tbuckley/cabot-search huggingface dataset:
Engineering synthetic RNA devices for cell control
Authors: Peter B. Dykstra, Matias Kaplan, Christina D. Smolke
Journal: Nature Reviews Genetics (2022)

The versatility of RNA in sensing and interacting with small molecules, proteins and other nucleic acids while encoding genetic instructions for protein translation makes it a powerful substrate for engineering biological systems. RNA devices integrate cellular information sensing, processing and actuation of specific signals into defined functions and have yielded programmable biological systems and novel therapeutics of increasing sophistication. However, challenges centred on expanding the range of analytes that can be sensed and adding new mechanisms of action have hindered the full realization of the field’s promise. Here, we describe recent advances that address these limitations and point to a significant maturation of synthetic RNA-based devices. Synthetic RNA devices integrate sensing, processing and actuation of signals into defined, programmable functions to control cell behaviour. This Review discusses the emerging applications of RNA devices in biomedical research and biomanufacturing, as well as progress in creating new ligand sensors and new mechanisms of action with engineered RNAs.
Editorial board
Authors: James Field, Samuel Soskin, Beverly Hills, Garfield Duncan, Salman Azhar, Palo Alto, Hisham Barakat, George Bray, Jorge Calles-Escandon, Jose ´caro, M Charles, George Chrousos, Bernard Bethesda, St Davis, Leslie Louis, Frederick Degroot, Mario Derubertis, Atlanta Digirolamo, William Ga, Louis Duckworth, John Elsas, Kenneth Fain, San Feingold, Irving Francisco, Andrew Fox, New Frantz, Saul York, Henry Cleveland, New Ginsberg, Charles York, Abbas Glueck, Fredric Kitabchi, Stanford Kraemer, Nelly Mauras, James May, Donald Mcnamara, Glenn Mortimore, Maria New, New York, Caroline Pace, Michael Pagliassotti, Ft Collins, William Pandak, Alan Richmond, Los Robinson, Stanton Angeles, Peter Segal, Richard Stacpoole, Marc Durham, John Tucson
Journal: Metabolism (2003)
Biomarker testing in patients (pts) with metastatic colorectal cancer (mCRC): Perspectives from U.S. oncologists (ONC) in rural areas and urban clusters.
Authors: Mark Andrew Lewis, Lindsay Stansfield, John M. Kelton, Michelle L. Edwards, Christopher Hanyoung Lieu
Journal: Journal of Clinical Oncology (2022)

70 Background: In the US, pts living in rural areas have higher CRC mortality rates than urban areas. Clinical guidelines recommend testing for BRAF and RAS mutations and deficient mismatch repair/microsatellite instability in pts with mCRC. However, data on biomarker testing rates in rural communities compared with urban areas are limited. We surveyed ONC in the US who practice in rural areas or urban clusters to identify biomarker testing patterns and barriers (data previously reported) and conducted interviews with a select group of respondents to further understand key differences that may contribute to substandard biomarker testing rates in rural areas. Methods: A 2-part (quantitative and qualitative) survey was conducted with ONC who spend &gt; 40% of their time providing direct care to pts in rural areas or urban clusters and who had treated ≥2 pts with stage IV mCRC in the month prior to the survey. After screening, a subset of those who completed the quantitative survey participated in the qualitative survey (a 30-minute, web-assisted, telephone interview). The interview questions targeted 6 areas: clinical practice description, biomarker and genomic testing patterns, pathology and molecular tumor board, tumor tissue journey, electronic health records, and training/educational opportunities. Results: Of the 99 ONC who responded to the quantitative survey, 17 were interviewed for the qualitative survey from June 16–29, 2021. A key finding of the quantitative survey was that although ONC reported being familiar with biomarkers relevant to mCRC, the reported rate of biomarker testing was suboptimal. The interviews probed reasons why testing does not align with current guidelines and found that challenges exist throughout the tumor tissue journey including insufficient tumor tissue available for testing (especially in the relapsed/refractory setting); lack of or limited protocols, clinical decision support systems, reflexive testing, and molecular tumor boards; lengthy and difficult-to-navigate next-generation sequencing reports; and financial toxicity surrounding biomarker tests (especially for underinsured pts), among other barriers. Despite these challenges, ONC reported easy access to third-party reference labs and electronic references, such as NCCN and UpToDate. Although telehealth visits have nearly quadrupled during the COVID pandemic, access to telehealth may be limited for pts living in rural areas or urban clusters. Conclusions: The ONC surveyed reported that practicing in rural/urban clusters poses unique challenges related to tissue acquisition, practice resources, pts’ ability to pay, and clinical knowledge gaps that may affect biomarker testing rates in pts with mCRC. Addressing these gaps is warranted if optimal utilization of precision medicine tools is to be realized.
Stable Angina Pectoris: One-Year Outcomes of Patients with Obstructive Coronary Artery Disease: Multicenter Sutdy in Dakar (Senegal)
Authors: Paul Coffi HESSOU, Joseph Salvador MINGOU, Maboury DIAO, Fatou AW LEYE, Mouhamadou Bamba NDIAYE, Simon Antoine SARR, Malick BODIAN, Papa Guirane NDIAYE, Paul Coffi HESSOU, Bouna DIACK, Allasane MBAYE, Aliou Alassane NGAÏDE
Journal: Clinical Cardiology and Cardiovascular Interventions (2022)

Background: CAD management is important in prevention of disease progression. But we have very little study or research on the evolution of stable angina in amulatory patients without coronary antecedents and with obstructive coronary disease. Purpose: The objective of our study was to analyze the clinical and angiographic profil of patients with stable chest pain and to assess their angina status one year outcomes. Patients and methods: All patients who presented with symptomatic angina pectoris and/or signs of ischemia and first diagnosis of obstructive CAD in the Cardiology Departments of Idrissa Pouye General Hospital and Aristide Le Dantec National University Hospital Center of Dakar, from March 01, 2019 to December 31, 2020 were selected. The clinical characteristics, initial angiographic findings, therapeutic strategy and outcome within the first year were analyzed. Results: During the study period, 84 outpatients presenting with symptomatic stable chest pain and first obstructive coronary artery disease were selected. The mean age was 63.01± 9.37 years. Male preponderance was observed with 63(75%) patients; Clinical symptoms were dominated by typical pain with 46.4% (n=39) ; the risk factors were dominated by hypertension 61.9% (n=52); diabetes 41.7% (n=35) and dyslipidemia 33.3% (n=28). During follow-up, 10 patients (11.90%) remained untraceable while 9 patients (10.71%) were not available for check-up; 3 patients (3.57%) died during follow-up. Only 62 patients (73.80) could be evaluated; among those who were alive and controlled, 26 patients (41.93%) with angina at baseline still had angina symptoms, 2 patients (3.22%) had undergone myocardial infarction; one (1.61%) had undergone urgent revascularization; one (1.61%) patient developed heart failure. Finally 32 patients (51.61%) were event-free and angina-free Conclusion: The management of outpatients with stable chest pain and first obstructive CAD appears favourable, with good adherence to guideline-based therapies one year outcomes. Stable chest pain is not associated with an increased risk for adverse cardiovascular outcomes but there remains room for improvement in terms of risk factor control.
Stents and glycoprotein IIb/IIIa inhibitors do not improve 30-day outcome in bypass graft percutaneous interventions: A retrospective registry-based analysis Marco Roffi, Albert Chan, Derek P. Chew, Marc A. Robbins, Debabrata Mukherjee, Deepak L. Bhatt, Abdulhay Albirini, Leslie Cho, Ramtin Agah, Eric J. Topol, Stephen G. Ellis. Cleveland Clinic Foundation, Cleveland
Journal: Journal of the American College of Cardiology (2001)
Increased right ventricular thallium uptake in chronic ischemic left ventricular dysfunction: Evidence for improvement after coronary artery revascularization Maung M. Khin, Anastasia N. Kitsiou, Joann Carson, Stephen L. Bacharach, Vasken Dilsizian. National Institutes of Health, Bethesda, MD
Journal: Journal of the American College of Cardiology (2001)
An Outbreak of Covid-19 on an Aircraft Carrier
Authors: Matthew R Kasper, Jesse R Geibe, Christine L Sears, Asha J Riegodedios, Tina Luse, Annette M Von Thun, Michael B McGinnis, Niels Olson, Daniel Houskamp, Robert Fenequito, Timothy H Burgess, Adam W Armstrong, Gerald DeLong, Robert J Hawkins, Bruce L Gillingham
Journal: New England Journal of Medicine (2020)

An outbreak of coronavirus disease 2019 (Covid-19) occurred on the U.S.S. Theodore Roosevelt, a nuclear-powered aircraft carrier with a crew of 4779 personnel.We obtained clinical and demographic data for all crew members, including results of testing by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). All crew members were followed up for a minimum of 10 weeks, regardless of test results or the absence of symptoms.The crew was predominantly young (mean age, 27 years) and was in general good health, meeting U.S. Navy standards for sea duty. Over the course of the outbreak, 1271 crew members (26.6% of the crew) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by rRT-PCR testing, and more than 1000 infections were identified within 5 weeks after the first laboratory-confirmed infection. An additional 60 crew members had suspected Covid-19 (i.e., illness that met Council of State and Territorial Epidemiologists clinical criteria for Covid-19 without a positive test result). Among the crew members with laboratory-confirmed infection, 76.9% (978 of 1271) had no symptoms at the time that they tested positive and 55.0% had symptoms develop at any time during the clinical course. Among the 1331 crew members with suspected or confirmed Covid-19, 23 (1.7%) were hospitalized, 4 (0.3%) received intensive care, and 1 died. Crew members who worked in confined spaces appeared more likely to become infected.SARS-CoV-2 spread quickly among the crew of the U.S.S. Theodore Roosevelt. Transmission was facilitated by close-quarters conditions and by asymptomatic and presymptomatic infected crew members. Nearly half of those who tested positive for the virus never had symptoms.
Analysis of antibody binding specificities in twin and SNP-genotyped cohorts reveals that antiviral antibody epitope selection is a heritable trait
Authors: Thiagarajan Venkataraman, Cristian Valencia, Massimo Mangino, William Morgenlander, Steven J. Clipman, Thomas Liechti, Ana Valencia, Paraskevi Christofidou, Tim Spector, Mario Roederer, Priya Duggal, H. Benjamin Larman
Journal: Immunity (2022)
CDC minority health office: 'social epidemiology'
Authors: T. Randall
Journal: JAMA (1990)

THE CDC's newly established Office of Assistant Director for Minority Health marks an expansion from the federal centers' traditional approach to health and disease into the less familiar realm of "social epidemiology." "This, in my view, is the CDC's new frontier," says Rueben Warren, DDS, MPH, DrPH, the CDC's assistant director for minority health. The office, set up in August 1988, strives to improve the health of all African-American, Hispanic-American, Native American, and Asian-American citizens, and the health of non-US citizens of similar ethnic and racial backgrounds where appropriate, such as migrant farm workers in the border states. People from these diverse groups suffer the highest incidence and prevalence of the most common preventable diseases, yet they remain the most difficult populations to reach. <h3>Gap Is Clear, Reasons Hazy</h3> A recent CDC study of excess mortality among black adults in the United States illustrates the striking gap between the black
Trauma Anesthesia
Authors: Joseph H. McIsaac
Journal: JAMA (2010)

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
Dynamic RNA Fitness Landscapes of a Group I Ribozyme during Changes to the Experimental Environment
Authors: Gianluca Peri, Clémentine Gibard, Nicholas H Shults, Kent Crossin, Eric J Hayden
Journal: Molecular Biology and Evolution (2022)

Abstract Fitness landscapes of protein and RNA molecules can be studied experimentally using high-throughput techniques to measure the functional effects of numerous combinations of mutations. The rugged topography of these molecular fitness landscapes is important for understanding and predicting natural and experimental evolution. Mutational effects are also dependent upon environmental conditions, but the effects of environmental changes on fitness landscapes remains poorly understood. Here, we investigate the changes to the fitness landscape of a catalytic RNA molecule while changing a single environmental variable that is critical for RNA structure and function. Using high-throughput sequencing of in vitro selections, we mapped a fitness landscape of the Azoarcus group I ribozyme under eight different concentrations of magnesium ions (1–48 mM MgCl2). The data revealed the magnesium dependence of 16,384 mutational neighbors, and from this, we investigated the magnesium induced changes to the topography of the fitness landscape. The results showed that increasing magnesium concentration improved the relative fitness of sequences at higher mutational distances while also reducing the ruggedness of the mutational trajectories on the landscape. As a result, as magnesium concentration was increased, simulated populations evolved toward higher fitness faster. Curve-fitting of the magnesium dependence of individual ribozymes demonstrated that deep sequencing of in vitro reactions can be used to evaluate the structural stability of thousands of sequences in parallel. Overall, the results highlight how environmental changes that stabilize structures can also alter the ruggedness of fitness landscapes and alter evolutionary processes.
AASLD practice guidelines the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension update 2009
Authors: Thomas D. Boyer, Ziv J. Haskal
Journal: Hepatology (2009)

The 2009 update of the American Association for the Study of Liver Diseases (AASLD) Practice Guideline “The Role of Transjugular Intrahepatic Portosystemic Shunt (TIPS) in the Management of Portal Hypertension” is now posted online at www.aasld.org. This is the first update of the original guideline published in 2005.1 DSRS, distal splenorenal shunt; TIPS, transjugular intrahepatic portosystemic shunt. The key changes in the 2009 guidelines are new recommendations on the use of covered versus bare stents in the creation of the TIPS. Use of expanded polytetrafluoroethylene (ePTFE)-covered stents is now preferred. The lower risk of shunt dysfunction and perhaps improved outcomes using covered as opposed to bare stents are the basis for this recommendation.2, 3 Creation of a TIPS increases the risk of hepatic encephalopathy but the prophylactic use of nonabsorbable disaccharides or antibiotics does not appear to reduce this risk and is not recommended.4 The value of TIPS versus a surgical shunt in the prevention of variceal rebleeding in patients who have failed medical therapy has been clarified by the publication of a controlled trial comparing TIPS to distal splenorenal shunt (DSRS).5 Both were effective in preventing rebleeding (rebleeding incidence in 5.5% of DSRS versus 10.5% of TIPS; not significant) with no difference in encephalopathy or survival. The patients in whom TIPS was performed required significantly more interventions to maintain patency because of the use of bare stents. A cost analysis showed TIPS to be slightly more cost effective than DSRS at year 5,6 and these two approaches are now considered to be of equal efficacy in the prevention of variceal rebleeding. The other significant change to the guidelines is how TIPS should be used in the management of patients with Budd-Chiari syndrome. A large (221 patients) retrospective study was published in which patients who failed to improve with use of anticoagulation had a TIPS created (133 patients). One-year and 10-year transplant-free survival was 88% and 69%, respectively, which is better than predicted.7 TIPS patency was best in those who received a covered stent. The recommendation now is for creation of a TIPS in those who fail to improve with anticoagulation.
Author Correction: Uveal melanoma
Authors: Martine J. Jager, Carol L. Shields, Colleen M. Cebulla, Mohamed H. Abdel-Rahman, Hans E. Grossniklaus, Marc-Henri Stern, Richard D. Carvajal, Rubens N. Belfort, Renbing Jia, Jerry A. Shields, Bertil E. Damato
Journal: Nature Reviews Disease Primers (2022)
Prognostic significance of serum CA 19-9 response and dynamics in patients with intrahepatic cholangiocarcinoma undergoing surgical resection.
Authors: Timothy P. DiPeri, Timothy E. Newhook, Ching-Wei D. Tzeng, Yun Shin Chun, Sunyoung S. Lee, Milind M. Javle, Jean-Nicolas Vauthey, Hop Sanderson Tran Cao
Journal: Journal of Clinical Oncology (2022)

479 Background: Pre and post-operative elevation of serum CA 19-9 have been associated with poor outcomes and increased risk of recurrence in patients with resected intrahepatic cholangiocarcinoma (ICC). We sought to investigate the impact of CA 19-9 response and dynamics on survival for patients with ICC undergoing surgical resection. Methods: Clinicopathologic characteristics were abstracted from a prospectively maintained database at a tertiary cancer care center for patients with ICC undergoing surgical resection from 2003 to 2020. Exclusion criteria included CA 19-9 non-producers (≤ 1 U/mL at baseline), missing baseline/pre-operative or postoperative CA 19-9 value, or total bilirubin &gt; 2 mg/dL. Overall (OS) and recurrence-free survival (RFS) was compared among patients when categorized by baseline (neoadjuvant)/pre-operative (upfront surgery) and post-operative CA 19-9 values: normal (&gt; 1 to 37 U/mL), intermediate (&gt; 37 to 200 U/mL), and elevated (&gt; 200 U/mL). Patients were then stratified by perioperative CA 19-9 response (responder [non-normal to normal CA 19-9 OR 50% reduction in CA 19-9; normal to normal CA 19-9], non-responder [non-normal to non-normal CA 19-9 OR &lt; 50% reduction in CA 19-9; normal to non-normal CA 19-9]) and CA 19-9 dynamics (normal to normal, non-normal to normal, non-normal to non-normal, normal to non-normal CA 19-9 values). Results: A total of 112 patients were identified including 67 (59.8%) who underwent upfront surgery and 45 (40.2%) who received neoadjuvant therapy. Patients with a normal CA 19-9 at diagnosis had median RFS and OS durations of 61 and 163 months, followed by intermediate CA 19-9 (20 and 98 months) and elevated CA 19-9 (18 and 46 months, p = 0.308 RFS; p = 0.295 OS). Those who had a normal CA 19-9 post-operatively had the best median RFS and OS (46 and 163 months), followed by intermediate CA 19-9 (13 and 58 months) and elevated CA 19-9 (5 and 8 months, p = 0.059 RFS; p = 0.005 OS). When stratified by perioperative CA 19-9 response, responders had a median RFS of 36 vs. 13 months in non-responders (p = 0.143), and a median OS of 98 months vs. 88 months in non-responders (p = 0.077). Patients with normal CA 19-9 post-operatively had longer RFS/OS (normal to normal, 48/98 months; non-normal to normal, 30/not estimable months) than those who had non-normal CA 19-9 both pre- and post-operatively (non-normal to non-normal, 7/34 months, p = 0.018 RFS; p = 0.007 OS). Conclusions: Patients with normal CA 19-9 levels post-operatively, who had either normal or elevated CA 19-9 pre-operatively, had the greatest RFS and OS durations. A normal (or normalized) post-operative CA 19-9 may inform patient-centered decisions on adjuvant therapy and/or surveillance intensity.
Impact of Venetoclax and Azacitidine in Treatment-Naïve Patients with Acute Myeloid Leukemia and <i>IDH1/2</i> Mutations
Authors: Daniel A. Pollyea, Courtney D. DiNardo, Martha L. Arellano, Arnaud Pigneux, Walter Fiedler, Marina Konopleva, David A. Rizzieri, B. Douglas Smith, Atsushi Shinagawa, Roberto M. Lemoli, Monique Dail, Yinghui Duan, Brenda Chyla, Jalaja Potluri, Catherine L. Miller, Hagop M. Kantarjian
Journal: Clinical Cancer Research (2022)

Abstract Purpose: To evaluate efficacy and safety of venetoclax + azacitidine among treatment-naïve patients with IDH1/2-mutant (mut) acute myeloid leukemia (AML). Patients and Methods: Data were pooled from patients enrolled in a phase III study (NCT02993523) that compared patients treated with venetoclax + azacitidine or placebo + azacitidine and a prior phase Ib study (NCT02203773) where patients were treated with venetoclax + azacitidine. Enrolled patients were ineligible for intensive therapy due to age ≥75 years and/or comorbidities. Patients on venetoclax + azacitidine received venetoclax 400 mg orally (days 1–28) and azacitidine (75 mg/m2; days 1–7/28-day cycle). Results: In the biomarker-evaluable population, IDH1/2mut was detected in 81 (26%) and 28 (22%) patients in the venetoclax + azacitidine and azacitidine groups. Composite complete remission [CRc, complete remission (CR)+CR with incomplete hematologic recovery (CRi)] rates (venetoclax + azacitidine/azacitidine) among patients with IDH1/2mut were 79%/11%, median duration of remission (mDoR) was 29.5/9.5 months, and median overall survival (mOS) was 24.5/6.2 months. CRc rates among patients with IDH1/2 wild-type (WT) were 63%/31%, mDoR 17.5/10.3 months, and mOS 12.3/10.1 months. In patients with IDH1mut, CRc rates (venetoclax + azacitidine/azacitidine) were 66.7%/9.1% and mOS 15.2/2.2 months. In patients with IDH2mut, CRc rates were 86.0%/11.1% and mOS not reached (NR)/13.0 months. Patients with IDH1/2 WT AML treated with venetoclax + azacitidine with poor-risk cytogenetics had inferior outcomes compared with patients with IDH1/2mut, who had superior outcomes regardless of cytogenetic risk (mOS, IDH1/2mut: intermediate-risk, 24.5 months; poor-risk, NR; IDH1/2 WT: intermediate, 19.2 and poor, 7.4 months). There were no unexpected toxicities in the venetoclax + azacitidine group. Conclusions: Patients with IDH1/2mut who received venetoclax + azacitidine had high response rates, durable remissions, and significant OS; cytogenetic risk did not mitigate the favorable outcomes seen from this regimen for IDH1/2mut. See related commentary by Perl and Vyas, p. 2719