tbuckley/cabot-search huggingface dataset:
Suicides Among Opioid Overdose Deaths
Authors: Paul S. Nestadt
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Assessment of Evidence About Common Infant Symptoms and Cow’s Milk Allergy
Authors: Daniel Munblit, Michael R. Perkin, Debra J. Palmer, Katie J. Allen, Robert J. Boyle
Journal: JAMA Pediatrics (2020)

Sales of specialized formula for managing cow's milk allergy (CMA) have increased, triggering concern that attribution of common infant symptoms, such as crying, vomiting, and rashes, to CMA may be leading to overdiagnosis, which could undermine breastfeeding.To understand whether CMA guideline recommendations might promote CMA overdiagnosis or undermine breastfeeding.We reviewed recommendations made in CMA guidelines and critically appraised 2 key recommendations. First, we reviewed relevant literature summarizing whether maternal or infant dietary exclusion of cow's milk is effective for managing common infant symptoms. Second, we reviewed published data on breastmilk composition and thresholds of reactivity in CMA to estimate the probability that cow's milk protein in human breastmilk can trigger symptoms in infants with CMA. We also documented the level of commercial involvement in CMA guidelines.We reviewed 9 CMA guidelines published from 2012 to 2019. Seven suggest considering CMA as a cause of common infant symptoms. Seven recommend strict maternal cow's milk exclusion for managing common symptoms in breastfed infants. We found CMA proven by food challenge affects approximately 1% of infants, while troublesome crying, vomiting, or rashes are each reported in 15% to 20% of infants. We found clinical trials do not provide consistent support for using maternal or infant cow's milk exclusion to manage common symptoms in infants without proven CMA. We estimated that for more than 99% infants with proven CMA, the breastmilk of a cow's milk-consuming woman contains insufficient milk allergen to trigger an allergic reaction. Three CMA guidelines were directly supported by formula manufacturers or marketing consultants, and 81% of all guideline authors reported a conflict of interest with formula manufacturers.Recommendations to manage common infant symptoms as CMA are not evidence based, especially in breastfed infants who are not directly consuming cow's milk. Such recommendations may cause harm by undermining confidence in breastfeeding.
Lung Cancer Screening Websites—Balanced Information vs Advertisement
Authors: Steven Woloshin, William C. Black, Barnett S. Kramer
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
Strategies of Wait-listing for Heart Transplant vs Durable Mechanical Circulatory Support Alone for Patients With Advanced Heart Failure
Authors: Anuradha Lala, John C. Rowland, Bart S. Ferket, Annetine C. Gelijns, Emilia Bagiella, Sean P. Pinney, Alan J. Moskowitz, Marissa A. Miller, Francis D. Pagani, Donna M. Mancini
Journal: JAMA Cardiology (2020)

Given the shortage of donor hearts and improvement in outcomes with left ventricular assist device (LVAD) therapy, a relevant but, to date, unanswered question is whether select patients with advanced heart failure should receive LVAD destination therapy as an alternative to heart transplant.To determine whether a strategy of LVAD destination therapy is associated with similar survival benefit as wait-listing for heart transplant with or without LVAD therapy among patients with advanced heart failure.This retrospective propensity-matched cohort analysis used data on heart transplants from the United Network for Organ Sharing registry and LVAD implants from the Interagency Registry for Mechanically Assisted Circulatory Support from January 1, 2010, to December 31, 2014. The matched LVAD destination therapy cohort included 3411 patients. Data analysis for this study was conducted from December 22, 2017, to May 24, 2019.Survival at 5 years was analyzed using Cox proportional hazards models.In total, 8281 patients had albumin level, creatinine level, and BMI data recorded and were included in the analysis. Despite propensity score matching, the 3411 patients receiving LVAD destination therapy still tended to be slightly older than the 3411 patients wait-listed for heart transplant (64.0 years [interquartile range, 55.0-70.0 years] vs 60.0 [interquartile range, 54.0-65.0 years]; P < .001), but there was no significant difference in sex (2701 men [79.2%] vs 2648 men [77.6%]; P = .13). After propensity score matching for age, sex, body mass index, renal function, and albumin level, 3411 patients were wait-listed for heart transplant. This included 1607 patients with bridge to transplant LVAD therapy and 1804 patients without LVAD. The strategy of wait-listing for heart transplant was associated with better 5-year survival than LVAD destination therapy (risk ratio, 0.42; 95% CI, 0.38-0.46) after matching and adjusting for key clinical factors. This survival advantage was associated with heart transplant (adjusted risk ratio for time-dependent transplant status, 0.27; 95% CI, 0.24-0.32).The present analysis suggests that heart transplant with or without bridge to transplant LVAD therapy was associated with superior 5-year survival compared with LVAD destination therapy among patients matched on several relevant clinical factors. Continued improvement in LVAD technology, along with prospective comparative research, appears to be needed to amend this strategy.
Association Between Visit-to-Visit Blood Pressure Variability in Early Adulthood and Myocardial Structure and Function in Later Life
Authors: Chike C. Nwabuo, Yuichiro Yano, Henrique T. Moreira, Duke Appiah, Henrique D. Vasconcellos, Queen N. Aghaji, Anthony Viera, Jamal S. Rana, Ravi V. Shah, Venkatesh L. Murthy, Norrina B. Allen, Pamela J. Schreiner, Donald M. Lloyd-Jones, João A. C. Lima
Journal: JAMA Cardiology (2020)

Long-term blood pressure (BP) variability has emerged as a reproducible measure that is associated with heart failure independent of systemic BP. Visit-to-visit BP variability may be associated with the risk of heart failure early in the life course and thus may be reflected in subclinical alterations in cardiac structure and function.To evaluate the association between visit-to-visit BP variability in early adulthood and myocardial structure and function in middle age.This cohort study used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a community-based cohort study of 5115 participants aged 18 to 30 years at baseline (year 0; March 25, 1985, to June 7, 1986) and followed up over a 30-year interval. A total of 2400 CARDIA study participants underwent evaluation at 4 field sites (Birmingham, Alabama; Oakland, California; Chicago, Illinois; and Minneapolis, Minnesota). Blood pressure was measured at 8 visits over a 25-year interval and participants received echocardiograms at year 25 (June 1, 2010, to August 31, 2011). Data analysis was conducted from June 7, 1986, to August 31, 2011.Visit-to-visit systolic and diastolic BP variability measures included SD, average real variability, and variability independent of the mean.Echocardiographic indices of myocardial structure, systolic function, and diastolic function at the year 25 examination.Of the 2400 participants, 1024 were men (42.7%) and 976 were African American (40.7%); mean (SD) age at the year 25 examination was 50.4 (3.6) years. Per 1-SD increment, greater visit-to-visit systolic BP variability independent of the mean was associated with higher left-ventricular (LV) mass index (β [SE], 2.66 [0.4] g/m2, P < .001), worse diastolic function (early peak diastolic mitral annular velocity [é]) (β [SE], -0.40 [0.1] cm/s, P < .001), higher LV filling pressures (mitral inflow velocity to early diastolic mitral annular velocity [E/é]) β [SE], 0.37 [0.1] cm/s, P < .001), and worse global longitudinal strain (β [SE], 0.17 [0.1], P = .002). Similarly, greater visit-to-visit diastolic BP variability was associated with higher LV mass index (β [SE], 3.21 [0.5] g/m2, P < .001), worse diastolic function (é: β [SE], -0.24 [0.1] cm/s [P < .001]; E/é: β [SE], 0.23 [0.1] cm/s [P < .001]), and worse global longitudinal strain (β [SE], 0.13 [0.1], P = .02). The findings remained consistent when other BP variability measures were used (SD and average real variability).In this cohort study using data from the CARDIA study, greater visit-to-visit systolic and diastolic BP variability have been associated with adverse alterations in cardiac structure as well as systolic and diastolic function independent of mean BP levels.
Online Education Is Non-Inferior to Group Education for Irritable Bowel Syndrome: A Randomized Trial and Patient Preference Trial
Authors: Perjohan Lindfors, Erland Axelsson, Karin Engstrand, Stine Störsrud, Pernilla Jerlstad, Hans Törnblom, Brjánn Ljótsson, Magnus Simrén, Gisela Ringström
Journal: Clinical Gastroenterology and Hepatology (2020)
Dual-engineered, “Trojanized” macrophages bio-modally eradicate tumors through biologically and photothermally deconstructing cancer cells in an on-demand, NIR-commanded, self-explosive manner
Authors: Lei Huang, Wenxi Yan, Bo Cai, Yu Song, Qiying Lv, Guobin Wang, Lin Wang, Zheng Wang
Journal: Biomaterials (2020)
Four Biomarkers Linked to Activation of Cluster of Differentiation 8–Positive Lymphocytes Predict Clinical Outcomes in Pediatric Acute Liver Failure
Authors: Mike A. Leonis, Alexander G. Miethke, Lin Fei, Sean Maynor, Catherine A. Chapin, Jacob J.H. Bleesing, Estella M. Alonso, Robert H. Squires
Journal: Hepatology (2020)

Immune dysregulation contributes to the pathogenesis of pediatric acute liver failure (PALF). Our aim was to identify immune activation markers (IAMs) in PALF that are associated with a distinct clinical phenotype and outcome.Among 47 PALF study participants, 12 IAMs collected ≤6 days after enrollment were measured by flow cytometry and IMMULITE assay on blood natural killer and cluster of differentiation 8-positive (CD8+ ) lymphocytes and subjected to unsupervised hierarchical analyses. A derivation cohort using 4 of 12 IAMs which were available in all participants (percent perforin-positive and percent granzyme-positive CD8 cells, absolute number of CD8 cells, soluble interleukin-2 receptor level) were sufficient to define high (n = 10), medium (n = 15), and low IAM (n = 22) cohorts. High IAM was more frequent among those with indeterminate etiology than those with defined diagnoses (80% versus 20%, P < 0.001). High IAM was associated with higher peak serum total bilirubin levels than low IAM (median peak 21.7 versus 4.8 mg/dL, P < 0.001) and peak coma grades. The 21-day outcomes differed between groups, with liver transplantation more frequent in high IAM participants (62.5%) than those with medium (28.2%) or low IAM (4.8%) (P = 0.002); no deaths were reported. In an independent validation cohort (n = 71) enrolled in a prior study, segregation of IAM groups by etiology, initial biochemistries, and short-term outcomes was similar, although not statistically significant. High serum aminotransferases, total bilirubin levels, and leukopenia at study entry predicted a high immune activation profile.Four circulating T-lymphocyte activation markers identify a subgroup of PALF participants with evidence of immune activation associated with a distinct clinical phenotype and liver transplantation; these biomarkers may identify PALF participants eligible for future clinical trials of early targeted immunosuppression.
Inference of single-cell phylogenies from lineage tracing data using Cassiopeia
Authors: Matthew G Jones, Alex Khodaverdian, Jeffrey J Quinn, Michelle M Chan, Jeffrey A Hussmann, Robert Wang, Chenling Xu, Jonathan S Weissman, Nir Yosef
Journal: Genome biology (2020)

Abstract The pairing of CRISPR/Cas9-based gene editing with massively parallel single-cell readouts now enables large-scale lineage tracing. However, the rapid growth in complexity of data from these assays has outpaced our ability to accurately infer phylogenetic relationships. First, we introduce Cassiopeia—a suite of scalable maximum parsimony approaches for tree reconstruction. Second, we provide a simulation framework for evaluating algorithms and exploring lineage tracer design principles. Finally, we generate the most complex experimental lineage tracing dataset to date, 34,557 human cells continuously traced over 15 generations, and use it for benchmarking phylogenetic inference approaches. We show that Cassiopeia outperforms traditional methods by several metrics and under a wide variety of parameter regimes, and provide insight into the principles for the design of improved Cas9-enabled recorders. Together, these should broadly enable large-scale mammalian lineage tracing efforts. Cassiopeia and its benchmarking resources are publicly available at www.github.com/YosefLab/Cassiopeia .
An Infectious cDNA Clone of SARS-CoV-2
Authors: Xuping Xie, Antonio Muruato, Kumari G. Lokugamage, Krishna Narayanan, Xianwen Zhang, Jing Zou, Jianying Liu, Craig Schindewolf, Nathen E. Bopp, Patricia V. Aguilar, Kenneth S. Plante, Scott C. Weaver, Shinji Makino, James W. LeDuc, Vineet D. Menachery, Pei-Yong Shi
Journal: Cell Host & Microbe (2020)
Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: EAGLE, a randomized, open-label phase III study
Authors: R.L. Ferris, R. Haddad, C. Even, M. Tahara, M. Dvorkin, T.E. Ciuleanu, P.M. Clement, R. Mesia, S. Kutukova, L. Zholudeva, A. Daste, J. Caballero-Daroqui, B. Keam, I. Vynnychenko, C. Lafond, J. Shetty, H. Mann, J. Fan, S. Wildsmith, N. Morsli, J. Fayette, L. Licitra
Journal: Annals of Oncology (2020)

Targeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis has demonstrated clinical benefit in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Combining immunotherapies targeting PD-L1 and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) has shown evidence of additive activity in several tumor types. This phase III study evaluated the efficacy of durvalumab (an anti-PD-L1 monoclonal antibody) or durvalumab plus tremelimumab (an anti-CTLA-4 monoclonal antibody) versus standard of care (SoC) in R/M HNSCC patients.Patients were randomly assigned to receive 1 : 1 : 1 durvalumab (10 mg/kg every 2 weeks [q2w]), durvalumab plus tremelimumab (durvalumab 20 mg/kg q4w plus tremelimumab 1 mg/kg q4w × 4, then durvalumab 10 mg/kg q2w), or SoC (cetuximab, a taxane, methotrexate, or a fluoropyrimidine). The primary end points were overall survival (OS) for durvalumab versus SoC, and OS for durvalumab plus tremelimumab versus SoC. Secondary end points included progression-free survival (PFS), objective response rate, and duration of response.Patients were randomly assigned to receive durvalumab (n = 240), durvalumab plus tremelimumab (n = 247), or SoC (n = 249). No statistically significant improvements in OS were observed for durvalumab versus SoC [hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.72-1.08; P = 0.20] or durvalumab plus tremelimumab versus SoC (HR: 1.04; 95% CI: 0.85-1.26; P = 0.76). The 12-month survival rates (95% CI) were 37.0% (30.9-43.1), 30.4% (24.7-36.3), and 30.5% (24.7-36.4) for durvalumab, durvalumab plus tremelimumab, and SoC, respectively. Treatment-related adverse events (trAEs) were consistent with previous reports. The most common trAEs (any grade) were hypothyroidism for durvalumab and durvalumab plus tremelimumab (11.4% and 12.2%, respectively), and anemia (17.5%) for SoC. Grade ≥3 trAE rates were 10.1%, 16.3%, and 24.2% for durvalumab, durvalumab plus tremelimumab, and SoC, respectively.There were no statistically significant differences in OS for durvalumab or durvalumab plus tremelimumab versus SoC. However, higher survival rates at 12 to 24 months and response rates demonstrate clinical activity for durvalumab.ClinicalTrials.gov: NCT02369874.
Resurrecting the phoenix: When an assay fails
Authors: Bharath Srinivasan, Vasudev Kantae, James Robinson
Journal: Medicinal Research Reviews (2020)

Abstract Understanding protein‐small‐molecule interactions is a critical component of rational drug‐design. Structure‐activity relationship (SAR)‐guided medicinal chemistry is informed by the biological outcome, as assessed by biochemical activity or cellular effect, of chemical modifications on small molecules. The effectiveness of SAR is reliant on the sturdiness and durability of assay design and the quality of information garnered from assays. Lack of quality data at this step can lead to obstruction of the drug discovery pipeline with profound implications for the timelines of introducing a drug into the market. Hence, it would not be an overstatement to consider biochemical/biological assays as the backbone of drug‐discovery. Enzyme assays can fail for many different reasons, with the enzyme and the substrate being the principal players. Lack of clarity can hamper progress and can lead to mounting costs and potentially losing competitive advantage. Although each assay is unique and requires a specific approach to troubleshoot the problem at hand, there are general guidelines that can be followed to maximize the chances of success. This review is a step‐by‐step attempt at reintroducing fundamental biochemical concepts within the context of an enzyme assay, delineating probable causes for failure and potential approaches to get an assay back up and running.
Commercially Available Insulin Products Demonstrate Stability Throughout the Cold Supply Chain Across the U.S.
Authors: Timothy J. Garrett, Philip Atkinson, Eoin P. Quinlivan, Lynn Ang, Irl B. Hirsch, Lori Laffel, Massimo Pietropaolo, Michael J. Haller, Mark A. Atkinson
Journal: Diabetes Care (2020)

OBJECTIVE A recent publication questioned the integrity of insulin purchased from U.S. retail pharmacies. We sought to independently validate the method used, isotope dilution solid-phase extraction (SPE) liquid chromatography mass spectrometry (LC-MS), and expand analysis to two U.S. Pharmacopeia (USP) methods (high-performance LC with ultraviolet detection and LC-MS). RESEARCH DESIGN AND METHODS Each method was used to evaluate nine insulin formulations, purchased at four pharmacies, within five geographic locations in the U.S. RESULTS All human and analog insulins measured by the USP methods (n = 174) contained the expected quantity of active insulin (100 ± 5 units/mL). When using isotope dilution SPE-LC-MS, units-per-milliliter values were well below product labeling due to unequal recovery of the internal standard compared with target insulin. CONCLUSIONS Insulin purchased from U.S. pharmacies is consistent with product labeling.
Abstract 17106: Determining the Contributing Factors of Heterogeneity in LV Mass: Results From a Collegiate-Level Football Screening Study
Authors: Kegan J Moneghetti, Hong Q Lu, Tamanna Singh, Jeffrey W Christle, Sarah Bouajila, Zoe Kooreman, Yukari Kobayashi, Vic Froelicher, Matthew Wheeler, Euan Ashley, Francois Haddad
Journal: Circulation (2017)

Background: Multiple studies have reported physiologic cardiac remodeling among collegiate-level athletes, however, there is marked variation in reported left ventricular (LV) remodelling parameter...