tbuckley/cabot-search huggingface dataset:
Abstract 443: <i>l-cis-</i> Diltiazem Ameliorates Impaired Calcium Channel Inactivation in a Patient-specific Stem Cell Model of Long-QT Syndrome with a Calmodulin Mutation
Authors: Fumika Yokoi, Takeru Makiyama, Yuta Yamamoto, Takeshi Harita, Mamoru Hayano, Suguru Nishiuchi, Yimin Wuriyanghai, Hirohiko Kohjitani, Sayako Hirose, Yoshinori Yoshida, Futoshi Toyoda, Minoru Horie, Takeshi Kimura
Journal: Circulation Research (2017)

Background: Calmodulin is a ubiquitous Ca 2+ sensor molecule encoded by three distinct calmodulin genes, CALM1-3 . Recently, mutations in CALM1-3 have been reported to be associated with severe early-onset long-QT syndrome (LQT) due to impaired Ca 2+ dependent inactivation of L-type Ca 2+ channel (LTCC). However, pharmacotherapeutic agents for the treatment of CALM-related LQT have not been established. Objective: We aimed to assess new pharmacotherapies for the treatment of CALM-related LQT using human induced pluripotent stem cell (hiPSC) model. Methods and Results: We used CALM-LQT-hiPSC derived cardiomyocytes (CMs) with a CALM2- N98S mutation which exhibited prolonged action potential durations. First, we confirmed impaired LTCC inactivation in the CALM-LQT-hiPSC-CMs: the ratio of current remaining after 100 ms depolarization (r100) of LTCC currents was significantly larger in CALM-LQT-hiPSC-CMs (r100; CALM-LQT: 0.333 ± 0.016, control: 0.181 ± 0.025 at 0 mV; P &lt; 0.05). Next, we assessed candidate drugs, l-cis- Diltiazem (the stereoisomer of clinically used d-cis -Diltiazem) and Cyclosoprin A, which were reported to enhance voltage-dependent inactivation of LTCC for the treatment of impaired LTCC inactivation. We found that 10 μM l-cis -Diltiazem attenuated impaired LTCC inactivation in CALM-LQT-iPSC-CMs (r100; baseline: 0.333 ± 0.016, with l-cis: 0.294 ± 0.013 at 0 mV; P &lt; 0.05; Figure A and B). On the other hand, Cyclosporine A had less effect compared to l-cis- Diltiazem (Figure A). Conclusion: Using patient-derived hiPSC model, we identified that l-cis -Diltiazem is a promising candidate drug for treating CALM-LQT resulting from impaired LTCC inactivation.
SAT0463 Olfactory impairment in patients with primary sjÖgren’s syndrome and its correlation with organ involvement and immunological abnormalities
Authors: X. Xu, L.-Y. Geng, Z.-Y. Chen, J. Liang, L.-Y. Sun
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Recent findings suggest that autoimmune disorders predispose to a diminished capacity to smell. This has been shown for patients with systemic lupus erythematosus as well as for patients with rheumatoid arthritis. However, this problem has not received much attention in primary Sjögren's syndrome (pSS). <h3>Objectives</h3> The aim of the study was to assess the olfactory functions of patients with primary Sjögren's syndrome and to correlate these findings with their disease activity. <h3>Methods</h3> Fifty-two patients with primary SS and 52 age- and sex-matched healthy control subjects underwent clinical and laboratory examination. Olfactory functions were evaluated using olfactory function assessment by computerised testing including the three stages of smell: threshold, identification and memory of the different odours. The disease activity was assessed by the EULAR SS Patient Reported Index (ESSPRI) and the EULAR SS Disease Activity Index (ESSDAI). <h3>Results</h3> All the olfactory scores (odour threshold, odour memory and identification) in patients with pSS were significantly below the scores in the control group (all p&lt;0.001). Multivariable regression analysis revealed that smell threshold score correlated negatively with ESSPRI and ESSDAI (adjusted R<sup>2</sup>=0.381, p&lt;0.05). Smell threshold score was decreased in pSS patients with anti-SSA antibody compared with those without (p&lt;0.05). Total smell scores were significantly reduced in patients with thyroid involvement (p&lt;0.01). <h3>Conclusions</h3> Our findings indicate that olfactory functions are impaired in pSS patients. There was close correlation between olfactory dysfunction with disease severity and serological abnormalities. Therefore, imperative that physicians should make their patients to be aware of these sensory dysfunctions and educate them on methods to cope with it for better quality of life. <h3>References</h3> [1] Shoenfeld N, Agmon-Levin N, Flitman-Katzevman I, Paran D, Katz BS, Kivity S, et al. The sense of smell in systemic lupus erythematosus. Arthritis Rheum2009;60:1484–1487. [2] Proft F, Steinbach S, Schulze-Koops H, Hundt W, Heinrich P, Gruenke M. Gustatory and olfactory function in rheumatoid arthritis. Scand J Rheumatol2011;40:169–177. <h3>Disclosure of Interest</h3> None declared
OC-068 Blue light imaging for barrett’s neoplasia classification (blinc): the development and validation of a new endoscopic classification system to identify barrett’s neoplasia
Authors: S Subramaniam, K Kandiah, F Chedgy, R Bhattacharyya, P Basford, G Longcroft-Wheaton, P Bhandari
Journal: Gut (2017)

Introduction  Neoplasia in Barrett’s can be subtle and difficult to identify. Blue light imaging (BLI) by Fujifilm is a novel advanced endoscopic technology that provides high intensity contrast imaging for superior visualisation of mucosal surface and vessel patterns. This can improve the identification of Barrett’s neoplasia. To date there is no formal classification system that enables the characterisation of neoplastic and non-neoplastic Barrett’s for BLI. The aim of our study was to develop and validate a classification to identify Barrett’s neoplasia using BLI.  Method  3 expert endoscopists formed a working group to identify criteria characterising neoplastic and non-neoplastic Barrett’s on BLI using a modified Delphi method. A simple classification system utilising pit, vessel pattern and colour was developed using a database of 40 images. 6 experienced endoscopists then assessed a library containing 45 images of neoplastic and non-neoplastic Barrett’s using the proposed criteria. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated to assess its performance. The same parameters were then evaluated for each component criteria.  Results  The BLINC criteria are as follows:  The table below shows the overall sensitivity, specificity, PPV and NPV of the classification in the identification of Barrett’s neoplasia.   When each category in the classification was analysed separately the predictive values of pit and vessel pattern in neoplasia characterisation were high compared to colour.   Conclusion  We have developed the first internally validated simple classification system for the diagnosis of Barrett’s neoplasia using BLI. The classification criteria demonstrated high sensitivity and specifity. We aim to use the proposed classification in future studies for real time optical diagnosis of Barrett’s neoplasia.  Disclosure of Interest  S. Subramaniam: None Declared, K. Kandiah: None Declared, F. Chedgy: None Declared, R. Bhattacharyya: None Declared, P. Basford: None Declared, G. Longcroft-Wheaton: None Declared, P. Bhandari Conflict with: Receives educational grants from Fujifilm, Olympus, Pentax
Interpreting the Association of First-in-Class Immune Checkpoint Inhibition and Targeted Therapy With Survival in Patients With Stage IV Melanoma—Reply
Authors: Andrew J. Sinnamon, Phyllis A. Gimotty, Giorgos C. Karakousis
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
FRI0202 Inertial motion sensors using the vimove© system is a valid method to assess spinal mobility in patients with axial spondyloarthritis
Authors: I.C. Aranda-Valera, J.L. Garrido-Castro, I. Martinez-Sanchez, C. Gonzalez, P. Gardiner, P.M. Machado, E. Collantes
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Spinal mobility measures are recommended for the assessment axial spondyloarthritis (axSpA). Simple, low-tech tools as goniometers and metric tapes are commonly used, resulting in high variability and low accuracy of the measurements. More recently, advanced technological systems have facilitated the measurement of human mobility with high precision, such as motion capture systems like the UCOTrack and its index, the UCOASMI, validated for use in axSpA patients. The development on inertial measurement units (IMUs) has produce wearable, cheap and self-contained devices that can measure motion usually using triads of gyroscopes, accelerometers and magnetometers. Some of the mobility angles measured using motion capture systems can also be measured using IMUs placed in pre-defined anatomical locations. <h3>Objectives</h3> To evaluate the validity of IMUs using the ViMove© system for measuring spinal mobility in patients with axSpA. <h3>Methods</h3> We recruited 20 patients with axSpA from the HU Reina Sofia of Cordoba. The UCOTrack was used as the gold-standard system to obtain mobility measurements. UCOTrack measurements were compared with ViMove© measurements, a system that includes two IMU sensors located in the lumbar spine (pelvis and L1- figure 1) or in the neck (occiput and T3). Conventional metrology measures and patient-reported outcomes were also collected. <h3>Results</h3> The table presents the measurements obtained at the L1 and occiput levels. UCOTrack and ViMove© measurements were very similar, with Root Mean Square Errors (RMSE) less than 10° and Variation Coefficients (VC) less than 10%. We found high intraclass correlation coefficients (ICC) between the two systems (0.84–0.99). Measurements with both systems correlated strongly and significantly with BASMI (0.60–0.92) and BASFI (0.51–0.84), but not with BASDAI. <h3>Conclusions</h3> The ViMove©, an IMU based system, is a valid method to assess spinal mobility in patients with axSpA. There was excellent agreement between ViMove© and UCOTrack and a strong correlations with conventional metrology (BASMI) and patient-reported physical function (BASFI). IMU systems are more feasible than motion capture systems because they do not require a motion laboratory and results can be obtained more quickly in an objective and quantitative way. The ViMove© system has potential for use both in the clinical and research setting and further evaluation of its reproducibility and sensitivity to change should be undertaken. <h3>Acknowledgements</h3> This study has been funded by Foreum (Foundation for Research in Rheumatology) <h3>Disclosure of Interest</h3> None declared
Macroglossia in Light-Chain Amyloidosis
Authors: João Melo Alves, Natália Marto
Journal: New England Journal of Medicine (2018)

Macroglossia in Light-Chain Amyloidosis A 78-year-old man presented with enlargement and stiffening of the tongue. Biopsy confirmed that this finding of macroglossia was due to light-chain amyloidosis.
Abstract 15578: Adiposity, Systolic Blood Pressure, Smoking and Atrial Fibrillation: Analyses of 2.3 Million US Adults Attending Cardiovascular Screening
Authors: Richard Bulbulia, Paul Sherliker, Rachel Clack, Alison Halliday, Richard Peto, Sarah Lewington
Journal: Circulation (2015)

Aims: Unlike other vascular conditions, and for reasons that are incompletely understood, the prevalence of atrial fibrillation (AF) is rising sharply. Analysis of a large healthy cohort which was screened for AF allows reliable assessment of its association with several classical vascular risk factors. Methods: Between 2009 and 2013, around 3 million US adults attended cardiovascular screening clinics and had an ECG to identify AF. Personal and family medical history, medication use, smoking and alcohol consumption were recorded via questionnaires, and height, weight and blood pressure were measured. Age and gender-specific incidence of AF and associations between body mass index (BMI), systolic blood pressure (SBP) and smoking were measured in 2,320,190 participants with no reported prior history of AF, stroke or CHD. Results: The median age was 65, and two-thirds were female. The overall incidence of AF was 0.36%, but it was over twice as common in males (0.59%) than in females (0.23%) and rose sharply with age, doubling in each decade in both men and women. A positive association was seen between adiposity and AF in men and women across all ages studied: approximately 50% increase per 5 unit rise in BMI. By contrast, AF was only weakly associated with SBP - 10% increase per 10mmHg rise in SBP among participants aged under 70 years, and flat or even inversely associated among those over 70 years. Smoking was not associated with AF in men or women at any age (Odds Ratio for current vs never smokers = 0.97 [95% CI 0.79-1.19]). Conclusion: A 10 unit increase in BMI (ie, going from an “ideal” weight to “obese”) doubled the risk of AF. However, blood pressure was less strongly associated with AF, and only in those under 70 years, suggesting some other mechanism behind the BMI - AF association. Current smoking was not associated with AF. Rising rates of obesity may be driving the observed increase in AF in the developed world.
On the Origin of Isoprenoid Biosynthesis
Authors: Yosuke Hoshino, Eric A Gaucher
Journal: Molecular Biology and Evolution (2018)

Isoprenoids and their derivatives represent the largest group of organic compounds in nature and are distributed universally in the three domains of life. Isoprenoids are biosynthesized from isoprenyl diphosphate units, generated by two distinctive biosynthetic pathways: mevalonate pathway and methylerthritol 4-phosphate pathway. Archaea and eukaryotes exclusively have the former pathway, while most bacteria have the latter. Some bacteria, however, are known to possess the mevalonate pathway genes. Understanding the evolutionary history of these two isoprenoid biosynthesis pathways in each domain of life is critical since isoprenoids are so interweaved in the architecture of life that they would have had indispensable roles in the early evolution of life. Our study provides a detailed phylogenetic analysis of enzymes involved in the mevalonate pathway and sheds new light on its evolutionary history. The results suggest that a potential mevalonate pathway is present in the recently discovered superphylum Candidate Phyla Radiation (CPR), and further suggest a strong evolutionary relationship exists between archaea and CPR. Interestingly, CPR harbors the characteristics of both the bacterial-type and archaeal-type mevalonate pathways and may retain signatures regarding the ancestral isoprenoid biosynthesis pathway in the last universal common ancestor. Our study supports the ancient origin of the mevalonate pathway in the three domains of life as previously inferred, but concludes that the evolution of the mevalonate pathway was more complex.
Analysis of Fractures in Patients With Type 2 Diabetes Treated With Empagliflozin in Pooled Data From Placebo-Controlled Trials and a Head-to-Head Study Versus Glimepiride
Authors: Sven Kohler, Stefan Kaspers, Afshin Salsali, Cordula Zeller, Hans J. Woerle
Journal: Diabetes Care (2018)

OBJECTIVE To assess the effect of empagliflozin on bone fractures and bone mineral density in patients with type 2 diabetes in pooled placebo-controlled trial data and a head-to-head study versus glimepiride. RESEARCH DESIGN AND METHODS Pooled data were analyzed from patients who were randomized 1:1:1 to empagliflozin 10 mg, empagliflozin 25 mg, or placebo in phase I–III clinical trials. Data were also analyzed from the EMPA-REG H2H-SU trial in which patients received empagliflozin 25 mg or glimepiride as an add-on to metformin for 104 weeks with a 104-week extension. Bone fracture adverse events (AEs) were evaluated through a search of investigator-reported (nonadjudicated) events. RESULTS In the pooled analysis, bone fracture AEs were reported in 119 of 4,221 (2.8%), 105 of 4,196 (2.5%), and 123 of 4,203 (2.9%) patients in the empagliflozin 10 mg, empagliflozin 25 mg, and placebo groups, respectively (rates of 1.55, 1.36, and 1.69/100 patient-years, respectively). In the EMPA-REG H2H-SU trial, bone fracture AEs were reported in 31 of 765 (4.1%) patients receiving empagliflozin 25 mg and in 33 of 780 (4.2%) patients receiving glimepiride (rates of 1.28 and 1.40/100 patient-years, respectively). CONCLUSIONS Empagliflozin did not increase the risk of bone fracture compared with placebo in a pooled analysis of &amp;gt;12,000 patients or compared with glimepiride in a 4-year head-to-head study.
Reduction of immune inhibitory myeloid derived suppressor cells by low dose sunitinib combined with a cancer vaccine to provide therapeutic benefit to tumor-bearing mice.
Authors: Helen Kim Cho, Paul Cockle, Cindy Wei Li, Steve Burgess, Terrence Coleman, Terri Harder, Dan Xu, Kam Chan, Steve Kurzyniec, Joan Guo, Oscar Maldonado, James Merson, Karin Jooss
Journal: Journal of Clinical Oncology (2017)

e23084 Background: Sunitinib is a receptor tyrosine kinase inhibitor (RTK) approved as a monotherapy for the treatment of advanced RCC, gastrointestinal stromal tumors and advanced pancreatic neuroendocrine tumors. At the approved doses, it inhibits angiogenesis in tumors and targets RTKs (PDGF receptor, VEGF receptor, KIT, FLT-3, and RET) involved in tumor cell growth. Sunitinib also has been shown in murine studies and patients, to exhibit immunomodulatory properties that reduce a heterogeneous population of cells termed myeloid derived suppressor cells (MDSCs) and restore the immune stimulatory Th1 cytokine profile of T cells. The approved anti-angiogenic sunitinib dosing regimens in RCC have a safety profile that is overall manageable with the most commonly reported sunitinib-related grade 3 adverse events including hypertension, fatigue, diarrhea and hand-foot syndrome. Although the tolerability of sunitinib as monotherapy was acceptable in advanced stage diseases, the drug’s side effect profile could potentially pose challenges for use in combination with other oncology therapies. Thus, if the dose of sunitinib could be lowered to improve the side effect profile without impacting its immune modulatory properties, it could be combined with cancer vaccine regimens, offering a better tolerated and highly potent immunotherapy for patients with cancer of all stages. Methods: To evaluate the relationship of dose of sunitinib on its immunomodulatory properties, the pharmacokinetic profile, the frequency of MDSCs, cytokine profile, vaccine induced immune responses and anti-tumor efficacy were monitored in a subcutaneous tumor bearing BALB-neuT mice in the presence or absence of a cancer vaccine. Results: The data suggested that sunitinib doses below the approved daily dose of 50 mg may maintain the drug’s immune modulatory properties and improve overall survival when given concurrently with a cancer vaccine. Conclusions: The data suggested that low dose sunitinib can be administered as an immunomodulator to reduce MDSCs safely in combination with potent, multi-component cancer vaccine regimens.
Powerful anti-colon cancer effect of modified nanoparticle-mediated IL-15 immunogene therapy through activation of the host immune system
Authors: Xiaoxiao Liu, Yanyan Li, Xiaodong Sun, Yagmur Muftuoglu, Bilan Wang, Ting Yu, Yuzhu Hu, Lu Ma, Mingli Xiang, Gang Guo, Chao You, Xiang Gao, Yuquan Wei
Journal: Theranostics (2018)

Rationale: Colorectal cancer (CRC) is the third most commonly diagnosed cancer around the world.Over the past several years, immunotherapy has demonstrated considerable clinical benefit in CRC therapy, and the number of immunologic therapies for cancer treatment continues to climb each year.Interleukin-15 (IL15), a potent pro-inflammatory cytokine, has emerged as a candidate immunomodulator for the treatment of CRC.Methods: In this study, we developed a novel gene delivery system with a self-assembly method using DOTAP and MPEG-PLA (DMA) to carry pIL15, denoted as DMA-pIL15 which was used to treat tumor-bearing mice.Results: Supernatant from lymphocytes treated with supernatant derived from CT26 cells transfected with DMA-pIL15 inhibited the growth of CT26 cells and induced cell apoptosis in vitro.Treatment of tumor-bearing mice with DMA-pIL15 complex significantly inhibited tumor growth in both subcutaneous and peritoneal models in vivo by inhibiting angiogenesis, promoting apoptosis, and reducing proliferation through activation of the host immune system. Conclusion:The IL-15 plasmid and DMA complex showed promise for treating CRC clinically as an experimental new drug.
Tai chi reduced severity of fibromyalgia symptoms at 24 weeks compared with aerobic exercise
Authors: Roland Staud
Journal: Annals of Internal Medicine (2018)

ACP Journal Club19 June 2018Tai chi reduced severity of fibromyalgia symptoms at 24 weeks compared with aerobic exerciseRoland Staud, MDRoland Staud, MDUniversity of Florida, Gainesville, Florida, USA (R.S.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2018-168-12-070 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationWang C, Schmid CH, Fielding RA, et al. Effect of tai chi versus aerobic exercise for fibromyalgia: comparative effectiveness randomized controlled trial. BMJ. 2018;360:k851. https://pubmed.ncbi.nlm.nih.gov/29563100Clinical Impact RatingsGIM/FP/GP: Rheumatology: References1 Häuser W, Klose P, Langhorst J, et al. Efficacy of different types of aerobic exercise in fibromyalgia syndrome: a systematic review and meta-analysis of randomised controlled trials. Arthritis Res Ther. 2010;12:R79. [PMID: 20459730] Google Scholar2 Langhorst J, Klose P, Dobos GJ, Bernardy K, Häuser W. Efficacy and safety of meditative movement therapies in fibromyalgia syndrome: a systematic review and meta-analysis of randomized controlled trials. Rheumatol Int. 2013;33:193-207. [PMID: 22350253] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Florida, Gainesville, Florida, USA (R.S.)This article was published at Annals.org on 5 June 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCiteSpace-based metrical and visualization analysis of tai chi chuan an algesia 19 June 2018Volume 168, Issue 12Page: JC70KeywordsAerobic exerciseExercise therapyFibromyalgiaMedical conditionsPainPregnancyQuestionnairesRheumatic painRheumatology ePublished: 19 June 2018 Issue Published: 19 June 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...