tbuckley/cabot-search huggingface dataset:
Characterization of the microRNAome in a patient with acute myeloid leukemia.
Authors: G. Ramsingh, D. Koboldt, V. Magrini, M. Trissal, S. Koul, L. Chang, R. Nagarajan, T. J. Ley, E. Mardis, D. C. Link
Journal: Journal of Clinical Oncology (2010)

10501 Background: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have been implicated in the pathogenesis of human cancer. Herein, we use next generation sequencing approaches to comprehensively assess miRNA expression, discover novel miRNAs and identify genetic variants of all known miRNA genes and miRNA binding sites in a patient with AML. Methods: The patient (AML1) was a female in her 50s with FAB M1 AML with normal 46XY karyotype. Massively-parallel sequencing of small RNAs isolated from the myeloblasts of AML1 was performed using the ABI SOLiD sequencing platform. Pooled RNA isolated from CD34+ bone marrow cells of 4 healthy volunteers (CD34) was used as control. To detect genetic variants of miRNA genes, we used 454-based sequencing of all 695 miRNA genes in the Sanger miR database (version 12.0). Finally, we analyzed the previously generated whole genome sequence for AML1 for genetic variants in the 3′- untranslated regions (3′-UTR) of all coding genes. Results: 28×106 and 20×106 small RNA sequence reads were obtained from AML1 and CD34 respectively. 8 novel miRNAs were identified from sequences that mapped to unannotated regions of human genome. Expression of 498 known miRNAs were detected with miR-233 being the most highly expressed miRNA in both AML1 and CD34; remarkably, it represented 47.3% of all miRNA reads in AML1. MiRNA gene sequencing of AML1 leukemic blast identified several single nucleotide variants. The whole genome sequence of AML1 skin DNA was used to differentiate germline polymorphism (SNPs) from somatic mutations. 13 novel SNPs and no somatic mutation were detected. Analysis of the 3′UTR of all coding genes in leukemic blasts and skin of AML1 revealed a single somatic mutation in the 3′-UTR of TNFAIP2. This mutation results in suppression of TNFAIP2 protein expression possibly by creating one or more new miRNA binding site. However, no recurrent mutations in the 3′-UTR of TNFAIP2 were detected in an additional 180 patients with AML. Conclusions: These data demonstrate the feasibility of next generation sequencing technologies to identify novel miRNAs, accurately measure mature miRNA expression, and identify both somatic and germline genetic variants of miRNA genes in primary cancer. No significant financial relationships to disclose.
Incidence of Aplastic Anemia and Agranulocytosis in Brazil and Argentina - The LATIN Study.
Authors: Nelson Hamerschlak, Eliane Maluf, Ricardo Pasquini, Frederico R. Moreira, Alexandre B. Cavalcante, Iria R. Okano, Roberto P. Falcao, Marimilia T. Pita, Sandra R. Looggetto, Luiz G. Rosenfeld, Lorand-Metze G. Irene, Eluf Neto Jose
Journal: Blood (2005)
Newborn With a Diffuse Rash
Authors: Sara M. James, Amy L. Gagnon, Adam B. Blechman
Journal: JAMA Pediatrics (2016)

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 Pediatrics 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 Pediatrics journal
Endothelial cell-derived pentraxin 3 limits the vasoreparative therapeutic potential of circulating angiogenic cells
Authors: Christina L. O’Neill, Jasenka Guduric-Fuchs, Sarah E. J. Chambers, Michelle O’Doherty, Barbara Bottazzi, Alan W. Stitt, Reinhold J. Medina
Journal: Cardiovascular Research (2016)

Circulating angiogenic cells (CACs) promote revascularization of ischaemic tissues although their underlying mechanism of action and the consequences of delivering varying number of these cells for therapy remain unknown. This study investigates molecular mechanisms underpinning CAC modulation of blood vessel formation. CACs at low (2 × 105 cells/mL) and mid (2 × 106 cells/mL) cellular densities significantly enhanced endothelial cell tube formation in vitro, while high density (HD) CACs (2 × 107 cells/mL) significantly inhibited this angiogenic process. In vivo, Matrigel-based angiogenesis assays confirmed mid-density CACs as pro-angiogenic and HD CACs as anti-angiogenic. Secretome characterization of CAC-EC conditioned media identified pentraxin 3 (PTX3) as only present in the HD CAC-EC co-culture. Recombinant PTX3 inhibited endothelial tube formation in vitro and in vivo. Importantly, our data revealed that the anti-angiogenic effect observed in HD CAC-EC co-cultures was significantly abrogated when PTX3 bioactivity was blocked using neutralizing antibodies or PTX3 siRNA in endothelial cells. We show evidence for an endothelial source of PTX3, triggered by exposure to HD CACs. In addition, we confirmed that PTX3 inhibits fibroblast growth factor (FGF) 2-mediated angiogenesis, and that the PTX3 N-terminus, containing the FGF-binding site, is responsible for such anti-angiogenic effects. Endothelium, when exposed to HD CACs, releases PTX3 which markedly impairs the vascular regenerative response in an autocrine manner. Therefore, CAC density and accompanying release of angiocrine PTX3 are critical considerations when using these cells as a cell therapy for ischaemic disease.
Does physical activity moderate the association between alcohol drinking and all-cause, cancer and cardiovascular diseases mortality? A pooled analysis of eight British population cohorts
Authors: K Perreault, A Bauman, N Johnson, A Britton, V Rangul, E Stamatakis
Journal: British Journal of Sports Medicine (2016)

To examine whether physical activity (PA) moderates the association between alcohol intake and all-cause mortality, cancer mortality and cardiovascular diseases (CVDs) mortality.Prospective study using 8 British population-based surveys, each linked to cause-specific mortality: Health Survey for England (1994, 1998, 1999, 2003, 2004 and 2006) and Scottish Health Survey (1998 and 2003).36 370 men and women aged 40 years and over were included with a corresponding 5735 deaths and a mean of 353 049 person-years of follow-up.6 sex-specific categories of alcohol intake (UK units/week) were defined: (1) never drunk; (2) ex-drinkers; (3) occasional drinkers; (4) within guidelines (<14 (women); <21 (men)); (5) hazardous (14-35 (women); 21-49 (men)) and (6) harmful (>35 (women) >49 (men)). PA was categorised as inactive (≤7 MET-hour/week), active at the lower (>7.5 MET-hour/week) and upper (>15 MET-hour/week) of recommended levels.Cox proportional-hazard models were used to examine associations between alcohol consumption and all-cause, cancer and CVD mortality risk after adjusting for several confounders. Stratified analyses were performed to evaluate mortality risks within each PA stratum.We found a direct association between alcohol consumption and cancer mortality risk starting from drinking within guidelines (HR (95% CI) hazardous drinking: 1.40 (1.11 to 1.78)). Stratified analyses showed that the association between alcohol intake and mortality risk was attenuated (all-cause) or nearly nullified (cancer) among individuals who met the PA recommendations (HR (95% CI)).Meeting the current PA public health recommendations offsets some of the cancer and all-cause mortality risk associated with alcohol drinking.
Pembrolizumab expanded access program (EAP) in Spain: clinical activity.
Authors: Ana Arance, Josep M. Piulats, Ivan Marquez Rodas, Jose Luis Manzano, Alfonso Berrocal, Salvador Martin Algarra, Guillermo Crespo, Delvys Rodriguez, Miguel Ángel Berciano Guerrero, Ainara Soria, Elisabeth Perez Ruiz, Almudena Garcia Castano, Clara Montagut, Teresa Puértolas, Carlos Aguado, Maria Angeles Royo, Remei Blanco, Eva Muñoz-Couselo, Pilar Mut Sanchis, Maria Gonzalez-Cao
Journal: Journal of Clinical Oncology (2016)

e21029 Background: The programmed death (PD-1) inhibitor pembrolizumab has recently been approved for treatment of advanced melanoma patients (p), based on a significant improvement in terms of survival demonstrated in advanced melanoma p (phase III KEYNOTE-006 trial). We evaluated the clinical activity of pembrolizumab in melanoma p treated in 23 centers from the Spanish Melanoma Group (GEM) under the expanded access program (EAP). Methods: Patients with unresectable stage III/IV melanoma who had failed to previous treatments lines received treatment with pembrolizumab 2 mg/kg every three weeks. Results: Data were collected from 66 advanced melanoma p (46 cutaneous, 8 uveal, 7 mucosal and 4 unknown primary). Forty nine p were stage M1c (74.2%), 37 p had high LDH levels (56.1%), 26 p had ECOG 0 (39.4%) and 50 p were treated in 3-4th line (75.8% ). Median overall survival (OS) was 6.8 months (m) (CI 95% 1.8; 11.8), OS12m 41.8%. For cutaneous melanoma p, median OS was 14 m (CI 95% 4.3; 23.6), OS12m 50.5%. Three p (including one refractory to previous ipilimumab) achieved a complete response (CR), and 9 p (5 refractory to ipilimumab) achieved a partial response (PR), with an overall response rate (ORR) of 18.1%. For those p who achieved ORR, stable disease (SD) and progressive disease (PD) to pembrolizumab, OS18m was 80%, 64.6% and 7% respectively (p = 0.0001). Other significant prognostic factors for OS were LDH levels (elevated/normal NR vs 3.7 m; p = 0.00001) and ECOG PS (ECOG 0, 1 and 2; NR vs 6.8 m vs 1.1 m; p = 0.0001). There were no significant differences by sex, clinical stage, previous response to ipilimumab, BRAF status or treatment line. Two of 6 p (33%) with previous G3-4 toxicity to ipilimumab achieved a long response to pembrolizumab (18.7 m+ and 13.8 m+) without relevant adverse events. Conclusions: Although this was a heavily pretreated cohort with very advanced disease, pembrolizumab activity was confirmed, with long-term responders. Low LDH levels and ECOG 0 were significant prognostic factors for survival.
Incidence, prevalence and mortality of patients with psoriasis: a U.K. population-based cohort study
Authors: D.A. Springate, R. Parisi, E. Kontopantelis, D. Reeves, C.E.M. Griffiths, D.M. Ashcroft
Journal: British Journal of Dermatology (2016)

The burden of psoriasis across many world regions is high and there is a recognized need to better understand the epidemiology of this common skin disorder. To examine changes in the prevalence and incidence of psoriasis, and mortality rates over a 15‐year period. Cohort study involving analysis of longitudinal electronic health records between 1999 and 2013 using the U.K. Clinical Practice Research Datalink (CPRD). The prevalence of psoriasis increased steadily from 2·3% (2297 cases per 100 000) in 1999 to 2·8% (2815 per 100 000) in 2013, which does not appear to be attributable to changes in incidence rates. We observed peaks in age bands characteristic of early‐onset (type I) and late‐onset (type II) psoriasis, and changes in incidence and prevalence rates with increasing latitude in the U.K. All‐cause mortality rates for the general population and for patients with psoriasis have decreased over the last 15 years. However, the risk of all‐cause mortality for patients with psoriasis remains elevated compared with people without psoriasis (hazard ratio 1·21; 95% confidence interval 1·13–1·3) and we found no significant change in this relative excess mortality gap over time. We found an increasing population living longer with psoriasis in the U.K., which has important implications for healthcare service delivery and for resource allocation. Importantly, early mortality in patients with psoriasis remains elevated compared with the general population and we found no evidence of change in this premature mortality gap.
Phase 1, open-label, dose-escalation, and expansion study of ABT-700, an anti-C-met antibody, in patients (pts) with advanced solid tumors.
Authors: John H. Strickler, Patricia LoRusso, Chia-Jui Yen, Chia-Chi Lin, Yoon-Koo Kang, Patrick Kaminker, Peter Ansell, Anahita Bhathena, Shekman Wong, Matthew W. Dudley, Louie Naumovski, Ramesh K. Ramanathan
Journal: Journal of Clinical Oncology (2014)

2507 Background: MET amplification (MA) is an oncogenic driver in multiple malignancies. MA is relatively rare in primary tumors (~1-5%), but may increase after treatment with inhibitors of the EGFR pathway or cytotoxic chemotherapy. We are developing ABT-700 (hz224G11), an antagonistic antibody directed against c-Met, as monotherapy in MA tumors. Methods: In a 3+3 dose escalation design, ABT-700 was administered at doses of 5, 10, 15 and 25 mg/kg once every 21 days. ABT-700 was then studied at the recommended single-agent dose of 15 mg/kg (chosen based on safety, pharmacokinetic (PK), and biomarker analyses) in 26 pts with advanced solid tumors (10 colorectal, 5 non-small cell lung, 4 ovarian, 3 gastric, 2 esophageal, 1 renal, 1 uterine). MA was assessed by fluorescence in situ hybridization (FISH). Results: As of Dec 17, 2013, 41 pts received between 1-12 doses of ABT-700. The PK demonstrated target-mediated disposition with a mean T1/2 of 13.9 days at 15 mg/kg. (n=10, cycle 1 of expansion cohort). There were no acute infusion reactions. Common toxicities at the 15 mg/kg dose occurring in ≥15% of pts included constipation (24%), fatigue (24%), decreased appetite (21%), peripheral edema (21%), hypoalbuminemia (17%), hypokalemia (17%) and vomiting (17%). There was no dose limiting toxicity and no maximum tolerated dose identified. By RECIST, 3/5 (60%) of pts with MA tumors had a partial response (1 each ovarian, gastric and esophageal). Among these 3 pts, the duration of response was 19, 23, and 24 weeks, respectively. Two other pts with MA did not respond: 1 pt with papillary renal cancer treated at 5 mg/kg (considered to be sub-therapeutic based on preclinical studies) and 1 pt with gastric cancer treated at 15 mg/kg. Among pts with non-amplified tumors (n=36), no objective responses were observed, however 5 pts had stable disease at the 12 week assessment. Conclusions: ABT-700 is well tolerated at the recommended single-agent dose of 15mg/kg. ABT-700 monotherapy has demonstrated promising anti-tumor activity in pts with MA solid tumors. The study has been expanded to identify and enroll pts with MA tumors to better define predictive biomarkers of clinical benefit. Clinical trial information: NCT01472016.
Live Attenuated Versus Inactivated Influenza Vaccine in Hutterite Children
Authors: Mark Loeb, Margaret L. Russell, Vanessa Manning, Kevin Fonseca, David J.D. Earn, Gregory Horsman, Khami Chokani, Mark Vooght, Lorne Babiuk, Lisa Schwartz, Binod Neupane, Pardeep Singh, Stephen D. Walter, Eleanor Pullenayegum
Journal: Annals of Internal Medicine (2016)

Background: Whether vaccinating children with intranasal live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in providing both direct protection in vaccinated persons and herd protection in unvaccinated persons is uncertain. Hutterite colonies, where members live in close-knit, small rural communities in which influenza virus infection regularly occurs, offer an opportunity to address this question. Objective: To determine whether vaccinating children and adolescents with LAIV provides better community protection than IIV. Design: A cluster randomized blinded trial conducted between October 2012 and May 2015 over 3 influenza seasons. (ClinicalTrials.gov: NCT01653015) Setting: 52 Hutterite colonies in Alberta and Saskatchewan, Canada. Participants: 1186 Canadian children and adolescents aged 36 months to 15 years who received the study vaccine and 3425 community members who did not. Intervention: Children were randomly assigned according to community in a blinded manner to receive standard dosing of either trivalent LAIV or trivalent IIV. Measurements: The primary outcome was reverse transcriptase polymerase chain reaction–confirmed influenza A or B virus in all participants (vaccinated children and persons who did not receive the study vaccine). Results: Mean vaccine coverage among children in the LAIV group was 76.9% versus 72.3% in the IIV group. Influenza virus infection occurred at a rate of 5.3% (295 of 5560 person-years) in the LAIV group versus 5.2% (304 of 5810 person-years) in the IIV group. The hazard ratio comparing LAIV with IIV for influenza A or B virus was 1.03 (95% CI, 0.85 to 1.24). Limitation: The study was conducted in Hutterite communities, which may limit generalizability. Conclusion: Immunizing children with LAIV does not provide better community protection against influenza than IIV. Primary Funding Source: The Canadian Institutes for Health Research.
Surprise as an ideal case for the interplay of cognition and emotion
Authors: Meadhbh I. Foster, Mark T. Keane
Journal: Behavioral and Brain Sciences (2015)

Abstract The target article is a timely exposition on the impact of how emotion and cognition interact, a specifically important issue in surprise research. Psychologists debate whether disconfirmed expectations or sense-making processes determine surprise levels experienced for an event. We posit that, in surprise, cognition and emotion are intertwined, making it an interesting test case for the proposals in this article.
EGFR mutation detection in plasma of lung tumor patients to predict success in treatment with tyrosine kinase inhibitors in a routine clinical setting.
Authors: Marc G. Denis, Sandrine Hiret, Stephanie Bordenave, Anne-Marie Chiappa, Philippe Masson, Clarisse Audigier-Valette, Herve Lacroix, Claire Alizon, Bertrand Guy, Isabelle Caby, Thierry Chatellier, Valérie Delecroix, Thierry Jeanfaivre, Marie Marcq, Thierry Pigeanne, Gilles Quere, Roland Schott, Thierry Urban, Sandrine Theoleyre, Audrey Vallee
Journal: Journal of Clinical Oncology (2016)

e20545 Background: EGFR alterations can be detected in the plasma of lung cancer patients mutated in their tumor. But there has been no prospective report evaluating the efficacy of tyrosine kinase inhibitors (TKI) in patients only tested on circulating DNA (ctDNA) in the absence of contributive tissue testing. We report here the results obtained for 27 patients treated with an EGFR TKI on the basis of ctDNA testing in a clinical setting. Methods: Blood was collected in EDTA-containing tubes and plasma was prepared within 3 hours. Cell-free DNA was extracted using the QIamp Circulating Nucleic Acid Kit (Qiagen). Detection of EGFR alterations was performed using the approved Therascreen EGFR RGQ kit (Qiagen). Results: We routinely analyze ctDNA for lung tumor patients before treatment initiation. We thus identified an EGFR mutation in ctDNA for 27 patients that could not be evaluated on tissue : 16 patients tested prior to any therapy (11 exon 19 deletions and 5 p.L858R mutations), and 11 patients relapsing after TKI treatment (p.T790M mutation). The rationale for plasma testing was “not possible to obtain tissue” (n = 10), “tissue testing not contributive” (n = 8), and “rapid degradation of the patient not compatible with the longer turn around time of tissue testing” (n = 9). We could collect information on treatment efficiency for 21 of these patients. Among the 12 evaluated patients treated in first line with an EGFR TKI (gefitinib, n = 6; erlotinib, n = 4; afatinib, n = 2), 9 partial responses (PR) and 3 stable diseases (SD) were reported. Among the 9 evaluated patients tested positive for the T790M mutation and treated with osimertinib (AZD9291), we observed 1 complete response (CR), 7 PR and 1 progressive disease (PD). Conclusions: We show here that in routine clinical practice, when a tumor sample is not available for molecular testing, detection of an EGFR alteration in plasma is a relevant alternative for TKI prescription, both for TKI naïve patients, and for patients relapsing after TKI treatment.
Unique Reversible but Serious Adverse Events in Very Young Infants Undergoing Unrelated Donor Umbilical Cord Blood Transplantation for Non-Malignant Conditions: Increased Autoimmune Cytopenias and Hypertrophic Cardiomyopathy.
Authors: Sonali Lakshminarayanan, Paul Szabolcs, Suhag Parikh, Susan J. Wood, June Allison, Joanne Kurtzberg
Journal: Blood (2005)
Smallpox: The Fight to Eradicate a Global Scourge
Authors: D. J. Wear
Journal: JAMA (2003)

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