University of Chicago

METTL14 dimerizes with METTL3 to install N6‐methyladenosine (m⁶A) on mRNA (m⁶A writers). Subsequently, m⁶A readers bind to m⁶A‐marked RNA to influence its metabolism. RNA m⁶A emerges to critically regulate multiple intracellular processes; however, there is a gap in our understanding of m⁶A in liver metabolism. Glucose‐6‐phosphatase catalytic subunit (G6pc) mediates hepatic glucose production (HGP) and serves as the gatekeeper for glycogenolysis and gluconeogenesis; however, G6pc regulation is not fully understood. Here, METTL14 is identified as a posttranscriptional regulator of G6pc. Liver METTL14, METTL3, and m⁶A‐methylated G6pc mRNA are upregulated in mice with diet‐induced obesity. Deletion of Mettl14 decreases, whereas overexpression of METTL14 increases, G6pc mRNA m⁶A in hepatocytes in vitro and in vivo. Five m⁶A sites are identified, and disruption of them (G6pcΔ5A) blocks METTL14‐induced m⁶A methylation of G6pcΔ5A mRNA. METTL14 increases both stability and translation of G6pc but not G6pcΔ5A mRNA. YTHDF1 and YTHDF3 but not YTHDF2 (m⁶A readers) bind to m⁶A‐marked G6pc mRNA to increase its synthesis. Deletion of hepatic Mettl14 decreases gluconeogenesis in primary hepatocytes, liver slices, and mice. Hepatocyte‐specific restoration of G6pc reverses defective HGP in Mettl14 knockout mice. These results unveil a METTL14/G6pc mRNA m⁶A/G6pc biosynthesis/HGP axis governing glucose metabolism in health and metabolic disease.

Objective Rates of suicide, anxiety, and depression have soared in US youth, and professional organizations strongly urge earlier identification, particularly in pediatric emergency departments (PEDs). However, there are few commonly used suicide screeners that also identify other mental health (MH) problems. A new, electronically administered instrument, the K-CAT, screens for suicide and multiple MH problems. We hypothesized that the K-CAT would enhance suicide identification compared with routine screening and identify significant anxiety and depression in youth presenting with non-MH chief complaints. Methods This observational study was conducted in 2 PEDs. Eligible youth were 7 to 17 accompanied by a caregiver without: severe medical concerns, difficult behaviors, limited verbal language, or only a psychiatric complaint. Of the 341 eligible, 241 (70.7%) were screened, and 228 both presented with a non-MH problem and had complete K-CAT data. A Fisher exact test determined whether suicidal behaviors/ideation rates differed between the K-CAT and retrospective chart review data. Results Seventy-four or 32.46% of youth scored positive for suicide, anxiety, and/or depression on the K-CAT. Females were more likely to screen positive ( P <0.001). Compared with the retrospective data, more youth were identified with suicide risk by the K-CAT (3.95% vs. 0%; P =0.004). Youth identified by the K-CAT were 62.5% female and 33.3% 7 to 11 years. Conclusions The K-CAT increases the identification of suicidal ideation and behaviors overall and in younger children. It identifies significant rates of depression and anxiety in youth and could be an important first step in identifying MH problems in youth.

A well-known theorem of W. Fischer and H. Grauert states that analytic fiber spaces with all fibers isomorphic to a fixed compact connected complex manifold are locally trivial. Motivated by this result, we show that if k is an algebraically closed field of infinite transcendence degree over its prime field, then every smooth projective family over a reduced k-scheme of finite type with isomorphic fibers having reduced automorphism group schemes is locally trivial in the étale topology. We do so by reducing the problem to the case when the base is a smooth integral curve, and then, using the vanishing of the Kodaira–Spencer map, we prove formal triviality of such families at every geometric point of the base. We also provide examples of smooth projective fibrewise trivial families in positive characteristic whose Kodaira–Spencer map are nowhere vanishing.

Importance Despite the clinical benefits of treating obesity and related complications, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are not yet covered by Medicare Part D, partly due to high drug costs. The Biden administration’s proposal to expand Part D coverage underscores the need to assess the balance between fiscal costs and benefits to guide policy decisions. Objective To estimate the 10-year net fiscal impact of expanded Medicare coverage for GLP-1RAs for obesity treatment. Design, Setting, and Participants In this economic evaluation, a 10-year fiscal impact analysis was conducted between 2026 and 2035 using the validated Diabetes, Obesity, Cardiovascular Disease Microsimulation model. The base-case analysis incorporated a 10% 1-time uptake rate for eligible adults in each new cohort, 40% adherence beyond the first year, and a 10% additional price discount beyond current net prices. A 3-way sensitivity analysis was conducted with varying uptake, adherence, and additional price discounts. The model included current and future Medicare beneficiaries with body mass index (calculated as weight in kilograms divided by height in meters squared) of 30 and higher or 27 and higher with at least 1 obesity-related comorbidity. Data were analyzed from March to December 2024. Exposure GLP-1RA therapy. Main Outcomes and Measures Total Medicare drug costs for GLP-1RAs for obesity indications not covered by Medicare, long-term health care cost offsets from reduced obesity-related comorbidities, and net fiscal impact. Results Among 30 million cumulative Medicare beneficiaries (survey-weighted mean [SE] age, 64.5 [0.4] years; 54.1% female) identified as eligible for new GLP-1RAs for obesity treatment over the next 10 years, the base-case analysis estimated that 3 million would receive treatment. Medicare’s total drug costs were projected at $65.9 billion and health care cost offsets from clinical benefits at$18.2 billion, resulting in net increased spending of $47.7 billion. Three-way sensitivity analysis estimated that higher uptake and adherence would lead to increased health care savings from clinical benefits. However, these savings were estimated to remain less than additional spending on GLP-1RAs and to extensively increase net spending. Conclusions and Relevance This economic evaluation estimates that expanded Medicare coverage for GLP-1RAs would increase access and reduce obesity-related comorbidities but impose substantial costs over 10 years. Even with a moderate scenario (5$8 billion over a decade, underscoring the need for further price reductions, lower-cost strategies to prevent weight regain, and reductions in spending on low-value care.

Immigrants’ legal status has been described as a social determinant of health that shapes health outcomes through multiple channels. Furthermore, legal status matters not only for immigrants themselves, but also for their family members, including their U.S.-born citizen children. Nonetheless, few studies have empirically disentangled the possible mediating mechanisms through which parents’ legal status shapes their children’s health. This paper applies path analysis to data from the 2014–2019 California Health Interview Survey to examine how Latino immigrant parents’ unauthorized status impacts the health of their U.S.-born citizen children. I consider how the effects of parents’ unauthorized status for their children’s health are mediated by children’s healthcare access, household food insecurity, family income, and parents’ own physical and mental health. I find that parents’ unauthorized status has a negative but indirect effect on their children’s health through increasing household risk of poverty and food insecurity. These results have significant implications for the well-being of millions of children in the United States who have legally vulnerable parents.

This paper presents the development of an electrochemically‐driven variable emission thermoregulating device designed for efficient radiative heat management across various temperature environments. Utilizing the ionic liquid 1‐butyl‐3‐methylimidazolium tetrafluoroborate (BMIMBF4), the study explores its thermal and electrochemical stability, low vapor pressure, and excellent performance over a wide operational temperature range, making it an ideal electrolyte. The device uses mid‐infrared electrochromic technology, employing ultra‐wideband transparent conductive electrodes and reversible metal electrodeposition to dynamically adjust thermal emissivity between 0.06 and 0.89. This capability allows for significant improvements in heat management, offering a responsive and adaptable solution compared to current systems. The findings suggest that such advanced materials and mechanisms can enhance energy management in spacecraft, potentially extending to other space fields requiring precise thermal control.

Background Spinal epidural abscess (SEA) is an uncommon but potentially life-threatening infection that requires prompt identification and treatment. Early SEAs may present with non-specific symptoms, including fever, chills, headache, and back pain, before progressing to neurologic dysfunction. To our knowledge, there have been no reports of immunocompetent patients with a history of recurrent UTIs presenting with SEA following ureteroscopy (URS) and lithotripsy (LL). Case presentation In this article, we present two cases of spinal abscess formation after ureteroscopy in patients with histories of recurrent urinary tract infections but without previous spinal pathology. Both patients required procedural intervention and one patient sustained lasting neurological deficits. Conclusions It is important that urologists be aware of this possible complication to ensure the early diagnosis of the disease to facilitate appropriate management.

Decades of research indicate that growth versus fixed mindsets can influence important outcomes. Some, however, have recently questioned this conclusion, documenting small to nonexistent effects. Inspired by attitudes research, we propose that some growth mindsets may be stronger—more impactful—than others. Specifically, this work examines whether mindsets held with higher certainty are more likely to influence responses. A field study, a high-powered preregistered experiment, and an integrative data analysis test whether mindset certainty influences interest and engagement in organizations that endorse fixed versus growth mindsets. These studies found that when students held their mindsets with high levels of certainty, their personal mindset beliefs were highly predictive of their relative interest in growth versus fixed classrooms, but when they held their mindsets with less certainty, their personal mindsets did not predict relative interest in growth versus fixed classrooms in this same manner. Broadly, these studies support that mindsets vary in strength, which should encourage researchers to identify “when” rather than “whether” growth mindsets predict outcomes.

How does temperature variation affect signaling and mating behavior in wolf spiders? Rosenthal and Elias (2025) find that temperature affects courtship signal form in wolf spiders, with higher temperatures increasing courtship rates. Additionally, female preferences for courtship traits, such as ‘chirp’ duration, only appear at higher temperatures. These results highlight the importance of understanding how temperature influences signal evolution and function.

Background Obesity is associated with substantial thromboembolic risk, however, no standard laboratory method exists to stratify risk for post-operative thrombotic events. Our aim is to evaluate preoperative pro-thrombotic biomarkers and thromboelastometry in relationship to clinical VTE stratification in bariatric patients. Methods Preoperative blood samples were assessed for rotational thromboelastometry, D-Dimer, C-Reactive Protein (CRP), Plasminogen Activator Inhibitor-1 (PAI-1), von Willebrand factor (vWF), and P-selectin, and compared to 50 normal control (NC) samples. Patients were stratified into Caprini Risk Score (CRS) groups: moderate (3-4), high (5-8), and very high (>8) VTE risk. Results One hundred bariatric patients were assessed and risk stratified to CRS 3-4 (n=23), CRS 5-8 (n=67), and CRS >8 (n=10). D-dimer, PAI-1, and CRP were increased compared to NC, all p< 0.001, P-selectin and vWF demonstrated no differences compared to NC. D-dimer demonstrated significant differences between moderate, high, and very high-risk groups (all p <0.05) and positive correlation with CRS (r =0.44, p<0.001). On thromboelastometry, clot formation time (CFT) was faster than normal in 18% of patients, with maximum clot firmness (MCF) higher than normal in 54% of patients. No difference was found comparing thromboelastometry between CRS groups. Significant correlations were found between CRP and CFT (r= -0.44), α-angle (r=0.40) and MCF (r= 0.44) all p<0.05 respectively. D-dimer negatively correlated with CFT (r= -0.34, p<0.05), and clotting time (r=-0.78, p<0.05) in very high-risk patients. Conclusion Preoperative D-dimer and CRP are significantly increased in bariatric patients and correlate with prothrombotic features on thromboelastometry. No significant differences were found comparing viscoelastic tests among CRS groups , which suggests patients with marked prothrombotic findings are not being differentiated into higher risk categories by clinical assessment alone.

Evidence suggests disparities associated with race and ethnicity (R&E) in assessment in graduate medical education (GME). How these disparities manifest across competencies and training time and intersect with disparities associated with other factors such as gender is unclear. Examine the association of R&E and gender with clinical performance assessment in GME. Longitudinal analysis of resident clinical performance assessments. Assessment data of residents at seven internal medicine (IM) residency programs, 2014 to 2019 (9346 evaluations of 664 residents). Residents underrepresented in medicine (URiM) were identified using self-reported R&E. Standardized scores were calculated for the Accreditation Council for Graduate Medical Education competencies (patient care [PC], medical knowledge [MK], practice-based learning and improvement [PBLI], systems-based practice [SBP], professionalism [PROF], and interpersonal communication and skills [ICS]). Cross-classified mixed effects regression assessed differences in standardized competency ratings with R&E over time and the interaction of R&E and gender while controlling for time of year and setting; resident gender, post-graduate year (PGY), and IM in-training examination percentile rank; and faculty gender, educational role, specialty, rank, and years of experience. URiM resident scores were lower than non-URIM residents across competencies (difference in standardized scores between URiM and non-URiM residents [se] PC − 0.126 [0.035], p < 0.001; MK − 0.118 [0.035], p < 0.001; PBLI − 0.122 [0.042], p = 0.004; SBP − 0.128 [0.034], p < 0.001; PROF − 0.075 [0.036], p = 0.036; ICS − 0.124 [0.039], p = 0.002). The interaction between resident R&E, gender, and PGY was significant in PBLI (estimate − 0.15 [0.06], p = 0.02) and SBP (− 0.11 [0.05], p = 0.04) indicating smaller gains over time for URiM women. There were significant differences associated with R&E with lower scores for URiM residents across competencies. There was a significant interaction with resident gender and R&E over time in PBLI and SBP. Findings may reflect bias in faculty assessment, effects of non-inclusive learning environments, or structural inequities in assessment.

The surrounding environment influences how people feel, think, and behave. This effect is apparent when examining the multitude of ways interactions with natural environments impact people psychologically. In this Research Dialogue, we discuss work by ourselves and others that demonstrate the benefits of spending time in nature or interacting with natural stimuli, across three psychological domains. First, we discuss affective benefits, such as improved mood and decreased stress and rumination. Then, we discuss cognitive benefits, such as improved working memory. Lastly, we discuss social benefits, such as prosocial and proenvironmental attitudes. We introduce several environmental psychology theories that try to explain why these benefits occur. We present our own work that attempts to determine what characteristics of natural environments cause or are related to these effects by quantifying distinguishing characteristics of natural versus built environments along a variety of dimensions. We then investigate how these dimensions influence the psychological experience in a more natural versus a more built environment. We end by outlining the implications of the benefits of interacting with nature in influencing consumer behaviors.

Clinical trials of adults with prediabetes demonstrate that metformin can prevent or delay the risk of developing type 2 diabetes by approximately 30%. The association between socioeconomic disadvantage and elevated diabetes risk underscores the importance of using metformin in this high-risk group. To examine the prevalence of metformin prescriptions among patients with prediabetes served by federally qualified health centers (FQHCs), the largest national system of primary care clinics in socioeconomically disadvantaged communities. Retrospective cohort study using 2008–2019 electronic health record data from a national FQHC network. Patients with prediabetes were identified by the presence of: ≥ 1 diagnosis code; or ≥ 2 glycemic test results in the prediabetes range. We excluded patients with prior metformin prescription orders and those with prior evidence of diabetes by diagnosis code or two glycemic test results in the diabetes range. We examined metformin prescription orders, overall, and by patient characteristics including age and body mass index (BMI). A total of 59,232 FQHC patients were found to have prediabetes, of whom 48.4% reported Hispanic ethnicity, 27.2% reported Black race, 22.5% had Medicaid insurance, and 33.1% were uninsured. Within one and five years of prediabetes diagnosis, metformin was prescribed for 3.0% and 6.1% of patients, respectively. In multivariate analyses, increasing BMI was the strongest predictor of metformin prescription orders. Disparities in metformin prescription rates were observed among FQHCs patients from racial minority groups relative to White patients. Metformin prescriptions for prediabetes are rare among FQHC patients. Prescribing rates were higher among patients with elevated BMI, and lower among patients from racial minority groups. Further research is needed to understand reasons for low metformin use in this population and promote clinical guidelines for diabetes prevention in FQHCs.

Running quantum algorithms protected by quantum error correction requires a real time, classical decoder. To prevent the accumulation of a backlog, this decoder must process syndromes from the quantum device at a faster rate than they are generated. Most prior work on real time decoding has focused on an isolated logical qubit encoded in the surface code. However, for surface code, quantum programs of utility will require multi-qubit interactions performed via lattice surgery. A large merged patch can arise during lattice surgery—possibly as large as the entire device. This puts a significant strain on a real time decoder, which must decode errors on this merged patch and maintain the level of fault-tolerance that it achieves on isolated logical qubits. These requirements are relaxed by using spatially parallel decoding, which can be accomplished by dividing the physical qubits on the device into multiple overlapping groups and assigning a decoder module to each. We refer to this approach as spatially parallel windows. While previous work has explored similar ideas, none have addressed system-specific considerations pertinent to the task or the constraints from using hardware accelerators. In this work, we demonstrate how to configure spatially parallel windows, so that the scheme (1) is compatible with hardware accelerators, (2) supports general lattice surgery operations, (3) maintains the fidelity of the logical qubits, and (4) meets the throughput requirement for real time decoding. Furthermore, our results reveal the importance of optimally choosing the buffer width to achieve a balance between accuracy and throughput—a decision that should be influenced by the device’s physical noise.

The divergence of Homo from gracile australopiths has been described as a trend of decreasing dentognathic size and robusticity, precipitated by stone tool use and/or a shift to softer foods, including meat. Yet, mechanical evidence supporting this narrative is sparse, and isotopic and archaeological data have led to the suggestion that a shift away from a gracile australopith-like diet would not have occurred in the most basal members of Homo but rather only with the appearance of Homo erectus, implying that the origin of our genus is not rooted in dietary change. Here, we provide mechanical evidence that Homo habilis exhibits an australopith-like pattern of facial strain during biting but, unlike most australopiths, was not suited for a diet that required forceful processing by the molar teeth. Homo habilis was at elevated risk of distractive jaw joint forces during those bites, constraining muscle recruitment so as to avoid generating uncomfortable/dangerous levels of tension in the joint. Modern humans have similar limitations. This suggests that selection on skeletal traits favouring forceful postcanine processing was relaxed by the earliest stages in the evolution of our genus, implying that dietary or food processing changes played an important role in the emergence of Homo.

We live in an age of planetary crisis with threats from climate change, increasing rates of extinction, and outbreaks of infectious diseases like COVID-19, all exacerbated by land use change and global trade. This forces us to question the prevailing economic system of fossil-fuel-driven mass consumption and the notion of limitless growth. In the 1860s and 1870s, John Ruskin reoriented the imagination away from the marketplace toward the world of art, nature, and community and developed the theory and practice of what we call “sufficiency.” He called for ethical consumption to combat the degradation of nature and maintain the health of all living things. Rural communities offered an alternative model with their preindustrial land use, locally produced food, skilled craftsmen, and close community bonds. Corresponding with Francesca Alexander (1837–1917), who lived in Italy in a time of cholera, Ruskin learned about the resilience of just this sort of rustic community and helped her edit books about the lives of its inhabitants. While Ruskin’s concept of sufficiency might seem antiquated, his critique of consumer society challenges us to consider the new economics of degrowth and rethink the relation between desire and the environment.