Cortical circuits produce time-varying patterns of population and single-neuron activity that play a fundamental role in perceptual and behavioral processes. However, the functional contributions of individual neuron activity to population dynamics and behavior remain unclear. Here, we addressed this issue focusing on the mouse gustatory cortex (GC) and using a taste mixture-based decision-making task, high-density electrophysiology, and computational modeling. GC population dynamics represented stimuli linearly during taste sampling, and choices categorically before decisions. Single neurons were classified by their linear and categorical activity patterns, revealing sub-populations encoding sensory, perceptual, and decisional variables. To test their functional role, we built a recurrent neural network model of GC. Model perturbations showed linear and categorical neurons were essential for driving normal population dynamics and behavioral performance, whereas many units with other activity patterns could be silenced without consequence. These results have implications that extend beyond GC and demonstrate the role of linear and categorical coding neurons in cortical dynamics and behavior during perceptual decision-making.
Science Journals
Cancer progression involves extensive alterations in epigenetic and gene expression programs, but the accompanying changes in higher-order genome organization remain less well understood. Using high-resolution Micro-C mapping in the MCF10 cell model of breast cancer, we profiled chromatin compartments, topologically associated domains, and chromatin loops. We find large-scale compartmental shifts occur predominantly in early stages of cancer development, with more fine-scale structural changes in topologically associating domains and loops accumulating during the later transition to metastasis. Relating these chromatin features to gene expression and enhancer-associated histone marks revealed that many differentially expressed genes are physically connected to distal regulatory elements. While enhancer–promoter contact frequency and distal enhancer activity correlated with gene expression, strong changes in chromatin looping were relatively infrequent during progression, suggesting that alterations in chromatin contacts are not globally necessary, but may facilitate gene regulation at a subset of genes. These results elucidate the connection between gene regulation and genome remodeling in a cell-based cancer progression model.
The Faroe Islands are home to descendants of a North Atlantic founder population with a unique history shaped by both migration and periods of relative isolation. Here, we investigate the genetic diversity, population structure, and demographic history of the islands by analyzing whole genome sequencing data from 40 participants in the Faroe Genome Project. This represents the first whole genome sequencing panel of this size from the Faroe Islands. We observed numerous putatively functional private alleles, including stop gain variants and high impact missense variants in the cohort. Faroese individuals had a higher proportion of their genomes contained in long runs of homozygosity than other European groups, including Finnish, suggesting a more recent or stronger bottleneck in the Faroese population. Signals of positive selection were identified at loci containing genes that play roles in vitamin D and dietary fat absorption and DNA repair, while increased diversity on lactase persistence haplotypes was observed. Fine-scale analysis of haplotype structure in present-day and ancient European genomes revealed genetic affinities with ancient Iron Age individuals from the North and West of Europe, providing evidence for potential contributions to the Faroese gene pool from Celtic and Viking populations as well as information about the temporal order in which these events happened. This study highlights the impact of evolutionary processes, such as ancient admixture, founder events, and positive selection, on the present-day genetic architecture of North Atlantic founder populations like the Faroe Islands.
For frail older patients with non–ST-elevation myocardial infarction (NSTEMI), a conservative treatment strategy may be better than an invasive approach, new research suggests.
This Medical News article discusses the life and legacy of legendary cardiologist Eugene Braunwald, MD, who died on April 22, 2026.
Classically, type 1 diabetes has been diagnosed only after patients have lost a critical threshold of beta cell mass, resulting in symptoms of hyperglycemia due to insulin deficiency. Despite advances in glycemic monitoring and insulin delivery, patients with clinical type 1 diabetes experience enormous mental burden and health care costs and are at risk of developing complications from chronic hyper or hypoglycemia. Natural history studies have shown that type 1 diabetes can be diagnosed in presymptomatic stages via detection of 2 or more islet autoantibodies. Stage 1 is defined by the presence of 2 or more islet autoantibodies with normoglycemia and stage 2 by the presence of 2 or more islet autoantibodies and abnormal glucose metabolism. Stage 3 marks the clinical diagnosis of type 1 diabetes, characterized by hyperglycemia. Options for disease modification to intervene in the presymptomatic stages and delay insulin requirements are becoming available clinically or through prevention trials testing agents shown to have efficacy in stage 3 disease (NCT07222137 and NCT07216391). As these advances in prediction and disease modification evolve, the long sought–after possibility of prevention of clinical type 1 diabetes is now approaching reality. With this possibility for intervention, screening for presymptomatic type 1 diabetes begins to meet the criteria for the principles and practice of screening by Wilson and Jungner, which state that screening programs should target health conditions that are detectable at an early stage, have an effective intervention when applied early, and have a valid, reliable, and acceptable test available. In addition, Wilson and Junger outline the importance of cost-effectiveness and the existence of intrastructure and systems to support diagnosis, treatment, and follow-up to ensure that benefits outweigh potential harm.
Damp grey of a new year’s day and I’m conversing with a clown.
A common question asked when encountering a patient presenting with pain is “How would you describe your pain?” Although some descriptors are routinely taught during training (the 0 to 10 pain scale) or heard more frequently in clinic visits (stabbing, burning, or gnawing), pain remains a deeply personal experience. Despite medicine’s interest in patients characterizing their pain, quantitative scales and checkbox adjectives are too often insufficient. Hence, patients turn toward the arts, such as poetry, to help them best narrate their experiences of pain. While offering pharmacological or interventional treatments to alleviate pain, clinicians might also better help patients by validating and listening to their unique experiences of pain when expressed creatively. In the poem “Pain,” the speaker does just this, describing an unusual and even refreshing personification of pain. Featuring metaphors at once humorous and yet biting, pain is depicted not as necessarily punitive or adversarial, but as something to engage. It is “a clown,” both “misbehaving” and “scour[ing],” a persona that is certainly annoying but also almost comical. The speaker’s physiological pain becomes a metaphorically pestering pain, doing exactly what it should not be doing—it is “parading” and “screech[ing]”—always persistently “there.” Yet articulating what exactly is so irksome in these novel ways leads to a certain empowerment, especially when using metaphors that make pain seem more like an unruly friend than a malevolent presence. Perhaps, while pain might ultimately feel like something that cannot be shared, how it is named exerts a kind of control that the afflicted can still hold over it.
This Special Communication explores the challenges currently facing state investment in primary care and outlines how a common fund could address these challenges and sustain primary care as a public utility and common good.
A remarkable aspect of modern medicine is the ever-growing array of medications that fundamentally alter disease trajectories and improve quality of life. At the same time, persistent inequities in access to these medications remain a reality. Pharmacoequity, a term coined in a 2021 article in JAMA, is a specific component of health equity focused on fair and just access to appropriate medications, regardless of race, ethnicity, income, insurance coverage, and other social factors.
This trial assessed whether the diagnostic yield of transbronchial lung biopsy is higher with a 1.1-mm cryoprobe compared with 2.0-mm forceps in adults needing bronchoscopy for pulmonary evaluation.
This Viewpoint presents the history of the Health Resources & Services Administration (HRSA) 340B Drug Pricing Program and 340B Rebate Model Pilot Program, summarizes their controversies and limitations, and calls for action by Congress and HRSA to address these issues and strengthen support for safety-net hospitals and clinics.
In Reply We thank Mr Liu and Mr Chen and colleagues for their comments regarding our randomized clinical trial evaluating ERCP with minor papillotomy in patients with pancreas divisum and unexplained acute recurrent pancreatitis. Liu asks whether anatomical features of impaired dorsal duct outflow modified the treatment effect. In prespecified subgroup analyses stratified by duct diameter or a santorinicele (Figure 4 of the article), we did not find significant treatment × subgroup interactions for the primary outcome. As stated in the article’s Discussion section, the study was not powered for these subgroups. Notably, the prevalence of a santorinicele was 12% using a mix of standard and secretin-enhanced magnetic resonance cholangiopancreatography prior to randomization, which is consistent with the radiology literature. In small santorinicele cohorts, outcomes of minor papillotomy for acute pancreatitis and divisum suggest persistent acute pancreatitis clinically, biochemically, or both in 20% to 30% of patients. Therefore, even though a dilated duct or santorinicele is suggestive of a stenotic orifice, it is unlikely that they are sufficient to ensure a clinically significant benefit of minor papillotomy.
To the Editor A recent study of 10-year follow-up results from the Appendicitis Acuta (APPAC) trial reported a 37.8% true appendicitis recurrence rate and a 44.3% cumulative appendectomy rate among patients initially treated with antibiotics for uncomplicated acute appendicitis. While the authors concluded that antibiotics remain a viable treatment option for uncomplicated appendicitis, we wish to highlight several concerns about the generalizability, safety, and practicality of this approach.
To the Editor The 10-year follow-up of the APPAC trial provides valuable long-term data supporting antibiotics as a feasible treatment option for uncomplicated acute appendicitis. However, several aspects of the analysis and its interpretation warrant clarification.
In Reply We appreciate the Letters about our recent study. With currently available knowledge, treatment of uncomplicated acute appendicitis is no longer about correct vs incorrect management but rather a comprehensive assessment of 2 different treatment strategies, with implications ranging from patient-reported outcomes to health care cost savings. Similarly, for diagnosis of acute appendicitis—it is no longer yes or no—all outcomes, from treatment success to appendiceal tumor prevalence and resource savings, are closely related to the accurate diagnosis of appendicitis severity. The judicious use of CT advocated by Dr Dai and colleagues is important to limit unnecessary radiation exposure, especially because many patients with suspected acute appendicitis are young adults. However, imaging has been considered mandatory to achieve satisfactory accuracy in assessing appendicitis severity, which is achievable using low-dose CT with a marked radiation dose reduction without compromising diagnostic accuracy, underlining the importance of adapting these low-dose imaging protocols. Dai and colleagues also express concern about the use of broad-spectrum antibiotics. Ertapenem was initially selected to standardize the study group treatments for efficacy because ertapenem effectively covers all pathogens that can cause appendicitis. However, there is current evidence that some patients with uncomplicated acute appendicitis may have resolution of symptoms without antibiotic treatment, and most patients can be safely discharged from the emergency department. Therefore, future studies should examine the optimized nonoperative treatment of uncomplicated acute appendicitis in an outpatient setting.
This meta-analysis assesses the association of digitalis glycosides treatment with risk of the composite outcome of cardiovascular death or first worsening heart failure events in patients with heart failure with mildly reduced ejection fraction or in those with heart failure with reduced ejection fraction.
To the Editor A recent Review provided a valuable synthesis of management strategies for head and neck squamous cell carcinoma. It appropriately discussed use of systemic analgesics and local anesthetic mouthwashes to mitigate weight loss, decrease unplanned interruptions of radiotherapy, and reduce hospitalizations in patients with oral mucositis. However, photobiomodulation therapy, which involves the use of low-intensity laser or light to stimulate tissue repair, reduce inflammation, and alleviate pain, was not mentioned, despite accumulating evidence supporting its benefits for these clinical end points.
To the Editor A recent Review provided a comprehensive overview of the management of squamous cell carcinoma of the head and neck. From a medical oncologist’s perspective, the role of cisplatin and several important clinical considerations should have been highlighted because cisplatin remains the most important cytotoxic agent in both curative and palliative settings for patients with head and neck cancer.
In Reply In response to the important clinical considerations regarding alternate cisplatin dosing regimens that Dr Szturz outlines, we acknowledge that concurrent weekly cisplatin is widely practiced in lieu of high-dose cisplatin for toxicity concerns in the setting of definitive (rather than adjuvant) radiation. However, there is currently insufficient evidence to adopt weekly cisplatin as the standard of care in the definitive setting for individuals eligible to receive cisplatin, pending the completion of an ongoing clinical trial comparing high-dose cisplatin with weekly cisplatin at 40 mg/m2 (NRG-HN009; NCT05050162). In the adjuvant setting, there are data to support weekly cisplatin administration. As noted, JCOG1008 found that weekly , 40 mg/m2, was noninferior in overall survival with fewer toxicities compared with cisplatin, 100 mg/m2, administered every 3 weeks with postoperative radiation.
A Black woman of Hispanic ethnicity with a history of hypertension, obesity, and headaches had symmetrically distributed, well-demarcated hyperpigmented lines that had developed during pregnancy and that extended from her buttocks to the lower extremities; physical examination was otherwise unremarkable. What is the diagnosis and what would you do next?
This Perspective reviews the US Food and Drug Administration’s achievements toward eliminating unnecessary animal-based testing and outlines more human-relevant changes for the future.
This JAMA Patient Page describes the causes, risk factors, and methods for evaluating stillbirth before and after it occurs.
This Viewpoint discusses opportunities for policymakers and practitioners to make progress in the public health challenge of obesity while avoiding unintended consequences.
To the Editor Dr Coté and colleagues conducted a multicenter, sham-controlled, double-blind randomized clinical trial to address a long-standing practice question in patients with unexplained acute recurrent pancreatitis and pancreas divisum. The primary time-to-event outcome (acute pancreatitis >30 days after randomization) was not significantly reduced with the use of ERCP with minor papillotomy (adjusted hazard ratio, 0.83 [95% CI, 0.49-1.41]).