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The Centers for Medicare & Medicaid Services (CMS) announced that it will provide access to certain glucagon-like peptide-1 (GLP-1) medications for weight loss for $50 a month through a new pilot program for Medicare beneficiaries.
To the Editor Dr Coté and colleagues reported the Sphincterotomy for Acute Recurrent Pancreatitis (SHARP) trial, a multicenter, double-blind, sham-controlled randomized clinical trial evaluating endoscopic retrograde cholangiopancreatography (ERCP) with minor papillotomy for adults with unexplained acute recurrent pancreatitis and pancreas divisum. Recurrent acute pancreatitis beyond 30 days occurred in 34.7% of participants (26/75) in the ERCP with minor papillotomy group vs 43.8% of participants (32/73) in the sham ERCP group (adjusted hazard ratio, 0.83 [95% CI, 0.49-1.41]), whereas pancreatitis within 30 days occurred in 14.7% vs 8.2%, respectively.
JAMA+ AI Associate Editor Yulin Hswen spoke with Emily Tat of Columbia University Irving Medical Center and NewYork-Presbyterian Hospital and Peter Brodeur of Beth Israel Deaconess Medical Center for JAMA+ AI Conversations about a research network dedicated to the evaluation of clinical AI.
This Medical News article discusses a large measles outbreak in the populous South Asian country and the global implications amid declines in vaccination.
About 13% of US adults reported using sleep aids most days in 2024, according to the US Centers for Disease Control and Prevention (CDC).
The phyla making up the major animal clade of Spiralia have been clear since the advent of molecular phylogenetics; the relationships between these spiralian phyla have not. The lack of consensus over the relationships between these important animal phyla might be a clue implying their emergence in an explosive radiation. Focussing on the five largest spiralian clades (Annelida, Brachiozoa, Mollusca, Nemertea, and Platyhelminthes) and using two phylogenomic datasets, we have applied site-bootstrapping and taxon-jackknifing to explore this example of taxonomic instability. Analyses of the 105 possible rooted trees relating them showed that interphylum branches are very short. Preference for rooting Spiralia on Platyhelminthes is enhanced by a long-branch artefact. Most analyses on the 15 unrooted trees showed a preference for the same topology but the support for this tree over other solutions was not significant. We conclude that the spiralian phyla emerged in rapid succession resulting in a difficult-to-resolve radiation. The deep history we infer for Spiralia has wide-ranging implications for our interpretation of Cambrian fossils and for the evolution of traits such as biomineralisation, segmentation, and larvae.
This trial investigates the diagnostic yield of transbronchial lung biopsy with a 1.1-mm cryoprobe vs 2.0-mm forceps.
Human Papillomaviruses (HPVs) are the underlying cause of several types of cancer; albeit, they are mostly known for their association with cervical carcinoma. The virions reach their target cells through a break in the epithelial barrier. After binding to heparan sulfate (HS) of the extracellular matrix (ECM), they are recruited via actin-dependent mechanisms to the cell surface, where they co-internalize with the entry factor CD151. The in vivo occurring active recruitment from the ECM to the cell surface may be bypassed in cell culture, where virions reach the cell surface simply by passive diffusion. To specifically investigate these early events of the infection cascade, we use HaCaT keratinocytes as they produce a robust ECM enabling abundant virion binding to ECM components such as HS before transfer to cell surface receptors and infection. Employing microscopy, we focus on the basal membrane that for virions is difficult to access by diffusion. We block the active recruitment from ECM attachment sites to the cell body, release the blocking, and monitor the association of virions with CD151 or HS. We observe quick virion recruitment from the ECM to the cell body within 15 min. During recruitment, virions associate with the tetraspanin CD151 present at the cell border or at filopodia. These virions are decorated with HS, which they lose in the next few hours, presumably prior to endocytosis. Our observations reveal a rapid step in the HPV infection cascade: the transfer of HS-coated virions from the ECM to CD151. This step is too fast to account for the asynchronous uptake of HPVs, which is likely driven by glycan and capsid processing.
Widespread antibiotic usage has resulted in the rapid evolution of drug-resistant bacterial pathogens. Resolving how pathogens respond to antibiotics under different contexts is critical for understanding disease emergence. It remains unclear how interactions between hosts and antibiotics impact pathogen evolution. Here, we evolved <i>Staphylococcus aureus,</i> a major bacterial pathogen, varying exposure to host and antibiotics to tease apart the contributions of these selective pressures on pathogen adaptation. After 12 passages, <i>S. aureus</i> evolving in <i>Caenorhabditis elegans</i> nematodes exposed to a sub-minimum inhibitory antibiotic concentration became highly virulent, regardless of whether the ancestral pathogen was methicillin-resistant (MRSA) or methicillin-sensitive (MSSA). Host and antibiotic selected for reduced drug susceptibility in MSSA while increasing MRSA total growth outside hosts. We identified mutations in genes involved in regulatory networks linking virulence and metabolism, suggesting that rapid adaptation to infect hosts may have pleiotropic effects. Mutations that arose in these genes were also enriched in clinical isolates associated with systemic infections in humans. Despite evolving in similar environments, MRSA and MSSA populations—differing only in the presence of an intact accessory gene—proceeded on divergent evolutionary paths, with MSSA populations exhibiting more similarities across replicates. Our results underscore the importance of the host context as a driver of virulence and antibiotic resistance.
The US Food and Drug Administration (FDA) approved a new medication to treat agitation associated with dementia due to Alzheimer disease.
Glucagon-like peptide-1 (GLP-1) receptor agonists may benefit people with psoriasis, a review published in JAMA Dermatology suggests.
This cross-sectional cohort study examines inhaler use among US adults with asthma and how demographic, socioeconomic, clinical, and heath care access factors may affect treatment disparities in this population.
This randomized trial assesses the effect of treatment with digoxin vs placebo on a composite of all-cause death or new-onset or worsening heart failure among patients with symptomatic rheumatic heart disease.
This study evaluated whether digoxin, when added to usual care, reduced the risk of death or new-onset or worsening heart failure in patients with symptomatic rheumatic heart disease (RHD).
<p>by Benjamin Parrell, Minju Bae, Chris Naber, Olivia A. Kim, Caroline A. Niziolek, Samuel D. McDougle</p>
Observed outcomes of our movements sometimes differ from our expectations. These sensory prediction errors recalibrate the brain’s internal models for motor control, reflected in alterations to subsequent movements that counteract these errors (motor adaptation). While leading theories suggest that all forms of motor adaptation are driven by learning from sensory prediction errors, dominant models of speech adaptation argue that adaptation results from integrating time-advanced copies of corrective feedback commands into feedforward motor programs. Here, we tested these competing theories of speech adaptation by inducing planned, but not executed, speech. Human speakers were prompted to speak a word and, on a subset of trials, were rapidly cued to withhold the prompted speech. On standard trials, speakers were exposed to real-time playback of their own speech with an auditory perturbation of the first formant to induce single-trial speech adaptation. Speakers experienced a similar sensory error on movement cancellation trials, hearing a perturbation applied to a recording of their speech from a previous trial at the time they would have spoken. Speakers adapted to auditory prediction errors in both contexts, altering the spectral content of spoken vowels to counteract formant perturbations even when no actual produced speech coincided with the perturbed feedback. Such adaptation was not observed when participants passively listened to perturbed feedback without the intention to speak, ruling out observational learning as the cause of adaptation in movement cancellation trials. These results suggest that prediction errors, rather than corrective motor commands, drive audiomotor adaptation in speech, building on recent findings in reaching.
<p>by Alex M. Francette, Aakash Grover, Nathan Clark, Karen M. Arndt</p>
In eukaryotes, transcription elongation factors (TEFs) associate with RNA Polymerase II (RNAPII) to facilitate gene expression and couple transcription to co-transcriptional processes, including chromatin regulation and RNA processing. To further our understanding of TEF biology, we developed a domain-centric analysis pipeline to perform a broad survey of 10 TEF orthologs—Paf1, Ctr9, Cdc73, Rtf1, Leo1, Spt4, Spt5, Spt6, Spn1, and Elf1—across the Tree of Life and analyze their evolutionary patterns in a structural context. We report evidence for all 10 TEFs being present in the last eukaryotic common ancestor, indicating that mechanisms of TEF-mediated transcription regulation are both ancient and conserved. However, some early-diverging eukaryotic clades exhibit signs of altered TEF domain composition. A comparative phylogenetic analysis highlighted conserved regions of TEFs that are detected in both metazoans and fungi and other regions that appear clade-specific, detected only in metazoans. These observations, together with additional insights generated from evolutionary rate covariation analysis, shed light on under-characterized aspects of TEFs, including domains for which functions have yet to be dissected.
<p>by Joseph Westley, Paritosh Bedekar, Elizabeth Pursey, Mark D. Szczelkun, Mario Recker, Stineke van Houte, Edze R. Westra</p>
Bacterial pathogens commonly become drug resistant via horizontal acquisition of antimicrobial resistance genes (ARGs), which are often encoded on mobile genetic elements (MGEs). Although bacterial defence systems are typically considered barriers to horizontal gene transfer (HGT), previous studies revealed that bacteria with more restriction-modification (RM) systems (the most abundant bacterial defences) frequently carry more MGEs. It was suggested that this counterintuitive relationship might result from stronger selection for RM systems when exposure to costly MGEs increases. Here, we test this hypothesis using a combination of modeling and bioinformatics analysis of >40,000 bacterial genomes to better understand how eco-evolutionary feedbacks between selection for RM and acquisition of MGEs shape bacterial genome evolution. Our model predicts negative associations between HGT and RM, but only if RM diversity is high. By contrast, at low RM diversity, eco-evolutionary feedbacks drive the emergence of positive associations between HGT and RM. Consistent with these predictions, we identified negative relationships between acquired ARG counts and RM counts across species but positive relationships within individual species. Collectively, our work helps to understand how RM systems shape patterns of HGT of ARGs, which may offer opportunities for targeted surveillance of strains at higher risk of horizontally acquiring novel drug resistance alleles.
<p>by Nuria Galiana, Miguel B. Araújo</p>
The integration between biogeography and ecology has been historically limited due to the lack of data on biotic interactions across large spatial scales. The emergence of new methods and high-quality ecological network data at biogeographical scales are paving the way for a deeper integration of biogeography and ecology. This Essay examines this integration through three interconnected research areas: the effects of biotic interactions on species distributions; the influence of environmental gradients on biotic interactions; and the effects of biotic interactions on the environment. Recent progress and primary challenges are discussed, and suggestions provided on how to advance understanding of biodiversity patterns and processes across scales.
<p>by Asa Farahani, Zhen-Qi Liu, Filip Morys, Roqaie Moqadam, Yashar Zeighami, Mahsa Dadar, Alain Dagher, Bratislav Misic</p>
The brain and body undergo coordinated changes throughout the life span, yet studies of aging have traditionally examined these systems as separate entities. Here we ask how brain health relates to aging and peripheral biomarkers of metabolic and vascular function, including body mass index, blood pressure, and blood biochemistry. We use multivariate pattern learning to identify generalizable patterns of covariance between multi-modal neuroimaging data (structural, functional, diffusion, and arterial spin labeling MRI), demographic, and physiological markers in two large-scale deeply phenotyped datasets: the Human Connectome Project–Aging and UK Biobank. This data-driven approach isolates two principal axes of brain–body associations in both biological sexes. The first axis is driven by the dominant contribution of age. Across multiple brain measures, aging is associated with loss of brain structural integrity and cerebral vascular dysfunction. The second axis is driven by metabolic features, characterized by low high-density lipoprotein cholesterol, elevated body mass index, blood pressure, glycosylated hemoglobin, insulin, glucose, and alanine aminotransferase that predominantly converge on reduced cerebral perfusion. Importantly, the aging and the metabolic axes are independent of each other, meaning that age and metabolic dysfunction have separable influences on the brain. Finally, we show that deviations from a healthy metabolic profile are linked to cognitive deficits, particularly in females. Our study contributes to development of comprehensive translatable biomarkers for brain health assessment, and highlights the importance of metabolic health as a determinant of brain health in aging population.
The mammalian circadian clock is governed by a feedback loop in which the transcription activator CLOCK:BMAL1 induces expression of its inhibitors, PERs and CRYs, which form a complex with CK1δ, the main circadian kinase. However, the spatiotemporal dynamics of this feedback loop and the precise role of CK1δ remain incompletely understood. Using an inducible overexpression system, we show that nuclear availability of CK1δ is limited by both rapid nuclear degradation and active export of unassembled kinase, while cytoplasmic kinase is readily available for association with PERs. We demonstrate that CK1δ-mediated phosphorylation may disrupt PER2–CRY1 interaction, thereby resulting in cytoplasmic PER2 dimers containing substoichiometric amounts of CRY1. Analysis of endogenous PER2 localization in the context of an intact circadian clock reveals that PER2 accumulates in the cytoplasm late in the circadian cycle. Based on these findings, we propose that cytoplasmic accumulation of PER:CRY:CK1δ complexes contributes to the clearance of nuclear PER2, while the CK1δ-dependent release of CRY1 into the nucleus may sustain CLOCK:BMAL1 repression on DNA, supporting the transition from the early to the late repressive phase.
The experience of pain, like other interoceptive processes, has recently been conceptualized in terms of predictive coding and free energy frameworks. In these views, the brain integrates sensory, proprioceptive, and interoceptive signals to generate probabilistic inferences about upcoming events, which shape both the state and the perception of our inner body. Here, we ask whether it is possible to induce pain expectations by providing false faster (vs. slower) acoustic cardiac feedback before administering electrical cutaneous shocks. We test whether these expectations will shape both the perception of pain and the body’s physiological state toward prior predictions. Results confirmed that faster cardiac feedback elicited pain expectations that affected both perceptual pain judgments and the body’s physiological response. Perceptual pain judgments were biased toward the expected level of pain, such that participants illusorily perceived identical noxious stimuli as more intense and unpleasant. Physiological changes mirrored the predicted level of pain, such that participants’ actual cardiac response in anticipation of pain stimuli showed a deceleration in heart rate, in line with the well-known orienting cardiac response in anticipation of threatening stimuli (Experiment 1). In a control experiment, such perceptual and cardiac modulations were dramatically reduced when the feedback reproduced an exteroceptive, instead of interoceptive, cardiac feedback (Experiment 2). These findings show that cardiac perception can be understood as interoceptive inference that modulates both our perception and the physiological state of the body, thereby actively generating the interoceptive and autonomic consequences that have been predicted.
Ewing sarcoma is the second most common bone cancer in children and young adults. In 85% of patients, a translocation between chromosomes 11 and 22 results in a potent fusion oncoprotein, EWSR1::FLI1. EWSR1::FLI1 is the only genetic alteration in an otherwise unaltered genome of Ewing sarcoma tumors. The EWSR1 portion of the protein is an intrinsically disordered domain involved in transcriptional regulation by EWSR1::FLI1. The FLI portion of the fusion contains a DNA binding domain shown to bind core GGAA motifs and GGAA repeats. A small alpha-helix in the DNA binding domain of FLI1, DBD-α4 helix, is critical for the transcription function of EWSR1::FLI1. In this study, we aimed to understand the mechanism by which the DBD-α4 helix promotes transcription and therefore oncogenic transformation. We utilized a multi-omics approach to assess chromatin organization, active chromatin marks, genome binding, and gene expression in cells expressing EWSR1::FLI1 constructs with and without the DBD-α4 helix. Our studies revealed DBD-α4 helix is crucial for cooperative binding of EWSR1::FLI1 at GGAA microsatellites. This binding underlies many aspects of genome regulation by EWSR1::FLI1, such as formation of topologically associated domains (TADs), chromatin loops, enhancers, and productive transcription hubs.
<p>by Olav N. L. Aga, Sabrina J. Moyo, Joel Manyahi, Upendo Kibwana, Iren H. Löhr, Nina Langeland, Bjørn Blomberg, Iain G. Johnston</p>
Antimicrobial resistance (AMR) is a substantial and growing global health burden. Understanding, and predicting, its evolution in specific pathogens will help responses across scales from individual patient cases to large-scale policy. Here, we use global data on AMR features, predicted from 47k <i>Klebsiella pneumoniae</i> genomes, with hypercubic transition path sampling to infer the evolutionary pathways by which AMR features in <i>K. pneumoniae</i> (KpAMR) are acquired across 102 countries, territories, and areas. We identify “globally consistent” evolutionary behaviors that hold across countries, and “globally divergent” behaviors including carbapenem and fluoroquinolone resistance that vary across countries. We show how these divergent dynamics covary both with public health superregion and drug use policy, and reveal competing evolutionary pathways within and between countries. Using newly sequenced data across several decades from sub-Saharan Africa, we show that this inferred global roadmap of KpAMR evolution successfully predicts prospective evolutionary dynamics. Together, we hope that the ability to characterize and predict evolutionary dynamics of AMR acquisition, connected to socio-economic and drug policy predictors, will help strengthen our understanding of AMR evolution worldwide.