tbuckley/cabot-search huggingface dataset:
Targeted Metabolomics Demonstrates Distinct and Overlapping Maternal Metabolites Associated With BMI, Glucose, and Insulin Sensitivity During Pregnancy Across Four Ancestry Groups
Authors: Saya Jacob, Michael Nodzenski, Anna C. Reisetter, James R. Bain, Michael J. Muehlbauer, Robert D. Stevens, Olga R. Ilkayeva, Lynn P. Lowe, Boyd E. Metzger, Christopher B. Newgard, Denise M. Scholtens, William L. Lowe
Journal: Diabetes Care (2017)

OBJECTIVE We used targeted metabolomics in pregnant mothers to compare maternal metabolite associations with maternal BMI, glycemia, and insulin sensitivity. RESEARCH DESIGN AND METHODS Targeted metabolomic assays of clinical metabolites, amino acids, and acylcarnitines were performed on fasting and 1-h postglucose serum samples from European ancestry, Afro-Caribbean, Thai, and Mexican American mothers (400 from each ancestry group) who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and underwent an oral glucose tolerance test at ∼28 weeks gestation. RESULTS K-means clustering, which identified patterns of metabolite levels across ancestry groups, demonstrated that, at both fasting and 1-h, levels of the majority of metabolites were similar across ancestry groups. Meta-analyses demonstrated association of a broad array of fasting and 1-h metabolites, including lipids and amino acids and their metabolites, with maternal BMI, glucose levels, and insulin sensitivity before and after adjustment for the different phenotypes. At fasting and 1 h, a mix of metabolites was identified that were common across phenotypes or associated with only one or two phenotypes. Partial correlation estimates, which allowed comparison of the strength of association of different metabolites with maternal phenotypes, demonstrated that metabolites most strongly associated with different phenotypes included some that were common across as well as unique to each phenotype. CONCLUSIONS Maternal BMI and glycemia have metabolic signatures that are both shared and unique to each phenotype. These signatures largely remain consistent across different ancestry groups and may contribute to the common and independent effects of these two phenotypes on adverse pregnancy outcomes.
Multiple Myeloma Profile In Latin America: Clinical and Epidemiological Observational Study
Authors: Vania T M Hungria, Angelo Maiolino, Gracia Aparecida Martinez, Carmino A De Souza, Rosane Bittencourt, Lygia Goretti Bruggemann Peters, Gisele W. B. Colleoni, Luciana Correa Oliveira de Oliveira, Lais Sousa, Erika Coelho, Ricardo Pasquini, Silvia M. M. Magalhaes, Renata Nunes, Jorge Vaz Pinto Neto, Rosa Malena Delboni Faria, Mair Pedro de Souza, Nelson Hamerschlak, Dorotea Beatriz Fantl, Juan Ramon Navarro, Guillermo Conte, David Gomez Almaguer, Guillermo Ruiz-Arguelles, Brian G M Durie
Journal: Blood (2013)
Novel Near-Infrared Heptamethine Carbocyanine Fluorescent Dye-Cisplatin Conjugate Demonstrates Significant Antitumor Activity and Overcomes Cisplatin Resistance in MYC-Driven TP53 Mutated Aggressive B-Cell Burkitt's Lymphoma
Authors: Stefan Mrdenovic, Yi Zhang, Yin Lijuan, Wen-Chin Huang, Gina Chia-Yi Chu, Ruoxiang Wang, Jason Bojang Wu, Ronald Paquette, Haiyen E. Zhau, Leland W. K. Chung
Journal: Blood (2016)
Patterns of genetic screening for hereditary cancer syndromes: Effect of Supreme Court’s ruling invalidating single gene patent rights.
Authors: Zhen Ni Zhou, Melissa K Frey, Dimitrios Nasioudis, Ann Carlson, Jessica Fields, Kevin Holcomb, Eloise Chapman-Davis
Journal: Journal of Clinical Oncology (2017)

1580 Background: In 6/2013 the Supreme Court ruled that isolated DNA sequences found in nature could not be patented, resulting in rapid uptake of multigene panels. We sought to explore trends in genetic testing since this ruling. Methods: Results of all patients undergoing genetic testing and counseling at a single institution between 7/1/13 and 12/31/16 were reviewed. Associations between categorical variables were evaluated by chi-square tests or Fisher's exact tests as appropriate for category size. Results: 1663 patients underwent genetic testing over the study period. The median age was 49 years (range 18-86). Use of multigene panels versus targeted gene testing increased significantly in the years following the Supreme Court ruling (Table 1, P&lt;0.001). While the percentage of patients found to have pathogenic mutations remained stable over the study period (9%), detection of variants of uncertain significance (VUS) increased significantly (Table 1, P&lt;0.001). In 2013 BRCA1/2 mutations accounted for 91% of identified mutations; however this number decreased over time (2014-83%, 2015-70%, 2016-58%, P=0.01). Use of multigene panels detected 71% of mutations in non- BRCA1/2 genes such as CHEK(19), APC(44), MSH6(1), P53(1), and PTEN(1). Patients with a personal history of breast and/or ovarian cancer were more likely to have targeted testing than patients with other cancer types (590, 66% vs. 9, 33%, P=0.001). Conclusions: The uptake of multigene panels has increased since the 2013 Supreme Court ruling. While this technology allowed for the identification of many cancer-related genes that would be missed on targeted BRCA1/2 testing, it also resulted in a significantly increased detection of VUS, a finding with unknown clinical implications. [Table: see text]
Zolpidem for the Treatment of Neurologic Disorders
Authors: Martin N. Bomalaski, Edward S. Claflin, Whitney Townsend, Mark D. Peterson
Journal: JAMA Neurology (2017)

Given its selective action on the ω1 subtype of the γ-aminobutyric acid A receptor, zolpidem tartrate presents a potential treatment mechanism for other neurologic disorders.To synthesize studies that used zolpidem to treat neurologic disorders.Eligibility criteria included any published English-language article that examined the use of zolpidem for noninsomnia neurologic disorders in humans for all dates up to March 20, 2015. Searched databases included PubMed, Scopus, Web of Science Core Collection, the Cochrane Library, EMBASE, CENTRAL, and clinicaltrials.gov. Publication bias was mitigated by searching clinicaltrials.gov for unpublished studies. Two rounds of screening were performed based on title and then abstract, and coding was performed by 2 coders. All methods followed the PRISMA Reporting Guidelines for systematic reviews of the literature.The initial search produced 2314 articles after removing duplicates. After exclusion based on a review of abstracts, 67 articles remained for full manuscript review. Thirty-one studies treated movement disorders, 22 treated disorders of consciousness, and 14 treated other neurologic conditions, including stroke, traumatic brain injury, encephalopathy, and dementia. Study designs included case reports (n = 28), case series (n = 8), single-patient interventional (n = 13), pretest and posttest (n = 9), randomized clinical trials (n = 9), and crossover studies (n = 5). Only 11 studies had more than 10 participants. Effects of zolpidem were wide ranging (eg, improvement on the JFK Coma Recovery Scale-Revised, the Unified Parkinson Disease Rating Scale, and the Burke-Fahn-Marsden Dystonia Rating Scale) and generally lasted 1 to 4 hours before the participant returned to baseline. Sedation was the most common adverse effect.Zolpidem has been observed to transiently treat a large variety of neurologic disorders, most often related to movement disorders and disorders of consciousness. Much of what is known comes from case reports and small interventional trials. These findings may represent a new treatment mechanism for these disorders.
Production of a Chikungunya Vaccine Using a CHO Cell and Attenuated Viral-Based Platform Technology
Authors: Preethi Eldi, Tamara H. Cooper, Liang Liu, Natalie A. Prow, Kerrilyn R. Diener, Paul M. Howley, Andreas Suhrbier, John D. Hayball
Journal: Molecular Therapy (2017)

Vaccinia-based systems have been extensively explored for the development of recombinant vaccines. Herein we describe an innovative vaccinia virus (VACV)-derived vaccine platform technology termed Sementis Copenhagen Vector (SCV), which was rendered multiplication-defective by targeted deletion of the essential viral assembly gene D13L. A SCV cell substrate line was developed for SCV vaccine production by engineering CHO cells to express D13 and the VACV host-range factor CP77, because CHO cells are routinely used for manufacture of biologics. To illustrate the utility of the platform technology, a SCV vaccine against chikungunya virus (SCV-CHIK) was developed and shown to be multiplication-defective in a range of human cell lines and in immunocompromised mice. A single vaccination of mice with SCV-CHIK induced antibody responses specific for chikungunya virus (CHIKV) that were similar to those raised following vaccination with a replication-competent VACV-CHIK and able to neutralize CHIKV. Vaccination also provided protection against CHIKV challenge, preventing both viremia and arthritis. Moreover, SCV retained capacity as an effective mouse smallpox vaccine. In summary, SCV represents a new and safe vaccine platform technology that can be manufactured in modified CHO cells, with pre-clinical evaluation illustrating utility for CHIKV vaccine design and construction.
Prothèses oesophagiennes expansives extirpables dans le traitement des perforations non tumorales de l'œsophage
Authors: S Koch, A Weber, F Fein, D Guinier, G Mantion, B Heyd, F Carbonnel
Journal: Endoscopy (2005)

Les perforations oesophagiennes sont des complications sévères. La prise en charge recommandée est, selon les cas, le traitement chirurgical ou conservateur (nutrition parentérale exclusive, antibiothérapie, aspiration digestive; 1). Dans 2 études françaises, effectuées chez 426 et 270 patients ainsi traités, la mortalité était de 29% et 18% respectivement (1, 2). BUT.
Classification of diffuse large b-cell lymphoma (DLBCL) FFPE samples of the GELA LNH2003 program, using Lymph2Cx assay on the nCounter analysis system.
Authors: Karen Leroy, Jean-Philippe Jais, Philippe Ruminy, David Gentien, Cecile Reyes, David W. Scott, Lisa M Rimsza, George Wright, Randy D. Gascoyne, Louis M. Staudt, Corinne Haioun, Herve Tilly, Philippe Gaulard, Gilles A. Salles, Thierry Molina, Fabrice Jardin
Journal: Journal of Clinical Oncology (2016)

7547 Background: DLBCL comprises two molecular subgroups defined according to gene expression profiling of frozen tissue samples: the Germinal Center B-cell-like (GCB) and Activated B-cell-like (ABC) lymphomas, with different prognoses and therapeutic responses. We have compared the results obtained with the Lymph2Cx assay, using formalin fixed paraffin embedded (FFPE) tissue samples to the gold standard classification, based on Wright’s predictor using Affymetrix data on matched frozen samples, in a retrospective series of patients included in GELA clinical trials. Methods: Total RNA were extracted from FFPE tumor samples, diagnosed between March 2002 and April 2011, with a fully automated method (Siemens Healthcare Diagnostics), using 1 to 3 10µm tissue scrolls of 0,4 ± 0,3 cm2. 50ng RNA were hybridized to the Lymph2Cx CodeSet, using high sensitivity chemistry and analyzed with the Nanostring nCounter system (high resolution: 555 FOV). Digital counts were used to calculate the normalization and linear predictor score (LPS), ABC likelihood and “raw” subgroup prediction. The adjusted LPS were calculated after correction with the reference oligonucleotide counts. Results: Despite heterogeneity in fixatives, the experiments were successful in 166/177 (94%) cases. Duplicate extractions from the same block were classified identically in 6 cases, shifted from “GCB” to “unclassified” in 2 blocks showing tumor exhaustion, and failed in one case. The adjusted LPS reduced the number of unclassified samples and were considered as best choice. The series included 157 unique samples: 13 primary mediastinal B-cell lymphoma (PMBL), classified as ABC (n = 1), unclassified (n = 4) and GC (n = 8) and 144 DLBCL samples, classified as ABC (n = 69), unclassified (n = 17) and GC (n = 58). Considering DLBCL GC/ABC gold standard Affymetrix classification, the Lymph2Cx assay was concordant in 92.6%; inconclusive (unclassified) in 5.7% and misclassification was observed in 0.8% of the cases. Conclusions: The Lymph2Cx, performed in an independent series and a non-LLMPP laboratory, proved to be a highly efficient and reliable assay to classify FFPE samples of a large series of DLBCL.
Platycodin d induces g2/m cell-cycle arrest, leading to endoreduplication, inhibition of proliferation and apoptosis in leukemia cells
Authors: Mun-Ok Kim, Dong-Oh Moon, Sang-Hyuck Kang, Yung Hyun Choi, Jae-Dong Lee, Nam Deuk Kim, Gi-Young Kim
Journal: Clinical Cancer Research (2007)

B3  Platycodin D (PD), a major constituent of triterpene saponins in Platycodon grandiflorum, has also become an interesting candidate for cancer chemotherapy however, little is known about apoptotic mechanisms on cancer cells. We herein investigated the mechanisms that are related to PD-induced anti-proliferation and cell death in human leukemia cells (U937, THP-1 and K562 cells). Cell growth was assessed with proliferation assays, cell counting, flow cytometry, phase contrast microscopy and Western blot assay. Microtubule (MT) formation was measured with immunofluorescent staining and in vitro tubulin polymerization assay. Apoptotic effect was analyzed by assessing increase in annexin V-staining and caspase-3 activity. Treatment of synchronized leukemia cells with varying concentrations of PD resulted in significant G2/M cell cycle arrest and endoreduplication (END) via downregulation of Cdc2/cyclin B1 and upregulation of wee1 expression, and elevated the Cdk2 protein via downregulation of p21 within 48 h. We also researched PD’s induction of polyploidy through the MT polymerization. Immunofluorescent microscopy and Western blot analysis revealed that PD significantly caused MT polymerization in leukemia cells. We also found that very highconcentrations of PD (> 200 µM) were required to directly induce MT polymerization in vitro. Finally, PD exposure induced apoptosis and cell death significantly increased PARP and lamin A cleavage, and caspase-3 activity. We conclude that theprimary means by which PD induces END not only arrests cells in mitosis by suppressing spindle MT dynamics, but also promotes mitotic cell apoptosis in human leukemia cells.
An investigator-initiated phase I study of ONX-0801, a first-in-class alpha folate receptor targeted, small molecule thymidylate synthase inhibitor in solid tumors.
Authors: Udai Banerji, Alvaro Henrique Ingles Garces, Vasiliki Michalarea, Ruth Ruddle, Florence I. Raynaud, Ruth Riisnaes, Daniel Nava Rodrigues, Nina Tunariu, Joanna C Porter, Sarah Emily Ward, Mona Parmar, Alison Joanne Turner, Satyanarayana Seeramreddi, Emma Hall, Emma Jane Dean, Bristi Basu, Angela George, Stan B Kaye, Susana N. Banerjee, Johann S. De Bono
Journal: Journal of Clinical Oncology (2017)

2503 Background: ONX-0801 is a first-in-class alpha folate receptor (AFR) targeted thymidylate synthase inhibitor, engineered to differentially accumulate 6000-fold in AFR overexpressing cancer cells. Methods: A 3+3 dose escalation design was used and two IV schedules were explored. Schedule A, weekly dosing (QW) and schedule B, once every 2 weeks dosing (Q2W). A cycle consisted of 4 weeks and treatment was stopped after 6 cycles in both schedules. An expansion cohort to evaluate clinical activity in patients with AFR overexpressing high grade serous ovarian cancer (HGSOC) was planned. Results: 21 patients each were treated in schedule A and B exploring doses ranging from 1-6 mg/m 2 and 2-12 mg/m 2 , respectively. The dose limiting toxicity on schedule A was G3 cellulitis; no dose limiting toxicity was seen on schedule B. The most common toxicities were fatigue 15/42 (36%), nausea 9/42 (21%) and dysgeusia 5/42 (12%). Within schedule A at 4 mg/m 2 , 2 patients developed suspected drug-related changes on pulmonary function tests (drop in Dlco &gt; 15%) at cycles 5 and 6, respectively. No cases of suspected drug-related drop in Dlco were noted in patients treated in schedule B. No grade 3-4 diarrhea, mucositis or neutropenia were seen in either cohort. The Cmax, AUC and half-life at 12 mg/m 2 were 4952 ng/mL, 85170 h*ng/mL and 26 h, respectively. Pre-clinical PK-PD modelling aimed to achieve concentrations between 0.05-1 µM and this was achieved for periods of 48 h at doses of 4 mg/m 2 and above. Based on safety and PK, the recommended phase II dose (RP2D) of ONX-0801 was 12 mg/m 2 Q2W and an expansion in patients with HGSOC is ongoing. 5 patients with HGSOC had partial responses (PRs) in the dose escalation cohort. In the current expansion cohort in patients with HGSOC, 5/11 patients had PRs. Archival samples have been analyzed from 8/11 patients in the expansion cohort. 4/4 AFR+ve and 4/4 AFR-ve patients did and did not have a PR following treatment with ONX-0801, respectively. Conclusions: The RP2D of ONX-0801 is 12 mg/m 2 Q2W. At the RP2D, multiple patients with AFR overexpressing HGSOC have had PRs and further randomized biomarker prespecified phase II trials are warranted. Clinical trial information: NCT02360345.
A Core–Shell‐Satellite Structured Fe<sub>3</sub>O<sub>4</sub>@g‐C<sub>3</sub>N<sub>4</sub>–UCNPs–PEG for <i>T</i><sub>1</sub>/<i>T</i><sub>2</sub>‐Weighted Dual‐Modal MRI‐Guided Photodynamic Therapy
Authors: Lili Feng, Dan Yang, Fei He, Shili Gai, Chunxia Li, Yunlu Dai, Piaoping Yang
Journal: Advanced Healthcare Materials (2017)

Reactive oxygen species (ROS) produced in the specific tumor site plays the key role in photodynamic therapy (PDT). Herein, a multifunctional nanoplatform is designed by absorbing ultrasmall upconversion nanoparticles (UCNPs) on mesoporous graphitic‐phase carbon nitride (g‐C 3 N 4 ) coated superparamagnetic iron oxide nanospheres, then further modified with polyethylene glycol (PEG)molecules (abbreviated as Fe 3 O 4 @g‐C 3 N 4 –UCNPs–PEG). The inert g‐C 3 N 4 layer between Fe 3 O 4 core and outer UCNPs can substantially depress the quenching effect of Fe 3 O 4 on the upconversion emission. Upon near‐infrared (NIR) laser irradiation, the UCNPs convert the energy to the photosensitizer (g‐C 3 N 4 layer) through fluorescence resonance energy transfer process, thus producing a vast amount of ROS. In vitro experiment exhibits an obvious NIR‐triggered cell inhibition due to the cellular uptake of nanoparticles and the effective PDT efficacy. Notably, this platform is responsive to magnetic field, which enables targeted delivery under the guidance of an external magnetic field and supervises the therapeutic effect by T 1 / T 2 ‐weighted dual‐modal magnetic resonance imaging. Moreover, in vivo therapeutic effect reveals that the magnetism guided accumulation of Fe 3 O 4 @g‐C 3 N 4 –UCNPs–PEG can almost trigger a complete tumor inhibition without any perceived side effects. The experiments emphasize that the excellent prospect of Fe 3 O 4 @g‐C 3 N 4 –UCNPs–PEG as a magnetic targeted platform for PDT application.
Dilatation des sténoses caustiques oesophagiennes de l'enfant: à propos de 138 cas
Authors: N Oumnia, M Lahcene, A Tebaibia, N Matougui, MA Boudjella, B Touchene
Journal: Endoscopy (2005)

L'ingestion d'un produit caustique est un accident fréquent chez l'enfant en Algérie. Il peut entraîner des séquelles graves à type de sténose œsophagienne dont le traitement repose essentiellement sur la dilatation instrumentale. Le but de ce travail est d'évaluer l'efficacité et la sécurité d'emploi de la dilatation dans les sténoses caustiques œsophagiennes de l'enfant.
A Phase II Study With Carfilzomib, Cyclophosphamide and Dexamethasone (CCd) For Newly Diagnosed Multiple Myeloma
Authors: Sara Bringhen, Chiara Cerrato, Maria Teresa Petrucci, Mariella Genuardi, Fabiana Gentilini, Concetta Conticello, Stefania Oliva, Lucia Pantani, Massimo Offidani, Carmela Palladino, Giulia Benevolo, Vittorio Montefusco, Monica Astolfi, Oreste Villani, Agostina Siniscalchi, Alberto Rocci, Lorenzo De Paoli, Mario Boccadoro, Pieter Sonneveld, Antonio Palumbo
Journal: Blood (2013)
Evolution of HER2 testing practices in breast cancer in France from 2005 to 2015: Results of the PartenHER national survey.
Authors: Frederique Madeleine Penault-Llorca, Jerome Chetritt, Bruno Poulet, Marie-Pierre Chenard, Magali Lacroix-Triki, Laurent Arnould, Gaetan mac Grogan, Jean-Pierre Bellocq
Journal: Journal of Clinical Oncology (2016)

e12082 Background: For many years, French pathologists have been striving to standardize their practices and improve the quality of HER2 testing in breast cancer. The PartenHER survey aimed to assess how practices have evolved over the last decade. Methods: The PartenHER national survey is based on a questionnaire developed by a scientific committee and sent by postal mail in February 2015. Each French anatomo-cytopathology (ACP) labs received only one questionnaire. The formular was composed of 41 questions including typology of ACP labs, different technical conditions observed during pre-analytical, analytical, post-analytical steps, difficult-to-classify HER2 test results, quality controls, staff organization and training. Results: By 30 July 2015, 109 ACP labs (53% private, 47% public) regularly testing for HER2 and representing almost 620 pathologists (i.e. one third of the French pathologists) had completed the questionnaire. The study showed that in 2015, the immunohistochemistry (IHC) technique was performed by all labs, 42% of which were also performing the in situ hybridization (ISH) technique. The IHC technique was automated in 100 % of the labs, two thirds of them being automated for more than 10 years. ISH was automated in 83% of the structures and in place for more than 10 years in 20% of the cases and for five years in 56%. Several improvements in practices were also reported. Formalin is now the fixative used by 89% of labs. In 2015, 79% of the preformatted request forms were designed to collect the time of tissue removal (vs 12% in 2005), 87% were using a 3+ score reference tissue on each slide (vs 17% in 2005), 81% were tracking the HER2 overexpression rate mostly by using the HER-France national database, and 94% participated in proficiency testing, even though 42% of them had never been audited by an external authority. Conclusions: The PartenHER national survey showed that French pathologists, despite their diversity, have amended and standardized their practices regarding HER2 testing in breast cancer over the last 10 years. Further progress remains to be made, in particular to monitor the HER2 overexpression rate and resort to external audits.
Increased in vitro and in vivo generation of procoagulant activity (tissue factor) by mononuclear phagocytes after intralipid infusion in rabbits
Authors: P Montemurro, A Lattanzio, G Chetta, L Lupo, L Caputi-Iambrenghi, M Rubino, D Giordano, N Semeraro
Journal: Blood (1985)