tbuckley/cabot-search huggingface dataset:
Authors' Reply: Pharmacokinetic Issue May Influence the Perceived Cardiac Risk Posed by Ondansetron in Patients Undergoing Chronic Hemodialysis
Authors: Sherin Ismail, Michele Jonsson Funk, Jennifer E. Flythe
Journal: Journal of the American Society of Nephrology (2024)

We thank Hung and Chao1 for their interest in our study and their laudatory comments regarding the importance of the subject and the comprehensiveness of the analysis.2 In subgroup analyses, we found that patients using at least one other medication with known risk of Torsades de Pointes at the time of ondansetron initiation may have had a lower 10-day relative risk of sudden cardiac death compared with patients not using such medications at the time of ondansetron initiation. Small subgroup sample sizes limited a formal assessment of statistical interaction and also warrant caution when interpreting these findings. Hung and Chao propose that these unexpected findings, albeit exploratory in nature, may be attributable to a pharmacokinetic interaction. Specifically, they posit that coprescription of a proton pump inhibitor, a drug that induces hepatic 1A2 expression, could lessen the risk of sudden cardiac death by decreasing the serum concentration of ondansetron. We agree with the authors that this is a possible explanation for the finding. However, ondansetron is a substrate for multiple hepatic cytochrome P (CYP)-450 enzymes, including CYP1A2, CYP2D6, and CYP3A4. In vitro studies suggest that, in the presence of an inhibitor for one metabolizing enzyme, the other metabolizing enzymes would compensate, resulting in minimal change to the rate of ondansetron elimination.3 Although it is unknown whether a drug–drug interaction may have influenced the subgroup findings in our antiemetic study, the importance of drug–drug interactions should not be underestimated. In a prior study, we showed the potential for drug–drug interactions to potentiate the risk of sudden cardiac death associated with initiation of QT-prolonging drugs in the hemodialysis population.3 In an analysis of 72,559 individuals receiving maintenance hemodialysis, we showed that existing use of proton pump inhibitors, competitive inhibitors of CYP 2C19, enhances the 1-year risk of sudden cardiac death associated with the initiation of citalopram or escitalopram (drugs with known risks of Torsades de Pointes).4 Taken together, Hung and Chao's hypothesis and our prior drug interaction research (1) emphasize the importance of a further study of drug–drug interactions in the hemodialysis population and (2) underscore the urgency of developing effective strategies for reducing polypharmacy and medication-related harms in this population.
Analysis of gene expression in the postmortem brain of neurotypical Black Americans reveals contributions of genetic ancestry
Authors: Kynon J M Benjamin, Qiang Chen, Nicholas J Eagles, Louise A Huuki-Myers, Leonardo Collado-Torres, Joshua M Stolz, Geo Pertea, Joo Heon Shin, Apuã C M Paquola, Thomas M Hyde, Joel E Kleinman, Andrew E Jaffe, Shizhong Han, Daniel R Weinberger
Journal: Nature Neuroscience (2024)

Abstract Ancestral differences in genomic variation affect the regulation of gene expression; however, most gene expression studies have been limited to European ancestry samples or adjusted to identify ancestry-independent associations. Here, we instead examined the impact of genetic ancestry on gene expression and DNA methylation in the postmortem brain tissue of admixed Black American neurotypical individuals to identify ancestry-dependent and ancestry-independent contributions. Ancestry-associated differentially expressed genes (DEGs), transcripts and gene networks, while notably not implicating neurons, are enriched for genes related to the immune response and vascular tissue and explain up to 26% of heritability for ischemic stroke, 27% of heritability for Parkinson disease and 30% of heritability for Alzheimer’s disease. Ancestry-associated DEGs also show general enrichment for the heritability of diverse immune-related traits but depletion for psychiatric-related traits. We also compared Black and non-Hispanic white Americans, confirming most ancestry-associated DEGs. Our results delineate the extent to which genetic ancestry affects differences in gene expression in the human brain and the implications for brain illness risk.
Federal Trade Commission Actions on Prescription Drugs, 2000-2022
Authors: C. Joseph Ross Daval, Alexander C. Egilman, Ameet Sarpatwari, Aaron S. Kesselheim
Journal: JAMA (2024)

The Federal Trade Commission's (FTC) oversight role in the pharmaceutical market is critical to the health of patients and the health care system. This study characterized the FTC's policy on the pharmaceutical market in recent decades, identifying the types of actions it has favored, barriers it has faced, and authorities that remain untested.
What Are Humans Doing in the Loop? Co-Reasoning and Practical Judgment When Using Machine Learning-Driven Decision Aids
Authors: Sabine Salloch, Andreas Eriksen
Journal: The American Journal of Bioethics (2024)

Within the ethical debate on Machine Learning-driven decision support systems (ML_CDSS), notions such as "human in the loop" or "meaningful human control" are often cited as being necessary for ethical legitimacy. In addition, ethical principles usually serve as the major point of reference in ethical guidance documents, stating that conflicts between principles need to be weighed and balanced against each other. Starting from a neo-Kantian viewpoint inspired by Onora O'Neill, this article makes a concrete suggestion of how to interpret the role of the "human in the loop" and to overcome the perspective of rivaling ethical principles in the evaluation of AI in health care. We argue that patients should be perceived as "fellow workers" and epistemic partners in the interpretation of ML_CDSS outputs. We further highlight that a meaningful process of integrating (rather than weighing and balancing) ethical principles is most appropriate in the evaluation of medical AI.
Adverse Consequences of Legalization of Edible Cannabis in Older Adults
Authors: Lona Mody, Sharon K. Inouye
Journal: JAMA Internal Medicine (2024)

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 2024 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
The Physician’s Calling and Science Promote Health Equity and Outcomes
Authors: Gideon Steinbach
Journal: JAMA Pediatrics (2024)

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 Pediatrics 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 2024 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 Pediatrics journal
Susceptibility to innate immune activation in genetically-mediated myocarditis
Authors: Daniel F Selgrade, Dominic E Fullenkamp, Ivana A Chychula, Binjie Li, Lisa Dellefave-Castillo, Adi D Dubash, Joyce Ohiri, Tanner O Monroe, Malorie Blancard, Garima Tomar, Cory Holgren, Paul W Burridge, Alfred L George, Alexis R Demonbreun, Megan J Puckelwartz, Sharon A George, Igor R Efimov, Kathleen J Green, Elizabeth M McNally
Journal: Journal of Clinical Investigation (2024)

Background: Myocarditis is clinically characterized by chest pain, arrhythmias, and heart failure, and treatment for myocarditis is often supportive. Mutations in DSP, a gene encoding the desmosomal protein desmoplakin, have been increasingly implicated in myocarditis with biomarkers and pathological features indistinguishable from other forms of myocarditis. DSP-associated myocarditis can progress to dilated cardiomyopathy with heightened arrhythmia risk. Methods: To model the cardiomyocyte aspects of DSP-associated myocarditis and assess the role of innate immunity, we generated engineered heart tissues (EHTs) from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from patients and gene-edited healthy control hiPSC lines. Homozygous and heterozygous DSP disrupted EHTs were generated to contain 90% hiPSC-CMs and 10% healthy control human cardiac fibroblasts. We measured innate immune activation and function at baseline and in response to Toll-like receptor (TLR) stimulation in EHTs. Results: At baseline, DSP-/- EHTs displayed a transcriptomic signature of immune activation which was mirrored by EHT cytokine release. Importantly, DSP-/- EHTs were hypersensitive to TLR stimulation demonstrating greater contractile function impairment compared to isogenic controls. Compared to homozygous DSP-/- EHTs, heterozygous DSP patient-derived EHTs had less functionally impairment but also displayed heightened sensitivity to TLR stimulation. When subjected to strain, heterozygous DSP EHTs developed greater functional deficit indicating reduced contractile reserve compared to healthy control. Colchicine or NFΚB inhibitors improved baseline force production and strain-induced force deficits in DSP EHTs. Genomic correction of DSP p.R1951X using adenine base editing reduced inflammatory biomarker release from EHTs. Conclusions: Genetic reduction of DSP renders cardiomyocytes susceptible to innate immune activation and strain-dependent contractile deficits. EHTs replicate electrical and contractile phenotypes seen in human myocarditis implicating cytokine release as a key part of the myogenic susceptibility to inflammation. This heightened innate immune activation and sensitivity is a target for clinical intervention.
Maintenance of Certification’s Value to Patients and Physicians—Reply
Authors: Robert O. Roswell, Erica N. Johnson, Rajeev Jain
Journal: JAMA (2024)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 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
Intra-Arrest Transport vs On-Scene Cardiopulmonary Resuscitation for Children—Scoop and Run vs Stay and Play
Authors: Vinay M. Nadkarni, Janice Tijssen, Vanessa Denny
Journal: JAMA Network Open (2024)

Masashi Okubo, MD, MS; Sho Komukai, PhD; Junichi Izawa, MD, DrPH; SunHee Chung, MD; Ian R. Drennan, ACP, PhD; Brian E. Grunau, MD, MHSc; Joshua R. Lupton, MD, MPH, MPhil; Sriram Ramgopal, MD; Thomas D. Rea, MD, MPH; Clifton W. Callaway, MD, PhD
Beard Contamination With 131I Diagnosed by SPECT/CT in a Patient With Differentiated Thyroid Cancer
Authors: Jacek Makarewicz, Jan Rudzki
Journal: Clinical Nuclear Medicine (2024)

Abnormal focal accumulation of 131 I is generally a reliable indicator of differentiated thyroid cancer metastases. However, many examples of false-positive 131 I uptake were reported, some of them of unusual nature. We report a case of 32-year-old man with differentiated thyroid cancer who underwent thyroid remnants ablation with radioiodine. An area of considerable 131 I uptake projecting onto lateral cervical areas was detected on posttherapy planar whole-body scan. Neck SPECT/CT scan was done to elucidate localization of the uptake, and activity was found in the patient's beard.
Contemporary Prestroke Dual Antiplatelet Use and Symptomatic Intracerebral Hemorrhage Risk After Thrombolysis
Authors: Teng J. Peng, Lee H. Schwamm, Gregg C. Fonarow, Ameer E. Hassan, Michelle Hill, Steven R. Messé, Fatima Coronado, Guido J. Falcone, Richa Sharma
Journal: JAMA Neurology (2024)

Intravenous alteplase (IV-tPA) can be administered to patients with acute ischemic stroke but is associated with symptomatic intracerebral hemorrhage (sICH). It is unclear if patients taking prestroke dual antiplatelet therapy (DAPT) are at higher risk of sICH.
Pharmacokinetic Issue May Influence the Perceived Cardiac Risk Posed by Ondansetron in Patients Undergoing Chronic Hemodialysis
Authors: Kuo-Chin Hung, Chia-Ter Chao
Journal: Journal of the American Society of Nephrology (2024)

The JASN article titled "Ondansetron and the Risk of Sudden Cardiac Death among Individuals Receiving Maintenance Hemodialysis"1 provides a crucial exploration of treatment considerations for patients undergoing chronic hemodialysis. The authors use a comprehensive approach to validate the association, considering outcome type, ascertainment duration, indications, and the non-cancer subgroup. They propose that the heightened cardiac risk associated with ondansetron may be linked to its side effect of QT prolongation. Unexpectedly, they observe that concurrent use of other QT-prolonging medications mitigates this risk. We believe that pharmacokinetic issue may underlie this phenomenon. In human cells, ondansetron undergoes hepatic metabolism by various cytochrome P450 forms, including CYP1A1, 1A2, 2D6, and 3A subfamily enzymes.2 As an antiemetic agent, ondansetron is frequently coprescribed with other gastrointestinal medications that may act as inducers or inhibitors of cytochrome P450 enzymes. For instance, proton pump inhibitors such as omeprazole/rabeprazole induce hepatic 1A2 expression,3 while H2 blockers such as cimetidine and ranitidine are potent CYP2D6 inhibitors. The concurrent use of other QT-prolonging medications may indicate additional coprescribed agents affecting cytochrome P450 enzyme activity, resulting in fluctuations in ondansetron serum levels and influencing end points. A Medicare database analysis reveals a significant prevalence (10.5%) of multidrug interactions involving ondansetron, higher than the overall prevalence (1.3%), with QT prolongation being a common adverse drug reaction in such cases.4 Given the increased risk of polypharmacy and drug interactions in patients undergoing chronic hemodialysis, it is essential to consider these factors. Furthermore, cigarette smoking and exposure to environmental toxins are known inducers of CYP1A1 and 1A2, representing an additional source of potential influences on ondansetron levels. To better understand the effect of concurrent cytochrome P450 enzyme inducers or inhibitors, we recommend a more comprehensive retrieval of the medication list, extending beyond those potentially causing QT prolongation or Torsades de Pointes. Incorporating this factor into analysis will contribute to a more accurate estimation of the ondansetron-associated risk in patients undergoing chronic hemodialysis.
Effect of Sleep Restriction on Adolescent Cognition by Adiposity
Authors: Lindsay M. Stager, Caroline S. Watson, Edwin W. Cook, Aaron D. Fobian
Journal: JAMA Neurology (2024)

Pediatric obesity is associated with impaired cognitive function; however, the mechanisms underlying this association demand assessment. Sleep may be a relevant moderator, as poor sleep predicts both increased adiposity and impaired cognitive function.
The Physician’s Calling and Science Promote Health Equity and Outcomes—Reply
Authors: Kemar V. Prussien, Lori E. Crosby, Lisa A. Schwartz
Journal: JAMA Pediatrics (2024)

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 Pediatrics 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 2024 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 Pediatrics journal
Matched vs Nonmatched Placebos in a Randomized Trial of COVID-19 Treatments
Authors: Gilmar Reis, Leonardo Cançado Monteiro Savassi, Thiago Santiago Ferreira, Luiza Lanna França Reis, Maria Izabel Campos Simplicio, Luciene Barra Ribeiro, Eduardo Augusto dos Santos Moreira Silva, Prince Kumar Lat, Ofir Harari, Jamie I. Forrest, Louis Dron, Jay J. H. Park, Kristian Thorlund, Edward J. Mills
Journal: JAMA Network Open (2024)

Matched placebo interventions are complex and resource intensive. Recent evidence suggests matched placebos may not always be necessary. Previous studies have predominantly evaluated potential bias of nonmatched placebos (ie, differing on dose, frequency of administration, or formulation) in pain and mental health, but to date no systematic examination has been conducted in infectious disease.
Testing theory of mind in large language models and humans
Authors: James W. A. Strachan, Dalila Albergo, Giulia Borghini, Oriana Pansardi, Eugenio Scaliti, Saurabh Gupta, Krati Saxena, Alessandro Rufo, Stefano Panzeri, Guido Manzi, Michael S. A. Graziano, Cristina Becchio
Journal: Nature Human Behaviour (2024)

At the core of what defines us as humans is the concept of theory of mind: the ability to track other people's mental states. The recent development of large language models (LLMs) such as ChatGPT has led to intense debate about the possibility that these models exhibit behaviour that is indistinguishable from human behaviour in theory of mind tasks. Here we compare human and LLM performance on a comprehensive battery of measurements that aim to measure different theory of mind abilities, from understanding false beliefs to interpreting indirect requests and recognizing irony and faux pas. We tested two families of LLMs (GPT and LLaMA2) repeatedly against these measures and compared their performance with those from a sample of 1,907 human participants. Across the battery of theory of mind tests, we found that GPT-4 models performed at, or even sometimes above, human levels at identifying indirect requests, false beliefs and misdirection, but struggled with detecting faux pas. Faux pas, however, was the only test where LLaMA2 outperformed humans. Follow-up manipulations of the belief likelihood revealed that the superiority of LLaMA2 was illusory, possibly reflecting a bias towards attributing ignorance. By contrast, the poor performance of GPT originated from a hyperconservative approach towards committing to conclusions rather than from a genuine failure of inference. These findings not only demonstrate that LLMs exhibit behaviour that is consistent with the outputs of mentalistic inference in humans but also highlight the importance of systematic testing to ensure a non-superficial comparison between human and artificial intelligences.
Survival outcomes following urgent lung transplantation in France and the USA
Authors: Arnaud Roussel, Edouard Sage, Pierre-Emmanuel Falcoz, Pascal Alexandre Thomas, Yves Castier, Elie Fadel, Françoise Le Pimpec-Barthes, François Tronc, Jacques Jougon, Philippe Lacoste, Johanna Claustre, Laurent Brouchet, Richard Dorent, Edward Cantu, Michael Harhay, Raphaël Porcher, Pierre Mordant
Journal: Thorax (2024)

Lung graft allocation can be based on a score (Lung Allocation Score) as in the USA or sequential proposals combined with a discrete priority model as in France. We aimed to analyse the impact of allocation policy on the outcome of urgent lung transplantation (LT).
Signatures of adaptation and purifying selection in highland populations of <i>Dasiphora fruticosa</i>
Authors: Fu-Sheng Yang, Min Liu, Xing Guo, Chao Xu, Juan Jiang, Weixue Mu, Dongming Fang, Yong-Chao Xu, Fu-Min Zhang, Ying-Hui Wang, Ting Yang, Hongyun Chen, Sunil Kumar Sahu, Ruirui Li, Guanlong Wang, Qiang Wang, Xun Xu, Song Ge, Huan Liu, Ya-Long Guo
Journal: Molecular Biology and Evolution (2024)

High mountains harbor a considerable proportion of biodiversity, but we know little about how diverse plants adapt to the harsh environment. Here we finished a high-quality genome assembly for Dasiphora fruticosa, an ecologically important plant distributed in the Qinghai-Tibetan Plateau and lowland of the Northern Hemisphere, and resequenced 592 natural individuals to address how this horticulture plant adapts to highland. Demographic analysis revealed D. fruticosa underwent a bottleneck after Naynayxungla Glaciation. Selective sweep analysis of two pairs of lowland and highland populations identified 63 shared genes related to cell wall organization or biogenesis, cellular component organization, and dwarfism, suggesting parallel adaptation to highland habitats. Most importantly, we found that stronger purging of estimated genetic load due to inbreeding in highland populations apparently contributed to their adaptation to the highest mountain. Our results revealed how plants could tolerate the extreme plateau, which could provide potential insights for species conservation and crop breeding.
Type 1 Brugada Pattern May Be Provoked by Ajmaline in Some Healthy Subjects: Results From a Clinical Trial
Authors: Bode Ensam, Chiara Scrocco, David Johnson, Yanushi D. Wijeyeratne, Rachel Bastiaenen, Belinda Gray, Chris Miles, Yael Ben-Haim, Stathis Papatheodorou, Sanjay Sharma, Michael Papadakis, Brian Devine, Peter W. Macfarlane, Elijah R. Behr
Journal: Circulation (2024)