tbuckley/cabot-search huggingface dataset:
To Be or Not to Be a CaMKII Inhibitor?
Authors: Mark E. Anderson
Journal: JAMA Cardiology (2021)

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 Cardiology 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 Cardiology journal
Integration of genomic sequencing into the response to the Ebola virus outbreak in Nord Kivu, Democratic Republic of the Congo
Authors: Eddy Kinganda-Lusamaki, Allison Black, Daniel B. Mukadi, James Hadfield, Placide Mbala-Kingebeni, Catherine B. Pratt, Amuri Aziza, Moussa M. Diagne, Bailey White, Nella Bisento, Bibiche Nsunda, Marceline Akonga, Martin Faye, Ousmane Faye, Francois Edidi-Atani, Meris Matondo-Kuamfumu, Fabrice Mambu-Mbika, Junior Bulabula, Nicholas Di Paola, Matthias G. Pauthner, Kristian G. Andersen, Gustavo Palacios, Eric Delaporte, Amadou Alpha Sall, Martine Peeters, Michael R. Wiley, Steve Ahuka-Mundeke, Trevor Bedford, Jean-Jacques Muyembe Tamfum
Journal: Nature Medicine (2021)
Abstract 12261: Non-Apical Right Ventricular Lead Location is Associated with Higher Ventricular Arrhythmia Risk in CRT-D Patients - Findings from MADIT-CRT
Authors: Valentina Kutyifa, Poul Erik Bloch Thomsen, Christian Jons, Scott McNitt, Arthur J Moss, Wojciech Zareba, Helmut U Klein
Journal: Circulation (2012)

Background. Data on the influence of right ventricular (RV) lead location regarding clinical and arrhythmia outcomes are limited in CRT patients. Methods. We investigated 742 CRT-D patients with ad...
Quantitative self-assembly of pure drug cocktails as injectable nanomedicines for synergistic drug delivery and cancer therapy
Authors: Xiaona Chen, Binbin Xie, Lingling Huang, Jianqin Wan, Yuchen Wang, Xiaowei Shi, Yiting Qiao, Haihan Song, Hangxiang Wang
Journal: Theranostics (2021)

New strategies to fabricate nanomedicines with high translational capacity are urgently desired. Herein, a new class of self-assembled drug cocktails that addresses the multiple challenges of manufacturing clinically useful cancer nanomedicines was reported. Methods: With the aid of a molecular targeted agent, dasatinib (DAS), cytotoxic cabazitaxel (CTX) forms nanoassemblies (CD NAs) through one-pot process, with nearly quantitative entrapment efficiency and ultrahigh drug loading of up to 100%. Results: Surprisingly, self-assembled CD NAs show aggregation-induced emission, enabling particle trafficking and drug release in living cells. In preclinical models of human cancer, including a patient-derived melanoma xenograft, CD NAs demonstrated striking therapeutic synergy to produce a durable recession in tumor growth. Impressively, CD NAs alleviated the toxicity of the parent CTX agent and showed negligible immunotoxicity in animals. Conclusions: Overall, this approach does not require any carrier matrices, offering a scalable and cost-effective methodology to create a new generation of nanomedicines for the safe and efficient delivery of drug combinations.
Treponema pallidum detection in lesion and non-lesion sites in men who have sex with men with early syphilis: a prospective, cross-sectional study
Authors: Janet M Towns, David E Leslie, Ian Denham, Rebecca Wigan, Francesca Azzato, Deborah A Williamson, Darren Lee, Eric P F Chow, Christopher K Fairley, Stephen R Graves, Lei Zhang, Marcus Y Chen
Journal: The Lancet Infectious Diseases (2021)
Methods for studying pulmonary lymphatics
Authors: Victor E. Maldonado-Zimbron, Jiwon Hong, Peter Russell, Natalie L. Trevaskis, John Albert Windsor, Anthony Ronald John Phillips
Journal: European Respiratory Journal (2021)

<b>The pulmonary lymphatics are critical for proper lung function, yet seldom considered in lung pathology. Newer and more convenient methods for studying lung lymphatics are now available and might create new diagnosis and treatment opportunities.</b>https://bit.ly/3ldJGeo
Diagnosis, Education, and Care of Patients with APOL1-Associated Nephropathy: A Delphi Consensus and Systematic Review
Authors: Barry I. Freedman, Wylie Burke, Jasmin Divers, Lucy Eberhard, Crystal A. Gadegbeku, Rasheed Gbadegesin, Michael E. Hall, Tiffany Jones-Smith, Richard Knight, Jeffrey B. Kopp, Csaba P. Kovesdy, Keith C. Norris, Opeyemi A. Olabisi, Glenda V. Roberts, John R. Sedor, Erika Blacksher
Journal: Journal of the American Society of Nephrology (2021)

variants contribute to the markedly higher incidence of ESKD in Blacks compared with Whites. Genetic testing for these variants in patients with African ancestry who have nephropathy is uncommon, and no specific treatment or management protocol for
The pleiotropic roles of leptin in metabolism, immunity, and cancer
Authors: Paola de Candia, Francesco Prattichizzo, Silvia Garavelli, Carlo Alviggi, Antonio La Cava, Giuseppe Matarese
Journal: The Journal of Experimental Medicine (2021)

The discovery of the archetypal adipocytokine leptin and how it regulates energy homeostasis have represented breakthroughs in our understanding of the endocrine function of the adipose tissue and the biological determinants of human obesity. Investigations on leptin have also been instrumental in identifying physio-pathological connections between metabolic regulation and multiple immunological functions. For example, the description of the promoting activities of leptin on inflammation and cell proliferation have recognized the detrimental effects of leptin in connecting dysmetabolic conditions with cancer and with onset and/or progression of autoimmune disease. Here we review the multiple biological functions and complex framework of operations of leptin, discussing why and how the pleiotropic activities of this adipocytokine still pose major hurdles in the development of effective leptin-based therapeutic opportunities for different clinical conditions.
Abstract IA-028: Interaction of radiotherapy and immunotherapy: Maybe not what you think
Authors: Ralph R. Weichselbaum
Journal: Clinical Cancer Research (2021)

Abstract Immunotherapy has altered the cancer therapy landscape and has engendered significant investigative interest in the context of the basic mechanisms and clinical applications of radiotherapy/immunotherapy combinations from accomplished investigators, many of whom have presented at this conference. Despite high quality preclinical data and some intriguing hints of efficacy, most of the clinical trials to date have failed to show a benefit to radiotherapy/immunotherapy combinations except for small subsets of patients treated in phase 1 clinical trials. The often cited “PACIFIC” trial in stage 3 lung cancer shows that immunotherapy can safely be given after chemoradiotherapy and provides significant patient benefit in terms of progression free and overall survival but does not demonstrate a positive dependent interaction between radiotherapy and immunotherapy. I will critically review select clinical trials and present data from our (and other) laboratories that may in part explain the discrepancies between the encouraging preclinical data and the somewhat disappointing clinical results. Citation Format: Ralph R. Weichselbaum. Interaction of radiotherapy and immunotherapy: Maybe not what you think [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr IA-028.
Detection of the new SARS-CoV-2 variants of concern B.1.1.7 and B.1.351 in five SARS-CoV-2 rapid antigen tests (RATs), Germany, March 2021
Authors: Sabrina Jungnick, Bernhard Hobmaier, Lena Mautner, Mona Hoyos, Maren Haase, Armin Baiker, Heidi Lahne, Ute Eberle, Clara Wimmer, Sabrina Hepner, Annika Sprenger, Carola Berger, Alexandra Dangel, Manfred Wildner, Bernhard Liebl, Nikolaus Ackermann, Andreas Sing, Volker Fingerle
Journal: Eurosurveillance (2021)

SARS-CoV-2 variants of concern (VOC) should not escape molecular surveillance. We investigated if SARS-CoV-2 rapid antigen tests (RATs) could detect B.1.1.7 and B.1.351 VOCs in certain laboratory conditions. Infectious cell culture supernatants containing B.1.1.7, B.1.351 or non-VOC SARS-CoV-2 were respectively diluted both in DMEM and saliva. Dilutions were analysed with Roche, Siemens, Abbott, nal von minden and RapiGEN RATs. While further studies with appropriate real-life clinical samples are warranted, all RATs detected B.1.1.7 and B.1.351, generally comparable to non-VOC strain.
“A la carte” treatment of portal hypertension: Adapting medical therapy to hemodynamic response for the prevention of bleeding
Authors: Christophe Bureau, Jean-Marie Péron, Laurent Alric, Joséphine Morales, Jérôme Sanchez, Karl Barange, Jean-Louis Payen, Jean-Pierre Vinel
Journal: Hepatology (2002)

We report the results of adapting medical therapy to the monitoring of hemodynamic response in the prevention of a first variceal bleeding or rebleeding in patients with cirrhosis. Hepatic venous pressure gradient (HVPG) was measured before and after propranolol was initiated. The patients were considered responders if HVPG decreased below 12 mm Hg or at least 20% as compared with baseline value. If patients were not responders, isosorbide-5 mononitrate (I-5MN) was added, and a third hemodynamic study was performed. Thereafter, the patients were followed for a mean of 28 months. Thirty-four consecutive patients were treated to prevent a first bleeding episode in 20 patients and a rebleeding in 14 patients. HVPG value was initially 19.8 ± 4.6 mm Hg and decreased to 17.6 ± 5.7 mm Hg ( P &lt; (.05) after propranolol alone. Thirteen patients (38%) were responders to propranolol. I-5MN improved hemodynamic response in 7 cases. Among these 20 (59%) hemodynamic responders, only 2 (10%) experienced variceal bleeding, as compared with 9 of 14 (64%) nonresponders ( P &lt; 0.05). Using multivariate analysis, only hemodynamic response was found to have an independent predictive value for the risk of variceal bleeding. In conclusion, hemodynamic response to drug therapy identifies patients who are efficiently protected from variceal bleeding as well as nonresponders in whom an alternative treatment should be considered. (Hepatology2002;36:1361-1366).
A Rare Autosomal Dominant Variant in Regulator of Calcineurin Type 1 (RCAN1) Gene Confers Enhanced Calcineurin Activity and May Cause FSGS
Authors: Brandon M. Lane, Susan Murray, Katherine Benson, Agnieszka Bierzynska, Megan Chryst-Stangl, Liming Wang, Guanghong Wu, Gianpiero Cavalleri, Brendan Doyle, Neil Fennelly, Anthony Dorman, Shane Conlon, Virginia Vega-Warner, Damian Fermin, Poornima Vijayan, Mohammad Azfar Qureshi, Shirlee Shril, Moumita Barua, Friedhelm Hildebrandt, Martin Pollak, David Howell, Matthew G. Sampson, Moin Saleem, Peter J. Conlon, Robert Spurney, Rasheed Gbadegesin
Journal: Journal of the American Society of Nephrology (2021)

Podocyte dysfunction is the main pathologic mechanism driving the development of FSGS and other morphologic types of steroid-resistant nephrotic syndrome (SRNS). Despite significant progress, the genetic causes of most cases of SRNS have yet to be identified.
Development and Evaluation of a Method to Correct Misinterpretation of Clinical Trial Results With Long-term Survival
Authors: Chih-Yuan Hsu, Emily Pei-Ying Lin, Yu Shyr
Journal: JAMA Oncology (2021)

In immune checkpoint inhibitor (ICI) trials, long tails and crossovers in survival curves-which violate the proportional hazards (PH) assumption-are commonly observed, making cure or restricted mean survival time models preferable for analysis of ICI survival data. Cox PH analysis, however, still appears in major medical journals, leading to potential misinterpretation of clinical significance.To convert inappropriate Cox hazard ratios (HRs) to appropriate PH cure model treatment-effect estimates (HR for short-term survivors and difference in proportions [DP] for long-term survivors) for more accurate interpretation of published ICI trials.This study uses the Taylor expansion technique to demonstrate the mathematical relationship between Cox PH and PH cure models for data with long-term survival, and based on this relationship, proposes the Cox-TEL (Cox PH-Taylor expansion adjustment for long-term survival data) adjustment method. The proposed Cox-TEL method requires only 2 inputs: the reported Cox HRs and Kaplan-Meier-estimated survival probabilities.Comprehensive simulations show the strength of the proposed method in terms of power, bias, and type I error rate; these results, which are close to PH cure model estimates, were further verified in a melanoma data set (N = 285; Cox HR = 0.71; 95% CI, 0.51-0.91; Cox-TEL HR = 0.83; 95% CI, 0.60-1.07; PH cure HR = 0.86; 95% CI, 0.61-1.11; Cox-TEL DP = 0.10; 95% CI, 0.01-0.23; PH cure DP = 0.10; 95% CI, 0.00-0.21). The magnitude of potential difference between reported and adjusted HRs using real-world ICI trial results is demonstrated. For example, in the CheckMate 067 trial (nivolumab/ipilimumab combination therapy vs ipilimumab), the Cox HR was 0.54 (95% CI, 0.44-0.67), and the Cox-TEL HR was 0.90 (95% CI, 0.73-1.11).The findings of this study suggest the need to revisit published ICI survival data analysis to address potential misinterpretation. The Cox-TEL method not only is designed for this purpose, but also is user friendly and easy to implement using published clinical trial data and a freely available R software package.
Winter of Fear
Authors: Allison Coffelt
Journal: JAMA (2021)

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
Switching to Once-Weekly Insulin Icodec Versus Once-Daily Insulin Glargine U100 in Type 2 Diabetes Inadequately Controlled on Daily Basal Insulin: A Phase 2 Randomized Controlled Trial
Authors: Harpreet S. Bajaj, Richard M. Bergenstal, Andreas Christoffersen, Melanie J. Davies, Amoolya Gowda, Joakim Isendahl, Ildiko Lingvay, Peter A. Senior, Robert J. Silver, Roberto Trevisan, Julio Rosenstock
Journal: Diabetes Care (2021)

Insulin icodec (icodec) is a novel once-weekly basal insulin analog. This trial investigated two approaches for switching to icodec versus once-daily insulin glargine 100 units/mL (IGlar U100) in people with type 2 diabetes receiving daily basal insulin and one or more oral glucose-lowering medications.This multicenter, open-label, treat-to-target phase 2 trial randomized (1:1:1) eligible basal insulin-treated (total daily dose 10-50 units) people with type 2 diabetes (HbA1c 7.0-10.0% [53.0-85.8 mmol/mol]) to icodec with an initial 100% loading dose (in which only the first dose was doubled [icodec LD]), icodec with no loading dose (icodec NLD), or IGlar U100 for 16 weeks. Primary end point was percent time in range (TIR; 3.9-10.0 mmol/L [70-180 mg/dL]) during weeks 15 and 16, measured using continuous glucose monitoring. Key secondary end points included HbA1c, adverse events (AEs), and hypoglycemia.Estimated mean TIR during weeks 15 and 16 was 72.9% (icodec LD; n = 54), 66.0% (icodec NLD; n = 50), and 65.0% (IGlar U100; n = 50), with a statistically significant difference favoring icodec LD versus IGlar U100 (7.9%-points [95% CI 1.8-13.9]). Mean HbA1c reduced from 7.9% (62.8 mmol/mol) at baseline to 7.1% (54.4 mmol/mol icodec LD) and 7.4% (57.6 mmol/mol icodec NLD and IGlar U100); incidences and rates of AEs and hypoglycemic episodes were comparable.Switching from daily basal insulin to once-weekly icodec was well tolerated and provided effective glycemic control. Loading dose use when switching to once-weekly icodec significantly increased percent TIR during weeks 15 and 16 versus once-daily IGlar U100, without increasing hypoglycemia risk.
Malaria vaccine becomes first to achieve 75% efficacy goal in trial of children
Authors: Elisabeth Mahase
Journal: BMJ (2021)

A vaccine candidate for malaria has become the first to meet the World Health Organization’s 75% efficacy target, after a trial in 450 children reported 77% efficacy.1

The phase II trial included infants aged five to 17 months from 24 villages in Nanoro, Burkina Faso. Participants were split into three groups—low dose, high dose, and a rabies vaccine control group—with doses administered from May to August 2019.

The results, released through Preprints with The Lancet, showed that the higher dose version of the vaccine had 77% efficacy and the lower dose had 71% efficacy over a 12 month follow-up period. No serious adverse events related to …
Towards using climate to increase lead time of a malaria early warning system in Mozambique
Authors: Ryan D Harp, James M Colborn, Kristopher B Karnauskas, Baltazar Candrinho, Kathryn L Colborn, Lei Zhang, Daniel E Horton
Journal: The Lancet Planetary Health (2021)

BackgroundMalaria is one of the greatest recurring threats to public health in Mozambique with approximately 10 million cases and thousands of deaths reported annually. Although a malaria early warning system is being established in the country, it is focused on short-term (4–8 week) prediction windows. Increased understanding of the links between quasi-predictable interannual climate variability and malaria could lengthen the lead time for the malaria early warning system and enhance planning and actionable mitigation efforts by public health officials in the country.MethodsTo identify patterns of interannual variability, we did two principal component analyses of processed weekly district-level malaria incidences for the period 2010–17 in Mozambique and southern Africa regional precipitation for the period 1981–2019. We also did linear regression analyses of sea surface temperatures onto a precipitation index, and composites of various climate variables to establish links between precipitation and modes of climate variability.FindingsTwo dominant spatiotemporal patterns collectively account for 81% of the interannual variability of malaria in Mozambique. These patterns consisted of a primary hotspot over the central and southern part of the country and a secondary hotspot over the northern third of the country. We found these patterns to be closely related to precipitation variability driven by climate phenomena: the El Niño-Southern Oscillation and the Subtropical Indian Ocean Dipole.InterpretationQuasi-predictable global and regional climate phenomena influence regional precipitation over southern Africa. Knowledge of these associations can inform an enhancement of the malaria early warning system in Mozambique by lengthening early warning lead times. Similar analyses are possible for other countries whose climate is dominated by tropical modes of climate variability.FundingNone.
Abstract P049: Premature Ventricular Complexes Predict Mortality in a Population with Type 2 Diabetes - The Diabetes Heart Study
Authors: Sebastiano Virgadamo, Amir Azeem, Joseph Yeboah, Carlos J Rodriguez, Amanda J Cox, Donald W Bowden, David M Herrington
Journal: Circulation (2013)

BACKGROUND: Premature ventricular complexes (PVCs) are a common electrocardiographic finding in the general population with or without known cardiovascular disease. Previous population based studie...
Improving wellbeing by integrating health and conservation: findings from cross-sectional surveys
Authors: Craig Leisher, Cheryl Margoluis
Journal: The Lancet Planetary Health (2021)

BackgroundSince 2011, Pathfinder International, The Nature Conservancy, and local government authorities in western Tanzania have partnered on the Tuungane project to support communities facing multiple challenges not solved by a single sector, including poor access to health services such as maternal health and family planning, as well as a declining natural resource base. Tuungane uses a population, health, and environment approach that hypothesises that by integrating health and conservation activities, it can achieve greater overall benefits to both people and nature than single-sector projects. We investigated whether integrating health and conservation services and information leads to greater understanding of the links between people's health and the environment, resulting in more behaviours that improve health and increase sustainable natural resource management.MethodsUsing data from cross-sectional surveys done at the household level in western Tanzania, we assessed health and natural resource knowledge, attitudes, and practices, comparing baseline data collected in July, 2011, from 487 households (of 7700 households) with midterm data collected 5 years later in August, 2016, from 1010 households (of 9568 households). Data from a smaller assessment done in December, 2020, will be available later.FindingsBetween the baseline survey and the midterm survey, we found improvements in indicators for health and conservation knowledge, attitudes, and practices, and overall wellbeing. For example, most common illnesses, such as typhoid, decreased. Familiarity with family planning increased from 45% to 59%. Women who wished they could have postponed a pregnancy decreased from 43% to 34%. Fishermen reported an increase from 8% to 33% in fish catch in the main target species compared with 5 years ago. In 2016, a majority of people agreed that the village forest should be protected (88%). The ability of people to meet daily needs increased from 6% to 20%. People used fewer loans to buy food and had more assets.InterpretationThe results from the surveys suggest that not only the health and natural resource use of local people improved from 2011 to 2016, but also their overall wellbeing.FundingNone.