tbuckley/cabot-search huggingface dataset:
Designer Receptors Exclusively Activated by Designer Drugs Approach to Treatment of Sleep-disordered Breathing
Authors: Thomaz Fleury Curado, Huy Pho, Carla Freire, Mateus R. Amorim, Jordi Bonaventura, Lenise J. Kim, Rachel Lee, Meaghan E. Cabassa, Stone R. Streeter, Luiz G. Branco, Luiz U. Sennes, Kenneth Fishbein, Richard G. Spencer, Alan R. Schwartz, Michael J. Brennick, Michael Michaelides, David D. Fuller, Vsevolod Y. Polotsky
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Obstructive sleep apnea is recurrent upper airway obstruction caused by a loss of upper airway muscle tone during sleep. The main goal of our study was to determine if designer receptors exclusively activated by designer drugs (DREADD) could be used to activate the genioglossus muscle as a potential novel treatment strategy for sleep apnea. We have previously shown that the prototypical DREADD ligand clozapine-N-oxide increased pharyngeal diameter in mice expressing DREADD in the hypoglossal nucleus. However, the need for direct brainstem viral injections and clozapine-N-oxide toxicity diminished translational potential of this approach, and breathing during sleep was not examined.Objectives: Here, we took advantage of our model of sleep-disordered breathing in diet-induced obese mice, retrograde properties of the adeno-associated virus serotype 9 (AAV9) viral vector, and the novel DREADD ligand J60.Methods: We administered AAV9-hSyn-hM3(Gq)-mCherry or control AAV9 into the genioglossus muscle of diet-induced obese mice and examined the effect of J60 on genioglossus activity, pharyngeal patency, and breathing during sleep.Measurements and Main Results: Compared with control, J60 increased genioglossus tonic activity by greater than sixfold and tongue uptake of 2-deoxy-2-[18F]fluoro-d-glucose by 1.5-fold. J60 increased pharyngeal patency and relieved upper airway obstruction during non-REM sleep.Conclusions: We conclude that following intralingual administration of AAV9-DREADD, J60 can activate the genioglossus muscle and improve pharyngeal patency and breathing during sleep.
Serum NT/CT SIRT1 ratio reflects early osteoarthritis and chondrosenescence
Authors: George Batshon, Jinan Elayyan, Omar Qiq, Eli Reich, Louisa Ben-Aderet, Leonid Kandel, Amir Haze, Jürgen Steinmeyer, Veronique Lefebvre, Hong Zhang, Jennifer Elisseeff, Yves Henrotin, Ali Mobasheri, Mona Dvir-Ginzberg
Journal: Annals of the Rheumatic Diseases (2020)

Previous work has established that the deacetylase sirtuin-1 (SIRT1) is cleaved by cathepsin B in chondrocytes subjected to proinflammatory stress, yielding a stable but inactive N-terminal (NT) polypeptide (75SIRT1) and a C-terminal (CT) fragment. The present work examined if chondrocyte-derived NT-SIRT1 is detected in serum and may serve as an investigative and exploratory biomarker of osteoarthritis (OA).
Peroral endoscopic tunneling for restoration of esophagus in a patient with a post-radiation post-cricoid complete esophageal obstruction
Authors: Amol Bapaye, Parag Dashatwar, Siddharth Dharamsi, Rajendra Pujari
Journal: Endoscopy (2020)

Peroral endoscopic tunneling for restoration of esophagus (POETRE) is a novel third-space endoscopy procedure that has been reported for the treatment of complete esophageal obstruction [1] [2] [3]. To date, POETRE has been described only for mid-esophageal strictures. This case demonstrates the use of POETRE in a patient with a post-cricoid cervical complete esophageal obstruction.
Combined ERCP and endoscopic ultrasonography: a new treatment for rare hemorrhage from a duodenal papillary vascular malformation
Authors: Jingbo Yang, Yuqian Zhou
Journal: Endoscopy (2020)

Vascular malformation is the main cause of gastrointestinal bleeding, especially in patients with hemorrhage of unknown origin, accounting for approximately 10 % – 40 % of cases [1]. Endoscopic treatment is common; techniques include epinephrine injection [2], contact coagulation [3], and band ligation [4]. However, hemorrhage from a duodenal papillary vascular malformation is rare and challenging to treat; it has always been treated with papillectomy [5]. We present a new treatment using endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasonography (EUS) for cases of this kind.
Methadone for Opioid Use Disorder—Decades of Effectiveness but Still Miles Away in the US
Authors: Paul J. Joudrey, E. Jennifer Edelman, Emily A. Wang
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Hyperglycaemia is associated with impaired muscle signalling and aerobic adaptation to exercise
Authors: Tara L. MacDonald, Pattarawan Pattamaprapanont, Prerana Pathak, Natalie Fernandez, Ellen C. Freitas, Samar Hafida, Joanna Mitri, Steven L. Britton, Lauren G. Koch, Sarah J. Lessard
Journal: Nature Metabolism (2020)
Therapeutic antisense oligonucleotides for movement disorders
Authors: Epaminondas Doxakis
Journal: Medicinal Research Reviews (2020)

Abstract Movement disorders are a group of neurological conditions characterized by abnormalities of movement and posture. They are broadly divided into akinetic and hyperkinetic syndromes. Until now, no effective symptomatic or disease‐modifying therapies have been available. However, since many of these disorders are monogenic or have some well‐defined genetic component, they represent strong candidates for antisense oligonucleotide (ASO) therapies. ASO therapies are based on the use of short synthetic single‐stranded ASOs that bind to disease‐related target RNAs via Watson–Crick base‐pairing and pleiotropically modulate their function. With information arising from the RNA sequence alone, it is possible to design ASOs that not only alter the expression levels but also the splicing defects of any protein, far exceeding the intervention repertoire of traditional small molecule approaches. Following the regulatory approval of ASO therapies for spinal muscular atrophy and Duchenne muscular dystrophy in 2016, there has been tremendous momentum in testing such therapies for other neurological disorders. This review article initially focuses on the chemical modifications aimed at improving ASO effectiveness, the mechanisms by which ASOs can interfere with RNA function, delivery systems and pharmacokinetics, and the common set of toxicities associated with their application. It, then, describes the pathophysiology and the latest information on preclinical and clinical trials utilizing ASOs for the treatment of Parkinson′s disease, Huntington′s disease, and ataxias 1, 2, 3, and 7. It concludes with issues that require special attention to realize the full potential of ASO‐based therapies.
Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study
Authors: Meletios Dimopoulos, Hang Quach, Maria-Victoria Mateos, Ola Landgren, Xavier Leleu, David Siegel, Katja Weisel, Hui Yang, Zandra Klippel, Anita Zahlten-Kumeli, Saad Z Usmani
Journal: The Lancet (2020)
Typical Acute Traumatic Fracture Healing in an 83-Year-Old Man Undergoing 223Ra Treatment for Prostatic Cancer Bone Metastases
Authors: Thaís Minekawa, Mariana Lima, André Moraes, Allan Santos, Elba Etchebehere
Journal: Clinical Nuclear Medicine (2020)

Abstract We report the case of a fracture healing after 223 Ra in an 83-year-old wheelchair-bound man with prostate castration-resistant adenocarcinoma treated due to uncontrollable pain from widespread bone metastases. The patient fractured both right tibia and fibula 15 days prior to the first 223 Ra cycle. After the first cycle, there was complete remission of his metastatic bone pain; after the second cycle, he began walking with support, which helped improve fracture healing; and after the third cycle, he presented complete mobility. Posttreatment images showed consolidated fractures. By improving metastatic bone pain with 223 Ra, consolidation of the insufficiency fracture was possible.
SIV infection duration largely determines broadening of neutralizing antibody response in macaques
Authors: Fan Wu, Ilnour Ourmanov, Andrea Kirmaier, Sivan Leviyang, Celia LaBranche, Jinghe Huang, Sonya Whitted, Kenta Matsuda, David Montefiori, Vanessa M. Hirsch
Journal: Journal of Clinical Investigation (2020)

The development of broadly neutralizing antibodies (BNAbs) in HIV infection is a result of long-term coevolutionary interaction between viruses and antibodies. Understanding how this interaction promotes the increase of neutralization breadth during infection will improve the way in which AIDS vaccine strategies are designed. In this paper, we used SIV-infected rhesus macaques as a model to study the development of neutralization breadth by infecting rhesus macaques with longitudinal NAb escape variants and evaluating the kinetics of NAb response and viral evolution. We found that the infected macaques developed a stepwise NAb response against escape variants and increased neutralization breadth during the course of infection. Furthermore, the increase of neutralization breadth correlated with the duration of infection but was independent of properties of the inoculum, viral loads, or viral diversity during infection. These results imply that the duration of infection was the main factor driving the development of BNAbs. These data suggest the importance of novel immunization strategies to induce effective NAb response against HIV infection by mimicking long-term infection.
PTU-017 An on-site endoscopy room technique to increase the diagnostic success of endoscopic ultrasound sampling
Authors: A Saifuddin, N Inayet, S Uppal, B Baburajan
Journal: Gut (2017)

Introduction  Endoscopic ultrasound (EUS) provides tissue sampling from solid and cystic upper gastrointestinal and pancreatic lesions. After a critical multidisciplinary review in 2012, our service identified a need to improve acquisition rates. The cytopathology department was not in a position to provide rapid on-site evaluation (ROSE). We therefore introduced an on-site tissue separation (OTS) technique and submitted separate cytology and core biopsy samples to the laboratory for each needle pass.  Method  This is a retrospective review of the impact of OTS on improving tissue acquisition. Samples of all solid lesions underwent OTS. Briefly, the fine needle aspiration (FNA) sample is expressed onto a clean glass slide and solid material is separated out under direct vision for histology. The liquid material remaining on the slide is prepared into a thin film and dried. It is subsequently rehydrated in the cytology department and undergoes standard staining procedures. The solid histology samples undergo standard processing techniques as for core biopsy. All of the liquid material on the slide after separation would have been lost to pathology analysis if FNA material had been directly expressed into a specimen container, as occurred previously. Therefore, in this study, the solid histopathology sample pick up rates are taken as the diagnostic rates at our centre without OTS. Our trust provides a specialist cytologist service and the two samples are reported separately. 22G or 25G needles were used and an average of three passes were performed (range 2–4).  Results  All patients who underwent EUS from 2013 to 2016 were included. A total of 557 procedures were performed by a single operator. Of these, 129 had an FNA and biopsy. Cystic lesions have been excluded. The results are summarised in the table below:  Conclusion  OTS provided a technique to analyse material that would otherwise have been lost. This is the fine material that separates out from the solid material when the samples are in formaldehyde transport media. Our technique appears to significantly increase diagnostic rates for pancreatic mass lesions and lymph node masses. Although significance is not reached for submucosal lesions and mediastinal mass lesions, it is notable that OTS increases the rate of diagnosis across the board without additional needle passes. OTS can be an option in EUS units that do not have access to rapid on-site examination (ROSE) and wish to increase tissue acquisition rates.  Disclosure of Interest  None Declared
Abstract 11382: Catheter Ablation of Atrial Fibrillation in Patients With Arrythmia Induced Cardiomyopathy
Authors: Giichi Nitta, Osamu Inaba, Yohei Tamura, Gaku Narita, Hirotaka Yano, Shunichi Kato, Toshikazu Kono, Takashi Ikenouchi, Kazuya Murata, Yasuaki Hada, Miki Kanoh, Tomomasa Takamiya, Yukihiro Inamura, Ken Negi, Akira Sato, Tsunehiro Yamato, Yutaka Matsumura, Junichi Nitta
Journal: Circulation (2019)

Introduction: Congestive heart failure (CHF) and arrythmia represented by atrial fibrillation (AF) often coexist and exacerbate each other. Arrythmia induced cardiomyopathy (AIC) is known as a reve...
Atezolizumab Plus Nab-paclitaxel in PD-L1–Positive TNBC—Letter
Authors: Sara Bravaccini, Sara Ravaioli, Maria Maddalena Tumedei, Andrea Rocca, Michela Palleschi, Maurizio Puccetti, Paola Parrella, Mattia Altini, Roberta Maltoni
Journal: Clinical Cancer Research (2020)

Narayan and colleagues summarized the results and FDA's review leading to the accelerated approval of atezolizumab in combination with paclitaxel protein-bound for the treatment of patients with unresectable, locally advanced or metastatic triplenegative breast cancer (TNBC), whose tumors express programmed death ligand 1 (PD-L1) based on trial IMpassion130 (1).The authors concluded that despite the immaturity of the overall survival data accelerated approval was appropriate taking into account the potential clinical benefit in terms of progressionfree survival in the PD-L1 expressing population.We agree with the authors that atezolizumab plus nab-paclitaxel is an important therapeutic option for patients with PD-L1 immune cell-positive metastatic TNBC.However, it must be underlined that the type of PD-L1 testing used can impact the response to treatment, resulting in potentially different effectiveness across different countries based on the platform and antibody clones adopted.We would like to underline that the barriers to overcome are the lack of standardization of the PD-L1 IHC test methods and test reimbursability.As no classical clinicopathologic features are associated with PD-L1-positivity, PD-L1 testing is mandatory for patients with advanced TNBC before starting first-line treatment (1, 2).However, it must be underlined that the type of PD-L1 testing used can impact the response to treatment, resulting in potentially different effectiveness across different countries based on the platform and antibody clones adopted.The companion diagnostic test used in the IMpassion130 to select positive patients was Roche Ventana SP142 (Ventana Medical System) PD-L1 IHC assay (2, 3).As reported by Prof. Hope Rugo at ESMO 2019, not all PD-L1 assays are equal, the SP142 portending a stronger predicting value compared to other commercially available anti-PD-L1 antibodies (4).In fact, in previous studies and in our own experience (Fig. 1), the clone SP142 displayed greater positivity in inflammatory cells than other anti-PD-L1 antibody clones, such as SP263 by Roche Ventana (Ventana) or 22C3 and 28-8 Dako antibodies (Agilent; ref. 5).In the United States, the FDA approved the VEN-TANA PD-L1 (SP142) Assay as a companion diagnostic test for selecting patients with TNBC for first-line treatment with atezolizumab, and it is now routinely used.In Europe, the lack of specific guidelines leads to discrepancies in technical and/or clinical validation procedures for PD-L1 testing, which also impacts the efficacy and cost
P49Functional deployment of ventricular conduction system in mouse during development
Authors: B. Sankova, D. Sedmera
Journal: Cardiovascular Research (2012)

Individual compartments of cardiac conduction system (CCS) became functional in order which correlates with cardiac morphogenesis. Ventricular CCS compartments mature with ventricular septation and it is accompanied by shift of activation pattern from primitive base to apex, which follows blood flow
Estimating Glomerular Filtration Rate in African American Individuals—Reply
Authors: Andrew S. Levey, Silvia M. Titan, Lesley A. Inker
Journal: JAMA Internal Medicine (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 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
AB0232 Reliability and responsiveness of the radai, a self-assessed rheumatoid arthritis disease activity index
Authors: J Fransen, A Forster, D Uebelhart, BA Michel
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The Rheumatoid Arthritis Disease Activity Index (RADAI) is a self-administered questionnaire on signs and symptoms of rheumatoid arthritis (RA). The main goal of the RADAI is to evaluate the course of RA disease activity over time. The RADAI consists of 5 items and produces a single index from 0–10; higher scores are indicating higher levels of disease activity. The RADAI has shown to be cross-sectionally valid<sup>1</sup> and responsive to clinical important worsening of disease activity.<sup>2</sup> <h3>Objectives</h3> The study objectives are: 1) to determine the test-retest reliability of the RADAI, and 2) to determine if the RADAI is responsive to clinical important improvements in disease activity, using an intervention of known efficacy (Infliximab) as external standard. <h3>Methods</h3> Until now, 12 RA patients (ACR criteria) have been included (1 male), having high or moderate disease activity (DAS28 &gt;3.2);<sup>3</sup> 10 patients already had a 6-week follow-up. The intervention consisted of treatment with Infliximab and Methotrexate, which is likely to induce a relatively large improvement after 6 weeks. The RADAI was self-administered 1 week before the first infusion with Infliximab (T0). At the first infusion (T1), the patient filled in the RADAI again and the physician assessed the DAS28. After 6 weeks (T2), the RADAI and the DAS28 were again assessed. For analysis of reliability (T0 and T1) the ICC3,1 and the Limits-of Agreement [4] were used. Responsiveness was studied by judging the change in RADAI at T2 in relation to the Limits-of-Agreement and the DAS28 response criteria.<sup>3</sup> <h3>Results</h3> The RADAI scores at T0 and T1 were mean (sd) 5.0 (1.7) and 4.8 (1.9). The mean (sd) difference was -0.2 (0.8), (paired t-test, p = 0.41). The ICC3,1 was 0.89 (p &lt; 0.05). The Upper Limit-of-Agreement was at 1.6 and the Lower at -2.0. According to the DAS28 response criteria, 3 patients were classified as having no response at T2, 3 had a moderate and 4 a good response. The change in RADAI did not exceed the Lower Limit-of-Agreement for 4 of the 7 responders. The responders had a median (range) change in RADAI of -2.1 (-0.9 to -8.0), signed rank test, p = 0.02). <h3>Conclusion</h3> The data collection is ongoing till N = 20. The first results on reliability and responsiveness are promising. However, if the Limits-of-Agreement turn out to be much wider than -1 and +1, the reliability of the RADAI should be improved. <h3>References</h3> Fransen J, <i>et al</i>. Rheumatology 2000;39(3):321–7 Fransen J, <i>et al</i>. Arthritis Rheum., in press Van Gestel AM, <i>et al</i>. Arthritis Rheum. 1998;41(10):1845–50 Bland J, Altman D. Lancet 1986;1(8476):307–10