tbuckley/cabot-search huggingface dataset:
How to Attract and Hold an Audience, A Popular Treatise on the Nature, Preparation and Delivery of Public Discourse.
Journal: JAMA (1904)

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
“Long-term outcomes of bronchial thermoplasty in subjects with severe asthma: a comparison of 3-year follow-up results from two prospective multicentre studies.” Geoffrey Chupp, Michel Laviolette, Lauren Cohn, Charlene McEvoy, Sandeep Bansal, Adrian Shifren, Sumita Khatri, G. Mark Grubb, Edmund McMullen, Racho Strauven and Joel N. Kline. Eur Respir J 2017; 50: 1700017.
Journal: European Respiratory Journal (2017)
Pathological phosphorylation of tau and TDP-43 by TTBK1 and TTBK2 drives neurodegeneration
Authors: Laura M. Taylor, Pamela J. McMillan, Nicole F. Liachko, Timothy J. Strovas, Bernardino Ghetti, Thomas D. Bird, C. Dirk Keene, Brian C. Kraemer
Journal: Molecular Neurodegeneration (2018)

Progressive neuron loss in the frontal and temporal lobes of the cerebral cortex typifies frontotemporal lobar degeneration (FTLD). FTLD sub types are classified on the basis of neuronal aggregated protein deposits, typically containing either aberrantly phosphorylated TDP-43 or tau. Our recent work demonstrated that tau tubulin kinases 1 and 2 (TTBK1/2) robustly phosphorylate TDP-43 and co-localize with phosphorylated TDP-43 in human postmortem neurons from FTLD patients. Both TTBK1 and TTBK2 were initially identified as tau kinases and TTBK1 has been shown to phosphorylate tau epitopes commonly observed in Alzheimer's disease and other tauopathies. To further elucidate how TTBK1/2 activity contributes to both TDP-43 and tau phosphorylation in the context of the neurodegeneration seen in FTLD, we examined the consequences of elevated human TTBK1/2 kinase expression in transgenic animal models of disease. We show that C. elegans co-expressing tau/TTBK1 tau/TTBK2, or TDP-43/TTBK1 transgenes in combination exhibit synergistic exacerbation of behavioral abnormalities and increased pathological protein phosphorylation. We also show that C. elegans co-expressing tau/TTBK1 or tau/TTBK2 transgenes in combination exhibit aberrant neuronal architecture and neuron loss. Surprisingly, the TTBK2/TDP-43 transgenic combination showed no exacerbation of TDP-43 proteinopathy related phenotypes. Additionally, we observed elevated TTBK1/2 protein expression in cortical and hippocampal neurons of FTLD-tau and FTLD-TDP cases relative to normal controls. Our findings suggest a possible etiology for the two most common FTLD subtypes through a kinase activation driven mechanism of neurodegeneration.
Abstract 17637: Combination Therapy With Hypothermic Target Temperature Management and Valproic Acid After Cardiac Arrest
Authors: Joosuk Oh, Tulasi Jinka, Xiaodan Ren, Robert W Neumar
Journal: Circulation (2015)

Introduction: While hypothermic target temperature management (HTTM) has been regarded as a reliable strategy for post-cardiac arrest treatment, there are no pharmacologic agents proved to be neuroprotective against post-cardiac arrest brain injury. In recent years, many studies have shown that valproic acid (VPA), a well-known antiepileptic drug, is neuroprotective against various brain insults. VPA inhibits histone deacetylase activity and causes hyperacetylation of histones, followed by transcriptional activation of anti-apoptotic genes. In this study we tested the hypothesis that combination therapy of hypothermia and VPA could enhance neuroprotection and improve outcome. Methods: Male Long-Evans rats were instrumented for continuous telemetric EEG recording with video and then subjected to 8-minute asphyxia cardiac arrest. Nine rats that achieved the return of spontaneous circulation (ROSC) were allocated into the following 3 groups. Controlled normothermia (N group, 36.5-37.5 °C, n=3), HTTM (H group, 32-33 °C for 24 hours, n=3) and HTTM with VPA administration (HV group, 32-33 °C for 24 hours, 300 mg/kg, IV, n=3). Three-day survival, best achieved neurologic function score (NFS), the number of seizure event was compared between the 3 groups. Results: The 3-day survival was 33.3% in N group, 33.3 % in H group and 100 % in HV group (p=0.12). The best NFS averaged 263.33 ± 36.67 in N group, 380 ± 64.29 in H group and 468.33 ± 15.90 in HV group (p=0.13). The total number of seizure events in each group averaged 0.33 ± 0.33 in N group, 4.33 ± 2.96 in H group, 0 in HV group (p=0.20). Conclusions: These early results suggest that the combination of HTTM and VPA is a promising strategy that could result in synergistic neuroprotection after cardiac arrest.
Prevalence of Asthma, Asthma Attacks, and Emergency Department Visits for Asthma Among Working Adults — National Health Interview Survey, 2011–2016
Authors: Jacek M. Mazurek, Girija Syamlal
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

In 2010, an estimated 8.2% of U.S. adults had current asthma, and among these persons, 49.1% had had an asthma attack during the past year (1). Workplace exposures can cause asthma in a previously healthy worker or can trigger asthma exacerbations in workers with current asthma* (2). To assess the industry- and occupation-specific prevalence of current asthma, asthma attacks, and asthma-related emergency department (ED) visits among working adults, CDC analyzed 2011-2016 National Health Interview Survey (NHIS) data for participants aged ≥18 years who, at the time of the survey, were employed at some time during the 12 months preceding the interview. During 2011-2016, 6.8% of adults (11 million) employed at any time in the past 12 months had current asthma; among those, 44.7% experienced an asthma attack, and 9.9% had an asthma-related ED visit in the previous year. Current asthma prevalence was highest among workers in the health care and social assistance industry (8.8%) and in health care support occupations (8.8%). The increased prevalence of current asthma, asthma attacks, and asthma-related ED visits in certain industries and occupations might indicate increased risks for these health outcomes associated with workplace exposures. These findings might assist health care and public health professionals in identifying workers in industries and occupations with a high prevalence of current asthma, asthma attacks, and asthma-related ED visits who should be evaluated for possible work-related asthma. Guidelines intended to promote effective management of work-related asthma are available (2,3).
伊赛珠单抗对银屑病的治疗:三项双盲对照研究的综合药效分析(发现-1、发现-2、发现-3)
Authors: K.A. Papp, C.L. Leonardi, A. Blauvelt, K. Reich, N.J. Korman, M. Ohtsuki, C. Paul, S. Ball, G.S. Cameron, J. Erickson, L. Zhang, L. Mallbris, C.E.M. Griffiths
Journal: British Journal of Dermatology (2018)

银屑病是一种皮肤病,会导致皮肤形成发红、瘙痒、干燥、增厚的鳞屑。大约2~4%的西方人群患有银屑病。我们测试了伊赛珠单抗(一种经证实的银屑病药物)在改善银屑病症状方面是否优于安慰剂(一种无活性药物)或依那西普(另一种经证实的银屑病药物)。来自21个国家/地区的患者参与了测试。我们结合了3组不同研究的数据:患者每两周服用80mg伊赛珠单抗、每四周服用80mg伊赛珠单抗、每周服用两次50mg依那西普(仅在两种研究中)或安慰剂。服用伊赛珠单抗的患者的初始剂量为160mg。我们根据治疗12周后被医生评为只有很少或没有银屑病的患者的百分比来衡量银屑病的改善情况[sPGA(0、1)]。从初始(基线)银屑病评价的基础上改善了75%以上的患者[PASI 75]也被视为从治疗中获益。我们发现,按照获得上述结果的患者的百分比来衡量的话[sPGA 0、1和PASI 75],伊赛珠单抗治疗的效果要优于安慰剂和依那西普。早在第一周,服用伊赛珠单抗的患者情况就已好于服用安慰剂或依那西普的患者。患者在服用依那西普或伊赛珠单抗时会出现一些副作用,但约有95%的患者仍留在研究中。在最初的12周里,每两周服用伊赛珠单抗的患者情况要好于每四周服用伊赛珠单抗的患者。服用伊赛珠单抗来治疗银屑病的患者出现良好反应的几率较大。
Localization of Pulmonary Ground-Glass Opacities with Folate Receptor–Targeted Intraoperative Molecular Imaging
Authors: Jarrod D. Predina, Andrew Newton, Christopher Corbett, Leilei Xia, Lydia Frenzel Sulyok, Michael Shin, Charuhas Deshpande, Leslie Litzky, Eduardo Barbosa, Philip S. Low, John C. Kucharczuk, Sunil Singhal
Journal: Journal of Thoracic Oncology (2018)

PurposeIntraoperative localization and resection of ill-defined pulmonary ground-glass opacities (GGOs) during minimally invasive pulmonary resection is technically challenging. Current preoperative techniques to facilitate localization of GGOs include microcoil and hook wire placement, both of which have logistic limitations, carry safety concerns, and do not help with margin assessment. In this clinical trial, we explored an alternative method involving near-infrared molecular imaging with a folate receptor–targeted agent, OTL38, to improve localization of GGOs and confirmation of resection margins.MethodsIn a human trial, 20 subjects with pulmonary GGOs who were eligible for video-assisted thoracoscopic surgery (VATS) resection received 0.025 mg/kg of OTL38 before the resection. The primary objectives were to (1) determine whether use of OTL38 allows safe localization of GGOs and assessment of margins during VATS and (2) determine patient, radiographic, and histopathologic variables that predict the amount of fluorescence during near-infrared imaging.ResultsWe observed no toxicity. Of the 21 GGOs, 20 accumulated OTL38 and displayed fluorescence upon in situ or back table evaluation. Intraoperatively, near-infrared imaging localized 15 of 21 lesions whereas VATS alone localized 10 of 21 (p = 0.05). The addition of molecular imaging affected care of nine of 21 subjects by improving intraoperative localization (n = 6) and identifying close margins (n = 3). This approach was most effective for subpleural lesions measuring less than 2 cm. For lesions deeper than 1.5 cm from the pleural surface, intraoperative localization using fluorescent feedback was limited.ConclusionsThis approach provides a safe alternative for intraoperative localization of small, peripherally located pulmonary lesions. In contrast to alternative localization techniques, use of OTL38 also allows confirmation of adequate margins. Future studies will compare this approach to alternative localization techniques in a clinical trial.
Abstract MP06: Circulating Fatty Acids in the De Novo Lipogenesis Pathway and Total and Cause-Specific Mortality Among Older Adults: The Cardiovascular Health Study
Authors: Heidi T Lai, Marcia C de Oliveira Otto, Jason H Wu, Yujin Lee, Xiaoling Song, Irena B King, Bruce M Psaty, Rozenn N Lemaitre, Barbara McKnight, David S Siscovick, Dariush Mozaffarian
Journal: Circulation (2018)

De novo lipogenesis (DNL) is a crucial metabolic pathway that convert excess carbohydrates to fatty acids (FA) for energy and storage. Both DNL and the synthesized FA have biologic effects that may affect cardiometabolic risk. Yet, the association between DNL FA and mortality and CVD are not well-established in older adults, especially using serial biomarkers which objectively allow more accurate estimates of long-term FA exposure, as well as changes over time. We investigated the longitudinal association between serial levels of circulating DNL FA and total mortality, cause-specific mortality, and total CVD among 3,869 older U.S. adults (mean age 75 y) free of prevalent CVD at baseline. Levels of plasma phospholipid palmitic (16:0), palmitoleic (16:1n-7), stearic (18:0), and oleic acid (18:1n-9) were quantified at baseline, year 6, and year 13. Outcomes were centrally adjudicated using multiple sources. Risk was assessed in multivariable-adjusted Cox models with time-varying FA and covariates. During 46,974 person-years, 3,227 deaths (including 1,131 from CVD, 2,096 from non-CVD causes) and 1,754 incident total CVD events occurred. After multivariable-adjustment, cumulative levels of 16:0, 16:1n-7 and 18:1n-9 were each positively, while 18:0 was inversely, associated with total mortality ( Table ). Associations were generally similar for CVD vs. non-CVD mortality, and vs. total incident CVD (not shown). Among non-CVD deaths, associations for dementia and pulmonary deaths were generally similar to total mortality; while only 16:0 and 18:1n-9 were positively associated with cancer mortality. Higher long-term levels of circulating 16:0, 16:1n-7 and 18:1n-9 were positively, while 18:0 was inversely, associated with total mortality in older adults. Novel findings highlight the potential relevance of DNL later in life, and the need for further experimental research and interventions on the relevant underlying physiology and long-term health effects of DNL FA. Findings for FA changes over time to be presented.
Acute heart failure: lessons learned, roads ahead
Authors: Roberto Ferrari, Héctor Bueno, Ovidiu Chioncel, John G. Cleland, Wendy Gattis Stough, Maddalena Lettino, Marco Metra, John T. Parissis, Fausto Pinto, Piotr Ponikowski, Frank Ruschitzka, Luigi Tavazzi
Journal: European Journal of Heart Failure (2018)
67 Conscious sedation practice in ERCP: a single centre review
Authors: A Monged, D Cheriyan
Journal: Gut (2017)

Background  ERCP is a complex endoscopic procedure which requires adequate sedation to increase patient tolerance and improve procedural success. Achieving the desired level of conscious sedation which allows for satisfactory completion of a therapeutic ERCP can be challenging. Few guidelines exist to support appropriate conscious sedation practice in ERCP.  Aim  The aim of the study is to evaluate conscious sedation practices for ERCP in a single, tertiary referral centre in Dublin, Ireland.  Method  A retrospective analysis was conducted for ERCPs performed from October 2014 to October 2016. ENDORAAD software was utilised to collect data.  Results  904 patients had ERCPs in Beaumont hospital under conscious sedation between 2014-2016. The median age was 65.6 (range 19-89). 419 were ≥70 years. The most frequently used benzodiazepine and opiate used for ERCPs in our review was diazepam (89% of all patients), and Fentanyl (96% of all patients). 51% of patients  Conclusion  The use of more than one benzodiazepine or opiate was more common in patients
Action to address the household economic burden of non-communicable diseases
Authors: Stephen Jan, Tracey-Lea Laba, Beverley M Essue, Adrian Gheorghe, Janani Muhunthan, Michael Engelgau, Ajay Mahal, Ulla Griffiths, Diane McIntyre, Qingyue Meng, Rachel Nugent, Rifat Atun
Journal: The Lancet (2018)
Evaluation of lesion-based response at 12 weeks (LBR12) of treatment (Rx) in metastatic colorectal cancer (mCRC): Findings from 9,092 patients (pts) in the ARCAD database.
Authors: Fang-Shu Ou, Yiyue Lou, Eric Van Cutsem, Leonard Saltz, Hans-Joachim Schmoll, Richard M. Goldberg, Paulo Hoff, Jean-Yves Douillard, J. Randolph Hecht, Herbert Hurwitz, Cornelis J. A. Punt, Carsten Bokemeyer, Charles S. Fuchs, Eduardo Diaz-Rubio, Niall Tebbut, Alfredo Falcone, Fairooz F. Kabbinavar, Aimery De Gramont, Axel Grothey, Qian Shi
Journal: Journal of Clinical Oncology (2018)

612 Background: mCRC is a heterogeneous disease leading to possible disparate responses among lesions in a single pt. This study assesses the heterogeneity of lesion responses and evaluates the prognostic value of LBR12 and its mortality risk discrimination beyond RECIST responses. Methods: Pts with ≥ 2 lesions and no new lesions at 12 weeks (wks) were eligible. For each pt, after 12 wks of Rx, each lesion was categorized as progressive disease (L-PD: ≥20% increase in the longest diameter [LD]), partial response (L-PR: ≥30% decrease in LD), or stable disease (L-SD: neither L-PD nor L-PR). LBR12 was defined, per patient, by the combination of lesion responses: homogeneous LBR12 (L-PD, L-SD, L-PR only) and heterogeneous LBR12 (mixture of L-PD/L-SD, L-PD/L-PR, L-SD/L-PR). LBR12 and overall survival (OS) were correlated using stratified multivariate Cox models after adjusting for age, gender, and ECOG PS. Results: Among 9,092 mCRCs (Rx: chemo alone 44%; chemo + VEGF inhibitor [VEGFi] 42%; chemo + EGFR inhibitor [EGFRi] 10%) from 16 1 st -line studies. Median OS: 2.2 years. Per RECIST at 12 wks, CR 0%; PR 36.1%; SD 60.9%; PD 3.0%. Responses in 52% were heterogeneous (Table). VEGFi and EGFRi treated pts had the highest rate of L-SD/L-PR (45%) and L-PR only (22%) status, respectively. Median OS increased monotonically across pts with more L-PRs and fewer L-PDs (Table). Pts with L-SD/L-PR status, among which 51% had SD per RECIST, had longer OS than those with L-SD only status (HR adj. = .81, p adj. &lt; .0001), but shorter OS than those with L-PR only status (HR adj. = 1.46, p adj. &lt; .0001). Pts with L-PD/L-SD status, among which 71% were SD per RECIST, had shorter OS than those with L-SD only status (HR adj. = 2.22, p adj. &lt; .0001). These associations were consistent across treatment regimens. Conclusions: The lesion-based response captures the heterogeneity of within pt lesion responses and provides refinement in predicting outcome beyond RECIST response at 12 wks. [Table: see text]
Efficacy, immunogenicity, and safety evaluation of an MF59-adjuvanted quadrivalent influenza virus vaccine compared with non-adjuvanted influenza vaccine in children: a multicentre, randomised controlled, observer-blinded, phase 3 trial
Authors: Timo Vesikari, Judith Kirstein, Grace Devota Go, Brett Leav, Mary Ellen Ruzycky, Leah Isakov, Marianne de Bruijn, Janine Oberye, Esther Heijnen
Journal: The Lancet Respiratory Medicine (2018)
QAPA: a new method for the systematic analysis of alternative polyadenylation from RNA-seq data
Authors: Kevin C. H. Ha, Benjamin J. Blencowe, Quaid Morris
Journal: Genome biology (2018)

Alternative polyadenylation (APA) affects most mammalian genes. The genome-wide investigation of APA has been hampered by an inability to reliably profile it using conventional RNA-seq. We describe 'Quantification of APA' (QAPA), a method that infers APA from conventional RNA-seq data. QAPA is faster and more sensitive than other methods. Application of QAPA reveals discrete, temporally coordinated APA programs during neurogenesis and that there is little overlap between genes regulated by alternative splicing and those by APA. Modeling of these data uncovers an APA sequence code. QAPA thus enables the discovery and characterization of programs of regulated APA using conventional RNA-seq.
Integrated biology approach reveals molecular and pathological interactions among Alzheimer’s Aβ42, Tau, TREM2, and TYROBP in Drosophila models
Authors: Michiko Sekiya, Minghui Wang, Naoki Fujisaki, Yasufumi Sakakibara, Xiuming Quan, Michelle E. Ehrlich, Philip L. De Jager, David A. Bennett, Eric E. Schadt, Sam Gandy, Kanae Ando, Bin Zhang, Koichi M. Iijima
Journal: Genome Medicine (2018)

Cerebral amyloidosis, neuroinflammation, and tauopathy are key features of Alzheimer's disease (AD), but interactions among these features remain poorly understood. Our previous multiscale molecular network models of AD revealed TYROBP as a key driver of an immune- and microglia-specific network that was robustly associated with AD pathophysiology. Recent genetic studies of AD further identified pathogenic mutations in both TREM2 and TYROBP. In this study, we systematically examined molecular and pathological interactions among Aβ, tau, TREM2, and TYROBP by integrating signatures from transgenic Drosophila models of AD and transcriptome-wide gene co-expression networks from two human AD cohorts. Glial expression of TREM2/TYROBP exacerbated tau-mediated neurodegeneration and synergistically affected pathways underlying late-onset AD pathology, while neuronal Aβ42 and glial TREM2/TYROBP synergistically altered expression of the genes in synaptic function and immune modules in AD. The comprehensive pathological and molecular data generated through this study strongly validate the causal role of TREM2/TYROBP in driving molecular networks in AD and AD-related phenotypes in flies.
Another rescue mission: Does it make sense?
Authors: Piotr M. Patrzyk
Journal: Behavioral and Brain Sciences (2018)

Two misguided ideas dominate philosophical thinking on moral responsibility: (1) the idea that it obviously exists, and (2) the idea that even if it does not, it is nevertheless needed for the society to function properly. In his book, Doris (2015b) discusses the first illusion, while uncritically accepting the second. In this commentary, I question the utility of such endeavors.
Abstract 18729: Blood Pressure Trajectories, Carotid Artery Intima-Media Thickness and Left Ventricular Mass: Results From a 23-Year Longitudinal Study From Childhood to Young Adulthood
Authors: Guang Hao, Xiaoling Wang, Frank Treiber, Gregory Harshfield, Gaston Kapuku, Shaoyong Su
Journal: Circulation (2016)

Background: The aims of this study were to identify subgroups of individuals with similar trajectories in blood pressure (BP) from childhood to adulthood, and to determine the relationship of BP tr...
The clinical oncology treatment plan and summary implementation guide: An interoperable HL7 document standard to improve the quality of cancer care.
Authors: Jeremy Warner, Kevin S. Hughes, John C. Krauss, Suzanne Maddux, Peter Paul Yu, Lawrence N Shulman, Deborah Mayer, Edward P. Ambinder
Journal: Journal of Clinical Oncology (2014)

6603 Background: Cancer care is interdisciplinary and longitudinal, and increasingly depends on seamless electronic transmission of clinical data. Accurate health information exchange, using structured and unambiguous data elements, is critical for coordination of care across all phases of the cancer journey. However, sharing data across multiple clinical practices remains difficult due to lack of standardization and general incompatibility between electronic health records. There is a growing need for well-designed, oncology-specific interoperability standards. Thus, ASCO is developing standards to improve the quality of cancer care. Methods: ASCO volunteers formed a Standards Work Group (SWG), and ASCO engaged an independent consulting firm for technical work. The SWG adapted ASCO’s Breast Cancer Adjuvant Treatment Plan and Summary, originally developed as a paper-based form, for translation to an interoperable standard. The standard was developed using Health Level Seven International (HL7) Clinical Document Architecture (CDA), an ANSI-recognized standard in broad use. This required extensive input from medical and surgical oncologists, ASCO staff, and the consultants in order to define and disambiguate clinical concepts. Several concepts not represented in the Systematized Nomenclature of Medicine, Clinical Terms were added by the National Library of Medicine. Results: The HL7 Implementation Guide for CDA, Release 2: Clinical Oncology Treatment Plan and Summary, DSTU Release 1 (COTPS) was successfully balloted in May 2013 and published in late 2013. Several organizations have already expressed interest in the standard; the Athena Breast Health Network of five University of California sites has begun trial implementation. Conclusions: The COTPS is the first oncology-specific standard approved through the HL7 balloting process. Experience gained through trial implementation will continue to inform future work by the SWG. Oncology standards will improve quality by allowing efficient transmission of reliable, meaningful, and up-to-date clinical data between providers, patients, quality improvement initiatives, and registries.
The multiple functions of melatonin in regenerative medicine
Authors: Maryam Majidinia, Russel J. Reiter, Seyed Kazem Shakouri, Iraj Mohebbi, Mojgan Rastegar, Mojtaba Kaviani, Saber Ghazizadeh Darband, Rana Jahanban-Esfahlan, Seyed Mohammad Nabavi, Bahman Yousefi
Journal: Ageing Research Reviews (2018)