tbuckley/cabot-search huggingface dataset:
Acupuncture for Aromatase Inhibitor–Related Joint Pain Among Breast Cancer Patients
Authors: Jun J. Mao, John T. Farrar
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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
Targeting protein translation to prevent septic kidney injury
Authors: Sarah C. Huen
Journal: Journal of Clinical Investigation (2018)

The development of acute kidney injury (AKI) in patients with sepsis causes significant morbidity and mortality. The pathogenesis of AKI in sepsis is incompletely understood. In this issue of the JCI, Hato et al. investigate the renal translatome during bacterial sepsis and identify the global shutdown of renal protein translation mediated by the eukaryotic translation initiation factor 2-α kinase 2/eukaryotic translation initiation factor 2α (EIF2AK2/eIF2α) axis as a major pathway in mediating septic AKI. The results of this study suggest that inhibiting this pathway could be a potential therapeutic strategy for preventing septic AKI.
RNA is taking its Toll: Impact of RNA‐specific Toll‐like receptors on health and disease
Authors: Tim Vierbuchen, Karina Stein, Holger Heine
Journal: Allergy (2018)

RNA-sensing Toll-like receptors (TLRs) are often described as antiviral receptors of the innate immune system. However, the past decade has shown that the function and relevance of these receptors are far more complex. They were found to be essential for the detection of various bacterial, archaeal, and eukaryotic microorganisms and facilitate the discrimination between dead and living microbes. The cytokine and interferon response profile that is triggered has the potential to improve the efficacy of next-generation vaccines and may prevent the development of asthma and allergy. Nevertheless, the ability to recognize foreign RNA comes with a cost as also damaged host cells can release nucleic acids that might induce an inappropriate immune response. Thus, it is not surprising that RNA-sensing TLRs play a key role in various autoimmune diseases. However, promising new inhibitors and antagonists are on the horizon to improve their treatment.
Aggressive Squamous Cell Carcinoma in Organ Transplant Recipients
Authors: Joana Lanz, Jan Nico Bouwes Bavinck, Marlies Westhuis, Koen D. Quint, Catherine A. Harwood, Shaaira Nasir, Vanessa Van-de-Velde, Charlotte M. Proby, Carlos Ferrándiz, Roel E. Genders, Véronique del Marmol, Giulia Forchetti, Jürg Hafner, Domenic G. Vital, Guenther F. L. Hofbauer
Journal: JAMA Dermatology (2018)

<h3>Importance</h3> Squamous cell carcinoma (SCC) is the most frequent malignant neoplasm found in solid organ transplant recipients and is associated with a more aggressive disease course and higher risk of metastasis and death than in the general population. <h3>Objectives</h3> To report the clinicopathologic features of and identify factors associated with aggressive SCC in solid organ transplant recipients. <h3>Methods</h3> This retrospective multicentric case series included 51 patients who underwent solid organ transplantation and were found to have aggressive SCC, defined by nodal or distant metastasis or death by local progression of primary SCC. Standard questionnaires were completed by the researchers between July 18, 2005, and January 1, 2015. Data were analyzed between February 22, 2016, and July 12, 2016. <h3>Results</h3> Of the 51 participants, 43 were men and 8 were women, with a median age of 51 years (range, 19-71 years) at time of transplantation and 62 years (range, 36-77 years) at time of diagnosis of aggressive SCC. The distribution of aggressive SCC was preferentially on the face (34 [67%]) and scalp (6 [12%]), followed by the upper extremities (6 [12%]). A total of 21 tumors (41%) were poorly differentiated, with a median tumor diameter of 18.0 mm (range, 4.0-64.0 mm) and median tumor depth of 6.2 mm (range, 1.0-20.0 mm). Perineural invasion was present in 20 patients (39%), while 23 (45%) showed a local recurrence. The 5-year overall survival rate was 23%, while 5-year disease-specific survival was 30.5%. <h3>Conclusions and Relevance</h3> Results of this case series suggest that anatomical site, differentiation, tumor diameter, tumor depth, and perineural invasion are important risk factors in aggressive SCC in solid organ transplant recipients.
Evaluating the landscape of gene cooperativity with receptor tyrosine kinases in liver tumorigenesis using transposon-mediated mutagenesis
Authors: Yannan Fan, Sehrish K. Bazai, Fabrice Daian, Maria Arechederra, Sylvie Richelme, Nuri A. Temiz, Annie Yim, Bianca H. Habermann, Rosanna Dono, David A. Largaespada, Flavio Maina
Journal: Journal of Hepatology (2018)
Recurrent Genetic HLA Loss in Acute Myeloid Leukemia Relapsed after Matched Unrelated Allogeneic Hematopoietic Cell Transplant
Authors: Max Jan, Matt J Leventhal, Elizabeth A Morgan, Jordan Chase Wengrod, Anewsha Nag, Samantha D Drinan, Bruce M Wollison, Matthew D. Ducar, Aaron R. Thorner, Natasha Kekre, Vincent T. Ho, John Koreth, Corey S. Cutler, Sarah Nikiforow, Edwin P. Alyea, Joseph H. Antin, Robert J. Soiffer, Jerome Ritz, R. Coleman Lindsley, Benjamin L. Ebert
Journal: Blood (2018)
Sera from different age cohorts in Belgium show limited cross-neutralization between the mumps vaccine and outbreak strains
Authors: T. Vermeire, C. Barbezange, A. Francart, A. Hamouda, A. Litzroth, V. Hutse, L. Martens, E. Vandermarliere, S. Van Gucht
Journal: Clinical Microbiology and Infection (2018)

Mumps used to affect children between 2 and 15 years old. The mumps-measles-rubella (MMR) vaccine is available, with vaccine coverage rate of about 85% after two vaccine doses. Recently new mumps outbreaks have emerged in highly vaccinated populations; the causes for these new outbreaks are yet unknown. We tested if a difference in seroneutralizing capacity against the vaccine and wild-type viruses existed and if waning immunity could be detected.In this study, 570 serum samples (age group 2-3 years (n = 96), 8-9 years (n = 95), 13-14 years (n = 94), 18-20 years (n = 96), 24-26 years (n = 92) and 50 + years (n = 97)) in Belgium were tested in the rapid fluorescent foci inhibition test for their neutralizing capacity against the vaccine and wild-type viruses.Neutralizing antibodies against the vaccine strain were present in 84% (81/97) of the 2-3-year, 74% (70/95) of the 8-9-year, 81% (76/94) of the 13-14-year, 76% (73/96) of the 18-20-year, 67% (62/92) of the 24-26-year and 77% (75/97) of the 50+-year age group serum samples. For all age groups, only about half of these serum samples were also positive for the wild-type virus. The geometric mean titres for the vaccine and wild-type virus for all younger age groups, except for 24-26 years, were significantly different, demonstrating poor in vitro cross-neutralization.A possible contribution of antigenic differences between the genotype A and G mumps virus as well as other immune factors, in addition to lower-than-optimal vaccination coverage and waning immunity, could explain the poor in vitro cross-neutralization and should be further studied.
Annals Story Slam - Red All Over
Authors: Raphael P. Rush
Journal: Annals of Internal Medicine (2018)

Web Exclusives4 December 2018Annals Story Slam - Red All OverFREERaphael P. Rush, MDRaphael P. Rush, MDUniversity of Toronto, Mt. Sinai Hospital, and Toronto Grace Health Sciences Centre, Toronto, Ontario, Canada (R.P.R.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W18-0036 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Red All Over "Red All Over," by Raphael P. Rush, MD (Duration 5:38)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: University of Toronto, Mt. Sinai Hospital, and Toronto Grace Health Sciences Centre, Toronto, Ontario, Canada (R.P.R.)Current Author Address: Raphael P. Rush, MD; e-mail, raphael.[email protected]utoronto.ca. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 December 2018Volume 169, Issue 11Page: SS1 ePublished: 4 December 2018 Issue Published: 4 December 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.Loading ...
Hits and misses: A longitudinal examination of congruence between patient-reported quality-of-life concerns in advanced cancer and discussions with oncologists.
Authors: Karen Marie De Sola-Smith, Janice Bell, Daniel J Tancredi, Richard L Kravitz, Paul Duberstein, Ronald M. Epstein, Joshua J Fenton
Journal: Journal of Clinical Oncology (2018)

22 Background: Quality of life (QOL) support is critical to high quality advanced cancer care and is associated with improved patient outcomes, but most patients report unmet supportive care needs. To understand supportive care provision in routine oncology, we examined the agreement, or congruence, between patients’ self-reported symptoms and topics discussed with oncologists over an extended interval of care. Prior research suggests that patient-provider rapport and overall QOL influence discussion of patient concerns, therefore we estimated effects of two predictors of interest: therapeutic alliance between patient and oncologist, and global QOL. Methods: We conducted a secondary analysis of data collected in the VOICE study. Patients with advanced cancer (n=196) completed measures of symptoms (e.g., pain, nausea, emotional concerns) and QOL, as well as an inventory of topics discussed with oncologists over the prior 3 months. Data were collected at quarterly intervals for up to 48 months, resulting in 901 paired reports of patients’ symptoms and discussions with oncologists. We constructed congruence as a multinomial outcome with four discrete categories: congruence (symptom reported/discussed), unaddressed concern (symptom reported/not discussed), surveillance (symptom not reported/discussed), and no supportive care concern (symptom not reported/not discussed). We then estimated effects of global QOL and therapeutic alliance using multi-level logistic regression. Results: Congruence was most common for pain (49.9%), while emotional concerns were most likely to be unaddressed (50.5%). Higher therapeutic alliance with oncologists was associated with lower odds of unaddressed pain (OR 0.94, CI 0.89-1.00) and emotional concerns (OR 0.95, CI 0.91-0.98). Higher global QOL was associated with higher odds of unaddressed emotional concerns (OR 1.11, CI 1.02-1.20). Congruence outcomes were stable over time. Conclusions: Oncologists may improve congruence by strengthening therapeutic alliance, by more consistently discussing emotional concerns, and by prioritizing topics for discussion according to patients’ needs.
Overcoming chemotherapy resistance via simultaneous drug-efflux circumvention and mitochondrial targeting
Authors: Minglu Zhou, Lijia Li, Lian Li, Xi Lin, Fengling Wang, Qiuyi Li, Yuan Huang
Journal: Acta Pharmaceutica Sinica B (2018)

Multidrug resistance (MDR) has been considered as a huge challenge to the effective chemotherapy. Therefore, it is necessary to develop new strategies to effectively overcome MDR. Here, based on the previous research of N-(2-hydroxypropyl)methacrylamide (HPMA) polymer–drug conjugates, we designed an effective system that combined drug-efflux circumvention and mitochondria targeting of anticancer drug doxorubicin (Dox). Briefly, Dox was modified with mitochondrial membrane penetrating peptide (MPP) and then attached to (HPMA) copolymers (P-M-Dox). Our study showed that macromolecular HPMA copolymers successfully bypassed drug efflux pumps and escorted Dox into resistant MCF-7/ADR cells via endocytic pathway. Subsequently, the mitochondria accumulation of drugs was significantly enhanced with 11.6-fold increase by MPP modification. The excellent mitochondria targeting then resulted in significant enhancement of reactive oxygen species (ROS) as well as reduction of adenosine triphosphate (ATP) production, which could further inhibit drug efflux and resistant cancer cell growth. By reversing Dox resistance, P-M-Dox achieved much better suppression in the growth of 3D MCF-7/ADR tumor spheroids compared with free Dox. Hence, our study provides a promising approach to treat drug-resistant cancer through simultaneous drug efflux circumvention and direct mitochondria delivery.
Developmental Contributions of Schizophrenia Risk Alleles and Childhood Peer Victimization to Early-Onset Mental Health Trajectories
Authors: Lucy Riglin, Gemma Hammerton, Jon Heron, Stephan Collishaw, Louise Arseneault, Ajay K. Thapar, Barbara Maughan, Michael C. O’Donovan, Anita Thapar
Journal: American Journal of Psychiatry (2018)

Twin studies suggest that genetic factors contribute to continuity in mental health problems and that environmental factors are the major contributor to developmental change. The authors investigated the influence of psychiatric risk alleles on early-onset mental health trajectories and whether the trajectories were subsequently modified by exposure to childhood victimization.
Relationship between perceptions of treatment goals and psychological distress in patients with advanced cancer.
Authors: Amanda L. Jankowski, Deborah Anne Forst, Joseph Greer, Ryan David Nipp, Lauren Waldman, Jennifer S. Temel, Areej El-Jawahri
Journal: Journal of Clinical Oncology (2019)

11621 Background: Several studies have demonstrated discordance between how patients perceive their goal of treatment versus how they perceive their oncologist’s goal. Studies evaluating the extent and risk factors of this discordance are lacking. Methods: We conducted a cross-sectional study of 559 patients with incurable lung, gastrointestinal, breast, and brain cancers. We used the Perception of Treatment and Prognosis Questionnaire to assess patients’ perceptions of both their treatment goal and their oncologist’s goal and categorized responses: 1) patients who reported that both their goal and their oncologist’s goal was concordant (either to cure or not to cure); and 2) patients who reported discordant perceptions of their goal versus their oncologist’s goal. We assessed patients’ psychological distress using the Hospital-Anxiety-and-Depression-Scale and used linear regression to assess the relationship between patients’ perceptions of their treatment goal and psychological outcomes. Results: 61.7% of patients reported that both their goal and their oncologist’s goal was non-curative; 19.3% reported that both their goal and their oncologist’s goal was to cure their cancer; and 19.0% reported discordance between their goal and their perception of the oncologist’s goal. Older age (OR = 0.98, P = 0.01), non-Hispanic ethnicity (OR = 0.31, P = 0.049), and higher education (OR = 0.62, P = 0.042) were associated with lower likelihood of reporting discordant goals. Patients with discordant perceptions of their goal and their oncologist’s goal reported higher anxiety (B = 1.56, P = 0.003) compared to those who reported that both their goal and their oncologist’s goal was curative. Patients who reported both their goal and the oncologist’s goal was non-curative had higher depression symptoms (B = 1.06, P = 0.013) compared to those who reported that both their goal and the oncologists’ goal was curative. Conclusions: One-fifth of patients with advanced cancer report discrepancies between their perceptions of their own and their oncologists’ treatment goal which is associated with psychological distress. Tools are needed to identify patients at risk of cognitive dissonance about their prognosis.
Role of Intraneuronal Vesicles in the Synthesis, Storage, and Release of Noradrenaline
Authors: Lincoln Potter
Journal: Circulation Research (1967)

Adrenergic nerves have at least four special adaptations for chemical transmission: they synthesize, store, and release the neurotransmitter, noradrenaline; and they inactivate free noradrenaline by transporting it back into the nerves for degradation or reuse. This paper assesses present knowledge
Frequency, Regional Variation, and Predictors of Undetermined Cause of Death in Cardiometabolic Clinical Trials: A Pooled Analysis of 9259 Deaths in 9 Trials
Authors: Alexander C. Fanaroff, Robert Clare, Karen S. Pieper, Kenneth W. Mahaffey, Chiara Melloni, Jennifer B. Green, John H. Alexander, W. Schuyler Jones, Robert W. Harrison, Rajendra H. Mehta, Thomas J. Povsic, Humberto G. Moreira, Sana M. Al-Khatib, Matthew T. Roe, David F. Kong, Robin Mathews, Pierluigi Tricoci, Rury R. Holman, Lars Wallentin, Claes Held, Robert M. Califf, Karen P. Alexander, Renato D. Lopes
Journal: Circulation (2019)

Modern cardiometabolic clinical trials often include cardiovascular death as a component of a composite primary outcome, requiring central adjudication by a clinical events committee to classify cause of death. However, sometimes the cause of death cannot be determined from available data. The US Food and Drug Administration has indicated that this circumstance should occur only rarely, but its prevalence has not been formally assessed.Data from 9 global clinical trials (2009-2017) with long-term follow-up and blinded, centrally adjudicated cause of death were used to calculate the proportion of deaths attributed to cardiovascular, noncardiovascular, or undetermined causes by therapeutic area (diabetes mellitus/pre-diabetes mellitus, stable atherosclerosis, atrial fibrillation, and acute coronary syndrome), region of patient enrollment, and year of trial manuscript publication. Patient- and trial-level variables associated with undetermined cause of death were identified using a logistic model.Across 127 049 enrolled participants from 9 trials, there were 9259 centrally adjudicated deaths: 5012 (54.1%) attributable to cardiovascular causes, 2800 (30.2%) attributable to noncardiovascular causes, and 1447 (15.6%) attributable to undetermined causes. There was variability in the proportion of deaths ascribed to undetermined causes by trial therapeutic area, region of enrollment, and year of trial manuscript publication. On multivariable analysis, acute coronary syndrome or atrial fibrillation trial (versus atherosclerotic vascular disease or diabetes mellitus/pre-diabetes mellitus), longer time from enrollment to death, more recent trial manuscript publication year, enrollment in North America (versus Western Europe), female sex, and older age were associated with greater likelihood of death of undetermined cause.In 9 cardiometabolic clinical trials with long-term follow-up, approximately 16% of deaths had undetermined causes. This provides a baseline for quality assessment of clinical trials and informs operational efforts to potentially reduce the frequency of undetermined deaths in future clinical research.
A Transcription Factor Addiction in Leukemia Imposed by the MLL Promoter Sequence
Authors: Bin Lu, Olaf Klingbeil, Yusuke Tarumoto, Tim D.D. Somerville, Yu-Han Huang, Yiliang Wei, Dorothy C. Wai, Jason K.K. Low, Joseph P. Milazzo, Xiaoli S. Wu, Zhendong Cao, Xiaomei Yan, Osama E. Demerdash, Gang Huang, Joel P. Mackay, Justin B. Kinney, Junwei Shi, Christopher R. Vakoc
Journal: Cancer Cell (2018)
Association of Rankings With Cardiovascular Outcomes at Top-Ranked Hospitals vs Nonranked Hospitals in the United States
Authors: David E. Wang, Rishi K. Wadhera, Deepak L. Bhatt
Journal: JAMA Cardiology (2018)

The US News & World Report (USNWR) identifies the "Best Hospitals" for "Cardiology and Heart Surgery." These rankings may have significant influence on patients and hospitals.To determine whether USNWR top-ranked hospitals perform better than nonranked hospitals on mortality rates and readmission measures as well as patient satisfaction.This national retrospective study evaluated outcomes at 3552 US hospitals from 2014 to 2017.US News & World Report 2018 to 2019 Cardiology and Heart Surgery rankings (top-ranked vs nonranked hospitals).Hospital-level 30-day risk-standardized mortality and readmission rates for Medicare fee-for-service beneficiaries age 65 years or older hospitalized for 3 cardiovascular conditions: acute myocardial infarction (AMI), heart failure (HF), and coronary artery bypass grafting (CABG) as well as Hospital Consumer Assessment of Healthcare Providers and Systems patient satisfaction star ratings obtained from publicly available Centers for Medicaid and Medicare Services data.Thirty-day mortality rates at top-ranked hospitals (n = 50), compared with nonranked hospitals (n = 3502), were lower for AMI (11.9% vs 13.2%, P < .001), HF (9.5% vs 11.9%; P < .001), and CABG (2.3%vs 3.3%; P < .001). Thirty-day readmission rates at the top-ranked hospitals (n = 50) when compared with nonranked hospitals (n = 2841) were similar for AMI (16.7% vs 16.5%; P = .64) and CABG (14.1% vs 13.7%; P = .15) but higher for HF (21.0% vs 19.2%; P < .001), Finally, patient satisfaction was higher at top-ranked hospitals (n = 50) compared with nonranked hospitals (n = 3412) (3.9 vs 3.3; P < .001).We found that USNWR top-ranked hospitals for cardiovascular care had lower 30-day mortality rates for AMI, HF, and CABG and higher patient satisfaction ratings compared with nonranked hospitals. However, 30-day readmission rates were either similar (for AMI and CABG) or higher (for HF) at top-ranked compared with nonranked hospitals. This discrepancy between readmissions and other performance measures raises concern that readmissions may not be an adequate metric of hospital care quality.