tbuckley/cabot-search huggingface dataset:
LTBK-01. UPDATES ON THE PHASE II AND RE-TREATMENT STUDY OF AZD6244 (SELUMETINIB) FOR CHILDREN WITH RECURRENT OR REFRACTORY PEDIATRIC LOW GRADE GLIOMA: A PEDIATRIC BRAIN TUMOR CONSORTIUM (PBTC) STUDY
Authors: Jason R Fangusaro, Arzu Onar-Thomas, Tina Young Poussaint, Shengjie Wu, Azra H Ligon, Neal Ian Lindeman, Anuradha Banerjee, Roger Packer, Lindsay B Kilburn, Ian F Pollack, Ibrahim A Qaddoumi, Paul Graham Fisher, Girish Dhall, Patricia Ann Baxter, Susan G Kreissman, L Austin Doyle, Malcolm A Smith, Maryam Fouladi, Ira J Dunkel
Journal: Neuro-Oncology (2018)

The PBTC is conducting a phase II study (NCT01089101) evaluating selumetinib (AZD6244, ARRY-142886), a MEK I/II inhibitor, in children with recurrent/refractory LGG assigned to 6 strata. We present the updated data on Stratum 2 and 5. Also, data on subsequent progression after treatment completion in patients enrolled on Stratum 1 and 3 will be discussed. Finally, we present details on the re-treatment study (PBTC-029C). Both stratum 2 (pilocytic astrocytoma [PA] without common BRAF aberrations) and Stratum 5 (non-pilocytic LGG with BRAF aberrations) met response criteria for expansion (> 2 objective responses in 16 patients), and accrual to a total of 25 patients on each stratum is ongoing. Among 50 patients treated on Stratum 1 (PA with BRAF aberrations) or Stratum 3 (NF-associated LGG), 21 have progressed. Thirteen of 21 have progressed after stopping therapy. The median time to progression for these 13 patients is 119 days (10–928). The re-treatment study has enrolled 25 patients who received a median of 12 re-treatment courses (2–36). The most common attributable toxicities after re-treatment were grade 1 CPK elevation (44%), diarrhea (44%), hypoalbuminemia (40%), elevated AST (36%), rash (36%) and fatigue (32%). The most common grade 3/4 attributable toxicities were grade 3 paronychia (8%), CPK elevation (4%), AST elevation (4%), decreased ejection fraction (4%), neutropenia (4%), elevated triglycerides (4%), peripheral neuropathy (4%) and grade 4 CPK elevation (4%). There is not a significant difference between the toxicities observed during original therapy versus re-treatment. The most current response and patient demographic data will be presented.
Isorhythmic Atrioventricular Dissociation and the Purloined P Wave After Transcatheter Aortic Valve Replacement
Authors: Maia Eng, Ezra Amsterdam, Matthew S. Glassy
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine 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 Internal Medicine journal
Progression of Focal to Diffuse Thyroid Uptake Detected by 18F-FDG PET/CT
Authors: Philippe Thuillier, Geneviève Crouzeix, Renaud Descourt, Pierre-Yves Salaun, Ronan Abgral
Journal: Clinical Nuclear Medicine (2018)

A 49-year-old man was referred to our department for an assessment of a cerebral metastasis of unknown primary with F-FDG PET/CT. This imaging led to detection of a suspected pulmonary primary carcinoma, as well as an incidental left focal thyroid uptake. An ultrasonography, performed a month later, revealed a thyroiditis aspect. An anti-PD1 immunotherapy was also proposed 2 months later after confirmation of a lung adenocarcinoma. A second baseline FDG PET/CT surprisingly showed a diffuse thyroid uptake. A fine-needle aspiration biopsy of thyroid parenchyma finally revealed a diffuse involvement from lung adenocarcinoma (ie, primary lung metastasis to the thyroid gland).
Abstract 1415: Target sequencing of tumor driver genes in lung adenocarcinoma tissues
Authors: Jiawei Zhu, Lin Feng, Ting Xiao
Journal: Cancer Research (2018)

Abstract Background and objective As the main histological subtype of lung cancer, lung adenocarcinoma (ADC) contributes to a cancer-related death in the word. With the development of high-throughput genomic analysis, whole-genome sequencing provides a new opportunity to identify genetic mutations that drive the origination, growth, and spread of cancer. The aim of this study is to detect the mutated genes in lung adenocarcinoma tissues and to analyze its clinical significance, based on 483 tumor driver gene sequence of ADC samples. Methods We obtained 40 pairs of samples from ADC tumors and matched normal adjacent tissue, which included female (58%), male (43%), people over 60 years old (63%), stage I (40%), stage II (20%), stage III (38%), and stage IV (3%). Based on the Illumina HiSeq2500 sequencing technology platform, small fragment library was built, high coverage of the target area was captured by NovoP products (Agilent sure select XT Custom 0.5-2.9Mb kit, contains 483 tumor related target gene probe). DNA samples was examined by Paired-End sequencing; sequencing data of 40 cases of tumor samples was obtained. We analyzed the sequencing results of lung adenocarcinoma tumor and matched normal adjacent tissues by using bioinformatics analysis methods, and sought for somatic mutations in lung adenocarcinoma tumor and matched normal adjacent tissues. Results There were 31 ADC samples had reliable exons mutations in the target area, totally 142 (102 genes) mutation positions, including non-synonymous mutations (65%), synonymous mutations (26%), and terminating translation mutation (8%). Totally 116 mutation positions (81.69%) were located in the target capture area. Gene mutations were more frequent in smoking and aged patients. Top ten mutation frequency genes were TP53, EGFR, PIK3CA, ATN1, ATXN1, ABL1, ALK, EGF, EPHA3, and KRAS. And compared to The Cancer Genome Atlas (TCGA) data, the mutation frequency of EGFR was significantly higher in our research. Conclusion These data provided evidence for the further determination of the molecular mechanism and molecular typing of lung adenocarcinoma. Mutation frequency of TP53, EGFR and PIK3CA in lung adenocarcinoma tissue was the highest. Citation Format: Jiawei Zhu, Lin Feng, Ting Xiao. Target sequencing of tumor driver genes in lung adenocarcinoma tissues [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1415.
Circulating biomarkers may be unable to detect infection at the early phase of sepsis in ICU patients: the CAPTAIN prospective multicenter cohort study
Authors: Marianna Parlato, François Philippart, Alexandra Rouquette, Virginie Moucadel, Virginie Puchois, Sophie Blein, Jean-Pierre Bedos, Jean-Luc Diehl, Olfa Hamzaoui, Djillali Annane, Didier Journois, Myriam Ben Boutieb, Laurent Estève, Catherine Fitting, Jean-Marc Treluyer, Alexandre Pachot, Minou Adib-Conquy, Jean-Marc Cavaillon, Benoît Misset
Journal: Intensive Care Medicine (2018)
PEGylated enhanced cell penetrating peptide nanoparticles for lung gene therapy
Authors: Gizem Osman, Jason Rodriguez, Sze Yan Chan, Jane Chisholm, Gregg Duncan, Namho Kim, Amanda L. Tatler, Kevin M. Shakesheff, Justin Hanes, Jung Soo Suk, James E. Dixon
Journal: Journal of Controlled Release (2018)

The lung remains an attractive target for the gene therapy of monogenetic diseases such as cystic fibrosis (CF). Despite over 27 clinical trials, there are still very few gene therapy vectors that have shown any improvement in lung function; highlighting the need to develop formulations with improved gene transfer potency and the desirable physiochemical characteristics for efficacious therapy. Herein, we introduce a novel cell penetrating peptide (CPP)-based non-viral vector that utilises glycosaminoglycan (GAG)-binding enhanced transduction (GET) for highly efficient gene transfer. GET peptides couple directly with DNA through electrostatic interactions to form nanoparticles (NPs). In order to adapt the GET peptide for efficient in vivo delivery, we engineered PEGylated versions of the peptide and employed a strategy to form DNA NPs with different densities of PEG coatings. We were able to identify candidate formulations (PEGylation rates ≥40%) that shielded the positively charged surface of particles, maintained colloidal stability in bronchoalveolar lavage fluid (BALF) and retained gene transfer activity in human bronchial epithelial cell lines and precision cut lung slices (PCLS) in vitro. Using multiple particle tracking (MPT) technology, we demonstrated that PEG-GET complexes were able to navigate the mucus mesh and diffuse rapidly through patient CF sputum samples ex vivo. When tested in mouse lung models in vivo, PEGylated particles demonstrated superior biodistribution, improved safety profiles and efficient gene transfer of a reporter luciferase plasmid compared to non-PEGylated complexes. Furthermore, gene expression was significantly enhanced in comparison to polyethylenimine (PEI), a non-viral gene carrier that has been widely tested in pre-clinical settings. This work describes an innovative approach that combines novel GET peptides for enhanced transfection with a tuneable PEG coating for efficacious lung gene therapy.
Infographic. Exercise therapy for meniscal tears: evidence and recommendations
Authors: Jonas Bloch Thorlund, Jorge Rodriguez Palomino, Carsten B Juhl, Lina Holm Ingelsrud, Søren Thorgaard Skou
Journal: British Journal of Sports Medicine (2018)

Meniscal tears are common, and surgery to treat meniscal tears is one of the most frequently performed orthopaedic procedures.1 Recent evidence has challenged the clinical dogma of surgery as treatment for meniscal tears in patients aged 40 years or older, with exercise therapy emerging as a valid treatment alternative.2 3 

When treating meniscal tears, it is likely important to take the aetiology of the tear into account. Tears are typically categorised as traumatic or degenerative. Traumatic tears are most often observed in young sports active individuals and present as a tear to an otherwise healthy meniscus.4 Degenerative lesions are more common in middle-aged and older individuals and considered to be an early sign of knee osteoarthritis.5 Importantly, 60%–70% of meniscal surgeries are performed in patients aged 40 years or older, suggesting that most surgically treated meniscal tears are likely of degenerative nature.1 …
Leadership in physical activity: is this the currency of change in the student healthcare curriculum?
Authors: Ann Bernadette Gates, Ian K Ritchie, Fiona Moffatt, João Breda
Journal: British Journal of Sports Medicine (2018)

Non-communicable diseases (NCD) are the major healthcare challenge for many societies, including those that are more developed. Physical inactivity and deconditioning are inextricably linked to the present and future health outcomes for patients, communities and nations. This is a changed environment. Traditionally, Western healthcare was focused on curing disease such as infection and cancers. Now, the NCDs are the bigger problem. For this reason, it is imperative that the next generation of healthcare professionals are able to deliver both prevention and treatment services which emphasise the benefits of physical activity (PA). To do this they must be equipped with the knowledge and implementation skills to provide care and leadership.1 Indeed, given that this is the first generation of society who are expected to outlive their children, this has to be an immediate and transformational community of practice approach rather than the slower, traditional transactional leadership model. Physical inactivity and sedentary behaviour are well-known risk factors for the current epidemic of NCDs and the consequent problems of immobility, disability and premature death.2 Therefore, it is essential that healthcare students possess the basic facts and the necessary skills to enable them to deliver the best care to patients. This means that they must be confident, competent and capable in discussing and recommending PA as an intervention. As a bare minimum, students should be aware of the following four critical points:
CpG island composition differences are a source of gene expression noise indicative of promoter responsiveness
Authors: Michael D. Morgan, John C. Marioni
Journal: Genome biology (2018)

Population phenotypic variation can arise from genetic differences between individuals, or from cellular heterogeneity in an isogenic group of cells or organisms. The emergence of gene expression differences between genetically identical cells is referred to as gene expression noise, the sources of which are not well understood. In this work, by studying gene expression noise between multiple cell lineages and mammalian species, we find consistent evidence of a role for CpG islands as sources of gene expression noise. Variation in noise among CpG island promoters can be partially attributed to differences in island size, in which short islands have noisier gene expression. Building on these findings, we investigate the potential for short CpG islands to act as fast response elements to environmental stimuli. Specifically, we find that these islands are enriched amongst primary response genes in SWI/SNF-independent stimuli, suggesting that expression noise is an indicator of promoter responsiveness. Thus, through the integration of single-cell RNA expression profiling, chromatin landscape and temporal gene expression dynamics, we have uncovered a role for short CpG island promoters as fast response elements.
Abstract 19457: Collateral Blood Supply is Associated with Smaller Infarct Size, but less Ischemia, a Myocardial Perfusion Stress Cardiovascular Magnetic Resonance Study
Authors: Darach O h-Ici, Thomas Hovasse, Yves Louvard, Marie Claude Morice, Thierry Lefèvre, Jérôme Garot
Journal: Circulation (2010)

Introduction:  Cardiovascular magnetic resonance (CMR) allows the identification and quantification of ischemia, infarction size and myocardial viability. Coronary chronic total occlusions (CTOs) are commonly encountered complex lesions identified in up to 30% of all patients referred for coronary angiography. The physiological consequences of CTOs are incompletely understood. Single photon emission computed tomography has been used to investigate this, however, low spatial resolution is a compromising factor in these studies.   Methods and Results:  Fifty-two consecutive patients with a CTO scheduled for PCI underwent dipyridamole first-pass myocardial perfusion stress CMR. All patients underwent angiography with 90 days (mean 19) of stress testing. Collateral circulation was noted to be good (Rentrop grade 2, 3) in thirty-eight patients and poor (Rentrop grade 0, 1) in fourteen. All patients had abnormal stress perfusion. Forty-two patients had detectable myocardial infarction; twenty-five of these were known to have infarction by history or ECG findings. Patients with poor collateral blood supply had larger infarction size (2.4 vs 1.2 segments, p=0.02) and more non-viable segments (0.43 vs 0.11, p=0.03). Good collateral blood supply did not prevent detectable ischemia (3.6 vs 4.3 segments, p=0.31).   Conclusion:  CMR of patients with chronic total occlusions detects many more infarcts than history or ECG alone (80% vs 42%). Good collateral blood supply is associated with a smaller infarct size. However, Rentrop grade 2 or 3 blood supply does not imply adequate blood supply. Patients with CTOs should undergo stress testing, preferably with CMR, to identify viability and ischemia. This can select those that would benefit most from revascularization.
Bridging the Evidence-to-Practice Gap in Stroke Care
Authors: Michael D. Hill, Noreen Kamal, Thomas Jeerakathil
Journal: JAMA (2018)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Endoscopic transluminal water irrigation for duodenal diverticulitis
Authors: Taiki Aoyama, Masanobu Yukutake, Kenjiro Shigita, Naoki Asayama, Akira Fukumoto, Shinichi Mukai, Shinji Nagata
Journal: Endoscopy (2018)

Duodenal diverticula are usually asymptomatic, but complications such as cholestasis, inflammation, abscess formation, and perforation may occur, with clinically significant effects [1] [2]. In certain cases, endoscopic intervention may be chosen over surgery [3] [4]. However, the former is a complicated procedure requiring careful manipulation of the endoscope.
Abstract CT082: TTFields concurrent with standard of care for the treatment of stage 4 non-small cell lung cancer (NSCLC) following platinum failure: phase III LUNAR study
Authors: Uri Weinberg, Ori Farber, Moshe Giladi, Zeev Bomzon, Eilon Kirson
Journal: Cancer Research (2018)

Abstract Tumor Treating Fields (TTFields) are a non-invasive, anti-mitotic treatment modality. TTFields disrupt the formation of the mitotic spindle, and dislocation of intracellular constituents. TTFields significantly extend the survival of newly diagnosed glioblastoma patients when combined with temozolomide. Efficacy of TTFields in NSCLC has been shown preclinically and their safety in a phase I/II pilot study with pemetrexed. We hypothesize that adding TTFields to immune checkpoint inhibitor or docetaxel following platinum doublet failure will increase OS. Methods: Patients (N=534) with squamous or non-squamous NSCLC are enrolled in the LUNAR phase III study [NCT02973789]. Patients are stratified by their selected standard therapy (immune checkpoint inhibitors or docetaxel), histology (squamous vs. non-squamous) and geographical region. Key inclusion criteria are disease progression while on or after platinum-based systemic therapy, ECOG 0-2, no electronic medical devices in the upper torso, and absence of brain metastasis. Docetaxel or immune checkpoint inhibitors are given at standard doses. TTFields are applied to the upper torso for 18 hours/day, allowing patients to maintain daily activities. TTFields are continued until progression in the thorax and/or liver. Follow up is performed every 6 weeks, including CT scans of the chest and abdomen. On progression in the thorax and/or liver, patients have three post-progression follow up visits and are later followed monthly for survival. The primary endpoint is superiority in OS between patients treated with TTFields in combination with the standard of care treatments, compared to standard of care treatments alone. Key secondary endpoints compare the OS in patients treated with TTFields and docetaxel Vs. those treated with docetaxel alone, and patients treated with TTFields and immune checkpoint inhibitors Vs. those treated with immune checkpoint inhibitors alone. An exploratory analysis will test non-inferiority of TTFields with docetaxel compared to checkpoint inhibitors alone. Secondary endpoints include progression-free survival, radiological response rate, quality of life based on the EORTC QLQ C30 questionnaire and severity &amp; frequency of adverse events. The sample size is powered to detect a HR of 0.75 in TTFields-treated patients versus control group. Citation Format: Uri Weinberg, Ori Farber, Moshe Giladi, Zeev Bomzon, Eilon Kirson. TTFields concurrent with standard of care for the treatment of stage 4 non-small cell lung cancer (NSCLC) following platinum failure: phase III LUNAR study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT082.
Abstract 755: Synthesis and evaluation of sugar alcohol based molecules for drug conjugation and delivery
Authors: Yumei Huang, Shuyan Chen, Binyuan Sun, Amanda Griffin, Nathanial Sweet, Mingqian Feng, Mitchell Ho
Journal: Cancer Research (2018)

Abstract Hydrophilic linkers, which are available in different motifs, have been used as agents of drug delivery, as aqueous solubility enhancers for hydrophobic molecules, and as tethers or spacers in conjugation. Polyethylene glycol (PEG) is one of the most commonly used hydrophilic linkers and commercially available. Lower molecular weight (MW) heterobifunctional PEG linkers are the most frequently used linkers for linking hydrophobic compounds, whereas high MW polymers have been used to conjugate proteins, peptides, oligonucleotides, siRNA, and other therapeutic biopolymers. Here, we describe a new type of biomaterial based on sugar alcohols: AqueaTether™ (AqT™) molecules. Various AqT™ linkers with different lengths and end groups were synthesized and their hydrophilic nature and ability to enhance the water solubility of hydrophobic compounds compared to different commercial and PEG linkers. Various antibody drug conjugates (ADCs) with water soluble AqT™-drugs were prepared. An ADC made with AqT™-monomethyl auristatin E (MMAE) with only two sugar alcohol units attached and an average drug-to-antibody ratio (DAR) of 4 demonstrated significant improvements in minimizing the aggregation of antibodies and long-term stability during storage. Due to increased water solubility, AqT™ linkers also allow higher loading of drugs per antibody, enabling the use of less toxic drugs, potentially increasing the overall efficacy and safety profile of an ADC. For example, ADCs with average DARs of 8 and 15 have been made using AqT™-doxorubicin with only two sugar alcohol units attached. In peptide-based drug discovery, discrete high MW AqT™ linker is used to label peptide, resulting in an increased half-life in human serum. In summary, AqT™ molecules are by far the most hydrophilic and versatile linkers currently in development. AqT™ molecules represent a great tool for drug conjugation and delivery. Citation Format: Yumei Huang, Shuyan Chen, Binyuan Sun, Amanda Griffin, Nathanial Sweet, Mingqian Feng, Mitchell Ho. Synthesis and evaluation of sugar alcohol based molecules for drug conjugation and delivery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 755.