tbuckley/cabot-search huggingface dataset:
Loss of CD73-mediated actin polymerization promotes endometrial tumor progression
Authors: Jessica L. Bowser, Michael R. Blackburn, Gregory L. Shipley, Jose G. Molina, Kenneth Dunner, Russell R. Broaddus
Journal: Journal of Clinical Investigation (2015)

Ecto-5'-nucleotidase (CD73) is central to the generation of extracellular adenosine. Previous studies have highlighted a detrimental role for extracellular adenosine in cancer, as it dampens T cell-mediated immune responses. Here, we determined that, in contrast to other cancers, CD73 is markedly downregulated in poorly differentiated and advanced-stage endometrial carcinoma compared with levels in normal endometrium and low-grade tumors. In murine models, CD73 deficiency led to a loss of endometrial epithelial barrier function, and pharmacological CD73 inhibition increased in vitro migration and invasion of endometrial carcinoma cells. Given that CD73-generated adenosine is central to regulating tissue protection and physiology in normal tissues, we hypothesized that CD73-generated adenosine in endometrial carcinoma induces an innate reflex to protect epithelial integrity. CD73 associated with cell-cell contacts, filopodia, and membrane zippers, indicative of involvement in cell-cell adhesion and actin polymerization-dependent processes. We determined that CD73-generated adenosine induces cortical actin polymerization via adenosine A1 receptor (A1R) induction of a Rho GTPase CDC42-dependent conformational change of the actin-related proteins 2 and 3 (ARP2/3) actin polymerization complex member N-WASP. Cortical F-actin elevation increased membrane E-cadherin, β-catenin, and Na(+)K(+) ATPase. Together, these findings reveal that CD73-generated adenosine promotes epithelial integrity and suggest why loss of CD73 in endometrial cancer allows for tumor progression. Moreover, our data indicate that the role of CD73 in cancer is more complex than previously described.
Adjuvant Imatinib for GI Stromal Tumors: When and For How Long?
Authors: Robert S. Benjamin, Paolo Giovanni Casali
Journal: Journal of Clinical Oncology (2015)

A 45-year-old woman presented with syncope. She was severely anemic, with a hemoglobin level of 6 g/dL, and was found to have lower GI bleeding. A diagnostic colonoscopy was negative. A subsequent computed tomography scan of the abdomen and pelvis was performed, revealing a 3.2 × 3 × 2.9-cm contrast-enhancing right lower-quadrant mass arising from the wall of the ileum. There was no evidence of metastatic disease. The patient underwent laparotomy, and a 3.5-cm mass was resected with negative margins. Pathology revealed a GI stromal tumor with mixed spindle and epithelioid features involving the mucosa and submucosa (Fig 1A). The tumor cells were positive for CD117 (c-kit) (Fig 1B) and DOG-1(Fig 1C). There were eight to 10 mitoses per 50 high-power fields (Fig 1D). Molecular studies showed a 42-base pair deletion in exon 11 of the KIT gene that would delete all or part of codons 558 to 572 (V559_D572del) and would change the 558-encoding amino acid from Lys to Asn (K558N).
Pre-existing anti–polyethylene glycol antibody linked to first-exposure allergic reactions to pegnivacogin, a PEGylated RNA aptamer
Authors: Nancy J. Ganson, Thomas J. Povsic, Bruce A. Sullenger, John H. Alexander, Steven L. Zelenkofske, Jeffrey M. Sailstad, Christopher P. Rusconi, Michael S. Hershfield
Journal: Journal of Allergy and Clinical Immunology (2015)
Europeans are “world champions” at drinking and smoking
Authors: Anne Gulland
Journal: BMJ (2015)

An analysis of the brain weights of 168 alcoholics showed that the mean brain weight of male alcoholics was less (p less than 0.001) than that of a normal population. Two subgroups of alcoholics were identified. Firstly, those with nutritional brain damage (Wernicke9s encephalopathy, caused by vitamin B1 deficiency) and, secondly, those with brains which appeared "normal" macroscopically and microscopically. Any change in the brain weights of this second group was unlikely to be caused by nutritional damage. Both groups had abnormally low brain weights which suggests that alcohol, the factor common to both groups, is more important than nutritional deficiencies in causing brain damage and a reduction in brain weight.
Selective dysfunction of p53 for mitochondrial biogenesis induces cellular proliferation in bronchial smooth muscle from asthmatic patients
Authors: Thomas Trian, Benoit Allard, Annaig Ozier, Elise Maurat, Isabelle Dupin, Matthieu Thumerel, Olga Ousova, Jennifer Gillibert-Duplantier, Valérie Le Morvan, Hugues Begueret, Pierre-Olivier Girodet, Roger Marthan, Patrick Berger
Journal: Journal of Allergy and Clinical Immunology (2015)
Risk stratification of individuals with low-risk colorectal adenomas using clinical characteristics: a pooled analysis
Authors: Samir Gupta, Elizabeth T Jacobs, John A Baron, David A Lieberman, Gwen Murphy, Uri Ladabaum, Amanda J Cross, Rodrigo Jover, Lin Liu, Maria Elena Martinez
Journal: Gut (2015)

Objective For individuals with 1–2 small (&lt;1 cm) low-risk colorectal adenomas, international guidelines range from no surveillance to offering surveillance colonoscopy in 5–10 years. We hypothesised that the risks for metachronous advanced neoplasia (AN) among patients with low-risk adenomas differ based on clinical factors distinct from those currently used. Design We pooled data from seven prospective studies to assess the risk of metachronous AN. Two groups with 1–2 small adenomas were defined based on guidelines from the UK (n=4516) or the European Union (EU)/US (n=2477). Results Absolute risk of metachronous AN ranged from a low of 2.9% to a high of 12.2%, depending on specific risk factor and guideline used. For the UK group, the highest absolute risks for metachronous AN were found among individuals with a history of prior polyp (12.2%), villous histology (12.2%), age ≥70 years (10.9%), high-grade dysplasia (10.9%), any proximal adenoma (10.2%), distal and proximal adenoma (10.8%) or two adenomas (10.1%). For the EU/US group, the highest absolute risks for metachronous AN were among individuals with a history of prior polyp (11.5%) or the presence of both proximal and distal adenomas (11.0%). In multivariate analyses, strong associations for increasing age and history of prior polyps and odds of metachronous AN were observed, whereas more modest associations were shown for baseline proximal adenomas and those with villous features. Conclusions Risks of metachronous AN among individuals with 1–2 small adenomas vary according to readily available clinical characteristics. These characteristics may be considered for recommending colonoscopy surveillance and require further investigation.
A combined phase I/II trial of intravesical nanoparticle albumin-bound paclitaxel in the treatment of refractory non–muscle- invasive transitional cell bladder cancer
Authors: L. Barlow, M. Laudano, M. Mann, M. Desai, D. Petrylak, M. Benson, J. McKiernan
Journal: Journal of Clinical Oncology (2009)

e16047 Background: Up to 50% of patients treated with intravesical agents for non-muscle-invasive bladder cancer will recur. Response rates to current second line intravesical therapies average less than 20%. For these high risk patients, novel agents are necessary. Our previously completed phase I trial showed docetaxel to be a safe and efficacious agent for intravesical therapy. Nanoparticle albumin-bound (nab-) paclitaxel has been shown to have increased solubility and lower toxicity compared to docetaxel in systemic therapy and is therefore an appropriate candidate for further investigation as an intravesical agent. Methods: The ongoing phase I component of this combined phase I/II trial began enrollment on 1/1/08 and has reached 72% accrual as of 1/1/09. Inclusion criteria include recurrent high grade (HG) Ta, T1 and Tis transitional cell carcinoma failing at least one prior regimen with any intravesical agent. In phase I, 6 weekly instillations of nab-paclitaxel were administered beginning at a dose of 150 mg with a dose escalation model used until a maximal tolerated dose (MTD) was achieved. The primary endpoints were dose- limiting toxicity (DLT) and MTD; the secondary endpoint was response rate. Efficacy was evaluated by cystoscopy with biopsy, cytology, and CT imaging. Results: 13/18 patients have enrolled in this phase I trial to date, and the distribution of stages included 5 patients with Tis, 4 patients with HGTa, and 4 patients with HGT1. No patient has had any systemic absorption of nab-paclitaxel as measured by HPLC assays, and no grade 3 or 4 DLT has been encountered. Fifty-four percent (7/13) patients were noted to experience grade 1 toxicities, with dysuria being the most common. Forty-two percent (5/12) of completed patients had no evidence of disease at their post-treatment cystoscopy. None of the patients who developed recurrent disease have had disease progression. Conclusions: Intravesical nab-paclitaxel has exhibited minimal toxicity and no systemic absorption in the first ever human intravesical dose escalation trial. Upon completion of this ongoing phase I trial, we plan to evaluate this agent in a larger phase II efficacy study. No significant financial relationships to disclose.
Online multi-class brain-computer interface for detection and classification of lower limb movement intentions and kinetics for stroke rehabilitation
Authors: Mads Jochumsen, Imran Khan Niazi, Muhammad Samran Navid, Muhammad Nabeel Anwar, Dario Farina, Kim Dremstrup
Journal: Brain-Computer Interfaces (2015)

Closed-loop BCIs have recently been proposed for neurorehabilitation. This concept can be extended to complex motor tasks by decoding the type of the attempted movement in a multi-class BCI. Therefore, the objective of this study was to detect movements from real-time EEG and classify two movement types associated with the movement kinetics. EEG traces corresponding to executed and imagined movements of 12 healthy subjects and attempted movements of six stroke patients were detected using a template matching technique. Signal segments were characterized by six features and classified with a support vector machine. The system correctly detected and classified 57 ± 3%, 53 ± 6%, and 47 ± 7% of the executed, imaginary, and attempted movements, respectively. The performance of the detector was ~80%, and the classifier performance was in the range 63–70%. There were on average 1.6–1.9 false positive detections per minute. The results indicate that it is possible to detect executed, imaginary, and attempted movements in real time and classify movement kinetics. With improved performance, this could potentially be combined with functional electrical stimulation to promote neurorehabilitation by providing meaningful afferent feedback according to the attempted task.
A randomized trial comparing multiband mucosectomy and cap-assisted endoscopic resection for endoscopic piecemeal resection of early squamous neoplasia of the esophagus
Authors: Yue-Ming Zhang, David Boerwinkel, Xiumin Qin, Shun He, Liyan Xue, Bas Weusten, Sanford Dawsey, David Fleischer, Li-Zhou Dou, Yong Liu, Ning Lu, Jacques Bergman, Gui-Qi Wang
Journal: Endoscopy (2015)

<b>Background and aim:</b> Piecemeal endoscopic resection for esophageal high grade intraepithelial neoplasia (HGIN) or early squamous cell carcinoma (ESCC) is usually performed by cap-assisted endoscopic resection. This requires submucosal lifting and multiple snares. Multiband mucosectomy (MBM) uses a modified variceal band ligator without submucosal lifting. In high-risk areas where ESCC is common and endoscopic expertise is limited, MBM may be a better technique. We aimed to compare MBM to the cap-assisted technique for piecemeal endoscopic resection of esophageal ESCCs. <b>Methods: </b>Patients with mucosal HGIN/ESCC (2 – 6 cm, maximum two-thirds of esophageal circumference) were included. Lesions, delineated by 1.25 % Lugol staining, were randomized to MBM or cap-assisted piecemeal resection. Endpoints were procedure time and costs, complete endoscopic resection, adverse events, and absence of HGIN/ESCC at 3-month and 12-month follow-up. <b>Results:</b> Endoscopic resection was performed in 84 patients (59 men, mean age 60) using MBM (n = 42) or the endoscopic resection cap (n = 42). There were no differences in baseline characteristics. Endoscopic complete resection was achieved in all lesions. Procedure time was significantly shorter with MBM (11 vs. 22 minutes, <i>P</i> < 0.0001). One perforation, seen after using the endoscopic resection cap, was treated conservatively. Total costs of disposables were lower for MBM (€200 vs. €251, <i>P</i> = 0.04). At 3-month and 12-month follow-ups none of the patients had HGIN/ESCC at the resection site. <b>Conclusion:</b> Piecemeal endoscopic resection of esophageal ESCC with MBM is faster and cheaper than with the endoscopic resection cap. Both techniques are highly effective and safe. MBM may have significant advantages over the endoscopic resection cap technique, especially in countries where ESCC is extremely common but limited endoscopic expertise and resources exist. (Netherlands trial register: NTR 3246.)
A novel prepless X-ray imaging capsule for colon cancer screening
Authors: Nathan Gluck, Beni Shpak, Rita Brun, Thomas Rösch, Nadir Arber, Menachem Moshkowitz
Journal: Gut (2015)

The demand for bowel cleansing hampers participation in screening colonoscopy, while poor preparation impairs adenoma detection. A novel prepless X-ray imaging capsule for colon screening is presented; the capsule emits low dose X-rays, which are scattered by ingested contrast agent mixed with colon contents, and sensed by detectors in the capsule to generate high-resolution three-dimensional (3D) imagery of the colon without bowel cleansing. Following preliminary studies with implanted polyps in synthetic colon phantoms, bovine cadaver and live swine, and human experiments with dummy capsules (n=75), 49 patients swallowed the capsule with natural excretion in 48 after 73.2±45.4 h. Pedunculated and sessile polyps were clearly seen and validated by subsequent colonoscopy. Total radiation exposure was ultra low (0.03±0.007 mSv).

Bowel preparation remains a major obstacle limiting complete uptake of colonoscopy for colon cancer screening.1 ,2 Therefore any test which does not require preparation would probably increase compliance.3 However, the accuracy to depict cancers as well as adenomas should not suffer substantially. A new X-ray capsule is shown in a series of proof-of-concept studies to be safe and effective in 3D reconstruction of the colonic wall and lumen including identifying adenomatous polyps.

The capsule system includes a short-lived radio isotope within a collimator housing that emits three X-ray beams in all directions, by way of a rotating miniature electric motor as the capsule scans the length of the GI tract. A small volume of ingested radiopaque contrast agent increases the contrast of the colon's walls and differentiates them from stool content. Compton backscattered photons, attenuated by the contrast agent mixed with the colon contents, and X-ray fluorescence photons emitted from the contrast agent, are detected by sensors in …
Inhibition of the TNF Family Cytokine RANKL Prevents Autoimmune Inflammation in the Central Nervous System
Authors: Matteo M. Guerrini, Kazuo Okamoto, Noriko Komatsu, Shinichiro Sawa, Lynett Danks, Josef M. Penninger, Tomoki Nakashima, Hiroshi Takayanagi
Journal: Immunity (2015)
Balancing Service and Education in Residency Training
Authors: Teri L. Turner, Elaine Fielder, Mark A. Ward
Journal: JAMA Pediatrics (2015)

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
Endocardium Contributes to Cardiac Fat
Authors: Hui Zhang, Wenjuan Pu, Qiaozhen Liu, Lingjuan He, Xiuzhen Huang, Xueying Tian, Libo Zhang, Yu Nie, Shengshou Hu, Kathy O. Lui, Bin Zhou
Journal: Circulation Research (2016)

Unraveling the developmental origin of cardiac fat could offer important implications for the treatment of cardiovascular disease. The recent identification of the mesothelial source of epicardial fat tissues reveals a heterogeneous origin of adipocytes in the adult heart. However, the developmental origin of adipocytes inside the heart, namely intramyocardial adipocytes, remains largely unknown.To trace the developmental origin of intramyocardial adipocytes.In this study, we identified that the majority of intramyocardial adipocytes were restricted to myocardial regions in close proximity to the endocardium. Using a genetic lineage tracing model of endocardial cells, we found that Nfatc1(+) endocardial cells contributed to a substantial number of intramyocardial adipocytes. Despite the capability of the endocardium to generate coronary vascular endothelial cells surrounding the intramyocardial adipocytes, results from our lineage tracing analyses showed that intramyocardial adipocytes were not derived from coronary vessels. Nevertheless, the endocardium of the postnatal heart did not contribute to intramyocardial adipocytes during homeostasis or after myocardial infarction.Our in vivo fate-mapping studies demonstrated that the developing endocardium, but not the vascular endothelial cells, gives rise to intramyocardial adipocytes in the adult heart.
Long-Term Outcome of PCI Versus CABG in Insulin and Non–Insulin-Treated Diabetic Patients
Authors: George D Dangas, Michael E Farkouh, Lynn A Sleeper, May Yang, Mikkel M Schoos, Carlos Macaya, Alexandre Abizaid, Christopher E Buller, Gerard Devlin, Alfredo E Rodriguez, Alexandra J Lansky, F Sandra Siami, Michael Domanski, Valentin Fuster
Journal: Journal of the American College of Cardiology (2014)
<i>RICTOR</i> Amplification Defines a Novel Subset of Patients with Lung Cancer Who May Benefit from Treatment with mTORC1/2 Inhibitors
Authors: Haiying Cheng, Yiyu Zou, Jeffrey S. Ross, Kai Wang, Xuewen Liu, Balazs Halmos, Siraj M. Ali, Huijie Liu, Amit Verma, Cristina Montagna, Abraham Chachoua, Sanjay Goel, Edward L. Schwartz, Changcheng Zhu, Jidong Shan, Yiting Yu, Kira Gritsman, Roman Yelensky, Doron Lipson, Geoff Otto, Matthew Hawryluk, Philip J. Stephens, Vincent A. Miller, Bilal Piperdi, Roman Perez-Soler
Journal: Cancer Discovery (2015)

We identified amplification of RICTOR, a key component of the mTOR complex 2 (mTORC2), as the sole actionable genomic alteration in an 18-year-old never-smoker with lung adenocarcinoma. Amplification of RICTOR occurs in 13% of lung cancers (1,016 cases) in The Cancer Genome Atlas and at a similar frequency in an independent cohort of 1,070 patients identified by genomic profiling. In the latter series, 11% of cases harbored RICTOR amplification as the only relevant genomic alteration. Its oncogenic roles were suggested by decreased lung cancer cell growth both in vitro and in vivo with RICTOR ablation, and the transforming capacity of RICTOR in a Ba/F3-cell system. The mTORC1/2 inhibitors were significantly more active against RICTOR-amplified lung cancer cells as compared with other agents targeting the PI3K-AKT-mTOR pathway. Moreover, an association between RICTOR amplification and sensitivities to mTORC1/2 inhibitors was observed. The index patient has been treated with mTORC1/2 inhibitors that led to tumor stabilization for more than 18 months.RICTOR amplification may define a novel and unique molecular subset of patients with lung cancer who may benefit from treatment with mTORC1/2 inhibitors.
Providing Hospitalized Patients With an Educational Booklet Increases the Quality of Colonoscopy Bowel Preparation
Authors: William F. Ergen, Trisha Pasricha, Francie J. Hubbard, Tina Higginbotham, Tonya Givens, James C. Slaughter, Keith L. Obstein
Journal: Clinical Gastroenterology and Hepatology (2015)
Surveillance for pediatric deaths associated with 2009 pandemic influenza A (H1N1) virus infection - United States, April-August 2009.
Authors: S. Shannon, J. Louie, A. Siniscalchi, E. Rico, D. Richter, R. Hernandez, R. Lynfield, L. McHugh, C. Waters, E. Lee, A. Stoute, K. Landers, U. Bandy, N. Pascoe, V. Vernon, T. Haupt, C. Moore, L. Schieve, G. Peacock, C. Boyle, M. Honein, M. Yeargin-Allsopp, E. Trevathan, L. Finelli, T. Uyeki, R. Dhara
Journal: MMWR Morbidity and Mortality Weekly Report (2009)
An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors
Authors: Vasilis Bikos, Maria Karypidou, Evangelia Stalika, Panagiotis Baliakas, Aliki Xochelli, Lesley-Ann Sutton, George Papadopoulos, Andreas Agathangelidis, Evdoxia Papadopoulou, Zadie Davis, Patricia Algara, George Kanellis, Alexandra Traverse-Glehen, Manuela Mollejo, Achilles Anagnostopoulos, Maurilio Ponzoni, David Gonzalez, Sarka Pospisilova, Estella Matutes, Miguel Angel Piris, Theodora Papadaki, Paolo Ghia, Richard Rosenquist, David Oscier, Nikos Darzentas, Dimitrios Tzovaras, Chrysoula Belessi, Anastasia Hadzidimitriou, Kostas Stamatopoulos
Journal: Clinical Cancer Research (2015)

Prompted by the extensive biases in the immunoglobulin (IG) gene repertoire of splenic marginal-zone lymphoma (SMZL), supporting antigen selection in SMZL ontogeny, we sought to investigate whether antigen involvement is also relevant post-transformation.We conducted a large-scale subcloning study of the IG rearrangements of 40 SMZL cases aimed at assessing intraclonal diversification (ID) due to ongoing somatic hypermutation (SHM).ID was identified in 17 of 21 (81%) rearrangements using the immunoglobulin heavy variable (IGHV)1-2*04 gene versus 8 of 19 (40%) rearrangements utilizing other IGHV genes (P= 0.001). ID was also evident in most analyzed IG light chain gene rearrangements, albeit was more limited compared with IG heavy chains. Identical sequence changes were shared by subclones from different patients utilizing the IGHV1-2*04 gene, confirming restricted ongoing SHM profiles. Non-IGHV1-2*04 cases displayed both a lower number of ongoing SHMs and a lack of shared mutations (per group of cases utilizing the same IGHV gene).These findings support ongoing antigen involvement in a sizable portion of SMZL and further argue that IGHV1-2*04 SMZL may represent a distinct molecular subtype of the disease.