tbuckley/cabot-search huggingface dataset:
‘Trapped re-entry’ as source of acute focal atrial arrhythmias
Authors: Tim De Coster, Alexander S Teplenin, Iolanda Feola, Cindy I Bart, Arti A Ramkisoensing, Bram L den Ouden, Dirk L Ypey, Serge A Trines, Alexander V Panfilov, Katja Zeppenfeld, Antoine A F de Vries, Daniël A Pijnappels
Journal: Cardiovascular Research (2023)

Abstract Aims Diseased atria are characterized by functional and structural heterogeneities, adding to abnormal impulse generation and propagation. These heterogeneities are thought to lie at the origin of fractionated electrograms recorded during sinus rhythm (SR) in atrial fibrillation (AF) patients and are assumed to be involved in the onset and perpetuation (e.g. by re-entry) of this disorder. The underlying mechanisms, however, remain incompletely understood. Here, we tested whether regions of dense fibrosis could create an electrically isolated conduction pathway (EICP) in which re-entry could be established via ectopy and local block to become ‘trapped’. We also investigated whether this could generate local fractionated electrograms and whether the re-entrant wave could ‘escape’ and cause a global tachyarrhythmia due to dynamic changes at a connecting isthmus. Methods and results To precisely control and explore the geometrical properties of EICPs, we used light-gated depolarizing ion channels and patterned illumination for creating specific non-conducting regions in silico and in vitro. Insight from these studies was used for complementary investigations in virtual human atria with localized fibrosis. We demonstrated that a re-entrant tachyarrhythmia can exist locally within an EICP with SR prevailing in the surrounding tissue and identified conditions under which re-entry could escape from the EICP, thereby converting a local latent arrhythmic source into an active driver with global impact on the heart. In a realistic three-dimensional model of human atria, unipolar epicardial pseudo-electrograms showed fractionation at the site of ‘trapped re-entry’ in coexistence with regular SR electrograms elsewhere in the atria. Upon escape of the re-entrant wave, acute arrhythmia onset was observed. Conclusions Trapped re-entry as a latent source of arrhythmogenesis can explain the sudden onset of focal arrhythmias, which are able to transgress into AF. Our study might help to improve the effectiveness of ablation of aberrant cardiac electrical signals in clinical practice.
Imaging of Rotator Cuff Calcific Tendinopathy Using 18F-NaF and 18F-FDG PET/CT
Authors: Peter Sang Uk Park, Thomas J. Werner, Poul F. Høilund-Carlsen, Abass Alavi
Journal: Clinical Nuclear Medicine (2023)

Abstract Calcific tendinopathy is a common condition of the shoulder caused by the inflammation and deposition of hydroxyapatite crystals in the rotator cuff tendons. PET tracers capturing the molecular changes associated with the crystal deposition of calcific tendinopathy remain underinvestigated. In this report, we present calcified tendinopathy of the infraspinatus tendon demonstrating both 18 F-NaF and 18 F-FDG focal uptake in a 61-year-old woman.
Lipoprotein(a) and Risks of Peripheral Artery Disease, Abdominal Aortic Aneurysm, and Major Adverse Limb Events
Authors: Peter E. Thomas, Signe Vedel-Krogh, Sune F. Nielsen, Børge G. Nordestgaard, Pia R. Kamstrup
Journal: Journal of the American College of Cardiology (2023)
Correction to: 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines
Journal: Circulation (2023)

On Page e57, section "4.3.4.Colchicine, " under the "Synopsis" heading, the last sentence read, "The dose of colchicine available in the United States for secondary prevention in patients with ASCVD is 0.6 mg daily, although the published studies use a dose of 0.5 mg daily.
Randomized trial of dyadic-report vs proxy-report and self-report symptom assessment for pediatric patients receiving cancer treatments
Authors: Deborah Tomlinson, Cassandra Tardif-Theriault, Tal Schechter, L Lee Dupuis, Lillian Sung
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background We validated different approaches to symptom assessment for pediatric cancer patients based on the Symptom Screening in Pediatrics Tool (SSPedi) for self-report (SSPedi and mini-SSPedi), proxy-report (proxy-SSPedi), and structured dyadic-report (co-SSPedi). The objective was to compare co-SSPedi scores vs proxy-report (proxy-SSPedi) and self-report (SSPedi or mini-SSPedi) scores for pediatric patients receiving cancer treatments. Methods This was a single-center, randomized crossover study enrolling English-speaking dyads of pediatric patients with cancer or hematopoietic cell transplant recipients 4-18 years old and their guardians. Dyads were randomized to first complete the dyadic-report (co-SSPedi) or self-report (patients: SSPedi or mini-SSPedi) and proxy-report (guardians: proxy-SSPedi). Dyads then crossed over to the alternate approach. Primary analysis compared total SSPedi scores between randomized groups. Results We enrolled 420 dyads that were randomized to co-SSPedi first (n = 213) or proxy-SSPedi and self-report SSPedi first (n = 207). Mean total SSPedi scores (± standard deviation) were co-SSPedi (9.6 ± 7.1), proxy-SSPedi (9.7 ± 7.5; P = .950 for comparison vs co-SSPedi), and self-report SSPedi (9.7 ± 8.2; P = .981 for comparison vs co-SSPedi). Co-SSPedi scores were significantly different from proxy-SSPedi for feeling disappointed or sad, feeling cranky or angry, feeling tired, mouth sores, and changes in taste. Co-SSPedi scores were significantly different from self-report SSPedi scores for problems with thinking or remembering things, feeling tired, mouth sores, tingly or numb hands or feet, and diarrhea. Conclusions Total co-SSPedi scores were not significantly different compared with proxy-report or self-report scores, although there were differences in specific symptom scores. If different reporter types are used during clinical implementation, specifying reporter type will be important. The study was registered at clinicaltrials.gov (NCT #05012917). Symptoms are common and frequently severely bothersome in pediatric patients with cancer and hematopoietic cell transplant (HCT) recipients (1). To measure the extent of bothersome symptoms, the Symptom Screening in Pediatrics Tool (SSPedi) suite of symptom assessment tools was developed for pediatric patients receiving cancer treatments and currently consists of multiple validated instruments. SSPedi was developed for self-report by patients 8-18 years of age (2,3). Mini-SSPedi was developed for self-report by patients 4 to 7 years of age (4). Proxy-SSPedi was developed for proxy-report by guardians of pediatric patients 2-18 years of age (5). These 3 instruments can be categorized as either self-report (SSPedi or mini-SSPedi) or proxy-report (proxy-SSPedi).
Impaired O2 unloading from stored blood results in diffusion-limited O2 release at tissues: evidence from human kidneys
Authors: Richard Dumbill, Julija Rabcuka, John Fallon, Simon Knight, James Hunter, Daniel Voyce, Jacob Barrett, Matt Ellen, Annemarie Weissenbacher, Tetuko Kurniawan, Slawomir Blonski, Piotr Michal Korczyk, Rutger Ploeg, Constantin Coussios, Peter Friend, Pawel Swietach
Journal: Blood (2023)

The volume of oxygen drawn from systemic capillaries down a partial pressure gradient is determined by the oxygen content of red blood cells (RBCs) and their oxygen-unloading kinetics, although the latter is assumed to be rapid and, therefore, not a meaningful factor. Under this paradigm, oxygen transfer to tissues is perfusion-limited. Consequently, clinical treatments to optimize oxygen delivery aim at improving blood flow and arterial oxygen content, rather than RBC oxygen handling. Although the oxygen-carrying capacity of blood is increased with transfusion, studies have shown that stored blood undergoes kinetic attrition of oxygen release, which may compromise overall oxygen delivery to tissues by causing transport to become diffusion-limited. We sought evidence for diffusion-limited oxygen release in viable human kidneys, normothermically perfused with stored blood. In a cohort of kidneys that went on to be transplanted, renal respiration correlated inversely with the time-constant of oxygen unloading from RBCs used for perfusion. Furthermore, the renal respiratory rate did not correlate with arterial O2 delivery unless this factored the rate of oxygen-release from RBCs, as expected from diffusion-limited transport. To test for a rescue effect, perfusion of kidneys deemed unsuitable for transplantation was alternated between stored and rejuvenated RBCs of the same donation. This experiment controlled oxygen-unloading, without intervening ischemia, holding all non-RBC parameters constant. Rejuvenated oxygen-unloading kinetics improved the kidney's oxygen diffusion capacity and increased cortical oxygen partial pressure by 60%. Thus, oxygen delivery to tissues can become diffusion-limited during perfusion with stored blood, which has implications in scenarios, such as ex vivo organ perfusion, major hemorrhage, and pediatric transfusion. This trial was registered at www.clinicaltrials.gov as #ISRCTN13292277.
Occurrence of Gastrointestinal Adverse Events Upon GLP-1 Receptor Agonist Initiation With Concomitant Metformin Use: A Post Hoc Analysis of LEADER, STEP 2, SUSTAIN-6, and PIONEER 6
Authors: Klara R. Klein, Kim K.B. Clemmensen, Edwin Fong, Søren Olsen, Trine Abrahamsen, Ildiko Lingvay
Journal: Diabetes Care (2023)

OBJECTIVE To assess the impact of concomitant metformin use on gastrointestinal adverse events during the initiation and titration of a glucagon-like peptide 1 receptor agonist (GLP-1RA). RESEARCH DESIGN AND METHODS Using data from four clinical trials of liraglutide and semaglutide (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results [LEADER], Semaglutide Treatment Effect in People with Obesity [STEP 2], Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes [SUSTAIN-6], and Peptide Innovation for Early Diabetes Treatment [PIONEER] 6), we compared the incidence of gastrointestinal adverse events during GLP-1RA initiation and titration in participants with and without concomitant metformin use. RESULTS Of 16,996 participants, 12,928 (76%) were treated with metformin. Concomitant metformin use did not increase the percentage of participants who developed gastrointestinal adverse events or their severity during the observation window. Among participants experiencing gastrointestinal adverse events, metformin use did not increase study product discontinuation. Within treatment arms (GLP-1RA and placebo), a numerically higher percentage of metformin nonusers experienced gastrointestinal adverse events and discontinued the study product compared with metformin users. CONCLUSIONS Concomitant metformin use does not increase occurrence of gastrointestinal symptoms during GLP-1RA initiation or impact GLP-1RA discontinuation.
DNA methylation rates scale with maximum lifespan across mammals
Authors: Samuel J. C. Crofts, Eric Latorre-Crespo, Tamir Chandra
Journal: Nature Aging (2023)

DNA methylation rates have previously been found to broadly correlate with maximum lifespan in mammals, yet no precise relationship has been observed. We developed a statistically robust framework to compare methylation rates at conserved age-related sites across mammals. We found that methylation rates negatively scale with maximum lifespan in both blood and skin. The emergence of explicit scaling suggests that methylation rates are, or are linked to, an evolutionary constraint on maximum lifespan acting across diverse mammalian lineages.
Thalamic deep brain stimulation in traumatic brain injury: a phase 1, randomized feasibility study
Authors: Nicholas D. Schiff, Joseph T. Giacino, Christopher R. Butson, Eun Young Choi, Jonathan L. Baker, Kyle P. O’Sullivan, Andrew P. Janson, Michael Bergin, Helen M. Bronte-Stewart, Jason Chua, Laurel DeGeorge, Sureyya Dikmen, Adam Fogarty, Linda M. Gerber, Mark Krel, Jose Maldonado, Matthew Radovan, Sudhin A. Shah, Jason Su, Nancy Temkin, Thomas Tourdias, Jonathan D. Victor, Abigail Waters, Stephanie A. Kolakowsky-Hayner, Joseph J. Fins, Andre G. Machado, Brian K. Rutt, Jaimie M. Henderson
Journal: Nature Medicine (2023)
The transcription factor Aiolos restrains the activation of intestinal intraepithelial lymphocytes
Authors: Kentaro Yomogida, Tihana Trsan, Raki Sudan, Patrick F. Rodrigues, Alina Ulezko Antonova, Harshad Ingle, Blanda Di Luccia, Patrick L. Collins, Marina Cella, Susan Gilfillan, Megan T. Baldridge, Eugene M. Oltz, Marco Colonna
Journal: Nature Immunology (2023)
Backfilling Patients in Phase I Dose-Escalation Trials Using Bayesian Optimal Interval Design (BOIN)
Authors: Yixuan Zhao, Ying Yuan, Edward L. Korn, Boris Freidlin
Journal: Clinical Cancer Research (2023)

In recent years, there has been increased interest in incorporation of backfilling into dose-escalation clinical trials, which involves concurrently assigning patients to doses that have been previously cleared for safety by the dose-escalation design. Backfilling generates additional information on safety, tolerability, and preliminary activity on a range of doses below the maximum tolerated dose (MTD), which is relevant for selection of the recommended phase II dose and dose optimization. However, in practice, backfilling may not be rigorously defined in trial protocols and implemented consistently. Furthermore, backfilling designs require careful planning to minimize the probability of treating additional patients with potentially inactive agents (and/or subtherapeutic doses). In this paper, we propose a simple and principled approach to incorporate backfilling into the Bayesian optimal interval design (BOIN). The design integrates data from the dose-escalation and backfilling components of the design and ensures that the additional patients are treated at doses where some activity has been seen. Simulation studies demonstrated that the proposed backfilling BOIN design (BF-BOIN) generates additional data for future dose optimization, maintains the accuracy of the MTD identification, and improves patient safety without prolonging the trial duration.
Development and External Validation of Models to Predict Need for Nursing Home Level of Care in Community-Dwelling Older Adults With Dementia
Authors: W. James Deardorff, Sun Y. Jeon, Deborah E. Barnes, W. John Boscardin, Kenneth M. Langa, Kenneth E. Covinsky, Susan L. Mitchell, Sei J. Lee, Alexander K. Smith
Journal: JAMA Internal Medicine (2023)

Most older adults living with dementia ultimately need nursing home level of care (NHLOC).
Types of On-Screen Content and Mental Health in Kindergarten Children
Authors: Haiwa Wang, Jin Zhao, Zhangsheng Yu, Hao Pan, Saishuang Wu, Qi Zhu, Yuanyuan Dong, Huilin Liu, Yunting Zhang, Fan Jiang
Journal: JAMA Pediatrics (2023)

Excessive screen time has been associated with a higher risk for mental health problems, but whether the associations differ by screen content types is unclear.
Electrocardiogram Recording in the Prone Position—Reply
Authors: Hao Zhang, Tong Liu, Kang-Yin Chen
Journal: JAMA Internal Medicine (2023)

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 Journals 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
Efficacy and Safety of Cilostazol in Mild Cognitive Impairment
Authors: Satoshi Saito, Keisuke Suzuki, Ryo Ohtani, Takakuni Maki, Hisatomo Kowa, Hisatsugu Tachibana, Kazuo Washida, Nobuya Kawabata, Toshiki Mizuno, Rie Kanki, Shinji Sudoh, Hiroshi Kitaguchi, Katsuro Shindo, Akihiro Shindo, Nobuyuki Oka, Keiichi Yamamoto, Fumihiko Yasuno, Chikage Kakuta, Ryosuke Kakuta, Yumi Yamamoto, Yorito Hattori, Yukako Takahashi, Yuriko Nakaoku, Shuichi Tonomura, Naoya Oishi, Toshihiko Aso, Akihiko Taguchi, Tatsuo Kagimura, Shinsuke Kojima, Masanori Taketsuna, Hidekazu Tomimoto, Ryosuke Takahashi, Hidenao Fukuyama, Kazuyuki Nagatsuka, Haruko Yamamoto, Masanori Fukushima, Masafumi Ihara, Masahiro Tsuji, Atsushi Ouchi, Miho Yamauchi
Journal: JAMA Network Open (2023)

Recent evidence indicates the efficacy of β-amyloid immunotherapy for the treatment of Alzheimer disease, highlighting the need to promote β-amyloid removal from the brain. Cilostazol, a selective type 3 phosphodiesterase inhibitor, promotes such clearance by facilitating intramural periarterial drainage.
Time-Series Analysis of First-Time Pediatric Speech Delays From 2018 to 2022
Authors: Brianna M. Goodwin Cartwright, Peter D. Smits, Sarah Stewart, Patricia J. Rodriguez, Samuel Gratzl, Charlotte Baker, Nicholas Stucky
Journal: JAMA Pediatrics (2023)

This cohort study evaluates changes in pediatric speech delay diagnoses before and after the COVID-19 pandemic.
Photobiomodulation Therapy to Treat Snakebites Caused by <i>Bothrops atrox</i>
Authors: Érica da Silva Carvalho, Andrea Renata do Nascimento Souza, Dessana Francis Chehuan Melo, Altair Seabra de Farias, Bruna Barbosa de Oliveira Macedo, Marco Aurélio Sartim, Mariela Costa Caggy, Beatriz de Alcântara Rodrigues, Gabriela Salini Ribeiro, Heloísa Nunes Reis, Felipe Queiroz Araújo, Iran Mendonça da Silva, André Sachett, Vanderson de Souza Sampaio, Antônio Alcirley da Silva Balieiro, Stella Regina Zamuner, João Ricardo Nickenig Vissoci, Lioney Nobre Cabral, Wuelton Marcelo Monteiro, Jacqueline de Almeida Gonçalves Sachett
Journal: JAMA Internal Medicine (2023)

Bothrops venom acts almost immediately at the bite site and causes tissue damage.
Determinants of clinical response to empirical antibiotic treatment in patients with cirrhosis and bacterial and fungal infections—Results from the ICA “Global Study” (EABCIR-Global Study)
Authors: Rakhi Maiwall, Salvatore Piano, Virendra Singh, Paolo Caraceni, Carlo Alessandria, Javier Fernandez, Elza Cotrim Soares, Dong Joon Kim, Sung Eun Kim, Monica Marino, Julio Vorobioff, Rita de Cassia Ribeiro Barea, Manuela Merli, Laure Elkrief, Victor Vargas, Aleksander Krag, Shivaram Prasad Singh, Laurentius Adrianto Lesmana, Claudio Toledo, Sebastian Marciano, Xavier Verhelst, Florence Wong, Nicolas Intagliata, Liane Rabinowich, Luis Colombato, Sang Gyune Kim, Alexander Gerbes, Francois Durand, Juan Pablo Roblero, Kalyan Ram Bhamidimarri, Marina Maevskaya, Eduardo Fassio, Hyoung Su Kim, Jae Seok Hwang, Pere Gines, Tony Bruns, Adrian Gadano, Paolo Angeli, Shiv Kumar Sarin
Journal: Hepatology (2023)

Background: The administration of an appropriate empirical antibiotic treatment is essential in cirrhosis and severe bacterial infections. We aimed to investigate the predictors of clinical response of empirical antibiotic treatment in a prospective cohort of patients with cirrhosis and bacterial and fungal infections included in the International Club of Ascites “Global Study.” Methods: Patients hospitalized with cirrhosis and bacterial/fungal infection were prospectively enrolled at 46 centers. Clinical response to antibiotic treatment was defined according to changes in markers of infection/inflammation, vital signs, improvement of organ failure, and results of cultures. Results: From October 2015 to September 2016, 1302 patients were included at 46 centers. A clinical response was achieved in only 61% of cases. Independent predictors of lack of clinical response to empirical treatment were C-reactive protein (OR = 1.16; 95% CI = 1.02–1.31), blood leukocyte count (OR = 1.39;95% CI = 1.09–1.77), serum albumin (OR = 0.70; 95% CI = 0.55–0.88), nosocomial infections (OR = 1.96; 95% CI = 1.20–2.38), pneumonia (OR = 1.75; 95% CI = 1.22–2.53), and ineffective treatment according to antibiotic susceptibility test (OR = 5.32; 95% CI = 3.47–8.57). Patients with a lack of clinical response to first-line antibiotic treatment had a significantly lower resolution rate of infections (55% vs. 96%; p &lt; 0.001), a higher incidence of second infections (29% vs. 15%; p &lt; 0.001), shock (35% vs. 7%; p &lt; 0.001) and new organ failures (52% vs. 19 %; p &lt; 0.001) than responders. Clinical response to empirical treatment was an independent predictor of 28-day survival ( subdistribution = 0.20; 95% CI = 0.14–0.27). Conclusions: Four out of 10 patients with cirrhosis do not respond to the first-line antibiotic therapy, leading to lower resolution of infections and higher mortality. Broader-spectrum antibiotics and strategies targeting systemic inflammation may improve prognosis in patients with a high degree of inflammation, low serum albumin levels, and severe liver impairment.
Single-cell methylation analysis of brain tissue prioritizes mutations that alter transcription
Authors: Jonathan Flint, Matthew G. Heffel, Zeyuan Chen, Joel Mefford, Emilie Marcus, Patrick B. Chen, Jason Ernst, Chongyuan Luo
Journal: Cell Genomics (2023)

Relating genetic variants to behavior remains a fundamental challenge. To assess the utility of DNA methylation marks in discovering causative variants, we examined their relationship to genetic variation by generating single-nucleus methylomes from the hippocampus of eight inbred mouse strains. At CpG sequence densities under 40 CpG/Kb, cells compensate for loss of methylated sites by methylating additional sites to maintain methylation levels. At higher CpG sequence densities, the exact location of a methylated site becomes more important, suggesting that variants affecting methylation will have a greater effect when occurring in higher CpG densities than in lower. We found this to be true for a variant's effect on transcript abundance, indicating that candidate variants can be prioritized based on CpG sequence density. Our findings imply that DNA methylation influences the likelihood that mutations occur at specific sites in the genome, supporting the view that the distribution of mutations is not random.