tbuckley/cabot-search huggingface dataset:
A CASE REPORT OF SYNCOPE FOLLOWING INITIATION OF ISAVUCONAZONIUM
Authors: Ai-Chen Ho, George F. Wohlford, Benjamin Van Tassell, May T. Aziz, Kelly G. Hawks, Edoardo Bressi, Oveimar DeLa Cruz, Amir Toor, Antonio Abbate
Journal: Journal of the American College of Cardiology (2020)
FACILITY-LEVEL VARIATION IN CARDIAC STRESS TEST UTILIZATION AMONG PATIENTS WITH DIABETES MELLITUS: FINDINGS FROM THE VETERANS AFFAIRS NATIONAL DATABASE
Authors: Dhruv Mahtta, Sarah T. Ahmed, Nishant Shah, David J. Ramsey, Julia M. Akeroyd, Khurram Nasir, Ihab Hamzeh, Islam Elgendy, Stephen W. Waldo, Mouaz H. Al-Mallah, Hani Jneid, Christie M. Ballantyne, Laura Petersen, Salim Virani
Journal: Journal of the American College of Cardiology (2020)
Reframing Surgical Risk Using Geriatric Assessment Measures
Authors: Shelley R. McDonald, Atilio Barbeito, Sandhya A. Lagoo-Deenadayalan
Journal: JAMA Surgery (2020)

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 Surgery 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 Surgery journal
<i>MTMR4</i> SNVs modulate ion channel degradation and clinical severity in congenital long QT syndrome: insights in the mechanism of action of protective modifier genes
Authors: Yee-Ki Lee, Luca Sala, Manuela Mura, Marcella Rocchetti, Matteo Pedrazzini, Xinru Ran, Timothy S H Mak, Lia Crotti, Pak C Sham, Eleonora Torre, Antonio Zaza, Peter J Schwartz, Hung-Fat Tse, Massimiliano Gnecchi
Journal: Cardiovascular Research (2020)

Abstract Aims In long QT syndrome (LQTS) patients, modifier genes modulate the arrhythmic risk associated with a disease-causing mutation. Their recognition can improve risk stratification and clinical management, but their discovery represents a challenge. We tested whether a cellular-driven approach could help to identify new modifier genes and especially their mechanism of action. Methods and results We generated human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) from two patients carrying the same KCNQ1-Y111C mutation, but presenting opposite clinical phenotypes. We showed that the phenotype of the iPSC-CMs derived from the symptomatic patient is due to impaired trafficking and increased degradation of the mutant KCNQ1 and wild-type human ether-a-go-go-related gene. In the iPSC-CMs of the asymptomatic (AS) patient, the activity of an E3 ubiquitin-protein ligase (Nedd4L) involved in channel protein degradation was reduced and resulted in a decreased arrhythmogenic substrate. Two single-nucleotide variants (SNVs) on the Myotubularin-related protein 4 (MTMR4) gene, an interactor of Nedd4L, were identified by whole-exome sequencing as potential contributors to decreased Nedd4L activity. Correction of these SNVs by CRISPR/Cas9 unmasked the LQTS phenotype in AS cells. Importantly, the same MTMR4 variants were present in 77% of AS Y111C mutation carriers of a separate cohort. Thus, genetically mediated interference with Nedd4L activation seems associated with protective effects. Conclusion Our finding represents the first demonstration of the cellular mechanism of action of a protective modifier gene in LQTS. It provides new clues for advanced risk stratification and paves the way for the design of new therapies targeting this specific molecular pathway.
Elaboration of the Corticosteroid Synthesis Pathway in Primates through a Multistep Enzyme
Authors: Carrie F Olson-Manning
Journal: Molecular Biology and Evolution (2020)

Abstract Metabolic networks are complex cellular systems dependent on the interactions among, and regulation of, the enzymes in the network. Although there is great diversity of types of enzymes that make up metabolic networks, the models meant to understand the possible evolutionary outcomes following duplication neglect specifics about the enzyme, pathway context, and cellular constraints. To illuminate the mechanisms that shape the evolution of biochemical pathways, I functionally characterize the consequences of gene duplication of an enzyme family that performs multiple subsequent enzymatic reactions (a multistep enzyme) in the corticosteroid pathway in primates. The products of the corticosteroid pathway (aldosterone and cortisol) are steroid hormones that regulate metabolism and stress response in tetrapods. These steroid hormones are synthesized by a multistep enzyme Cytochrome P450 11B (CYP11B) that performs subsequent steps on different carbon atoms of the steroid derivatives. Through ancestral state reconstruction and in vitro characterization, I find that the primate ancestor of the CYP11B1 and CYP11B2 paralogs had moderate ability to synthesize both cortisol and aldosterone. Following duplication in Old World primates, the CYP11B1 homolog specialized on the production of cortisol, whereas its paralog, CYP11B2, maintained its ability to perform multiple subsequent steps as in the ancestral pathway. Unlike CYP11B1, CYP11B2 could not specialize on the production of aldosterone because it is constrained to perform earlier steps in the corticosteroid synthesis pathway to achieve the final product aldosterone. These results suggest that enzyme function, pathway context, along with tissue-specific regulation, both play a role in shaping potential outcomes of metabolic network elaboration.
MITRAL BALLOON VALVULOPLASTY OF BIOPROSTHETIC VALVE: AN ALTERNATIVE WHEN A VALVE-IN-VALVE PROCEDURE IS NOT AN OPTION
Authors: Jose Sleiman, Morvarid Zandiyeh, Mileydis Alonso, Rafael Miret, Hardik M. Bhansali, Diana Miranda Ruiz, Eduardo Perez, Nader Hanna, Luis Alonso Hernandez Mejia, Kevin Leung, Nicholas Ghiloni, Elsy Navas, Craig Asher, Roberto J. Cubeddu
Journal: Journal of the American College of Cardiology (2020)
Peptide mutation analysis results in potent GD2 mimotope peptides for DNA vaccination against neuroblastoma
Authors: Holger N. Lode, Mathias Bleeke, Stefan Fest, Nicole Huebener, Yan Zeng, Silke Weixler, Rudolf Volkmer, Elisabeth Förster-Waldl, Erika Jensen-Jarolim, Gerhard Gaedicke
Journal: Cancer Research (2006)

1407  The tumor-associated antigen disialoganglioside-GD2 is an established target for passive immunotherapy highly expressed in neuroectodermal tumors. The aim of this study was to develop an active immunization strategy leading to the induction of an anti-GD2 immune response. However, carbohydrates and glycolipids are T cell-independent antigens (TI) and evoke poor immune responses. Here, we describe the identification, characterization and in vivo efficacy of cyclic peptides mimicking the structure of glycolipid GD2 (GD2 mimotopes), in order to overcome T-cell independency. From a list of 13 GD2 mimotope dececapetides identified by biopanning experiments of a phage-display library against the anti-GD2 antibody (Ab) ch14.18 two superior peptide candidates, mimotope A (MA) and and mimotope D (MD), were selected based on competitive ELISA and peptide-antibody dissociation constants (biacore). The GD2 mimickry potential of these peptides (MA, MD) was optimized by peptide mutation analysis. This was accomplished by SPOT synthesis generating peptide microarrays on cellulose membranes introducing distinct changes into the amino acid sequence of the original GD2 peptide mimotopes. Mutation analysis reslulted in a 2 log increase in affinity of the mimotope peptides to ch14.18 antibody as determined in dot blot and biacore experiments. Based on these results, two plasmid DNA minigene vaccines were generated by overlapping PCR encoding for MA and MD, respectively. Minigene expression and GD2 mimikry was demonstrated following transfection of CHO-1 cells in western blot and dot blot experiments. The efficacy of these mimotope DNA vaccines to induce a tumor protective anti-GD2 immune response was tested in the syngeneic GD2+ NXS2 neuroblastoma mouse model. DNA vaccine delivery was accomplished with attenuated Salmonella typhimurium (SL 7207) used as an oral vaccine carrier. Only mice receiving the mimotope DNA vaccines revealed a reduction of spontaneous liver metastases with a mean liver weight of 1g in both groups (MA and MD) in contrast to negative controls (3g). Interestingly, mice immunized with KLH conjugated peptides (MA, MD) revealed an increased rate of s.c. tumor growth and spontaneous liver metastasis with average liver weights of 5g (MA) and 7g (MD), respecively. This finding suggests the induction of tolerance using a peptide vaccine approach entirely in contrast to vaccination with DNA. Finally, the highest anti-GD2 humoral immune response was observed in sera of mice from both GD2 mimotope DNA vaccine groups, consistent with the anti-tumor reponse observed in vivo. In summary, we demonstratre that GD2 mimotope DNA vaccines may provide a useful strategy for active immunization against neuroblastoma. Supported by DFG Lo 635-2 and Fordergesellschaft Kinderkrebs-Neuroblastom-Forschung
“Less is More” in mechanical ventilation
Authors: Luciano Gattinoni, Michael Quintel, John J. Marini
Journal: Intensive Care Medicine (2020)

Though formed in the late 1960s, the field of intensive care medicine solidified its place in the 1970s.Critical care practitioners were typically young and enthusiastic, but lacked the benefit of guidance from an established scientific literature or the experience of "older mentors, " as simply they did not exist.The rational basis of this new specialty was systems physiology and short-term observation, on which most of its monitoring and interventions are based.Interestingly, not only were the "intensivists" young, but so were the patients, compared to now.Very importantly, we naively assumed uniformity of diseases and disease mechanisms and translated our familiar deep knowledge of normal physiology to the pathologic state.Energy, enthusiasm and the pioneering attitudes of the young intensivists were associated with a widespread tendency to "exceed" the confines of prior experience.Adverse consequences gradually became evident.This exuberance characterized many elements of practice: in septic patients, if milligrams of corticosteroids are good, grams might be better [1].In nutrition, if 2000 kcal/day is good, 5000 must be better [2].The same applies to sedations and fluids administration.In hemodynamics, supranormal values of oxygen transport must be better [3], etc. Essentially, the intensivists of that era were doing the same things as we are now, but with far greater dosage, extent and intensity.ARDS is one of the best examples of our evolution from "more-to-less, " nurtured by the difficult lessons of our experience (Fig. 1).
Relationship of MRI tests and referral of malignant adnexal masses to gynecologic oncologists for surgery.
Authors: Rachel Kupets, Gennady Miroshnichenko, Lawrence Frank Paszat
Journal: Journal of Clinical Oncology (2012)

6134 Background: To evaluate the patterns of radiologic imaging by family physicians and gynecologists in the work up of women found to have an adnexal mass on pelvic ultrasound. To evaluate whether advanced imaging tests are associated with improved referral of high risk adnexal masses to gynecologic oncologists. Methods: Centralized provincial databases of healthcare utilization were used to identify women aged 45 and older who received a pelvic ultrasound between 2006-2008. Subsequent imaging tests ordered by physician specialty were identified. Of those women who proceeded to laparotomy, logistic regression was performed to determine which imaging tests were associated with referral of high risk adnexal tumors to a gynecologic oncologist. Results: 193, 261 women had a pelvic ultrasound; 19, 949 (10.3%) had a laparotomy. 2223 and 627 women were categorized with benign and malignant adnexal masses respectively. Up to 12% of women had a pelvic MRI and 58% of women had a CT scan after a pelvic ultrasound.Family physicians referred 58% and gynecologists referred 47% of high risk ovarian masses to a gynecologic oncologist respectively after imaging.Gynecologic Oncologists operated on only 55% of women with malignant adnexal masses. On multivariate analysis factors significant for surgery by a gynecologic oncologist include a preoperative CT Scan OR 3.58 (p&lt;.001) and CT Scan and MRI OR 7.78 (p&lt;.001). Preoperative MRI alone had an OR of 1.86 (p=0.09) and was not significant. Mean time to surgery significantly increased when further imaging tests were performed after a pelvic ultrasound (100 days), CT (131 days), MRI (170 days), CT and MRI (179 days),P 0.002. Conclusions: The addition of a pelvic MRI to a pelvic ultrasound does not improve the referral of high risk adnexal masses to a gynecologic oncologist. A consensus on appropriate imaging and triage is needed when an adnexal mass is identified on ultrasound.
LONG TERM MORTALITY TRENDS AMONG CHILDREN AND ADULTS WITH CONGENITAL HEART DISEASE IN THE UNITED STATES FROM 2007-2017
Authors: Krishna Kishore Umapathi, Aditi Gupta, Saif Aljemmali, Lamya Mubayed, Sawsan Awad, Hoang Nguyen
Journal: Journal of the American College of Cardiology (2020)
MANGANESE-ENHANCED T1MAPPING IN NON-ISCHAEMIC CARDIOMYOPATHY
Authors: Nick Spath, Nick Spath, Giorgos Papanastastiou, Trisha Singh, Gaurav Gulsin, Andrew Baker, Rob Janiczek, Gerry McCann, Marc Dweck, David E. Newby, Scott Semple
Journal: Journal of the American College of Cardiology (2020)
PREVALENCE, PREDICTORS AND OUTCOMES OF GASTROINTESTINAL(GI) BLEEDING FOLLOWING LEFT VENTRICLE ASSIST DEVICE (LVAD) IMPLANTATION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Muhammad Ishaq, Yamna Waseem, Muhammad Khan, Muhammad Shariq Usman, Safi Khan, Izza Shahid, Rami Doukky, Richard A. Krasuski
Journal: Journal of the American College of Cardiology (2020)
Editor's Note: Synergistic Killing Effect between Vorinostat and Target of CD146 in Malignant Cells
Authors: Xiaoli Ma, Jia Liu, Jiang Wu, Xiyun Yan, Peng Wu, Yong Liu, Shuang Li, Yuan Tian, Yang Cao, Gang Chen, Li Meng, Gang Xu, Shixuan Wang, Yunping Lu, Ding Ma, Jianfeng Zhou
Journal: Clinical Cancer Research (2020)

The editors are publishing this note to alert readers to a concern about [this article][1] ([1][2]). In Fig. 5D, similarities exist in the mAb AA98 and Vorinostat + mIgG slides. The authors stand by the conclusions in the article.

1.  1.[↵][3]1.  Ma X,     2.  Liu J,     3.  Wu J,     4.  Yan
PREDICTORS OF LONG-TERM MATERNAL CARDIOVASCULAR EVENTS AMONG WOMEN WITH CONGENITAL HEART DISEASE
Authors: Hayley Schultz, Nasim C. Sobhani, Sarah Blissett, Juan M Gonzalez Velez, Ian Stewart Harris, Nisha Parikh, Molly Killion, Yolanda Tinajero, Elyse Foster, Anushree Agarwal
Journal: Journal of the American College of Cardiology (2020)
Clarifying the Risk of Lung Disease in SZ Alpha-1 Antitrypsin Deficiency
Authors: Alessandro N. Franciosi, Brian D. Hobbs, Oliver J. McElvaney, Kevin Molloy, Craig Hersh, Louise Clarke, Cedric Gunaratnam, Edwin K. Silverman, Tomás P. Carroll, Noel G. McElvaney
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

: The ZZ genotype of alpha-1 antitrypsin deficiency (AATD) is associated with chronic obstructive pulmonary disease (COPD), even among never-smokers. The SZ genotype is also considered severe; yet, its effect on lung health remains unclear.
Phase I study to determine the bioavailability and tolerability of a tablet formulation of the PARP inhibitor olaparib in patients with advanced solid tumors: Dose-escalation phase.
Authors: Avinash Gupta, Victor Moreno, Emma Jane Dean, Yvette Drew, Shibani Nicum, Malcolm Ranson, Ruth Plummer, Helen Swaisland, Wendy Burke, Peter McCormack, Ilian Tchakov, Mark R. Middleton, Stanley B. Kaye, L Rhoda Molife
Journal: Journal of Clinical Oncology (2012)

3051 Background: We previously reported the comparative bioavailability of the olaparib tablet (TAB) up to 200 mg BID, with the initial capsule formulation; gmean AUC 0–T following 200 mg BID TAB was ~20% lower than 400 mg BID capsule (CAP; Molife et al ASCO 2010). Olaparib 200 mg BID TAB had an acceptable tolerability profile suggesting further dose escalation might be justified. Methods: Study NCT00777582 was amended to include a dose-escalation phase, to define the maximum tolerated dose (MTD) and safety profile of the TAB, and 2 expansion phases to compare safety and efficacy of TAB doses vs 400 mg BID CAP. Expansion phase data are reported separately. Here, we report preliminary data from the dose-escalation phase where patients (pts) with advanced solid tumors, ECOG PS 0–2 and adequate organ function were assigned to treatment with increasing olaparib BID TAB doses in 28-day continuous dosing cycles. Pharmacokinetic (PK) sampling was performed on days 1, 8, 15, 29, 57. Results: 30 pts (M:F, 3:27; median age 54 yrs [range 19–70]) were enrolled in the dose-escalation phase and received treatment at 5 dose levels: 250, 300, 350, 400 and 450 mg (each dose level, n=6). Overall, the most common AEs were nausea (80%), fatigue (73%) and diarrhea (36%). The majority of AEs were mild to moderate (CTC grade [G] 1/2). Hematologic toxicity in terms of, mostly mild, anemia, neutropenia and thrombocytopenia, appeared to increase at doses of 300 mg BID or higher. Two pts had dose-limiting toxicities at 450 mg (G3 thrombocytopenia and G3 anemia); the TAB MTD was 400 mg BID. Exposure increased proportionally with increasing dose: mean exposure after 400 mg BID was double that following the previously reported 200 mg BID dose. Following 300 and 400 mg doses, gmean C max ss , AUC 0–T and C min ss matched or exceeded the 400 mg BID CAP dose. Conclusions: The MTD of olaparib TAB was 400 mg BID. Based on PK analysis, the 300 and 400 mg BID doses were selected for evaluation in the MTD expansion phase to further define safety and preliminary efficacy.
Differences in White Matter Microstructure Among Children With Developmental Coordination Disorder
Authors: Meisan Brown-Lum, Sara Izadi-Najafabadi, Tim F. Oberlander, Alexander Rauscher, Jill G. Zwicker
Journal: JAMA Network Open (2020)

Developmental coordination disorder (DCD) is a motor impairment that significantly interferes with activities of daily living. Little is known about the cause of DCD and how it develops, making it difficult to understand why children with DCD struggle in learning motor skills and to determine the best intervention to optimize function.To characterize white matter differences using diffusion tensor imaging in children with and without DCD.This cross-sectional study collected diffusion tensor imaging data at BC Children's Hospital Research Institute in Vancouver, British Columbia, Canada, from September 2014 to January 2017. Using a sample of convenience, children with DCD and children without DCD aged 8 to 12 years underwent magnetic resonance imaging. Data analysis was conducted from January 2017 to January 2020.The main outcome measures were diffusion parameters, including fractional anisotropy and mean, axial, and radial diffusivity, which are thought to provide an indirect measure of white matter microstructure. Tract-based spatial statistics, a voxelwise statistical analysis of diffusion parameters, were conducted using a 2-group comparison design matrix with age and attention as covariates.Thirty children without DCD (mean [SD] age, 9.9 [1.4] years; 21 [70%] boys) and 31 children with DCD (mean [SD] age, 10.1 [1.2] years; 26 [84%] boys) were included in the study. Compared with children without DCD, children with DCD were characterized by significantly lower fractional anisotropy and axial diffusivity in regions of white matter pathways associated with motor and sensorimotor processing, including the corticospinal tract (fractional anisotropy: mean [SD], 0.54 [0.03] vs 0.51 [0.03]; P < .001; axial diffusivity: mean [SD], 0.13 [0.98] vs 0.12 [0.46]; P = .01), posterior thalamic radiation at the retrolenticular part of the internal capsule (axial diffusivity: mean [SD], 0.14 [0.57] vs 0.14 [0.44]; P = .01), and cerebellar pathways (eg, superior cerebellar peduncle, fractional anisotropy: mean [SD], 0.49 [0.05] vs 0.46 [0.03]; P = .03; axial diffusivity: mean [SD], 0.14 [0.66] vs 0.14 [0.63]; P = .009). There were no significant differences in mean diffusivity and radial diffusivity between children with and without DCD.These findings suggest that children with DCD show significant brain differences in motor and sensorimotor white matter pathways compared with children without DCD. The pattern of diffusion parameters in children with DCD suggests that axonal development may be disrupted in this neurodevelopmental disorder.
Prediction of response to neoadjuvant chemotherapy in breast cancer
Authors: J. Hannemann, H. Halfwerk, A. Velds, C. Loo, E. Rutgers, S. Rodenhuis, M. Van de Vijver
Journal: Journal of Clinical Oncology (2006)

20005 Background: Neoadjuvant chemotherapy is increasingly employed in operable breast cancer. Our initial studies on a cDNA array platform failed to identify gene expression patterns predicting response to neoadjuvant chemotherapy in breast cancer patients (J Clin Oncol 23:3331, 2005). Now we included more patients and used oligo microarrays. Methods: Patients with operable or locally advanced breast cancer were included in a randomized phase II study or received neoadjuvant chemotherapy off protocol. All except 7 patients began chemotherapy with 3 courses of dose-dense adriamycin and cyclophosphamide (ddAC) and response was evaluated by MRI. Patients with a response and a HER2-positive tumor were then randomized between either 3 additional courses of ddAC or six weekly courses of carboplatin, paclitaxel and trastuzumab (CPT). Patients without response were switched to CPT. Patients with HER2-negative tumors were randomized between 3 courses of either ddAC or capecitabine and docetaxel (CD). After evaluation, patients without response were switched to the alternative treatment arm. From all patients 14G core needle biopsies were taken before treatment and total RNA was isolated. Amplified mRNA was labeled and hybridized to 35k human oligo microarrays from our microarray facility. Results: So far, 77 patients have been included into the study. From 48 of these, good quality RNA from tissue with &gt;50% tumor cells was isolated. 43 patients had received ddAC as initial chemotherapy; 32 of these had not been switched to another regimen. In a training set containing 11 pathological complete remissions (pCR) and 9 non-responders (NR) we could separate these groups by using 20 genes in a supervised classification and a 9-step cross validation. These results could be validated in an independent set of 11 samples (6 pCR, 5 NR). From 10 out of 11 samples, response status could be predicted correctly, independent from the treatment regimen. Although ER-positive tumors have a lower pCR rate than ER-negative ones, the steroid hormone receptors were not present in the classifier. Conclusions: We conclude that it should be possible to identify a reliable gene expression profile associated with response to adriamycin based neoadjuvant chemotherapy in breast cancer. No significant financial relationships to disclose.
CHARACTERISTICS AND OUTCOMES OF HEART FAILURE WITH REDUCED EJECTION FRACTION PATIENTS ENROLLED IN MEDICARE ADVANTAGE WITH AND WITHOUT RECENT WORSENING HEART FAILURE
Authors: Robert John Mentz, Laurence Djatche, Zulkarnain Pulungan, Seung Kim, Christie Teigland, Robert Hilkert, Mei Yang
Journal: Journal of the American College of Cardiology (2020)