tbuckley/cabot-search huggingface dataset:
Proteasome-Dependent Regulation of Distinct Metabolic States During Long-Term Culture of Human iPSC-Derived Cardiomyocytes
Authors: Antje Ebert, Amit U. Joshi, Sandra Andorf, Yuanyuan Dai, Shrivatsan Sampathkumar, Haodong Chen, Yingxin Li, Priyanka Garg, Karl Toischer, Gerd Hasenfuss, Daria Mochly-Rosen, Joseph C. Wu
Journal: Circulation Research (2019)

Rationale: The immature presentation of human induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) is currently a challenge for their application in disease modeling, drug screening, and regenerative medicine. Long-term culture is known to achieve partial maturation of iPSC-CMs. However, little is known about the molecular signaling circuitries that govern functional changes, metabolic output, and cellular homeostasis during long-term culture of iPSC-CMs. Objective: We aimed to identify and characterize critical signaling events that control functional and metabolic transitions of cardiac cells during developmental progression, as recapitulated by long-term culture of iPSC-CMs. Methods and Results: We combined transcriptomic sequencing with pathway network mapping in iPSC-CMs that were cultured until a late time point, day 200, in comparison to a medium time point, day 90, and an early time point, day 30. Transcriptomic landscapes of long-term cultured iPSC-CMs allowed mapping of distinct metabolic stages during development of maturing iPSC-CMs. Temporally divergent control of mitochondrial metabolism was found to be regulated by cAMP/PKA (protein kinase A)- and proteasome-dependent signaling events. The PKA/proteasome-dependent signaling cascade was mediated downstream by Hsp90 (heat shock protein 90), which in turn modulated mitochondrial respiratory chain proteins and their metabolic output. During long-term culture, this circuitry was found to initiate upregulation of iPSC-CM metabolism, resulting in increased cell contractility that reached a maximum at the day 200 time point. Conclusions: Our results reveal a PKA/proteasome- and Hsp90-dependent signaling pathway that regulates mitochondrial respiratory chain proteins and determines cardiomyocyte energy production and functional output. These findings provide deeper insight into signaling circuitries governing metabolic homeostasis in iPSC-CMs during developmental progression.
Development and Validation of a Tool to Measure Patient Assessment of Clinical Compassion
Authors: Brian W. Roberts, Michael B. Roberts, Jady Yao, Joshua Bosire, Anthony Mazzarelli, Stephen Trzeciak
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Clinician compassion is a vital element of health care quality. Currently, there appears to be no validated and feasible method for health care organizations to measure patient assessment of clinician compassion on a large scale. <h3>Objective</h3> To develop and validate a tool for measuring patient assessment of clinician compassion that can be used in conjunction with the Clinician and Group Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS) survey. <h3>Design, Setting, and Participants</h3> This prospective cohort study took place from June 1 to August 30, 2018, at a US academic health care system among a pilot cohort consisting of 3325 adult patients and a validation cohort consisting of 3483 adult patients, both of whom had an outpatient clinic visit and completed the CG-CAHPS survey. <h3>Main Outcomes and Measurements</h3> After a comprehensive literature review, 12 candidate survey items were developed. Face and construct validity were performed. Candidate items were disseminated to patients in conjunction with the CG-CAHPS survey in a series of 2 studies: (1) exploratory factor analysis in one cohort to determine the factor structure and the most parsimonious set of items; and (2) validity testing in a second cohort using confirmatory factor analysis. Reliability was tested using Cronbach α. Convergent validity was tested with patient assessment of clinician communication and overall satisfaction questions from CG-CAHPS survey. <h3>Results</h3> Overall, 6493 patient responses were analyzed. The mean (SD) age was 60 (15) years, 4239 patients (65.3%) were women, and 5079 (78.2%) were white. Exploratory factor analyses identified a 5-item compassion measure to be the most parsimonious. Confirmatory factor analyses found good fit. The compassion measure demonstrated good internal consistency (α = 0.94) and convergent validity (clinician communication: ρ = 0.44; overall satisfaction: ρ = 0.52) but reflected a patient experience domain (compassionate care) distinct from what is currently captured in the CG-CAHPS survey. <h3>Conclusions and Relevance</h3> A simple 5-item tool to measure patient assessment of clinician compassion was developed and validated for use in conjunction with CG-CAHPS survey.
Academia and industry: allocating credit for discovery and development of new therapies
Authors: Jeffrey S. Flier
Journal: Journal of Clinical Investigation (2019)

The discovery and development of new therapies involves input from academic researchers and the biopharmaceutical industry, but the nature and relative importance of their contributions has been the subject of debate.Recent concerns about drug pricing are among the factors stimulating renewed interest in this question, which has important implications for academia, industry, and society at large.To facilitate understanding and informed public discussion, this Viewpoint will offer a high-level overview of the unique, overlapping, and evolving contributions of academia and industry to drug discovery (Figure 1).
Phase I study of emactuzumab single agent or in combination with paclitaxel in patients with advanced/metastatic solid tumors reveals depletion of immunosuppressive M2-like macrophages
Authors: C.A. Gomez-Roca, A. Italiano, C. Le Tourneau, P.A. Cassier, M. Toulmonde, S.P. D’Angelo, M. Campone, K.L. Weber, D. Loirat, M.A. Cannarile, A.-M. Jegg, C. Ries, R. Christen, G. Meneses-Lorente, W. Jacob, I. Klaman, C.-H. Ooi, C. Watson, K. Wonde, B. Reis, F. Michielin, D. Rüttinger, J.-P. Delord, J.-Y. Blay
Journal: Annals of Oncology (2019)
First-in-Human RNA Polymerase I Transcription Inhibitor CX-5461 in Patients with Advanced Hematologic Cancers: Results of a Phase I Dose-Escalation Study
Authors: Amit Khot, Natalie Brajanovski, Donald P. Cameron, Nadine Hein, Kylee H. Maclachlan, Elaine Sanij, John Lim, John Soong, Emma Link, Piers Blombery, Ella R. Thompson, Andrew Fellowes, Karen E. Sheppard, Grant A. McArthur, Richard B. Pearson, Ross D. Hannan, Gretchen Poortinga, Simon J. Harrison
Journal: Cancer Discovery (2019)

RNA polymerase I (Pol I) transcription of ribosomal RNA genes (rDNA) is tightly regulated downstream of oncogenic pathways, and its dysregulation is a common feature in cancer. We evaluated CX-5461, the first-in-class selective rDNA transcription inhibitor, in a first-in-human, phase I dose-escalation study in advanced hematologic cancers. Administration of CX-5461 intravenously once every 3 weeks to 5 cohorts determined an MTD of 170 mg/m2, with a predictable pharmacokinetic profile. The dose-limiting toxicity was palmar-plantar erythrodysesthesia; photosensitivity was a dose-independent adverse event (AE), manageable by preventive measures. CX-5461 induced rapid on-target inhibition of rDNA transcription, with p53 activation detected in tumor cells from one patient achieving a clinical response. One patient with anaplastic large cell lymphoma attained a prolonged partial response and 5 patients with myeloma and diffuse large B-cell lymphoma achieved stable disease as best response. CX-5461 is safe at doses associated with clinical benefit and dermatologic AEs are manageable. SIGNIFICANCE: CX-5461 is a first-in-class selective inhibitor of rDNA transcription. This first-in-human study establishes the feasibility of targeting this process, demonstrating single-agent antitumor activity against advanced hematologic cancers with predictable pharmacokinetics and a safety profile allowing prolonged dosing. Consistent with preclinical data, antitumor activity was observed in TP53 wild-type and mutant malignancies.This article is highlighted in the In This Issue feature, p. 983.
COMPUTER-AIDED DIAGNOSIS (CAD) BASED ON CONVOLUTIONAL NEURAL NETWORK (CNN) SYSTEM USING ARTIFICIAL INTELLIGENCE (AI) FOR COLORECTAL POLYP CLASSIFICATION
Authors: Y Komeda, H Handa, R Matsui, H Kashida, T Watanabe, T Sakurai, M Kudo
Journal: Endoscopy (2019)

Computer-aided diagnosis (CAD) is becoming a next-generation tool for the diagnosis of human disease. CAD for colon polyps has been suggested as a particularly useful tool for trainee colonoscopists, as the use of a CAD system avoids the complications associated with unnecessary endoscopic resections. In addition to conventional CAD, a convolutional neural network (CNN) system utilizing artificial intelligence (AI) has been developing rapidly over the past 5 years. We firstly reported to generate a unique CNN-CAD system with an AI function that studied endoscopic images extracted from movies obtained with colonoscopes used in routine examinations (Komeda Y, Handa H et al Oncology 2017). Here, we attempted a pilot study of this novel CNN-CAD system for the diagnosis of colon polyps.
ENDOSCOPIC MANAGEMENT OF PANCREATIC FLUID COLLECTIONS (PFC): A SINGLE CENTRE EXPERIENCE WITH LUMEN APPOSING METAL STENTS (LAMS)
Authors: S Rizza, P Cortegoso Valdivia, L Venezia, CG De Angelis
Journal: Endoscopy (2019)

PFC may require drainage in case of persistent symptoms, infection or rapid increase in size. The endoscopic management is challenging and the appearance of LAMS could overcome some limitations of surgical and percutaneous drainage, such as leakage and migration.
Abstract 15845: Serum Uromodulin Predicts Mortality Independently From the Presence of Type 2 Diabetes
Authors: Andreas Leiherer, Axel Muendlein, Christoph H Saely, Janine Ebner, Eva-Maria Brandtner, Alexandra Schuler, Peter Schwerzler, Arthur Mader, Karl-Martin Ebner, Peter Fraunberger, Heinz Drexel
Journal: Circulation (2017)

Introduction: Uromodulin is produced exclusively by the kidneys and present in urine and blood. Low serum uromodulin has recently been demonstrated to be associated with chronic kidney disease and ...
Reply to Wei: Are Rural Residence and Poverty Independent Risk Factors for Chronic Obstructive Pulmonary Disease in the United States?
Authors: Sarath Raju, Corinne A. Keet, Meredith C. McCormack
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

obstructive pulmonary disease among nonsmokers and eversmokers.In their study, Raju and colleagues used multivariate models adjusted for age, sex, race/ethnicity, region of residence, smoking duration, community poverty, urban/rural status, census-level data on the use of solid fuels in homes and the percentage of inhabitants in occupations associated with lung disease, and individual socioeconomic factors.However, some important factors that may affect the incidence of chronic obstructive pulmonary disease were not described in detail and seemed to be ignored in the study, such as FEV 1 (2) and the body mass index (3).It is quite possible that if the authors had adjusted for these factors in their multivariate models, they would have drawn a different conclusion.
A Troubling Court Decision for Reproductive Rights
Authors: Dov Fox, Eli Y. Adashi, I. Glenn Cohen
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
68Ga-DOTA-Exendin PET-MRI Fusion Imaging in a Case of Insulinoma
Authors: Apurva Sood, Rajender Kumar Basher, Mandeep Kang, Jaya Shukla, Arunanshu Behera, Rama Walia, Rithambhra Nada, Bhagwant Rai Mittal, Anish Bhattacharya
Journal: Clinical Nuclear Medicine (2019)

Abstract Persistent hyperinsulinemic hypoglycemia in adults is most commonly caused by insulinomas, which pose a diagnostic challenge to physicians, surgeons, and radiologists and require multimodality imaging for precise localization and staging. PET tracers such as 18 F-FDOPA and glucagon-like peptide 1 receptor analogs have been used for imaging insulinomas. Glucagon-like peptide 1 receptor analogs have recently shown promising results in preoperative localization of these tumors, as all insulinomas express glucagon-like peptide 1 receptors. 68 Ga-DOTA-Exendin PET and MRI done in the present case helped in precise localization and management of the culprit lesion, whereas contrast-enhanced CT and 18 F-FDOPA PET failed to do so.
THE ROLE OF COLON CAPSULE ENDOSCOPY IN COLORECTAL CANCER SCREENING: A SYSTEMATIC REVIEW
Authors: FER Vuik, SAV Nieuwenburg, C Spada, C Senore, EJ Kuipers, MCW Spaander
Journal: Endoscopy (2019)

Colorectal cancer (CRC) screening programs have been implemented in many countries in order to decrease CRC incidence and mortality. Primary colonoscopy (OC) and fecal immunochemical test (FIT) are the most commonly used screening modalities. An alternative screening instrument is colon capsule endoscopy (CCE). Although the accuracy has already been proven, information on the performance of CCE in a screening population remains scarce. This is the first systematic review on the role of CCE as a CRC screening tool.
CONSCIOUS SEDATION FOR ENDOSCOPIC ULTRASONOGRAPHY WITH FINE NEEDLE ASPIRATION IS EFFECTIVE AND WELL-TOLERATED
Authors: D Christodoulou, A Skamnelos, C Lamouri, S Kartsoli, A Kavvadias, V Theopistos, N Tzampouras
Journal: Endoscopy (2019)

Endoscopic ultrasonography (EUS) is an important procedure for the diagnosis of pancreatic disorders allowing fine-needle aspiration (FNA). We aimed to investigate the efficacy and tolerance of the procedure in patients who received only conscious sedation.
Using economic evidence to support policy decisions to fund interventions for non-communicable diseases
Authors: Melanie Bertram, Nick Banatvala, Alexey Kulikov, Itziar Belausteguigoitia, Rosa Sandoval, Anselm Hennis, Douglas Webb, Dudley Tarlton
Journal: BMJ (2019)

Economic analysis of interventions to reduce non-communicable diseases can encourage countries to increase investment, say Melanie Bertram and colleagues
Airway Bacterial Load and Inhaled Antibiotic Response in Bronchiectasis
Authors: Oriol Sibila, Elena Laserna, Amelia Shoemark, Holly R. Keir, Simon Finch, Ana Rodrigo-Troyano, Lidia Perea, Mike Lonergan, Pieter C. Goeminne, James D. Chalmers
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: The principal underlying inhaled antibiotic treatment in bronchiectasis is that airway bacterial load drives inflammation, and therefore antibiotic treatment will reduce symptoms. Objectives: To determine the relationship between bacterial load and clinical outcomes, assess the stability of bacterial load over time, and test the hypothesis that response to inhaled antibiotics would be predicted by baseline bacterial load. Methods: We performed three studies. Studies 1 and 2 were prospective studies including adults with bronchiectasis. Study 3 was a post hoc analysis of a randomized trial of inhaled aztreonam. A priori patients were divided into low (<105 cfu/g), moderate (105-106 cfu/g), and high bacterial load (≥107 cfu/g) using quantitative sputum culture. Measurements and Main Results: Bacterial load was a stable trait associated with worse quality of life and more airway inflammation in studies 1, 2, and 3. In study 3, patients with high bacterial load showed an improvement in the primary endpoint (Quality of Life-Bronchiectasis-Respiratory Symptoms Score at Week 4) in favor of aztreonam (mean difference of 9.7 points; 95% confidence interval, 3.4-16.0; P = 0.003). The proportion of patients who achieved an increase above the minimum clinically important difference was higher in the aztreonam group at Week 4 (63% vs. 37%; P = 0.01) and at Week 12 (62% vs. 38%; P = 0.01) only in high bacterial load patients. Conclusions: Improvement of quality of life with inhaled aztreonam was only evident in patients with high bacterial load. Bacterial load may be a useful biomarker of severity of disease and treatment response.
Treachery on the Rocks in the Pediatric Intensive Care Unit—Reply
Authors: Fernando M. de Benedictis
Journal: JAMA Pediatrics (2019)

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
Tissue patrol by resident memory CD8+ T cells in human skin
Authors: Feline E. Dijkgraaf, Tiago R. Matos, Mark Hoogenboezem, Mireille Toebes, David W. Vredevoogd, Marjolijn Mertz, Bram van den Broek, Ji-Ying Song, Marcel B. M. Teunissen, Rosalie M. Luiten, Joost B. Beltman, Ton N. Schumacher
Journal: Nature Immunology (2019)
Rituximab as Maintenance Treatment for Systemic Lupus Erythematosus: A Multicenter Observational Study of 147 Patients
Authors: Matthias A. Cassia, Federico Alberici, Rachel B. Jones, Rona M. Smith, Giovanni Casazza, Maria L. Urban, Giacomo Emmi, Gabriella Moroni, Renato A. Sinico, Piergiorgio Messa, Frances Hall, Augusto Vaglio, Maurizio Gallieni, David R. Jayne
Journal: Arthritis & Rheumatology (2019)

Objective The efficacy of rituximab (RTX) in systemic lupus erythematosus (SLE) is a subject of debate. This study was undertaken to investigate the outcomes of RTX treatment in a European SLE cohort, with an emphasis on the role of RTX as a maintenance agent. Methods All patients with SLE who were receiving RTX as induction therapy in 4 centers were included. Patients who received a single course of RTX and those who received RTX maintenance treatment (RMT) were followed up after treatment. Disease flares during the follow‐up period were defined as an increase in disease activity and the number or dose of immunosuppressive drugs. Results Of 147 patients, 27% experienced treatment failure at 6 months. In a multivariate analysis, a low number of previous immunosuppressive therapies ( P = 0.034) and low C4 levels ( P = 0.008) reduced the risk of treatment failure. Eighty patients received RMT over a median of 24.5 months during which 85 relapses, mainly musculoskeletal, were recorded (1.06 per patient). At the time of the last RTX course, 84% of the patients were in remission. Twenty‐eight (35%) of 80 patients never experienced a flare during RMT and had low damage accrual. Active articular disease at the time of the first RTX administration was associated with a risk of flare during RMT ( P = 0.011). After RMT, relapse‐free survival was similar to that in patients receiving a single RTX course ( P = 0.72). Conclusion RMT is a potential treatment option for patients with difficult‐to‐treat disease. Relapses occur during RMT and are more likely in those with active articular disease at the time of the first RTX administration. Relapse risk after RMT remains high and apparently comparable to that seen after a single RTX course.
IMPACT OF EUS-FNB FROM PERITONEAL LESIONS FOR AVOIDING DIAGNOSTIC LAPAROSCOPY: A PROSPECTIVE COHORT STUDY (THE IMPALA STUDY)
Authors: T Orprayoon, P Kongkam, N Sirisub, N Klaikaew, A Sanpawat, W Ridtitid, P Angsuwatcharakon, P Kullavanijaya, R Rerknimitr
Journal: Endoscopy (2019)

To prospectively study impact and amount of tissue for immunohistochemical staining (IHCS) of EUS-FNB from peritoneal lesions.
Letter to the Editor: Bone Health in Nonalcoholic Fatty Liver Disease: A Mechanistic Insight
Authors: Toshihiro Sugiyama
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. To the Editor: In their recent meta‐analysis of eight observational studies including a total of 632 children (mean age 13 years, ~55% male, and mean body mass index 30 kg/m2) that assessed association between nonalcoholic fatty liver disease (NAFLD) and areal bone mineral density (aBMD), Mantovani et al. found that age‐matched and sex‐matched aBMD z scores decreased with the progress of NAFLD, independently of body mass index.1 By contrast, the authors' previous meta‐analysis of 12 observational studies including a total of 30,041 adults (mean age 58 years, 63% female, and mean body mass index 26 kg/m2) on this topic showed that NAFLD did not influence aBMD but increased osteoporotic fracture incidence, independently of age, sex, and body mass index.2 Here, I would like to introduce one reasonable theory3 that is useful to interpret the noteworthy discrepancy in aBMD between children and adults. A chronic disease is potentially linked to osteoporosis and sarcopenia because many chronic diseases generally impair physical activity that could weaken the skeleton and cause minor trauma such as a fall; it can be therefore hypothesized that a chronic disease or a drug used in a chronic condition might be "indirectly" associated with osteoporotic fractures.3 Consequently, I fully agree with the authors' suggestion1 that an increase in physical activity is highly expected to improve not only NAFLD but also bone health. In NAFLD, the possible involvement of physical inactivity seems to be supported, for example, by the association of fat content between liver and bone marrow discussed by the authors1 on the basis of the relationship between bone marrow adiposity and physical inactivity.4 The aforementioned discrepancy in aBMD1 could reflect that skeletal response to physical activity during growth is obviously higher than that during aging, whereas the increased incidence of osteoporotic fractures independently of aBMD in adults with NAFLD2 might be associated with an increased risk of falls resulting from physical inactivity. Finally, I would also like to point out that, regarding physical activity, the appropriate adjustment of skeletal effects in future observational studies could require its measurement using accelerometers according to fundamental rules of mechanical strain‐related stimulus5; for example, bones normally respond to high‐impact and dynamic mechanical loading through resultant strain (i.e., elastic deformation), but their responses attenuate with continuation of the repeated skeletal loading.