tbuckley/cabot-search huggingface dataset:
Role of Cyclic AMP in Hormone Actions
Authors: R. W. Butcher
Journal: New England Journal of Medicine (1968)

THE biologic role of cyclic AMP (adenosine 3′,5′-monophosphate), at least as it is understood today, is shown in Figure 1. After release from an endocrine gland, a hormone is transported to its effector cell, where it interacts, and the inter action ultimately has a measurable physiologic effect. The interactions of several hormones with their target cells have been shown to result in the activation of a membrane enzyme system called adenyl cyclase, which catalyzes the transformation of adenosine triphosphate (ATP) to cyclic AMP. The increased cyclic AMP, acting intracellularly, then carries out the work of the hormone by affecting the activities . . .
pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion
Authors: Federico Iovino, Joo-Yeon Engelen-Lee, Matthijs Brouwer, Diederik van de Beek, Arie van der Ende, Merche Valls Seron, Peter Mellroth, Sandra Muschiol, Jan Bergstrand, Jerker Widengren, Birgitta Henriques-Normark
Journal: The Journal of Experimental Medicine (2017)

Streptococcus pneumoniae is the main cause of bacterial meningitis, a life-threating disease with a high case fatality rate despite treatment with antibiotics. Pneumococci cause meningitis by invading the blood and penetrating the blood–brain barrier (BBB). Using stimulated emission depletion (STED) super-resolution microscopy of brain biopsies from patients who died of pneumococcal meningitis, we observe that pneumococci colocalize with the two BBB endothelial receptors: polymeric immunoglobulin receptor (pIgR) and platelet endothelial cell adhesion molecule (PECAM-1). We show that the major adhesin of the pneumococcal pilus-1, RrgA, binds both receptors, whereas the choline binding protein PspC binds, but to a lower extent, only pIgR. Using a bacteremia-derived meningitis model and mutant mice, as well as antibodies against the two receptors, we prevent pneumococcal entry into the brain and meningitis development. By adding antibodies to antibiotic (ceftriaxone)-treated mice, we further reduce the bacterial burden in the brain. Our data suggest that inhibition of pIgR and PECAM-1 has the potential to prevent pneumococcal meningitis.
A Multicenter Open-Labeled Pilot Study on Recombinant Human Thrombopoietin in the Management of Immune Thrombocytopenia in Pregnancy
Authors: Zhangyuan Kong, Ping Qin, Hong Li, Renchi Yang, Xiaofan Liu, Jianmin Luo, Zhongguang Cui, Zhichun Li, Guochao Ji, Yusheng Bai, Yuxia Wu, Jun Peng, Jun Ma, Ming Hou
Journal: Blood (2016)
Keep within target range of blood oxygen levels, new guideline recommends
Authors: Susan Mayor
Journal: BMJ (2017)

Health professionals should always specify a target saturation range when prescribing oxygen and should then ensure that patients are monitored to avoid high or low levels that can cause serious complications, recommends an updated guideline from the British Thoracic Society on oxygen use in adults.1

The guideline is based on a review of evidence arising since previous recommendations in 2008 and has been expanded to include emergency oxygen …
Smoking Cessation in Patients With Cancer: Treatment Advances and the Oncologist's Role
Authors: Paul Cinciripini
Journal: Journal of the National Comprehensive Cancer Network (2017)

The harms of smoking cigarettes are well-known, and the benefits of smoking cessation are well-established. Smoking cessation is especially important for patients with cancer, because smoking compromises the effects of cancer treatment and shortens survival. Interventions to achieve tobacco abstinence include pharmacotherapy and counseling, and these often must be repeated. Patients should be encouraged at every juncture to continue attempts to stop smoking.
Aleukemic Mast Cell Leukemia (aMCL) - Clinical Characteristics and Outcomes
Authors: Preetesh Jain, Sa Wang, Hagop M. Kantarjian, Nawid Sarwari, Keyur P. Patel, Prithviraj Bose, Sherry Pierce, Tapan M. Kadia, Naval Daver, Naveen Pemmaraju, Jorge E. Cortes, Srdan Verstovsek
Journal: Blood (2016)
Enhancer-Derived RNA: A Primer
Authors: Feng Liu
Journal: Genomics Proteomics & Bioinformatics (2017)

Abstract Enhancer-derived RNAs (eRNAs) are a group of RNAs transcribed by RNA polymerase II from the domain of transcription enhancers, a major type of cis-regulatory elements in the genome. The correlation between eRNA production and enhancer activity has stimulated studies on the potential role of eRNAs in transcriptional regulation. Additionally, eRNA has also served as a marker for global identification of enhancers. Here I review the brief history and fascinating properties of eRNAs.
Abstract 15697: Acute Pharmacological Inhibition of PI3Kα by the Novel Cancer Drug, BYL-719, Has a Pro-arrhythmic Effect
Authors: Pavel Zhabyeyev, Brent McLean, Bart Vanhaesebroeck, Gavin Y Oudit
Journal: Circulation (2016)

Introduction: Phosphatidylinositol-3-kinase α (PI3Kα) is an oncogene with high activity in the heart. BYL-719 (BYL) is a specific PI3Kα inhibitor and a prospective cancer drug for advanced solid tu...
ENZYMES OF THE GLYCOLYTIC PATHWAY IN SKIN..
Authors: P. D. MIER, D. W. K. COTTON
Journal: British Journal of Dermatology (1966)

Journal Article ENZYMES OF THE GLYCOLYTIC PATHWAY IN SKIN.: II. Phosphoglucomutase. Get access P. D. MIER, P. D. MIER The Institute of Dermatology, St. John's Hospital for Diseases of the Skin, Homerton Grove, London, E.9 Search for other works by this author on: Oxford Academic Google Scholar D. W. K. COTTON D. W. K. COTTON The Institute of Dermatology, St. John's Hospital for Diseases of the Skin, Homerton Grove, London, E.9 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 78, Issue 11, 1 November 1966, Pages 581–585, https://doi.org/10.1111/j.1365-2133.1966.tb12151.x Published: 01 November 1966
Generation of DNA double strand breaks during trabectedin DNA damage measured through induction of γ H2AX
Authors: Jose Casado, Beatriz Albella, Paula Rio, Miguel Aracil, Juan Tercero, Jose Jimeno, Juan Bueren
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

1965 

Trabectedin (ET-743, Yondelis®) is a marine derived anticancer agent which forms covalent adducts with guanine residues present in the minor groove of the DNA. In order to investigate whether Trabectedin generates DNA double strand breaks, either directly or during the repair of the DNA damage, we have analyzed the presence of phosphorylated H2AX (γH2AX) nuclear foci in cells exposed to this drug. To this end, MRC-5 fibroblasts and EBV-transformed lymphoblasts were treated with Trabectedin (1, 3 and 10nM), with mitomycine C (MMC; 33 and 100nM) or exposed to 5 Gy of ionizing radiation (IR), and then analyzed for the presence of γH2AX foci. As expected, γH2AX nuclear foci were observed immediately after cell irradiation. In cells treated either with MMC (which generates inter-strands DNA cross-links) or with Trabectedin, a delayed formation of γH2AX foci was, however, clearly observed. Flow cytometry offers the possibility of rapidly analyzing γH2AX in a high number of cells and additionally facilitates the analysis of DSBs along the cell cycle. These analyses confirmed the immediate generation of IR-induced DSBs in both cell types, as well as the delayed induction of DSBs both in MMC- and Trabectedin -treated cells. Additionally, cytometric studies showed a predominant accumulation of DSBs in cells entering into cell division. Our studies suggest that the generation of DSBs constitutes an intermediate process required for the repair of the DNA damage produced by Trabectedin. Further studies are in progress aiming to discern the mechanism involved in the repair of the DNA damage generated by Trabectedin, and also the susceptibility to this new anticancer agent against cancer cells lacking an efficient repair of DBSs.
Identification of integrin as potential molecular markers in human glioblastoma multiforme: Microarray analysis guided by contrast-enhanced MRI
Authors: Y. Yang, Y. Chia, D. Rubin, G. Harsh, S. Atlas, M. Bednarski, S. Guccione
Journal: Journal of Clinical Oncology (2006)

10007 Background: Glioblastoma multiforme (GBM) is a primary brain tumor with poor prognosis and low survival rate. It is characterized as a highly infiltrative and vascular tumor, with morphologic heterogeneity including necrosis regions. We have used contrast enhanced (CE)-MRI to identify regions that differ in vascular permeability as delineated by the small molecule contrast agent Magnevist. Non-necrotic areas with and without contrast enhancement were sampled in the OR. The expression profiles for integrin family genes were investigated and validated using IHC. Genes encoding for integrin subunits with high expression levels in these regions of the tumor were identified and are presented here. Methods: Patients diagnosed with GBM, without any prior procedures were scanned on a GE 1.5T MRI scanner using standard T1- and T2-weighted pulse sequences and Gd(DTPA) as contrast agent. Samples from regions with vascular permeability to the contrast agent (contrast-enhancing, CE) and vascular regions that are not permeable to the contrast agent (non-enhancing, NE) were collected for gene expression profiling using the Affymatrix oligonucleotide microarray system. Genomic data was normalized at probe-level, and analyzed using a modified t-test, Significance Analysis of Microarray (SAM). Significant expression levels were identified. Immunohistochemical staining was used to validate protein expression of selected genes of interest. Results: Tissue samples from the CE and NE regions of 13 patients reveal significantly distinct gene expression patterns. In specific, genes in the integrin family such as integrin α IIb , α V and β 3 show high expression levels in the CE region. Immunohistochemical staining confirmed correlation of protein expression patterns with the observed genomic profile. Conclusions: Combination of CE-MRI using the clinical contrast agent and microarray analysis can reveal spatial genomic profiles correlated with imaging features associated with increased vascular permeability, vessel density, and areas of fluid accumulation. The identified genes from the integrin family can be potential molecular targets, and can be used for molecular imaging and therapeutic purposes. No significant financial relationships to disclose.
Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma
Authors: Christos Rossios, Stelios Pavlidis, Uruj Hoda, Chih-Hsi Kuo, Coen Wiegman, Kirsty Russell, Kai Sun, Matthew J. Loza, Frederic Baribaud, Andrew L. Durham, Oluwaseun Ojo, Rene Lutter, Anthony Rowe, Aruna Bansal, Charles Auffray, Ana Sousa, Julie Corfield, Ratko Djukanovic, Yike Guo, Peter J. Sterk, Kian Fan Chung, Ian M. Adcock
Journal: Journal of Allergy and Clinical Immunology (2017)
Studies of Immune Mechanisms in Leprosy
Authors: Ward E. Bullock
Journal: New England Journal of Medicine (1968)

Skin tests of delayed hypersensitivity performed on 107 patients with leprosy and 30 controls with six protein antigens and the hapten, picryl chloride, indicated that leprosy is associated with a generalized depression of the delayed allergic inflammatory response. The depression is of greatest severity in patients with lepromatous leprosy and is less among tuberculoid patients. Patients were assigned to groups according to time under therapy with diaminodiphenylsulfone, and the results of skin tests were compared. There was a significant progression toward "normal" reactivity to skin-test antigens in "long-term" as compared with "short-term" treatment groups. This trend was more evident among lepromatous patients; the possible salutary effects of chemotherapy upon skin reactivity were defined less sharply in tuberculoid patients. Attempts to establish primary sensitization to picryl chloride failed in a high percentage of patients with leprosy as compared with controls, regardless of type of disease or stage of convalescence. Factors directly related to the pathologic process itself appear to act, at least in part, as determinants of immunologic reactivity in leprosy.
A life-history theory perspective on obesity
Authors: Andrea G Dittmann, Jon K Maner
Journal: Behavioral and Brain Sciences (2017)

Abstract We extend Nettle et al.’s insurance hypothesis (IH) argument, drawing upon life-history theory (LHT), a developmental evolutionary perspective that documents downstream consequences of early-life exposure to unpredictable environments. We discuss novel evidence consistent with both IH and LHT, suggesting that early-life exposure to unpredictable environments is associated with reduced engagement in weight management behaviors and a greater probability of adulthood obesity.
Rook's Textbook of Dermatology, 9th edn. ChristopherGriffiths, JonathanBarker, TanyaBleiker, RobertChalmers, DanielCreamer, eds. Publisher: Wiley-Blackwell, 2016; 4696 pp. ISBN: 978-1118441190. Price €654·49.
Authors: L.E. French
Journal: British Journal of Dermatology (2017)
A man with chest pain and acute ST elevations on electrocardiogram
Authors: Erica O Miller, Vijay K Krishnamoorthy, Frederick S K Ling, Abhishek Chaturvedi, Scott J Cameron
Journal: BMJ (2017)

A 45 year old man with a history of dyslipidemia presented to the emergency department with chest pain. He was awakened from sleep one hour earlier with burning, pressure-like substernal chest pain radiating to his left arm with associated nausea. He denied dyspnoea, diaphoresis, or lightheadedness. The pain was constant, not worse with exertion, and not relieved by an antacid medication. He reported good health throughout his life, managing his dyslipidemia with diet and exercise and he did not take prescription medications. The man’s family history was notable for coronary artery disease in his father. He denied smoking cigarettes and using any drugs, and was quite physically active in martial arts. His blood pressure was 160/101 mm Hg on arrival, and his cardiovascular and respiratory examinations were unremarkable. A 12 lead electrocardiogram (fig 1⇓) and an emergent coronary angiogram were taken. Contrast ventriculography showed preserved left ventricular ejection fraction with hypokinesis of the inferior left ventricular wall. Serum creatine kinase was elevated to 1942 U/L (reference range 47-171 U/L) the morning after presentation.



Fig 1  Presenting electrocardiogram



1.  What is the most likely diagnosis?

2.  What is the underlying aetiology?

3.  How would you manage this patient?

### 1. What is the most likely diagnosis?

#### Short answer

The electrocardiogram shows inferior ST segment elevations consistent with an acute myocardial infarction. Coronary angiography shows coronary artery aneurysm of the right coronary artery with acute intracoronary thrombosis.

#### Discussion

The electrocardiogram shows sinus arrhythmia with first degree heart block, ST segment elevations in all three inferior leads (II, III, and aVF), and ST segment depressions in the right precordial leads (V1 and V2). Inferior ST segment elevations are generally observed with acute inferior wall …
HER2 and programmed death-1 ligand-1 (PD-L1) expression in gastric carcinoma.
Authors: Eiji Oki, Shinji Okano, Koji Ando, Yukiharu Hiyoshi, Shuhei Ito, Masaru Morita, Yoshihiko Maehara
Journal: Journal of Clinical Oncology (2014)

e15041 Background: Programmed death-1 ligand-1 (PD-L1) is an immune-inhibitory receptor that is widely expressed in human cancer but not in normal tissues. In vitro studies indicate that the interaction of activated T cells and tumor-associated PD-L1 leads to programmed cell death, while clinical studies have shown that PD-L1 expression is correlated with poor prognosis and/or more aggressive disease. Methods: We examined formalin fixed tumor samples of 144 patients with a primary diagnosis of gastric carcinoma. Immunohistochemistry was used to detect PD-L1 and HER2 expression. Loss of heterozygosity of PTEN was also investigated. An RNA interference approach was used to downregulate HER2 expression, while PD-L1 protein expression was assessed using flow cytometry. Results: In 144 samples from gastric cancer patients, PD-L1 overexpression was significantly correlated with tumor invasion (P=0.011) and LOH of PTEN. PD-L1–positive cases increased according to the HER2 scores of the clinical samples. The overall 5-year survival rates were 36.7% in patients with PD-L1 expression versus 48.9% in patients without PD-L1 expression. PD-L1 protein expression was significantly decreased in cells transfected with siRNA HER2 compared with the negative control (P<0.05). In addition, the presence of siRNA HER2 significantly increased HLA class I expression. Conclusions: HER2 possibly affects PD-L1 expression in gastric cancer. PTEN and HER2 should be candidate biomarkers for new clinical trials for the development of drugs targeting PD-1 and PD-L1.
Projecting the cost-effectiveness of pertuzumab with trastuzumab and docetaxel in the neoadjuvant treatment of HER2-positive, locally advanced, inflammatory or early breast cancer.
Authors: Joseph B. Babigumira, Eduardo Santos, Vincent Percival Antao, Bruce Wang, Chia C. Portera, Tripthi Kamath, Louis P Garrison
Journal: Journal of Clinical Oncology (2014)

642 Background: The NeoSphere trial (Gianni et al. [2012]) compared the following regimens for neoadjuvant treatment in HER2+, locally advanced, inflammatory or early breast cancer: 1) trastuzumab and docetaxel (TH) 2) pertuzumab, trastuzumab and docetaxel (THP), 3) pertuzumab plus trastuzumab (HP), and 4) pertuzumab plus docetaxel (TP). The pathological complete response (pCR) rates were 29.0% for TH, 45.8% for THP, 16.8% for HP, and 24.0% for TP. THP significantly increased the pCR rate. We performed a cost-effectiveness analysis of THP compared to other treatment regimens in the neoadjuvant setting based on the pCR results from NeoSphere. Methods: We constructed a combined decision-analytic (decision tree) and partitioned survival (area under the curve) model with three health states: disease-free (DF), progressive disease (PD), and death. The decision tree modeled the probability of pCR and the partitioned survival model projected life expectancy of patients who did or did not achieve pCR. Utility data for health states were assigned to calculate quality-adjusted life years (QALYs). We estimated the cost of early breast cancer systemic therapy, drug administration, drug monitoring, clinical management of adverse events, and progressive disease (PD). We performed univariate and probabilistic sensitivity analyses. Results: See Table. The incremental cost-effectiveness ratios (ICERs) comparing THP to TH were $34,700/LY and $38,500/QALY, THP to HP, $33,000/LY and $36,900/QALY, and THP to TP, $16,100/LY and $17,800/QALY. The ICERs (THP vs. TH) were most sensitive to pCR difference between THP and TH and the cost of pertuzumab. Conclusions: Pertuzumab combined with trastuzumab and docetaxel is projected to be cost-effective in the neoadjuvant setting. This study suggests that this regimen, in addition to being clinically effective, would be favorable from an economic standpoint in the U.S. Summary of results. Treatment regimens Lifetime cost ($) Life years (LYs) Quality-adjusted life years (QALYs) THP 143,000 18.41 16.51 TP 132,000 17.69 15.86 TH 124,000 17.85 16.01 HP 112,000 17.45 15.65
Outcome of male patients and black patients enrolled in S0221, an intergroup chemotherapy study.
Authors: G. Thomas Budd, William E. Barlow, Halle C. F. Moore, Timothy J. Hobday, James A. Stewart, Claudine Isaacs, Muhammad Salim, Jonathan K. Cho, Kathy S. Albain, Kristine Rinn, Helen K. Chew, Gary Von Burton, Timothy David Moore, Gordan Srkalovic, Bradley Alexander McGregor, Lawrence E. Flaherty, Robert B. Livingston, Danika Lew, Julie Gralow, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2014)

1016 Background: Assessment of the outcome of minority populations within clinical trials may give insight into important tumor and host factors relevant to those populations. Methods: S0221 is a phase III trial of various dose-schedules of doxorubicin, cyclophosphamide and paclitaxel. S0221 allowed enrollment of male patients, and was sufficiently large to enroll significant numbers of minority populations. Here, we report the outcome of male patients and patients of black race. Results: Among 3236 total patients entered on S0221, 23 (0.7%) were male and 378 (12%) were of self-reported black race. Non-significant differences in male/female patients were seen in HER2 positivity (9%/19%), hormone receptor (HR) positivity (100%/66%), lymph node negativity (17%/26%), and treatment completion rate (70%/74%), but men were more often ≥60 years old (48%/21%, p=0.006). Males had significantly worse disease-free survival (DFS), with 5-year DFS 49%/82%; HR=3.16, Log-Rank p=0.0003. Male sex remained an adverse factor for DFS in a Cox model adjusted for treatment, HER2 status, HR status, age, and nodal status (HR=3.53, p<0.001). Black/non-black patients did not significantly differ in HER2 positivity (22%/18%). Black patients were less likely to be HR-positive (51%/69%, p<0.001), to have >4 nodes involved (29%/36%, p=0.02), to be age >60 years (15%/22%, p=0.008) and to complete treatment (63%/75%, p<0.001). Black patients had worse DFS, with 5-year DFS of 75%/82%; HR=1.55, Log-Rank p=0.0001. Black race remained an adverse factor for DFS in a Cox model adjusted for treatment, HR status, HER2, age, and nodal status (HR=1.48, p=0.001) or when analysis was limited to those completing therapy, adjusted for treatment (HR=1.48, p=0.01). Conclusions: Male patients enrolled in S0221 had a markedly worse DFS, a finding which persisted after adjustment for tumor characteristics. Black patients in S0221 treated with 3rd generation regimens had a worse DFS than non-black patients. These results are similar to those for post-menopausal HR+ black patients treated with a 2nd generation regimen (5FU/doxorubicin/cyclophosphamide) in S8814, suggesting a generalized phenomenon which is not improved with contemporary regimens. Clinical trial information: NCT00070564.