tbuckley/cabot-search huggingface dataset:
Pharmacotherapy for Alcohol Use Disorder
Authors: Wenming Shi
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
Letter to the Editor: Statins as potential confounding factors to investigate the association between the use of GLP-1 receptor agonists and risk of HCC
Authors: Zheng Li, Yi Zhang, Ying Li, Jie Lan, Yuzhu Hu, Jiayun Yu, Qianqian Meng, Bingwen Zou
Journal: Hepatology (2024)

To the editor, The glucagon-like peptide-1 (GLP-1) receptor agonists were listed as the top of Science's 2023 Breakthrough of the Year on December 15, 2023. With great interest, we read the Scandinavian cohort study to investigate the association of GLP-1 receptor agonists with serious liver events among patients with type 2 diabetes by Engström et al1 published in Hepatology in December 2023. We congratulate Engström et al for their remarkable contribution in this intriguing subject.1 No significant association was found between the use of GLP-1 receptor agonists (vs. dipeptidyl peptidase-4 inhibitors) and the risk of HCC.1 The results were consistent in the sensitivity analyses by the authors.1 However, some novel findings, regarding statins and cardiovascular disease (CVD),2–4 open a new path to reevaluate the potential biases and confounding factors. Bell et al2 found that individuals with CVD (especially for atherosclerosis) have an increased risk of developing cancer (including HCC) compared with those without CVD. Statin use is associated with reduced HCC risk, which may be attributed to the reduced risk of CVD or cirrhosis.2–4 To facilitate understanding, Figure 1 presents the potentially multidimensional relationships among statins/GLP-1 receptor agonists, CVD/cirrhosis, and HCC. As shown in Figure 1, statins are potential confounding factors to investigate the aforementioned targeted relationships. There is a possibility that the use of GLP-1 receptor agonists (vs. dipeptidyl peptidase-4 inhibitors) is significantly associated with the reduced risk of HCC when the potential statins use could be well balanced between the GLP-1 receptor agonists group and dipeptidyl peptidase-4 inhibitors group.FIGURE 1: Statins as potential confounding factors to investigate the association between use of GLP-1 receptor agonists and risk of HCC through multidimensional complex pathways. Abbreviations: DPP4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide-1.The authors conducted prespecified subgroup analyses in the results section by age group (35–64 y and ≥65–84 y).1 However, the 65 age critical value setting is not an acknowledged evidence-based criterion for determining subgroups in the relevant investigation.5 Therefore, more detailed age-subgroup analyses are necessary to reduce the risk of criteria selection bias and get more convincing results. In addition, the more comprehensive subgroup analyses by different diabetes/CVD courses and medication histories are warranted to reach the ultimate truth of the association between GLP-1 receptor agonists and the risk of HCC.
Phasic/tonic glial GABA differentially transduce for olfactory adaptation and neuronal aging
Authors: Hankui Cheng, Du Chen, Xiao Li, Umar Al-Sheikh, Duo Duan, Yuedan Fan, Linhui Zhu, Wanxin Zeng, Zhitao Hu, Xiajing Tong, Guohua Zhao, Yongming Zhang, Wenjuan Zou, Shumin Duan, Lijun Kang
Journal: Neuron (2024)
Tuning of plasma cell lifespan by competition explains the longevity and heterogeneity of antibody persistence
Authors: Benjamin D. Simons, Omer Karin
Journal: Immunity (2024)

Plasma cells that emerge after infection or vaccination exhibit heterogeneous lifespans; most survive for days to months, whereas others persist for decades, providing antigen-specific long-term protection. We developed a mathematical framework to explore the dynamics of plasma cell removal and its regulation by survival factors. Analyses of antibody persistence following hepatitis A and B and HPV vaccination revealed specific patterns of longevity and heterogeneity within and between responses, implying that this process is fine-tuned near a critical "flat" state between two dynamic regimes. This critical state reflects the tuning of rates of the underlying regulatory network and is highly sensitive to variation in parameters, which amplifies lifespan differences between cells. We propose that fine-tuning is the generic outcome of competition over shared survival signals, with a competition-based mechanism providing a unifying explanation for a wide range of experimental observations, including the dynamics of plasma cell accumulation and the effects of survival factor deletion. Our theory is testable, and we provide specific predictions.
Medical Student Intent to Practice in Underserved Areas
Authors: Kai Salas Akimoto, Denise Taitano-Ritter, Kekoa Taparra
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
Hepatic malonyl-CoA synthesis restrains gluconeogenesis by suppressing fat oxidation, pyruvate carboxylation, and amino acid availability
Authors: Stanislaw Deja, Justin A. Fletcher, Chai-Wan Kim, Blanka Kucejova, Xiaorong Fu, Monika Mizerska, Morgan Villegas, Natalia Pudelko-Malik, Nicholas Browder, Melissa Inigo-Vollmer, Cameron J. Menezes, Prashant Mishra, Eric D. Berglund, Jeffrey D. Browning, John P. Thyfault, Jamey D. Young, Jay D. Horton, Shawn C. Burgess
Journal: Cell Metabolism (2024)

Acetyl-CoA carboxylase (ACC) promotes prandial liver metabolism by producing malonyl-CoA, a substrate for de novo lipogenesis and an inhibitor of CPT-1-mediated fat oxidation. We report that inhibition of ACC also produces unexpected secondary effects on metabolism. Liver-specific double ACC1/2 knockout (LDKO) or pharmacologic inhibition of ACC increased anaplerosis, tricarboxylic acid (TCA) cycle intermediates, and gluconeogenesis by activating hepatic CPT-1 and pyruvate carboxylase flux in the fed state. Fasting should have marginalized the role of ACC, but LDKO mice maintained elevated TCA cycle intermediates and preserved glycemia during fasting. These effects were accompanied by a compensatory induction of proteolysis and increased amino acid supply for gluconeogenesis, which was offset by increased protein synthesis during feeding. Such adaptations may be related to Nrf2 activity, which was induced by ACC inhibition and correlated with fasting amino acids. The findings reveal unexpected roles for malonyl-CoA synthesis in liver and provide insight into the broader effects of pharmacologic ACC inhibition.
Efforts in Organized Medicine to Eliminate Harmful Race-Based Clinical Algorithms
Authors: Emily C. Cleveland Manchanda, Blair Aikens, Fernando De Maio, William Jordan, Jennifer T. Brown, Karthik Sivashanker, Aletha Maybank
Journal: JAMA Network Open (2024)

This survey study describes efforts to eliminate harmful race-based clinical algorithms among state or territorial medical associations and specialty societies in the US.
Why I . . . cosplay
Authors: Adrian O’Dowd
Journal: BMJ (2024)

Playing a fantasy character in your spare time may just be the secret to being a better doctor, if the experience of paediatrics trainee Cristina Costache is anything to go by.Costache takes part in cosplay-"costume play"-in which a person dresses up as a character from a film, TV show, book, or video game, and acts as them at conventions or events where there are celebrity guests, professional photo shoots, stage panels, and retail exhibitors celebrating the genre."Cosplay is super fun," she says."You can gather with other people who enjoy cosplay at events such as MCM Comic Con."
Challenges of using whole genome sequencing in population newborn screening
Authors: Rachel Horton, Caroline F Wright, Helen V Firth, Clare Turnbull, Robin Lachmann, Richard S Houlston, Anneke Lucassen
Journal: BMJ (2024)

<b>Rachel Horton and colleagues</b> argue that making sense of genomic variation in newborn babies is difficult, so the UK Generation Study will analyse only a tiny proportion of the genome. Why then is it collecting entire genomes?
Behavioral strategy shapes activation of the Vip-Sst disinhibitory circuit in visual cortex
Authors: Alex Piet, Nick Ponvert, Douglas Ollerenshaw, Marina Garrett, Peter A Groblewski, Shawn Olsen, Christof Koch, Anton Arkhipov
Journal: Neuron (2024)

In complex environments, animals can adopt diverse strategies to find rewards. How distinct strategies differentially engage brain circuits is not well understood. Here, we investigate this question, focusing on the cortical Vip-Sst disinhibitory circuit between vasoactive intestinal peptide-postive (Vip) interneurons and somatostatin-positive (Sst) interneurons. We characterize the behavioral strategies used by mice during a visual change detection task. Using a dynamic logistic regression model, we find that individual mice use mixtures of a visual comparison strategy and a statistical timing strategy. Separately, mice also have periods of task engagement and disengagement. Two-photon calcium imaging shows large strategy-dependent differences in neural activity in excitatory, Sst inhibitory, and Vip inhibitory cells in response to both image changes and image omissions. In contrast, task engagement has limited effects on neural population activity. We find that the diversity of neural correlates of strategy can be understood parsimoniously as the increased activation of the Vip-Sst disinhibitory circuit during the visual comparison strategy, which facilitates task-appropriate responses.
Effect of Ergocalciferol on β-Cell Function in New-Onset Type 1 Diabetes
Authors: Benjamin Udoka Nwosu, Sadichchha Parajuli, Rohit B. Sharma, Austin F. Lee
Journal: JAMA Network Open (2024)

This secondary analysis of a randomized clinical trial evaluates the effectiveness of ergocalciferol vs placebo in youths with newly diagnosed type 1 diabetes.
An integrative, multiscale view on neural theories of consciousness
Authors: Johan F. Storm, P. Christiaan Klink, Jaan Aru, Walter Senn, Rainer Goebel, Andrea Pigorini, Pietro Avanzini, Wim Vanduffel, Pieter R. Roelfsema, Marcello Massimini, Matthew E. Larkum, Cyriel M.A. Pennartz
Journal: Neuron (2024)

How is conscious experience related to material brain processes? A variety of theories aiming to answer this age-old question have emerged from the recent surge in consciousness research, and some are now hotly debated. Although most researchers have so far focused on the development and validation of their preferred theory in relative isolation, this article, written by a group of scientists representing different theories, takes an alternative approach. Noting that various theories often try to explain different aspects or mechanistic levels of consciousness, we argue that the theories do not necessarily contradict each other. Instead, several of them may converge on fundamental neuronal mechanisms and be partly compatible and complementary, so that multiple theories can simultaneously contribute to our understanding. Here, we consider unifying, integration-oriented approaches that have so far been largely neglected, seeking to combine valuable elements from various theories.
Screen Time, Sociodemographic Factors, and Psychological Well-Being Among Young Children
Authors: Soyang Kwon, Bridget Armstrong, Nina Wetoska, Selin Capan
Journal: JAMA Network Open (2024)

Importance Young children’s screen time increased during the COVID-19 lockdown in 2020, but it is unknown whether their screen time returned to prepandemic levels in 2021. Knowledge of the relationship between screen time and child development and health will inform prevention and intervention targets and strategies. Objective To evaluate screen time by family income and race and ethnicity in the prepandemic (ie, 2018, 2019) and pandemic (ie, 2020, 2021) periods and to examine the relationship between screen time and psychological well-being among young children in the US. Design, Setting, and Participants Cross-sectional population-based web or mail survey study of 2018-2021 National Survey of Children’s Health participants aged 6 months to 5 years. Exposure Daily screen time (&amp;amp;lt;1, 1, 2, 3, or ≥4 h/d) reported by participants’ primary caregivers. Main outcomes and Measures Flourishing and externalizing behaviors, as indicators of psychological well-being. All analyses were weighted, accounting for the complex survey sample design. Results Of the 48 775 participants (50.7% female), the proportion of those with high screen time (defined as ≥1 h/d for children aged 6 months-1 year and ≥2 h/d for children aged 2-5 years) was 48.5% (95% CI, 46.3%-50.7%) in 2018, 49.2% (95% CI, 47.0%-51.5%) in 2019, 55.3% (95% CI, 53.4%-57.2%) in 2020, and 50.0% (95% CI, 48.3%-51.6%) in 2021. Among children living in poverty (federal poverty level &amp;amp;lt;100%), the proportion of those with high screen time was 48.7% (95% CI, 42.8%-54.6%) in 2018, 52.0% (95% CI, 45.4%-58.6%) in 2019, 60.9% (95% CI, 55.4%-66.4%) in 2020, and 58.9% (53.7%-64.1%) in 2021. Adjusted odds ratio of flourishing was 0.66 (95% CI, 0.51-0.85), 0.81 (95% CI, 0.66-0.99), 0.68 (95% CI, 0.52-0.88), and 0.53 (95% CI, 0.42-0.69) for less than 1, 2, 3, and 4 or more hours per day vs 1 hour per day of screen time, respectively, among children aged 3 to 5 years. No association between screen time and flourishing was found among children aged 6 months to 2 years. An adjusted externalizing behavior score was higher by 0.2 points (95% CI, −0.1 to 0.5), 0.5 points (95% CI, 0.3 to 0.8), 1.3 points (95% CI, 1.0 to 1.6), and 2.1 points (95% CI, 1.7 to 2.5) for less than 1, 2, 3, and 4 or more hours per day vs 1 hour per day of screen time, respectively, among children aged 3 to 5 years. Conclusions and Relevance In this multiyear cross-sectional study of a representative sample of young children in the US, the increased prevalence of high screen time in 2020 returned to prepandemic levels in 2021; however, it remained elevated in children living in poverty. Two hours or more of daily screen time was associated with lower psychological well-being among preschool-aged children.
FDA Approval Summary: Enfortumab Vedotin plus Pembrolizumab for Cisplatin-Ineligible Locally Advanced or Metastatic Urothelial Carcinoma
Authors: William F. Maguire, Daniel Lee, Chana Weinstock, Xin Gao, Catharine C. Bulik, Sundeep Agrawal, Elaine Chang, Salaheldin S. Hamed, Erik W. Bloomquist, Shenghui Tang, Richard Pazdur, Paul G. Kluetz, Laleh Amiri-Kordestani, Daniel L. Suzman
Journal: Clinical Cancer Research (2024)

On April 3, 2023, the FDA granted accelerated approval to enfortumab vedotin-ejfv (EV) plus pembrolizumab for treatment of patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy. Substantial evidence of effectiveness was obtained from EV-103/KEYNOTE-869 (NCT03288545), a multicohort study. Across cohorts, a total of 121 patients received EV 1.25 mg/kg (maximum of 125 mg) intravenously on days 1 and 8 of a 21-day cycle plus pembrolizumab 200 mg intravenously on day 1 of each 21-day cycle until disease progression or unacceptable toxicity. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DoR), determined by blinded independent central review using RECIST v1.1. The confirmed ORR in 121 patients was 68% (95% confidence interval, 59-76), including 12% with complete responses. The median DoR for the 82 responders was 22 months (range: 1+ to 46+). The safety profile of the combination comprised adverse reactions expected to occur with the corresponding monotherapies, but with overall increased frequency of adverse reactions, including skin toxicity, pneumonitis, and peripheral neuropathy. The article summarizes the data and the FDA thought process supporting accelerated approval of EV + pembrolizumab, as well as additional exploratory analyses conducted by the FDA.
A Nanopore Sequencing-based Pharmacogenomic Panel to Personalize Tuberculosis Drug Dosing
Authors: Renu Verma, Kesia Esther da Silva, Neesha Rockwood, Roeland E. Wasmann, Nombuso Yende, Taeksun Song, Eugene Kim, Paolo Denti, Robert J. Wilkinson, Jason R. Andrews
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Standardized dosing of antitubercular drugs leads to variable plasma drug levels, which are associated with adverse drug reactions, delayed treatment response, and relapse. Mutations in genes affecting drug metabolism explain considerable interindividual pharmacokinetic variability; however, pharmacogenomic assays that predict metabolism of antitubercular drugs have been lacking.
gp120-derived amyloidogenic peptides form amyloid fibrils that increase HIV-1 infectivity
Authors: Suiyi Tan, Wenjuan Li, Chan Yang, Qingping Zhan, Kunyu Lu, Jun Liu, Yong-Mei Jin, Jin-Song Bai, Lin Wang, Jinqing Li, Zhaofeng Li, Fei Yu, Yu-Ye Li, Yue-Xun Duan, Lu Lu, Tong Zhang, Jiaqi Wei, Lin Li, Yong-Tang Zheng, Shibo Jiang, Shuwen Liu
Journal: Cellular and Molecular Immunology (2024)
Helen Salisbury: The Generation Study
Authors: Helen Salisbury
Journal: BMJ (2024)

The arrival of a new baby brings fierce and strong emotions, and for some parents the feelings evoked by a tiny, dependent person are almost frightening in their intensity.You know without question that you'll do everything in your power to protect your child, keep them free of illness, and help them grow up to be as happy and healthy as possible.So, when the UK's Newborn Genomes Programme offers to look for hundreds of rare diseases that could affect your child, just by taking a blood sample, most parents are likely to say yes.This programme, also known as the Generation Study, is run by Genomics England, a company owned by the Department of Health and Social Care.It proposes to collect and analyse the genetic information of 100 000 babies, looking for variants linked to genetic conditions, and the study is set to start recruiting participants this year. 1 The idea is that, if we can detect conditions before a child becomes symptomatic, we may be able to intervene to prevent disease.This is the goal of every screening programme-to detect conditions at a stage when treatment is simpler or preventing severe disease is possible.
Lung Cancer in Switzerland
Authors: Raphael Sven Werner, Alessandra Curioni-Fontecedro, Laetitia A. Mauti, Alfredo Addeo, Solange Peters, Thomas Frauenfelder, Milo A. Puhan, Martina Haberecker, Lukas Bubendorf, Tobias Finazzi, Matthias Guckenberger, Stefano Cafarotti, Thomas Geiser, Isabelle Opitz
Journal: Journal of Thoracic Oncology (2024)
Population coding of strategic variables during foraging in freely moving macaques
Authors: Neda Shahidi, Melissa Franch, Arun Parajuli, Paul Schrater, Anthony Wright, Xaq Pitkow, Valentin Dragoi
Journal: Nature Neuroscience (2024)

Abstract Until now, it has been difficult to examine the neural bases of foraging in naturalistic environments because previous approaches have relied on restrained animals performing trial-based foraging tasks. Here we allowed unrestrained monkeys to freely interact with concurrent reward options while we wirelessly recorded population activity in the dorsolateral prefrontal cortex. The animals decided when and where to forage based on whether their prediction of reward was fulfilled or violated. This prediction was not solely based on a history of reward delivery, but also on the understanding that waiting longer improves the chance of reward. The task variables were continuously represented in a subspace of the high-dimensional population activity, and this compressed representation predicted the animal’s subsequent choices better than the true task variables and as well as the raw neural activity. Our results indicate that monkeys’ foraging strategies are based on a cortical model of reward dynamics as animals freely explore their environment.
Neuron–astrocyte metabolic coupling facilitates spinal plasticity and maintenance of inflammatory pain
Authors: Sebastián Marty-Lombardi, Shiying Lu, Wojciech Ambroziak, Katrin Schrenk-Siemens, Jialin Wang, Anna A DePaoli-Roach, Anna M Hagenston, Hagen Wende, Anke Tappe-Theodor, Manuela Simonetti, Hilmar Bading, Jürgen G Okun, Rohini Kuner, Thomas Fleming, Jan Siemens
Journal: Nature Metabolism (2024)

Abstract Long-lasting pain stimuli can trigger maladaptive changes in the spinal cord, reminiscent of plasticity associated with memory formation. Metabolic coupling between astrocytes and neurons has been implicated in neuronal plasticity and memory formation in the central nervous system, but neither its involvement in pathological pain nor in spinal plasticity has been tested. Here we report a form of neuroglia signalling involving spinal astrocytic glycogen dynamics triggered by persistent noxious stimulation via upregulation of the Protein Targeting to Glycogen (PTG) in spinal astrocytes. PTG drove glycogen build-up in astrocytes, and blunting glycogen accumulation and turnover by Ptg gene deletion reduced pain-related behaviours and promoted faster recovery by shortening pain maintenance in mice. Furthermore, mechanistic analyses revealed that glycogen dynamics is a critically required process for maintenance of pain by facilitating neuronal plasticity in spinal lamina 1 neurons. In summary, our study describes a previously unappreciated mechanism of astrocyte–neuron metabolic communication through glycogen breakdown in the spinal cord that fuels spinal neuron hyperexcitability.