tbuckley/cabot-search huggingface dataset:
Enterovirus and Human Parechovirus Surveillance — United States, 2009–2013
Authors: Glen R. Abedi, John T. Watson, Huong Pham, W. Allan Nix, M. Steven Oberste, Susan I. Gerber
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

Enteroviruses (EVs) and human parechoviruses (HPeVs) are small, non-enveloped RNA viruses in the Picornaviridae family, which are known or suspected to cause a spectrum of clinical manifestations in humans. Although most infected persons are asymptomatic, mild presentations can include respiratory infections, herpangina, and hand, foot, and mouth disease. Among the more severe syndromes associated with EV and HPeV infection are acute flaccid paralysis, meningitis, encephalitis, myocarditis, and sepsis. Neonates and infants are at higher risk for infection and for severe clinical outcomes than older children or adults (1–3). As of August 2015, a total of 16 HPeV types and 118 EV types (within four EV species known to infect humans: A, B, C, and D) had been identified, and the spectrum of illness caused differed among virus types (4). To describe trends in EV and HPeV circulating in the United States during 2009–2013, CDC summarized detections reported through two surveillance systems. The most commonly reported types of EV and HPeV during this period were coxsackievirus (CV) A6 and HPeV3. The large number of CVA6 detections likely reflected an increase in testing in response to an outbreak of severe hand, foot, and mouth disease in late 2011 and 2012 (5). Most HPeV3 detections originated from a single hospital that routinely tested for HPeV (6). Clinicians and public health practitioners should consider the EV and HPeV types recently circulating in the United States to inform diagnostic and surveillance activities. When EV and HPeV typing is performed, clinical and public health laboratories should routinely report their results to improve the reliability and generalizability of surveillance data.
Clinical Comparison between Friedman Test and in Vitro Test for Pregnancy
Authors: J Eden, I Black
Journal: JAMA (1963)

Latex pregnancy tests were performed on 737 urine samples submitted to a hospital laboratory for Friedman tests. Clinical confirmation of the diagnoses was obtained in 666. Nine Friedman and 31 latex tests were falsely positive in 199 samples having specific gravities over 1.015. Each test gave four false-positive results in 65 samples with specific gravities under 1.015. Between six and 13 weeks of gestation, nine Friedman and 45 latex tests were negative in 176 samples with specific gravities above 1.015; below 1.015, five Friedman and 15 latex tests were false in 42 samples. At other stages of pregnancy, seven Friedman and 18 latex tests were negative in 56 samples with specific gravities over 1.015 and, under 1.015, nine samples had four negative latex tests.The latex test requires careful control and is less reliable than the Friedman test.
Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants
Authors: Samar Kulkarni, Ray Powles, Jennie Treleaven, Unell Riley, Seema Singhal, Clive Horton, Bhawna Sirohi, Niyati Bhagwati, Simon Meller, Radovan Saso, Jayesh Mehta
Journal: Blood (2000)
Abstract 219: Combination of Algorithms to Decrease Preshock Pause for Automated External Defibrillators
Authors: Jean-philippe Didon, Irena Jekova, Sarah Ménétré, Todor Stoyanov, Vessela Krasteva
Journal: Circulation (2011)

BACKGROUND Long pre-shock ‘hands-off’ intervals without chest compressions (CC) are associated with defibrillation failure. Current guidelines recommend shortening the ‘hands-off’ intervals. The aim of this study is to present the performance of a Shock advisory System (SAS) which is designed for triggering a fast ECG analysis at minimal delay after the end of chest compression (EoCC). METHOD A subset of 1263 strips is identified from 311 Out-of-hospital cardiac arrest (OHCA) interventions. AED rhythms include 1182 Non-Shockable strips (788 asystoles (ASYS), 394 other non-shockable rhythms (ONS)), and 81 ventricular fibrillations (VF). The SAS with minimum ‘hands-off’ intervals first detect the real end of CC (ReEoCC) offset considered as the earliest triggering point for a reliable ECG analysis without CC artifacts. Then, it performs a fast ECG analysis to lead to “Shock/No shock” decision. Specificity (Sp) for ASYS and ONS and sensitivity (Se) for VF are computed RESULTS The ECG analysis is triggered immediately at ReEoCC. The gain in time for earlier starting of the ECG analysis is found to be 5.6±3.6 seconds. The accuracy of the SAS is tested for 6 seconds analysis duration. The SAS “Shock/No shock” decision is provided 10.6±3.9 seconds earlier than the current AED decision. The SAS performance is compared to the AHA recommendations for Sp, Se and 90% one-sided lower confidence limit (LCL90) for noise-free signals (Table 1). CONCLUSION The accuracy of SAS for fast ECG analysis at minimal delay after the end of CC fulfills the AHA goals (Sp/Se and LCL90) for ASYS, ONS and VF rhythms. A reduction of ‘hands-off’ time of 10.6 seconds (between end of CC and end of analysis) in average can be expected, when compared to current AED decision delay. Table 1: Accuracy of SAS with minimum ‘hands-off’ intervals
Second-line dovitinib (TKI258) in patients with FGFR2-mutated or FGFR2-non-mutated advanced or metastatic endometrial cancer: a non-randomised, open-label, two-group, two-stage, phase 2 study
Authors: Gottfried E Konecny, Neil Finkler, Agustin A Garcia, Domenica Lorusso, Paula S Lee, Rodney P Rocconi, Peter C Fong, Matt Squires, Kaushal Mishra, Allison Upalawanna, Yongyu Wang, Rebecca Kristeleit
Journal: The Lancet Oncology (2015)
Propranolol in the treatment of rage and violent behavior in patients with chronic brain syndromes
Authors: S Yudofsky, D Williams, J Gorman
Journal: American Journal of Psychiatry (1981)

The authors successfully treated four patients who had irreversible CNS lesions and socially disabling aggressiveness and outbursts of rage, which had not been affected by high doses of major tranquilizers or anticonvulsants, with 320-520 mg/day of propranolol. Disorientation, memory impairment, and psychotic thought processes associated with the CNS lesions were not altered by the propranolol.
Nicotine withdrawal symptoms and psychiatric disorders: findings from an epidemiologic study of young adults
Authors: N Breslau, M M Kilbey, P Andreski
Journal: American Journal of Psychiatry (1992)

Earlier, the authors reported on the association of nicotine dependence with major depression and anxiety disorders in a group of young adults. This report describes the occurrence of withdrawal symptoms and their sociodemographic and psychiatric correlates in persons in that group who tried unsuccessfully to abstain from smoking.A random sample of 1,007 members of a health maintenance organization, 21-30 years old, were interviewed with a revised version of the NIMH Diagnostic Interview Schedule. Data on nicotine withdrawal came from a subset of 239 smokers who had tried unsuccessfully to quit or cut down on smoking.With two exceptions, each of the DSM-III-R nicotine withdrawal symptoms was reported by more than one-half of these smokers. Withdrawal symptoms were more severe in white than in black smokers but were unrelated to sex, educational level, or marital status. Persons with histories of major depression or any anxiety disorder reported more severe withdrawal symptoms than persons with neither of these disorders. Severity of withdrawal, or any specific symptom, did not account for the association between major depression and continued smoking. Furthermore, severity of withdrawal was unrelated to continued smoking.While the long-term clinical significance of nicotine withdrawal is unclear, the evidence indicates that in the general population, abstinence from smoking is associated with a variety of disturbances, including a craving for cigarettes, dysphoria, and symptoms of irritability or nervousness. In this study disturbances were more severe in persons with histories of major depression or anxiety disorders.
Dopamine Stimulation of Active Na and Cl Absorption in Rabbit Ileum
Authors: Mark Donowitz, Sheila Cusolito, Laurie Battisti, Ronald Fogel, Geoffrey W. G. Sharp
Journal: Journal of Clinical Investigation (1982)

The effects of dopamine on active intestinal ion transport have been evaluated. An epithelial sheet preparation of rabbit ileum was used in vitro with the Ussing chamber-voltage clamp technique. Dopamine, in the presence of 1 mM ascorbic acid, added to the serosal bathing solution caused a dose-dependent decrease in short-circuit current, with a half-maximal effect at 1.2 μM and maximal effect of −50 μA/cm2 at 50 μM; dopamine decreased the potential difference, and increased the conductance and net Na and net Cl absorption. There was no effect on the residual ion flux. Dopamine did not alter the change in short-circuit current caused by mucosal glucose (10 mM) or serosal theophylline (10 mM). Mucosal dopamine had no effect. The effect of dopamine on short-circuit current was inhibited by the dopamine antagonists haloperidol and domperidone and the α2-adrenergic antagonist yohimbine; there was no effect of the α1-antagonist prazosin and the β-antagonist propranolol. In addition, the α2-adrenergic agonist clonidine, but not the α1-agonist methoxamine caused a dose-dependent decrease in short-circuit current. The ileal effects of dopamine did not occur via conversion into norepinephrine or release of norepinephrine from the peripheral nerves since “peripheral sympathectomy” with 6-hydroxydopamine did not alter the dopamine-induced change in ileal short-circuit current. The dopamine effects were not associated with a change in basal ileal cyclic AMP content but were associated with a decrease in total ileal calcium content as measured by atomic absorption spectrometry and as estimated by 45Ca++ uptake. The decrease in calcium content could be attributed to a dopamine-induced decrease in 45Ca++ influx from the serosal surface. Because of the presence of dopamine in ileal mucosa and these effects on ileal electrolyte transport, it is possible that dopamine may be involved in the physiologic regulation of active intestinal electrolyte absorption.
The role of PI3K-p110α in breast cancer
Authors: Jean J. Zhao, Zhenning Liu, Alexander Miron, Xin Lu, Li Wang, J. Dirk Iglehart, Thomas M. Roberts
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

2589 

The PI3K signaling pathway has been known to be up-regulated in many tumors via activation of receptor tyrosine kinases (RTKs) or inactivation of PTEN. It was only realized recently that the PIK3CA gene encoding the catalytic subunit p110α, a member of the PI3K family, is mutated at high frequency in human cancers. Mutations in PIK3CA were found in 40% of breast tumors, making this the most commonly mutated gene in breast cancer. Mutations in PIK3CA cluster into two major “hot spots” located in the helical and kinase domains. To evaluate the oncogenic potential of these mutant forms of p110α and investigate their mechanism(s) of action, we have developed a transformation system utilizing telomerase immortalized primary human mammary epithelial cells (HMECs). The study of kinases in HMECs demanded creation of a system devoid of interfering viral oncogenes. In the absence of viral oncogenes HMECs transformation is dependent on the activation of PI3K for growth in soft agar and as xenografts in mice. Interestingly, the kinase activities and transforming potencies of the two “hot spot” mutant alleles of p110α (E545K and H1047R) derived from human cancers are much higher than those of constitutively activated p110α by myristoylation (Myr-p110α). Unlike activating EGFR mutations, the activation of both E545K and H1047R is independent of growth factor stimulation. Thus HMEC cells transformed with activated PI3K-p110α are relatively insensitive to RTK inhibitors, including specific IGF-1R and EGFR inhibitors. Moreover, tumors derived from transformed HMEC cells expressing constitutively activated PI3K-p110α are highly vascularized particularly in the peripheral zone. We have also constructed a corresponding helical “hot spot” mutant allele in p110α that was roughly 10 fold less effective in activating Akt but still showed residual transforming ability. We have been able to analyze transcriptional profiles of our PI3K transformed HMEC to identify unique signatures of PIK3CA mutants in human breast tumor samples. Finally we have constructed a conditional knockout of the PIK3CA gene in mice to study the role of PI3K-p110α in breast development and breast cancer formation in vivo. Taken together, using our HMEC derived functional transformation system, we have demonstrated the oncogenic potential of tumor derived mutant alleles of PIK3CA in breast cancer formation and established a valuable model for preclinical studies of new specific inhibitors.
Abstract 2783: Variability of HER2 expression between <i>in vitro</i> and <i>in vivo</i> models within gastric cancer cell lines
Authors: Youme Gim, Hee Seo Park, Hae Rim Jung, Hae Ryung Chang, Seungyoon Nam, Yong Doo Choi, Ja-Lok Ku, Yon Hui Kim
Journal: Cancer Research (2014)

Abstract In the process of developing individualized cancer therapeutics, tumor derived cell line based preclinical (in vitro and in vivo) methods have been widely used. Patient derived genome analysis revealed significant cancer biomarkers for targeted drug development. Classic cancer biomarker, HER2, overexpression was discovered as a cancer biomarker and as a druggable target in breast cancer, which lead to the development of Trastuzumab. HER2 is overexpressed in 10-25% of gastric cancer, and treatment with Trastuzumab showed positive yet limited activity in advanced gastric cancer treatment in the ToGA study. These results present HER2 as an attractive target for gastric cancer. However, Gillet and colleagues reported the challenges in the use of in vitro and in vivo studies for drug validation and development. They reported variance in gene expression patterns between the in vitro and in vivo context within a single cancer cell line. In our study using gastric cancer derived cell lines, we observed differences in HER2 expression between in vitro and in vivo xenograft model. Also, we show the potential promising in vivo xenograft model in the development of HER2 targeting agents for gastric cancer. Eleven out of 25 gastric cancer cell lines showed HER2 expression, which was demonstrated using the IHC assay on a cell microarray. Sixteen out of 25 cell lines successfully produced xenograft models. Gastric cancer cell lines (SNU-5, SNU-16, SNU-638, SNU-1967, MKN-1, MKN-28, and NUGC-3) that had no HER2 expression when cultured in vitro showed HER2 expression in vivo. Two cell lines (NCC-19 and NCI-N87) that had HER2 expression in vitro showed a decrease in HER2 expression in vivo. Three cell lines (SNU-484, SNU-668, and SNU-719) showed various levels of increase in HER2 expression. Two cell lines showed minor to no changes in HER2 expression. NUGC-4 had consistent significant HER2 expression levels in both assays, while MKN-45 had consistent insignificant to no HER2 expression. Our study demonstrates inconsistency in HER2 gene expression between in vitro and in vivo cancer cell line models for the first time in gastric cancer. Citation Format: Youme Gim, Hee Seo Park, Hae Rim Jung, Hae Ryung Chang, Seungyoon Nam, Yong Doo Choi, Ja-Lok Ku, Yon Hui Kim. Variability of HER2 expression between in vitro and in vivo models within gastric cancer cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2783. doi:10.1158/1538-7445.AM2014-2783
New Deep Brain Stimulation Device
Authors: Rebecca Voelker
Journal: JAMA (2015)

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Inequalities in health
Authors: P. Martikainen, T. Valkonen, J F. Mustard
Journal: BMJ (1999)

Low dose aspirin for preventing and treating pre-eclampsia Author of editorial did not criticise studies' methodologyEditor-In her editorial discussing the value or otherwise of aspirin for preventing and treating pre-eclampsia Duley wonders why the small trials have such different results from the large trials. 1 We suggest the following answer.Evidence based medicine means integrating individual skill with the best available evidence from systematic research.Duley's conclusions, based on several multicentre studies, seem to rely on the conclusions of these studies without her making criticisms of the methodology used.Firstly, the timing of the start of treatment with low dose aspirin is important.The studies consistently fail to show the percentage of women who were < 16 weeks pregnant, the crucial time when maximum trophoblastic invasion is taking place (table ).This issue was raised by de Swiet in Bower's news article 2 and by Beaufilis et al. 3 Secondly, the dose of aspirin used in the later large trials is low.A meta-analysis by Leitich et al (not quoted in the editorial) shows that aspirin was more effective at higher doses (100-150 mg/day) than at lower doses (50-80 mg/day). 4It seems that these large studies have looked at the wrong dose of aspirin used at the wrong time of pregnancy.The editorial's conclusions are based on trials with flawed methodology.The question of whether aspirin given in early pregnancy in an appropriate dose is effective in preventing pre-eclampsia remains unanswered.
Evaluation of IL-8 and MEF25-75 in patients with severe COPD who were treated with combined therapy of ICSs / LABAs plus tiotropium bromide
Authors: Elena Janeva, Zlatica Goseva, Angelko Gjorcev, Suzana Arbutina, Marija Zdraveska, Deska Dimitrievska, Dejan Todevski, Dejan Trajkov
Journal: European Respiratory Journal (2013)

The aim of this study was to determine the effect of combined therapy of ICSs/LABAs plus tiotropium bromide in patients with COPD, by analyzing of IL-8 and MEF25-75 at the beginning and after 6 months of therapy.

The study included 33 patients with severe COPD. In each of them were measured serum IL-8 levels by the ELISA method and MEF25-75 which are indicated the small airways obstruction. They were treated with combined therapy of ICSs/LABAs (500mcg) plus Tiotropium Bromide (18mcg) daily in duration of 6 months.

The results were statistically elaborated according to the T-test for Dependent Samples. The obtained results of IL-8 showed that the level of IL-8 before the start of therapy were much higher and that treatment significantly reduces their value (t=3.13, p=0.003, p<0.05). The results of MEF 25-75 at the start of therapy were lower and after 6 months of treatment showed a slight improvement of lung function but statistically insignificant (t= -0.83, p=0.41,p<0.05).

The concentration of IL-8 is closely related with airway obstruction in patients with COPD and may serve as a marker for evaluating the severity of airway inflammation. ICSs/LABAs and tiotropium bromide have inhibitory effect on neutrophilic inflammation through the suppression of IL-8 production from epithelial cells and thus may contribute to lower cellular inflammation in COPD. Because it is a progressive disease and airflow limitation is not fully reversible, we cannot expect spectacular results like we show with the value of MEF25-75, but should strive to prevent progression and reduce airway remodeling with education, pharmacologic and non-pharmacologic treatment.
Commentary on the Contribution by Faedo et al. (Clin Cancer Res 2004;10:4417-4419)
Authors: Beatriz Pogo, Sylvie Menard, James F. Holland
Journal: Clinical Cancer Research (2005)

To the Editor: The contribution by Faedo et al. (Clin Cancer Res 2004;10:4417-4419) reports interesting and significant findings. They compare their data on tumors that are positive for the mouse mammary tumor virus–like env gene sequences with respect to p53 nuclear accumulation and progesterone receptor status with our published data (Pogo etal., Clin Cancer Res 1999;5:2108-2111). Unfortunately, they citeour data for p53 incorrectly. We have analyzed 69 specimensnot 26 as they stated in the discussion section of their study. We found 12 of 26 (46%) env (+) tumors positive for p53versus 13 of 43 (30%) env (−) tumors. The difference between env (+) and env (−) tumors among our 69 specimens is consistent with the data of Faedo et al. Differences in techniques and antibodies as well as sample size are likely contributing factors for some of the variation found.Beatriz PogoSylvie MenardJames F. HollandMount Sinai School of Medicine,Box 1129, 1 Gustaave L. Levy Place,New York, NY 10029E-mail: beatriz.pogo@mssm.eduIn Response: We thank Pogo et al. for their letter, highlighting the misquotation in the discussion section. In fact, the number quoted in our article (26) corresponds to the number of samples positive for mouse mammary tumor virus (MMTV)– like DNA sequences, not the total number tested (69). We would, however, like to emphasize that this does not affect the findings reported. In our study, we tested 50 samples positive for MMTV-like DNA sequences from a total number tested of 128, representing almost double the number of samples in the article referenced (Pogo et al., Clin Cancer Res 1999;5:2108-2111). This is especially valid for progesterone receptor, in which 18 of 50 (36%) were positive for progesterone receptor compared with 13 of 78 (17%) MMTV-negative samples (i.e., more than double the proportion of MMTV-positive samples compared with MMTV-negative samples were positive for progesterone receptor). Although differences in techniques and antibodies exist, we do not consider such a significant difference can be attributed to these effects. In fact, it is plausible that progesterone receptor is associated with MMTV prevalence, given that the long terminal repeat of MMTV contains hormone-responsive elements.Margaret FaedoCaroline E. FordWilliam D. RawlinsonVirology Division, Department ofMicrobiology, South Eastern Area LaboratoryServices, The Prince of Wales Hospital,Randwick, New South Wales, AustraliaE-mail: faedom@sesahs.nsw.gov.au