tbuckley/cabot-search huggingface dataset:
Prospective pilot study of Merkel cell carcinoma.
Authors: Kristina Vyacheslavovna Orlova, Alla Anatolievna Markovich, Vladimir Yur'evich Selchuk, Lev V. Demidov, Nadezhda Fedorovna Orel, Somasundaram Subramanian
Journal: Journal of Clinical Oncology (2012)

e19005 Background: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer. The annual incidence for MCC, based on SEER database, was 0.6 cases per 100,000 in 2006 (0.15 cases per 100,000 in 1986), with slightly more males affected (60%). Due to its rarity, data on its clinico-pathological features and impact of therapy are limited. Aim: To characterize MCC based on immunohistochemical (IHC) features and serum levels of biochemical markers such as chromogranin A (CgA) and serotonin and select treatment options. Methods: This prospective pilot study included 7 patients (pts) since 2009 and their age, sex, primary site, IHC features and serum levels of biochemical markers, progression-free-survival (PFS) were recorded. Median of overall survival was not achieved. Results: Pts characteristics were: age 44–67 years (mean 57), male–female ratio = 4:3. Most common primary sites were extremities (5pts), lymphnode metastases from unknown primary (1pt) and genitals (1pt). IHC showed diffuse positivity for CgA (6pts), dot-like staining for cytokeratin 20 (7pts), synaptophysin (6pts), Ki-67 (40%-1pt, 50%-1pt, 60–70%-5pts). The tumors did not express vimentin, TTF1. Serum levels of Cg A (2pts) and serotonin (1pt) were above normal. Treatment: Local disease – surgery, either alone (1pt) or as part of multimodality plan (2pts); Locoregional disease – surgery plus chemotherapy (2pts) and chemotherapy alone (1pt); Distant disease – chemotherapy plus surgery (1pt). Median of PFS was 16 months.Two patients with improvement of biochemical markers continue to receive maintenance therapy with somatostatin (SST) analogues for 16 and 24 months with complete remission. Conclusions: SST analogues facilitates treatment of MCC without reducing quality of life and increase PFS in patients with high CgA serum level. In spite of recent advances in understanding the biology of MCC, many molecular mechanisms that influence behavior stills are unknown.
Changing Prevalence of Helicobacter pylori Infection in Elderly Dyspeptic Patients
Authors: S Sarwar, MM Anwar, B Egan, B Ryan, N Breslin, C O'Morain
Journal: Endoscopy (2006)

Aims: Helicobacter pylori infection increases with age. The prevalence in elderly dyspeptic patients was reported as 65.5% in 1991 in a crossectional study conducted in Dublin teaching hospital. The aim of this study was to re-evaluate the prevalence of Helicobacter pylori.
A Very High Intake of Conjugated Linoleic Acid, a Trans Fat from Milk and Meat, Does Not Affect Blood Pressure in Normotensive Humans
Authors: A.J. Wanders, M.F. Engberink, J.M. Geleijnse, I.M. Wagenaar, E. Siebelink, M.B. Katan, I.A. Brouwer
Journal: Circulation (2009)
Long sleep duration and health outcomes: A systematic review, meta-analysis and meta-regression
Authors: Maki Jike, Osamu Itani, Norio Watanabe, Daniel J. Buysse, Yoshitaka Kaneita
Journal: Sleep Medicine Reviews (2017)

We examined the dose–response relationship between long sleep duration and health outcomes including mortality and the incidence of diabetes mellitus, hypertension, cardiovascular diseases, stroke, coronary heart diseases, obesity, depression and dyslipidemia. We collected data from 5,134,036 participants from 137 prospective cohort studies. For the independent variable, we categorized participants at baseline as having long sleep duration or normal sleep duration. Risk ratios (RRs) for mortality and incident health conditions during follow-up were calculated through meta-analyses of adjusted data from individual studies. Meta-regression analyses were performed to investigate the association between each outcome and specific thresholds of long sleep. Long sleep was significantly associated with mortality (RR, 1.39; 95% CI, 1.31–1.47), incident diabetes mellitus (1.26, 1.11–1.43), cardiovascular disease (1.25, 1.14–1.37), stroke (1.46, 1.26–1.69), coronary heart disease (1.24, 1.13–1.37), and obesity (1.08, 1.02–1.15). Long sleep was not significantly related to incident hypertension (1.01, 0.95–1.07). Insufficient data were available for depression and dyslipidemia. Meta-regression analyses found statistically significant linear associations between longer sleep duration and increased mortality and incident cardiovascular disease. Future studies should address whether the relationship between long sleep and health outcomes is causal and modifiable.
The Joint Commission and the Opioid Epidemic—Reply
Authors: David W. Baker
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
EPR and uDCDD: A Response to Commentaries
Authors: Arjun Prabhu, Lisa S. Parker, Michael A. DeVita
Journal: The American Journal of Bioethics (2017)

We appreciate the thoughtful, careful, and insightful commentaries on our article (Prabhu, Parker, and DeVita 2017). The diversity of points raised and the number of commentaries received underscor...
Abstract 281: Studying Structural And Contractility Defects Of Cardiomyocytes In An In Vitro Model Of Human Hypertrophic Cardiomyopathy
Authors: Marcelo C Ribeiro, Hedde van Hoorn, Jantine J Monshouwer-Kloots, Christine L Mummery, Thomas Schmidt, Robert Passier
Journal: Circulation Research (2013)

Hypertrophic Cardiomyopathy (HCM) is a cardiac disease, morphologically characterized by cardiac hypertrophy, fibrosis and impaired heart function. HCM is primarily associated with mutations in sarcomeric proteins. Mutations in sarcomeric Myosin Binding Protein C (MYBPC3) account for approximately 25% of all HCM patients. The majority of mutations in MYBPC3 are nonsense mutations, predicted to produce truncated proteins. However, instead of truncated proteins, lower levels of full-length protein of MYPBC3 are frequently found in heart samples of patients with mutations in MYBPC3, strongly suggesting that haploinsufficiency is responsible for the cardiac disease phenotype. It has been previously shown that upon ablation of MYBPC3 the myosin cross-bridges are localized closer to the actin filament, suggesting that MYBPC3 functions as a structural restraint, holding a fraction of the myosin heads at a specific distance from the actin filament. We hypothesize that the shortening of the distance between the myosin cross-bridges and the actin filaments is responsible for the increase of stretch activation kinetics leading to an increase in calcium sensitivity and contractile dysfunction. In order to develop a human in vitro model for HCM we mimicked MYBPC3 haploinsufficiency by generating stable lines in human pluripotent stem cells-derived cardiomyocytes (hPSC-CM) in which MYPBC3 protein levels were reduced by 40 to 90% using short-hairpin RNA sequences. To analyze structural and Ca2+ kinetic changes induced by the MYBPC3 knockdown we are using stochastic optical reconstruction microscopy (STORM), a superresolution fluorescence imaging method, to measure the distances between sarcomeric proteins in combination with Ca2+ imaging using a ratiometric method. At a mechanical level we are able to measure total cell force of contraction by measuring the deflection of pillars on a micropillar array generated by control and MYBPC3 knockdown hPS-CM during contraction. In conclusion, we successfully developed a human in vitro model for cardiac MYBPC3 haploinsufficiency in combination with state of the art biophysical and imaging techniques, which will allow us to comprehend the molecular mechanisms responsible for the development of HCM.
Inter-Synaptic Lateral Diffusion of GABAA Receptors Shapes Inhibitory Synaptic Currents
Authors: Emanuela de Luca, Tiziana Ravasenga, Enrica Maria Petrini, Alice Polenghi, Thierry Nieus, Stefania Guazzi, Andrea Barberis
Journal: Neuron (2017)

The lateral mobility of neurotransmitter receptors has been shown to tune synaptic signals. Here we report that GABAA receptors (GABAARs) can diffuse between adjacent dendritic GABAergic synapses in long-living desensitized states, thus laterally spreading "activation memories" between inhibitory synapses. Glutamatergic activity limits this inter-synaptic diffusion by trapping GABAARs at excitatory synapses. This novel form of activity-dependent hetero-synaptic interplay is likely to modulate dendritic synaptic signaling.
The prognostic impact of serum albumin in double hit/double expressing aggressive B cell lymphomas: A pilot study evaluating SAAB scoring system.
Authors: Chetasi Talati, Jose David Sandoval-Sus, Samir Dalia, Bijal D. Shah, Celeste M. Bello, Paul A. Chervenick, Ernesto Ayala, Frederick Lundry Locke, Mohamed A. Kharfan-Dabaja, Eduardo M. Sotomayor, Lubomir Sokol, Julio C. Chavez
Journal: Journal of Clinical Oncology (2016)

e19044 Background: Double hit lymphomas (DHL) [rearrangements of MYC and BCL2/BCL6, and double expressing lymphomas (DEL) [expression of MYC and BCL6/BCL2 by immunohistochemistry] represent a subset of diffuse large B-cell lymphoma (DLBCL) with poor overall survival (OS). Several prognostic scores have been tested to clinically stratify these patients with the double hit score (DHS) being the most recently developed model (Petrich 2014). We explored the use of serum albumin (SA) as prognostic factor in DHL as previously shown in DLBCL (Dalia 2013). Methods: We included 100 patients from Moffitt Cancer Center database from January 2008 to December 2015 with DHL and performed a retrospective chart review. Recorded clinical data included SA, hemoglobin, age, International Prognostic Index (IPI), DHS, and lymphopenia. Pairwise Cox Comparison was used to develop a weighted scoring system. Kaplan-Meier method with Cox proportional hazard model was used to determine OS. Results: The median age was 63 (18-87), stage III/IV in 73.1%, bulky disease (>10cm) in 47.4%, B symptoms in 41.67%, CNS involvement in 14.1% , extranodal (EN) involvement in 34.7% of the patients. Patients with DHL and DEL were 60.2% and 39.8%, respectively. The median OS for the cohort was 15 months. Multivariate analysis identified Age > 60 (1 point), SA <3.7 (4 points), bulky disease (2 points) and Stage III/IV (1 point) as prognostically significant. LDH and EN dropped from the model. SAAB scoring consisted of 3 groups: Very good (0-2), Good (3-5), Poor (6-8). The 3-years OS was compared among scoring systems (Table 1). Conclusions: Compared to the R-IPI and DHS, the new SAAB score better discriminated prognostic groups in DHL/DEL. Confirmation in a larger and multicenter study is needed to validate these findings. SA might represent a surrogate of comorbid status and worse biology in patients with DHL/DEL. Score (N=100) 3 Year-OS P-value SAAB 0.005 Very good (SAAB = 0-2) 45% Good (SAAB 3-5) 30% Poor (SAAB = 6-8) NA* R-IPI 0.437 Very Good (R-IPI = 0) 100% Good (R-IPI = 1-2) 30% Poor (R-IPI = 3-5) 32% Double Hit Score (DHS) 0.281 Low (DHS = 0) 26% Intermediate (DHS = 1) 29% High (DHS = 2 or more) 27% *Highest survival was 18 months.
The impact of pathologic differentiation (well/poorly) and the degree of Ki-67 index in patients with metastatic WHO grade 3 GEP-NECs
Authors: Song Ee Park, Jeeyun Lee, Hoon Park Se, Oh Park Joon, Yeong Lim Ho, Ki Kang Won, Young-Suk Park, Tae Kim Seung
Journal: Annals of Oncology (2017)
Nab-paclitaxel (nab-p) in association with FOLFIRI (Nab-FOLFIRI) or FOLFOX (Nab-FOLFOX) for metastatic pancreatic cancer: A phase I/II trial by Italian Oncology Group for Clinical Research (GOIRC)—NabucCO Trial.
Authors: Elisa Giommoni, Evaristo Maiello, Laura Toppo, Francesco Cognetti, Giampaolo Tortora, Antonio Febbraro, Maria Banzi, Elena Molinara, Luciano Nanni, Cinzia Lamperini, Wanda Liguigli, Rosa Laface, Vanja Vaccaro, Lorenzo Antonuzzo, Davide Melisi, Silvia Fanello, Guido Giordano, Luca Boni, Francesco Di Costanzo
Journal: Journal of Clinical Oncology (2015)

e15242 Background: FOLFIRINOX and nab-paclitaxel (nab-p) plus gemcitabine are approved regimens for metastatic pancreatic cancer (mPC).NabucCO study was a phase I/II trial designed in two steps.The first one defines dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of Nab-FOLFIRI and Nab-FOLFOX, obtained by the substitution of oxaliplatin or irinotecan with nab-p in FOLFIRINOX classical schedule. In the second step (phase II) we will evaluate the activity of these new regimens.Now we report final results of dose-finding (DLTs/ MTD) for Nab-FOLFIRI. Methods: Study started on February 2014 and patients (pts) with mPC without prior treatment for metastatic disease and PS ECOG 0-1 received irinotecan 180 mg/m2iv, leucovorin 400 mg/m2iv, 5FU bolus 400 mg/m2iv and 5-FU 48h ci 2400 mg/m2iv plus nab-p iv through 6 levels of escalation (level 1:90 mg/m2,level 2:100 mg/m2,level 3:110 mg/m2,level 4:120 mg/m2,level 5:130 mg/m2,level 6:140 mg/m2) every 2 weeks for up to12 cycles.The design was the standard 3+3 phase I dose escalation. The MTD was established by DLTs according with Common Toxicity Criteria for Adverse Events (CTCAE) v. 4.03 during the first cycle of therapy. Results: A total of27 pts were treated with Nab FOLFIRI. The median age was 62 yr (38-75).We treated 3 pts at level 1, 3 pts at level 2, 6 pts at level 3, 6 pts at level 4, 6 pts at level 5, 3 pts at level 6. At level 6, one pt experimented neutropenia gr4, thrombocytopenia gr3, and we also registered one serious adverse event for another pt (hospitalization for fever, asthenia gr3 and anorexia gr2). We planned another 3 pts at level 5 and unexpectedly we observed DLTs in 2 pts: neutropenia gr4, leucopenia gr3, thrombocytopenia gr3. So we defined the MTD at level 4 through a cohort expansion of 3 pts without toxicities. At this time,14 pts completed Nab-FOLFIRI and are evaluable for overall safety and secondary end-points.In the Nab-FOLFOX arm12 pts have been enrolled and no DLTs are detected at level 4. Conclusions: The MTD of nab-p with FOLFIRI is 120mg/m2. Dose finding for Nab-FOLFOX could be completed in May 2015 (Clinicaltrials.gov NCT02109341). Clinical trial information: NCT02109341.
Anaemia in Upper and Lower Gastrointestinal (GI) Malignancies. Taking Nice Guidance Further
Authors: A Shah, A Koulaouzidis, E Said, D Nicolaides, AA Saeed
Journal: Endoscopy (2006)

Aims: NICE suggest urgent colonoscopy in males and females with Haemoglobin (Hb) <11 gr/dl & 10 gr/dl respectively. We aim to check the safety of the recommended threshold-level and the potential use in the upper GI guidance.
Chemoradiation in patients with locally advanced pancreatic adenocarcinoma
Authors: Oana Trifanescu, Laurentia Gales, Luiza Serbanescu, Iulia Ristea, Ioana Voica, Radu Ionescu, Buta Tiberiu, Corina Ionescu, Radu Toma, Rodica Anghel
Journal: Annals of Oncology (2017)
Omalizumab prevents anaphylaxis and improves symptoms in systemic mastocytosis: Efficacy and safety observations
Authors: S. Broesby‐Olsen, H. Vestergaard, C. G. Mortz, B. Jensen, T. Havelund, A. P. Hermann, F. Siebenhaar, M. B. Møller, T. K. Kristensen, C. Bindslev‐Jensen
Journal: Allergy (2017)

Abstract Background Patients with systemic mastocytosis (SM) may suffer from mast cell (MC) mediator‐related symptoms insufficiently controlled by conventional therapy. Omalizumab is an established treatment in other MC‐driven diseases, but experiences in SM are limited. Objective To assess the efficacy and safety of omalizumab in SM. Methods In our patient cohort, we evaluated all SM patients treated with omalizumab. A physician global assessment of type and severity of symptoms was performed at baseline, at 3 and 6 months and at latest follow‐up. Quality of life was assessed by visual analogue scale. S‐tryptase and KIT D816V allele burden were monitored. Results A total of 14 adult SM patients (10 ISM, 2 BMM, 1 SSM, and 1 ASM‐AHN) received omalizumab with a median duration of 17 months (range: 1‐73 months). One patient was excluded due to concomitant cytoreductive therapy. In the remaining 13 patients, we observed a significant reduction in symptoms, with complete symptom control in five (38.5%), major response in three (23.1%), and a partial response in three (23.1%) patients, whereas two patients (15.4%) withdrew due to subjective side‐effects at first dose. The treatment was most effective for recurrent anaphylaxis and skin symptoms, less for gastrointestinal, musculoskeletal, and neuropsychiatric symptoms. Patient‐reported quality of life showed significant improvement. No significant changes in s‐tryptase/ KIT D816V allele burden were observed. No severe adverse events were recorded. Conclusions Omalizumab appears to be a promising treatment option in SM, effectively preventing anaphylaxis and improving chronic MC mediator‐related symptoms, insufficiently controlled by conventional therapy. Controlled studies are needed to substantiate findings.
An Oral GnRH Antagonist for Endometriosis — A New Drug for an Old Disease
Authors: Mark D. Hornstein
Journal: New England Journal of Medicine (2017)

Endometriosis, a chronic gynecologic disease characterized by attachment and proliferation of endometrial cells outside the endometrial cavity, occurs in 6 to 10% of women of reproductive age1 and is associated with dysmenorrhea, nonmenstrual pelvic pain, dyspareunia, and infertility. The disease is also associated with an increased prevalence of depression, reduction in sexual satisfaction, disrupted personal relations, and loss of work leading to substantial economic cost. The pathogenesis is incompletely understood, but estrogen is integral to endometrial proliferation and function. Although surgical treatment of endometriosis-associated pelvic pain results in symptomatic improvement in most patients,2 medical treatment remains the mainstay of long-term . . .
Contemporary Treatment Patterns and Outcomes for Clinical Stage IS Testicular Cancer
Authors: Sophia C. Kamran, Thomas Seisen, Sarah C. Markt, Mark A. Preston, Quoc-Dien Trinh, Lindsay A. Frazier, Toni K. Choueiri, Neil E. Martin, Paul L. Nguyen, Clair J. Beard
Journal: European Urology (2017)
Biomarkers to diagnostics: Developing an automated, quantitative and standardized assay platform
Authors: Mark Gustavson, Jason Christiansen, Robert Pinard, Melissa Cregger, Jane Mayotte, Dylan Reilly, Brian Bourke
Journal: Clinical Cancer Research (2007)

A14  While traditional immunohistochemistry (IHC) methods have been used for diagnostic tests, the current assays do have significant limitations: They are limited to a bin-based scoring system which relies on subjective assignment, thus final diagnosis can vary significantly between operators, locations and methods. For a clinical diagnostic assay, the ideal platform must be able to produce normalized/standardized data derived from objective quantitative assignment. We have developed an AQUA® scoring system which provides a continuous variable measuring protein expression in defined regions of formalin-fixed paraffin embedded tissue samples. This approach combines fluorescent immunoassay sensitivity and dynamic range with the location information typically provided by traditional IHC. In order to fully realize the potential of this system for widespread use in a regulated environment, we have now developed an automated platform which provides standardized AQUA® analysis results. This is a complete solution encompassing the immunoassay, acquisition hardware and analysis software. The platform consists of an automated fluorescence microscopy system which is controlled by a PC which also includes analysis and data quality control software. Slides are stained using standard immunochemistry techniques with an assay that can be readily configured for different biomarkers of interest. Minimal operator interaction is required for set-up and acquisition of stained slides (either whole tissue sections or tissue microarrays (TMA)), while the hardware and assay are configured to produce standardized results correcting for variations in the assay, microscopy and imaging of samples. Results can then be compared across multiple testing sites and even to other analysis platforms (i.e. ELISA). This is a crucial step in facilitating the leap from biomarker identification to practical diagnostic use. This presentation will describe how this new platform is capable of repeatedly producing diagnostic assay results which provide maximal predictive value and reliability.
HER2 oncogenic function escapes EGFR tyrosine kinase inhibitors via activation of alternative HER receptors in breast cancer cells
Authors: Anthony Kong, Veronique Calleja, Pierre Leboucher, Adrian Harris, Peter Parker, Banafshe Larijani
Journal: Clinical Cancer Research (2008)

A26   The response rate to EGFR tyrosine kinase inhibitors (TKIs) may be poor and unpredictable in cancer patients with EGFR expression itself being an inadequate response indicator. There is limited understanding of the mechanisms underlying this resistance. Although TKIs suppress the growth of HER2-overexpressing breast tumor cells, they do not fully inhibit HER2 oncogenic function at physiological doses. Here we have provided a molecular mechanism of HER2 oncogenic function escapes TKIs9 inhibition via alternative HER receptor activation as a result of autocrine ligand release. Using both Forster Resonance Energy Transfer (FRET) which monitors in situ HER receptor phosphorylation as well as classical biochemical analysis, we have shown that the specific tyrosine kinase inhibitors (TKIs) of EGFR (HER1), AG1478 and Iressa (Gefitinib) decreased EGFR and HER3 phosphorylation through the inhibition of EGFR/HER3 dimerization. Consequent to this, we demonstrate that cleavage of HER4 and dimerization of HER4/HER2 occur together with reactivation of HER3 via HER2/HER3, leading to persistent HER2 phosphorylation in the now resistant, surviving cells. These drug treatment-induced processes were found to be mediated by the release of ligands including heregulin and betacellulin that activate HER3 and HER4 via HER2. Whereas an anti-betacellulin antibody in combination with Iressa increased the anti-proliferative effect in resistant cells, ligands such as heregulin and betacellulin rendered sensitive SKBR3 cells resistant to Iressa. These results demonstrate the role of drug-induced autocrine events leading to the activation of alternative HER receptors in mediating resistance to EGFR tyrosine kinase inhibitors (TKIs) in breast cancer cells, and hence specify treatment opportunities to overcome resistance in patients.
Colonic Adenoma Patients have Higher Incidence of Hyperplastic Polyps on Surveillance Colonoscopy
Authors: A Qasim, D Byrne, A Byrne, N Keeling, C Muldoon, S Norris, S McKiernan
Journal: Endoscopy (2006)

Background: Distal hyperplastic polyps may be associated with an increased risk of proximal adenomas. However significance of hyperplastic polyps in surveillance colonoscopy is not known in adenoma patients.