tbuckley/cabot-search huggingface dataset:
Abstract P106: Polymorphisms in Candidate Genes and Early Atherosclerosis: A Study of 115 Autopsy Cases of Young Adults
Authors: Débora S Faffe, Wiliam R Miranda, José B Netto, Fabiane S Lima, Leonardo Baumworcel, Rosane Silva, Turan P Urményi, José Carlos P Esperança, Edson Rondinelli
Journal: Circulation Research (2011)

Atherosclerosis, a major cause of death, is a complex disease, involving both genetic and environmental factors. Chronic inflammation plays a central role in its pathogenesis; however, the influence of genetic variations on early development of atherosclerosis has been poorly investigated. We examined the relationship of five common single-nucleotide polymorphisms (SNPs) with atherosclerotic severity in the anterior descendent coronary artery (DA) in 115 consecutive individuals under 30 years autopsied at the Legal Medical Institute of Rio de Janeiro. Histological sections were stained with hematoxilin-eosin and classified for atherosclerosis lesion accordingly to the American Heart Association. DNA was extracted and genotyped for SNPs in the angiotensin conversion enzyme, tumoral necrosis factor-alpha (−308G/A and −238 G/A), interferon-gama (+874 A/T), and metalloproteinase-9 (−1562 C/T) genes by automatic sequencing. Fire weapon lesion was the major causa mortis (72%). Population mean age was 26 years, 100 male and 15 female; 35% were slims, 58% regular weight and 7% obese; 22% white, 51% non-white, and 17% blacks. Only 2 subjects had normal DA histology, while 17 presented level II lesions, 74 level III, 7 level IV, 14 level V. and 1 level VI. 49 individuals presented genotype DD, related to high serum levels of ECA, while 18 were II (related with low ECA levels) and 48 DI (allele frequencies of D = 0,635; I = 0,365). For TNF-α promoter polymorphisms (where allele A is associated with high TNF-α level), 59 presented genotype GG, 21 GA, and 8 AA at position -308 (G = 0,790; A = 0,210), while 84 were GG, 3 GA, and 2 AA at position -238 (G = 0,961; A = 0,039). The allele T at position +874 of INF-γ (related to high INF-γ levels) was present in 45 subjects, while for MMP-9 SNP 49 individuals presented genotype CC, 14 CT, and 3 TT (C = 0,848; T = 0,152). In conclusion, we observed a high prevalence of early atherosclerotic lesions (level III) in young adults, with high prevalence of DD genotype, associated with high ECA serum levels.
The Increasing Call for Protective Ventilation During Anesthesia
Authors: João Batista Borges, Marcelo B. P. Amato, Göran Hedenstierna
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs
Authors: Abraham J. Kandathil, Florian P. Breitwieser, Jaiprasath Sachithanandham, Matthew Robinson, Shruti H. Mehta, Winston Timp, Steven L. Salzberg, David L. Thomas, Ashwin Balagopal
Journal: Annals of Internal Medicine (2017)

Next-generation metagenomic sequencing (NGMS) has opened new frontiers in microbial discovery but has been clinically characterized in only a few settings.
Abstract AP01: HE4 IS A BIOMARKER FOR NEWLY DIAGNOSED AND RECURRENT HIGH–GRADE SEROUS OVARIAN CANCERS WITH NORMAL CA–125 VALUES
Authors: Katherine LaVigne, Fanny Dao, Nadeem Abu–Rustum, Petar Jelinic, Lakshmi V. Ramanathan, Martin Fleisher, Douglas A. Levine
Journal: Clinical Cancer Research (2017)

Abstract PURPOSE: CA125 is widely used for the diagnosis and monitoring of women with epithelial ovarian cancer. However, CA125 will not be elevated in ~20% of patients. Human epididymis protein 4 (HE4) was approved by the FDA in 2008 to monitor ovarian cancer. The objective of this study was to evaluate whether HE4 would serve as a useful biomarker in patients with a normal CA125 at either the time of diagnosis or at the time of recurrence. METHODS: Twenty–one patients with high–grade serous ovarian cancer and CA125 values &amp;lt;50U/ml at the time of diagnosis were identified from a bank of serum specimens collected between 2006–2012. Twenty patients with high–grade serous ovarian cancer and CA125 values &amp;gt;1000U/ml served as positive controls and 11 patients without disease served as negative controls. Fourteen patients with an elevated CA125 at diagnosis (&amp;gt;50 U/ml) and a normal CA125 at the time of recurrence were also identified. HE4 was measured using the Abbott Architect i2000 assay and validation was performed using the Fujirebio HE4 ELISA assay. Normal age–based HE4 values were obtained from the published literature (Urban N, et al.; PMID: 22962406). Data was compared between groups using standard two–sided statistical tests. RESULTS: At the time of diagnosis, the mean HE4 was 1082±437.9 in the positive control patients with elevated CA125, the mean HE4 was 50.96±11.43 in the patients without disease, and 214.4±236.9 in patients with a normal CA–125 (P = &amp;lt;.0001 compared to normal controls; Student's t–test). At the time of recurrence, the mean HE4 was 102.7±83.29 in patients with normal CA125 levels. For 12 of 14 (86%) patients, the HE4 value was greater than the expected normal age–based reference. CONCLUSIONS: These preliminary data suggest that HE4 values are elevated in newly diagnosed ovarian cancer patients with a normal CA125 value. HE4 also appears to be a potentially useful biomarker for detecting recurrent disease in patients with an elevated CA125 at the time of diagnosis who have a normal CA125 level at the time of recurrence. Citation Format: Katherine LaVigne, MD, Fanny Dao, MS, Nadeem Abu–Rustum, MD, Petar Jelinic, PhD, Lakshmi V. Ramanathan, PhD, Martin Fleisher, PhD, Douglas A. Levine, MD. HE4 IS A BIOMARKER FOR NEWLY DIAGNOSED AND RECURRENT HIGH–GRADE SEROUS OVARIAN CANCERS WITH NORMAL CA–125 VALUES [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr AP01.
Towards personalized medicine: Utilizing biomarkers to track response of the inosine monophosphate dehydrogenase (IMPDH) inhibitor AVN944 patient samples from a Phase I clinical trial in AML and evaluation of a patient stratification signature.
Authors: Jeffrey Strovel, J. Michael Hamilton, Tammy Lawrence, Marion Chakiath, Pachai Natarajan, Karina Zuck, Simon Katz, Stephen Glanowski, David Bol
Journal: Clinical Cancer Research (2007)

A58  AVN944 is an orally bioavailable inhibitor of inosine monophosphate dehydrogenase 1 and 2 (IMPDH). IMPDH2 is highly up regulated and required for the de novo production of guanine nucleotides in many malignancies, including hematologic cancers. AVN944 has been in a repeat-dose, dose escalation trial in patients with advanced hematologic cancers including AML, CLL, Multiple Myeloma, and lymphomas. In addition to the objective of defining the maximum tolerated dose and repeat dose pharmacology of AVN944 (given bid for 21 days on a 28 day cycle), we have examined a comprehensive set of pharmacodynamic biomarkers. We have isolated peripheral blood samples from all patients in this trial both before and after receiving AVN944. These samples have been used to determine the effects of the drug on GTP pools and IMPDH enzyme activity, and to correlate these changes to the genetic response of the circulating cells using gene expression detection technologies. Examination of the behavior of these genes in patient samples from this phase I trial show a dynamic response of subsets of these genes depending on 1) the type of malignancy, 2) the predominant cell type in the peripheral blood, 3) the dose of AVN944 received, and 4) the number of treatment cycles completed. Perturbation of biomarkers in these samples relate directly to cellular pathways and functions dependent upon IMPDH activity and include guanine nucleotide biosynthesis, purine and pyrimidine biosynthesis, mitochondrial functions, metabolic pathways and energy production, cell proliferation and the apoptotic cascade. Increasing doses resulted in increases in the number of genes changing per individual, and/or an increase in the magnitude of change in a gene-dependent manner. These genetic markers, correlated with biochemical effects of the drug on protein function and guanine nucleotide levels, can be used as important biomarkers in selecting the optimal dose for additional studies with this drug and for enriching for patients most likely to respond to the drug.
Human <i>RELA</i> haploinsufficiency results in autosomal-dominant chronic mucocutaneous ulceration
Authors: Yousef R. Badran, Fatma Dedeoglu, Juan Manuel Leyva Castillo, Wayne Bainter, Toshiro K. Ohsumi, Athos Bousvaros, Jeffrey D. Goldsmith, Raif S. Geha, Janet Chou
Journal: The Journal of Experimental Medicine (2017)

The treatment of chronic mucocutaneous ulceration is challenging, and only some patients respond selectively to inhibitors of tumor necrosis factor-α (TNF). TNF activates opposing pathways leading to caspase-8–mediated apoptosis as well as nuclear factor κB (NF-κB)–dependent cell survival. We investigated the etiology of autosomal-dominant, mucocutaneous ulceration in a family whose proband was dependent on anti-TNF therapy for sustained remission. A heterozygous mutation in RELA, encoding the NF-κB subunit RelA, segregated with the disease phenotype and resulted in RelA haploinsufficiency. The patients’ fibroblasts exhibited increased apoptosis in response to TNF, impaired NF-κB activation, and defective expression of NF-κB–dependent antiapoptotic genes. Rela+/− mice have similarly impaired NF-κB activation, develop cutaneous ulceration from TNF exposure, and exhibit severe dextran sodium sulfate–induced colitis, ameliorated by TNF inhibition. These findings demonstrate an essential contribution of biallelic RELA expression in protecting stromal cells from TNF-mediated cell death, thus delineating the mechanisms driving the effectiveness of TNF inhibition in this disease.
A Combined AFLP - Multiplex PCR Assay for Typing of Escherichiacoli Strains Using Variable Bacterial Interspersed MosaicElements (BIMEs)
Authors: Miloš Dendis, Radek Horváth, Marcelo Grijalva, Jarmila Schlegelová, Filip Růžička, Jaroslav Benedík
Journal: Clinical Microbiology and Infection (2003)
Comprehensive assessment of cancer stem cell like cells in prediction of pathologic complete response to preoperative dual anti–HER2 therapy for HER2–positive primary breast cancer.
Authors: Jose Rodrigo Espinosa Fernandez, Teruo Yamauchi, Chiyo K. Imamura, Hideko Yamauchi, Hiromitsu Jinno, Maiko Takahashi, Yuko Kitagawa, Seigo Nakamura, Bora Lim, Savitri Krishnamurthy, James M. Reuben, Diane D Liu, Debu Tripathy, Helen X. Chen, Naoko Takebe, Hideyuki Saya, Naoto T. Ueno
Journal: Journal of Clinical Oncology (2017)

e12123 Background: Chemotherapy for breast cancer destroys non–stem cells while sparing cancer stem cells (CSCs). In contrast, anti–HER2 therapy may eliminate resistant cells because HER2 may be a key driver of CSCs. CSC biomarkers have been found to be prognostic of poor outcome and predictive of resistance to therapy. However, there are no comprehensive studies of the impact of anti-HER2 therapies on CSC–related biomarkers. We conducted a prospective biomarker determination study of breast CSCs characterized by CD44v expression and increased aldehyde dehydrogenase 1 (ALDH1) enzymatic activity or expression. Methods: In a prospective trial (ClinicalTrials.gov: NCT01688609), 18 patients with operable primary HER2+ breast cancer (≥T2 excluding inflammatory, any N; median age of 54 yrs) were treated with preoperative anti–HER2 therapy following the NeoALTTO trial dual therapy arm regimen, with a goal of identifying novel predictive biomarkers for pCR. Proportions of tumor cells with CSC characteristics, defined as CD44v+ and ALDH1+, were estimated at baseline, at 6 weeks (after therapy with lapatinib/trastuzumab) and at 18 weeks (after therapy with lapatinib/trastuzumab and paclitaxel) to assess adaptive response. We determined changes in the quantity and characteristics of CSC–related biomarkers during preoperative therapy and correlated them to tumor response. Results: Out of 18 patients, 8 (44%) had a pCR; 5 of these 8 patients (62%) were positive for CD44v staining on tumor cells at baseline and none were positive on the 6–week biopsy. In contrast, 6 of the 10 patients without pCR exhibited persistent levels, or enrichment of CD44v proportion and expression at 6 and 18 weeks (p = 0.0128). ALDH1 expression and other biomarkers were not statistically significant predictors of pCR. Conclusions: Enrichment of CD44v+ tumor cells after double anti–HER2 therapy may predict poor response to dual anti–HER2 therapy with cytotoxic chemotherapy. A second biopsy after the start of preoperative therapy may reflect biological changes useful for the guidance and application of therapeutic strategies for patients with HER2+ breast cancer. Clinical trial information: NCT01688609.
Multicenter Comparison of Contrast-Enhanced FDG PET/CT and 64-Slice Multi–Detector-Row CT for Initial Staging and Response Evaluation at the End of Treatment in Patients With Lymphoma
Authors: Nieves Gómez León, Roberto C. Delgado-Bolton, Lourdes del Campo del Val, Beatriz Cabezas, Reyes Arranz, Marta García, Jimena Cannata, Saturnino González Ortega, Mª Ángeles Pérez Sáez, Begoña López-Botet, Beatriz Rodríguez-Vigil, Marta Mateo, Patrick M. Colletti, Domenico Rubello, José L. Carreras
Journal: Clinical Nuclear Medicine (2017)

To compare staging correctness between contrast-enhanced FDG PET/ceCT and 64-slice multi-detector-row CT (ceCT64) for initial staging and response evaluation at the end of treatment (EOT) in patients with Hodgkin lymphoma, diffuse large B cell lymphoma (DLBCL), and follicular lymphoma.This prospective study compared initial staging and response evaluation at EOT. One hundred eighty-one patients were randomly assigned to either ceCT64 or FDG PET/ceCT. A nuclear medicine physician and a radiologist read FDG PET/ceCT scans independently and achieved post hoc consensus, whereas another independent radiologist interpreted ceCT64 separately. The reference standard included all clinical information, all tests, and follow-up. Ethics committees of the participating centers approved the study, and all participants provided written consent.Ninety-one patients were randomized to ceCT64 and 90 to FDG PET/ceCT; 72 had Hodgkin lymphoma, 72 had DLBCL, and 37 had follicular lymphoma. There was excellent correlation between the reference standard and initial staging for both FDG PET/ceCT (κ = 0.96) and ceCT64 (κ = 0.84), although evaluation of the response at EOT was excellent only for FDG PET/ceCT (κ = 0.91).Our study demonstrated satisfactory agreement between FDG PET/ceCT (κ = 0.96) and ceCT64 (κ = 0.84) in initial staging compared with the reference standard (P = 0.16). Response evaluation at EOT with FDG PET/ceCT (κ = 0.91) was superior compared with ceCT64 (κ = 0.307) (P < 0.001).
External validation of a biomarker and clinical prediction model for hospital mortality in acute respiratory distress syndrome
Authors: Zhiguo Zhao, Nancy Wickersham, Kirsten N. Kangelaris, Addison K. May, Gordon R. Bernard, Michael A. Matthay, Carolyn S. Calfee, Tatsuki Koyama, Lorraine B. Ware
Journal: Intensive Care Medicine (2017)
Blood Pressure Control Among US Veterans
Authors: Ross D. Fletcher, Richard L. Amdur, Robert Kolodner, Chris McManus, Ronald Jones, Charles Faselis, Peter Kokkinos, Steven Singh, Vasilios Papademetriou
Journal: Circulation (2012)

Hypertension treatment and control remain low worldwide. Strategies to improve blood pressure control have been implemented in the United States and around the world for several years. This study was designed to assess improvement in blood pressure control over a 10-year period in a large cohort of patients in the Department of Veterans Affairs.
Molecular chaperone HSP90 regulation of the alternative splicing of numb as a clue for HCC progression.
Authors: Yin Ying Lu, Wanping Xu, Junfang Ji, Dechun Feng, Carole Sourbier, Jianhui Qu, Chunping Wang, Xin Wei Wang, Yongping Yang, Len Neckers
Journal: Journal of Clinical Oncology (2014)

e15114 Background: The human NUMB gene transcript is alternatively spliced; two splice variants, PRRL and PRRS, were reported to promote the growth or differentiation, respectively, of neural cells. PRRL was recently reported to also promote the growth of breast cancer cells. However, the involvement of Numb in hepatocellular carcinoma (HCC) remains unknown. Methods: We performed immunohistochemical, western blotting and quantitative RT-PCR to examine the expression of different Numb PRR isoforms in HCC tissues and cell lines. Overexpression, siRNA-mediated knockdown and specific inhibitors were used to investigate the effects and the underlying mechanism of the two Numb isoforms on cell proliferation, invasion and migration. Results: PRRL is strongly expressed in HCC tumor tissues, while PRRS is mainly expressed in adjacent normal tissues. Elevated expression of Numb PRRL in HCC is associated with earlier recurrence and shorter overall survival of HCC patients after radical surgery. Experimentally, Numb knockdown in Huh1 cells, which mainly express the PRRL isoform, resulted in decreases in cell proliferation, colony formation, and invasion. In contrast, Numb knockdown in SK-Hep1 cells, which predominantly express the PRRS isoform, led to increased cell proliferation and invasion. These data suggest that Numb-PRRL promotes, while Numb-PRRS suppresses the growth and invasion of HCC cancer cells. Furthermore, we showed that Numb-PRRS may exert its effects by inhibiting Akt activation and the expression of c-Myc. Numb-PRRS knockdown increased Akt phosphorylation as well as the expression of c-Myc; Akt inhibition or c-Myc knockdown dampened the growth promoting effect of Numb-PRRS knockdown. Moreover, we found the splicing ratio of the two Numb isoforms is regulated by Hsp90. Hsp90 inhibition increased the levels of Numb-PRRS at the expense of Numb-PRRL. Knockdown of Hsp90 yielded similar results; and re-expression of Hsp90 reversed the ratio toward normal. Conclusions: The expression profile of the Numb PRR isoforms could serve as a useful prognostic biomarker for HCC; targeting Hsp90 could be a novel therapeutic approach to modulate Numb-regulated pathways.
Bread Affects Clinical Parameters and Induces Gut Microbiome-Associated Personal Glycemic Responses
Authors: Tal Korem, David Zeevi, Niv Zmora, Omer Weissbrod, Noam Bar, Maya Lotan-Pompan, Tali Avnit-Sagi, Noa Kosower, Gal Malka, Michal Rein, Jotham Suez, Ben Z. Goldberg, Adina Weinberger, Avraham A. Levy, Eran Elinav, Eran Segal
Journal: Cell Metabolism (2017)
Abstract 20421: Polarizing State Induced by Adenosine, Lidocaine and Magnesium Administration After Prolonged Circulatory Arrest Improves Cardioprotection and Neuroprotection in a Rat Model of Cardiac Arrest With Extracorporeal Life Support
Authors: Alessio Rungatscher, Geoffrey P Dobson, Daniele Linardi, Elisabetta Milani, Maddalena Tessari, Paolo F Fabene, Giang Tong, Katharina Schmitt, Giuseppe Faggian
Journal: Circulation (2014)

BACKGROUND: Polarized arrest, a new concept of myocardial protection, has been recently demonstrated to improve cardiac function after cardioplegic arrest during cardiac surgery. The present study investigated whether polarizing state after prolonged cardiac arrest would provide cardioprotective and neuroprotective effects after extracorporeal life support (ECLS). METHODS AND RESULTS: Ventricular fibrillation (VF) was induced in male Wistar rats. After 8 min of untreated VF, veno-arterial ECLS was instituted for 60 min inducing mild therapeutic hypothermia (32°C). At the beginning of ECLS animals were randomized to receive a single iv bolus of 4.5 mL/kg of polarizing solution with adenosine (47 μM), lidocaine (92 μM) and MgSO4 (1 mM) or same volume of saline as control. Restoration of spontaneous circulation was higher in rats that received polarizing solution (p = 0.03). After 24 h survival and neurologic deficit scores were improved and histological damage scores and brain TNF-α were attenuated compared to control (all p&lt;0.05). Polarizing solution administration led to better recovery of left ventricle end-systolic pressure-volume relationship (Ees), preload recruitable stroke work (PRSW), end-diastolic pressure-volume relationship (EDPVR) and Tau (p&lt;0.01). Polarized state enhanced phosphorilation of myocardial ERK1 and 2 and Akt, resulting in a lower apoptotic index (TUNEL, p&lt;0.01). CONCLUSIONS: Polarized state induced by adenosine, lidocaine and magnesium increased survival, neurologic outcome and cardiac function after prolonged cardiac arrest treated with ECLS. Moreover it improved cardioprotection through activation of the pro-survival kinases Akt and ERK1/2.
Recent advances in the use of PI3K inhibitors for glioblastoma multiforme: current preclinical and clinical development
Authors: Hua-fu Zhao, Jing Wang, Wei Shao, Chang-peng Wu, Zhong-ping Chen, Shing-shun Tony To, Wei-ping Li
Journal: Molecular Cancer (2017)

Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary tumor in the central nervous system. One of the most widely used chemotherapeutic drugs for GBM is temozolomide, which is a DNA-alkylating agent and its efficacy is dependent on MGMT methylation status. Little progress in improving the prognosis of GBM patients has been made in the past ten years, urging the development of more effective molecular targeted therapies. Hyper-activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is frequently found in a variety of cancers including GBM, and it plays a central role in the regulation of tumor cell survival, growth, motility, angiogenesis and metabolism. Numerous PI3K inhibitors including pan-PI3K, isoform-selective and dual PI3K/mammalian target of rapamycin (mTOR) inhibitors have exhibited favorable preclinical results and entered clinical trials in a range of hematologic malignancies and solid tumors. Furthermore, combination of inhibitors targeting PI3K and other related pathways may exert synergism on suppressing tumor growth and improving patients' prognosis. Currently, only a handful of PI3K inhibitors are in phase I/II clinical trials for GBM treatment. In this review, we focus on the importance of PI3K/Akt pathway in GBM, and summarize the current development of PI3K inhibitors alone or in combination with other inhibitors for GBM treatment from preclinical to clinical studies.