expression of ERG in K562 cells induces erythroid to megakaryoblastic phenotypic switch. We also show that ERG activates the gpIb megakaryocytic promoter and binds the gpIIb promoter in vivo. Furthermore, both ERG and ETS2 bind in vivo the hematopoietic enhancer of SCL/TAL1, a key regulator of hematopoietic stem cell and megakaryocytic development. We propose that trisomy 21 facilitates the occurrence of megakaryoblastic leukemias through a shift toward the megakaryoblastic lineage caused by the excess expression of ERG, and possibly by other chromosome 21 genes, such as RUNX1 and ETS2, in hematopoietic progenitor cells, coupled with a differentiation arrest caused by the acquisition of mutations in GATA1.
Science and advertising.
Authors: J N Cohn
Journal: Circulation (1982)

CHANGING TRENDS in government and industry support for medical research and education have brought into focus an issue that has infrequently been addressed: separating science from advertising.The problem is obvious in many of the regularly recurring activities of the cardiology community: seeking grant support, accepting industry support for speakers and meetings, selecting abstracts for presentation at meet- ings, selecting topics for discussion at symposia, deal- ing with the media, reporting one's own research and clinical findings, and attracting new referrals.Science may be defined as a critical analysis of data from well-designed studies.Advertising, on the other
Lyme borreliosis: Clinical case definitions for diagnosis and management in Europe
Authors: G. Stanek, V. Fingerle, K.-P. Hunfeld, B. Jaulhac, R. Kaiser, A. Krause, W. Kristoferitsch, S. O'Connell, K. Ornstein, F. Strle, J. Gray
Journal: Clinical Microbiology and Infection (2010)