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This study examined the sustainability of shared micromobility services using data from 48 cities in the US using a 21-day smartphone travel diary and survey data. Population-weighted analysis indicated a much smaller share of transit connection than in prior reported studies, with more reliable data. However methodological decisions could be a cause for such discrepancies suggesting a sensitivity analysis of this same data may be a good next research step. Results also indicated median VMT reduced per micromobility trip to be roughly 0.15 miles for e-scooter share trips and 0.25 miles for bike share (including e-bike) trips. Models of mode substitution confirm prior evidence of factors affecting car substitution including trip distance as the strongest factor. This study also proposed two frameworks for building a sketch planning tool for examining VMT reduction from future micromobility services. This tool could help cities and regions better plan for the micromobility services to achieve real VMT and GHG reduction goals. While more research is needed to employ this framework, it helps motivate a series of additional research topics to inform a decision support tool for shared micromobility planning. View the NCST Project Webpage

Bicycles and other forms of micromobility have been anecdotally used in past disasters to help save lives and improve community recovery. However, research and practice are scarce on this resilient transportation strategy, which limits its usefulness and possible benefits. To fill this gap, our paper investigates the potential role bicycles and micromobility in facilitating (or limiting) disaster response and recovery. Given the lack of exploration on the topic, we convened an online workshop where we conducted brainstorming and focus group discussions with disaster experts from various government agencies, not-for-profit organizations, academia, and policy groups. We present a synthesis of that discussion, along with a review of the existing literature. We conclude there is strong potential for bicycles and micromobility for different disaster phases, hazard types, and groups of people. However, multiple barriers exist related to implementation and safety, suggesting a need for future research and policy in the transportation and emergency management fields and practices.

Rhyme is regarded as a powerful mnemonic device that facilitates cognitive processing. Previous studies mainly examined rhyme-perception development in the case of children (e.g., Kiràly et al., 2017); thus, instead, the present research focuses on information-recall processes in the adult population. In cultural transmission processes, rhyme and memory are closely connected (cf. Kirby et al., 2008); therefore, there is a need for research investigating whether and how the adult population's recall ability is enhanced by rhymes to gain a better understanding of the rhyme‚Äìmemory relationship. The present study examines whether rhyming words are more likely to be recalled than their non-rhyming counterparts. Results suggest that rhymes affect short- and long-term consolidation of real words and pseudowords in the case of adult participants (N = 38). By gaining insight into recall processes related to rhyming, it may be possible to understand information retrieval procedures in the context of cognitive poetics.

BackgroundPericoronary adipose tissue (PCAT) may influence plaque development through inflammatory mechanisms. We assessed PCAT density, as a measure of pericoronary inflammation, in relationship to coronary plaque among people with human immunodeficiency virus (HIV [PWH]) and to a matched control population.MethodsIn this baseline analysis of 727 participants of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) Mechanistic Substudy, we related computed tomography-derived PCAT density to presence and extent (Leaman score) of coronary artery disease (CAD), noncalcified plaque, coronary artery calcium (CAC), and vulnerable plaque features using multivariable logistic regression analyses. We further compared the PCAT density between PWH and age, sex, body mass index, CAC score, and statin use-matched controls from the community-based Framingham Heart Study (N = 464), adjusting for relevant clinical covariates.ResultsAmong 727 REPRIEVE participants (age 50.8 ± 5.8 years; 83.6% [608/727] male), PCAT density was higher in those with (vs without) coronary plaque, noncalcified plaque, CAC >0, vulnerable plaque, and high CAD burden (Leaman score >5) (P < .001 for each comparison). PCAT density related to prevalent coronary plaque (adjusted odds ratio [per 10 HU]: 1.44; 95% confidence interval, 1.22-1.70; P < .001), adjusted for clinical cardiovascular risk factors, body mass index, and systemic immune/inflammatory biomarkers. Similarly, PCAT density related to CAC >0, noncalcified plaque, vulnerable plaque, and Leaman score >5 (all P ≤ .002). PCAT density was greater among REPRIEVE participants versus Framingham Heart Study (-88.2 ± 0.5 HU versus -90.6 ± 0.4 HU; P < .001).ConclusionsAmong PWH in REPRIEVE, a large primary cardiovascular disease prevention cohort, increased PCAT density independently associated with prevalence and severity of coronary plaque, linking increased coronary inflammation to CAD in PWH.

Abstract Defining “dance” is challenging, because many distinct classes of human movement may be considered dance in a broad sense. Although the most obvious category is rhythmic dancing to a musical beat, other categories of expressive movement such as dance improvisation, pantomime, tai chi, or Japanese butoh suggest that a more inclusive conception of human dance is needed. Here we propose that a specific type of conscious awareness plays an overarching role in most forms of expressive movement and can be used to define dance (in the broad sense). We can briefly summarize this broader notion of dance as “mindful movement.” However, to make this conception explicit and testable, we need an empirically verifiable characterization of “mindful movement.” We propose such a characterization in terms of predictive coding and procedural learning theory: mindful movement involves a “suspension” of automatization. When first learning a new motor skill, we are highly conscious of our movements, and this is reflected in neural activation patterns. As skill increases, automatization and overlearning occurs, involving a progressive suppression of conscious awareness. Overlearned, habitual movement patterns become mostly unconscious, entering consciousness only when mistakes or surprising outcomes occur. In mindful movement, this automatization process is essentially inverted or suspended, reactivating previously unconscious details of movement in the conscious workspace, and crucially enabling a renewed aesthetic attention to such details. This wider perspective on dance has important implications for potential animal analogs of human dance and leads to multiple lines of experimental exploration.

Abstract Background Secondary autoimmune disease (SAID) in the context of alemtuzumab treatment is one of the main safety concerns that may arise following administration in people with multiple sclerosis (pwMS). Contributing factors underlying this adverse event are not well understood. The purpose of this systematic review was to appraise the literature investigating the role of alemtuzumab in the development of SAID in pwMS following treatment and identify potential biomarkers/ risk factors that may be predictive of onset of this manifestation. Methods Relevant publications were retrieved from PubMed, Embase, and Web of Science using a three-pronged search strategy containing the following keywords: “multiple sclerosis”; “alemtuzumab”; and “autoimmunity”. Studies that fulfilled the specified eligibility criteria and investigated SAID development after alemtuzumab in pwMS were included in the final analysis. Results 19 papers were included in the final review. Approximately, 47.92% of pwMS treated with alemtuzumab experienced SAID. A variety of biomarkers and risk factors were noted in the development of SAID, with a focus on immunological changes, including: increased homeostatic proliferation and T cell cycling, along with consistently elevated baseline serum IL-21 levels and thyroid autoantibodies. There was no significant association between known human leukocyte antigen (HLA) risk alleles, lymphocyte profile or dynamics and SAID development. Conclusions While the mechanism underlying SAID following alemtuzumab is not fully understood, potential biomarkers and risk factors that may assist in elucidating mechanisms underlying this phenomenon have been documented in several independent studies. Following immunodepletion from alemtuzumab, an IL-21 driven increase in homeostatic proliferation and T cell cycling may disrupt tolerance mechanisms leading to an increase in the propensity toward alemtuzumab-induced autoimmunity. Further research is necessary to clarify the physiological changes after alemtuzumab therapy that trigger SAID in pwMS.

Abstract Stormwater ponds manage urban runoff and mitigate storm-event flooding. Stormwater ponds also offer various secondary advantages such as filtering pollutants, providing a habitat for wildlife, and adding recreational value and access to green spaces to communities. However, stormwater pond features and their potential to offer secondary benefits can vary based on the initial construction and the ongoing maintenance practices. This study developed an assessment tool for evaluating stormwater ponds’ expected functioning for secondary benefits, including potential for pollutant filtering by shoreline vegetation, safety, and access by people for activities like walking or wildlife viewing. We used the tool to compare stormwater ponds in East Tampa and Riverview, Florida, communities with contrasting socioeconomic backgrounds. The overall pond functioning was consistent between both communities; however, several distinctions emerged between specific pond attributes. Suburban ponds exhibited narrower buffer zones, lower bank stability, and less lighting. Conversely, ponds in the lower-income East Tampa had lower accessibility due to a higher number of fences, more litter, and inferior water appearance. This study uncovered a need for consideration of stormwater pond secondary benefits in both communities and an untapped potential to transform stormwater ponds into vibrant green spaces.

Abstract Background Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complicated, heterogeneous condition distinguished by post-exertional neuroimmune exhaustion and multisystem symptoms. Its complexity poses challenges for physicians, researchers and those inflicted by its presence. Due to conflicting evidence and limiting consensus, the association and contribution autoimmunity serves in the pathophysiology or aetiology of ME/CFS is yet to be confirmed. This systematic review synthesises the currently available data to clarify the role autoimmunity has in the pathogenesis of ME/CFS and explore the therapeutic limitations. Methods This systematic review was conducted in accordance with the PRISMA and Cochrane guidelines. Full-text articles containing the primary key terms “Autoimmunity/Autoimmune” and “ME/CFS” were included provided their suitability to the inclusion and exclusion criteria. Results Ten publications investigating the role of autoimmunity in ME/CFS were examined. One investigated the role of cytokine signalling; Three investigated the genetic nature of autoimmunity in ME/CFS patients; One examined the immune lineage of ME/CFS patients; Six investigated the presence and role of autoantibodies in ME/CFS patients. Conclusion The findings generated from this systematic review highlight inconsistent and insufficient evidence to classify ME/CFS as an autoimmune disease. Additionally, it further emphasises the complexity of ME/CFS and highlights the challenges in distinguishing autoreactivity from deregulatory processes. Future research is urgently needed to advance the development of diagnostic and treatment strategies. PROSPERO Registration Code CRD42024533447.

Abstract Meaningful engagement with stakeholders in research demands intentional approaches. This paper describes the development of a framework to guide stakeholder engagement as research partners in a pragmatic trial proposed to evaluate behavioral interventions for dysphagia in head and neck cancer patients. We highlight the core principles of stakeholder engagement including representation of all perspectives, meaningful participation, respectful partnership with stakeholders, and accountability to stakeholders; and describe how these principles were operationalized to engage relevant stakeholders throughout the course of a large clinical trial.

Our goal is to reduce the negative impacts of bicycle theft by better understanding patterns in bicycle theft and recovery. We analyzed data from 1823 responses to a North American survey on bicycle theft conditions, recovery circumstances, and demographics. Survey recruitment was done in partnership with BikeIndex, a non-profit bicycling registration service. Most bikes were stolen from inside a shed or garage (28%) or from outdoor bicycle racks (18%) and most thefts occur overnight (41%). 15% of stolen bicycles were recovered. Key factors in recovery include police involvement, bike registration, and reporting the theft through multiple channels.

The cell type-specific expression of key transcription factors is central to development and disease. Brachyury/T/TBXT is a major transcription factor for gastrulation, tailbud patterning, and notochord formation; however, how its expression is controlled in the mammalian notochord has remained elusive. Here, we identify the complement of notochord-specific enhancers in the mammalian Brachyury/T/TBXT gene. Using transgenic assays in zebrafish, axolotl, and mouse, we discover three conserved Brachyury-controlling notochord enhancers, T3, C, and I, in human, mouse, and marsupial genomes. Acting as Brachyury-responsive, auto-regulatory shadow enhancers, in cis deletion of all three enhancers in mouse abolishes Brachyury/T/Tbxt expression selectively in the notochord, causing specific trunk and neural tube defects without gastrulation or tailbud defects. The three Brachyury-driving notochord enhancers are conserved beyond mammals in the brachyury/tbxtb loci of fishes, dating their origin to the last common ancestor of jawed vertebrates. Our data define the vertebrate enhancers for Brachyury/T/TBXTB notochord expression through an auto-regulatory mechanism that conveys robustness and adaptability as ancient basis for axis development.

Plasma vascular endothelial growth factor (VEGF) coreceptor neuropilin-1 (NRP-1) had the largest association with coronary plaque in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) proteomics analysis. With little known about NRP-1 in people with human immunodeficiency virus (PWH), we explored its relation to other proteins in REPRIEVE and validated our findings through a Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) case-cohort study by assessing its relation to host factors and incident cardiovascular disease and cancer. Within REPRIEVE, NRP-1 was associated with proteins involved in angiogenesis, signal transduction, immunoregulation, and cell migration/adhesion. Within CNICS, NRP-1 was associated with key host factors, including older age and male sex. NRP-1 was associated with an increased hazard of multiple cancers but a decreased prostate cancer risk. Finally, NRP-1 was most strongly associated with mortality and type 2 myocardial infarction. These data suggest that NRP-1 is part of a clinically relevant immunoregulatory pathway related to multiple comorbidities in PWH. Clinical Trials Registration. NCT02344290.

Abstract Computed tomography (CT) is used as a valuable tool for device selection for interventional therapy in tricuspid regurgitation (TR). We aimed to evaluate predictors of TR reduction using CT and automated deep learning algorithms. Patients with severe to torrential TR and CTs prior to either percutaneous annuloplasty (PA) or tricuspid transcatheter edge-to-edge repair (T-TEER) were enrolled. CTs were analyzed using automated deep learning algorithms to assess tricuspid valve anatomy, right heart morphology, and function. Outcome parameters comprised post-interventional TR ≤ 1 and all-cause mortality. 84 patients with T-TEER (n = 32) or PA treatment (n = 52) were enrolled. Patients with a post-interventional TR ≤ 1 presented lower tenting heights and smaller tenting angles compared to patients with a TR > 1. Tenting height showed the best accuracy for post-interventional TR > 1 with an AUC of 0.756 (95% CI 0.560–0.951) in the T-TEER and 0.658 (95% CI 0.501–0.815) in the PA group, consistent with a suggested threshold of 6.8 mm and 9.2 mm, respectively. Patients with a post-interventional TR ≤ 1 exhibited a mortality of 4% and those with a TR > 1 of 12% during a follow-up of 331 ± 300 and 370 ± 265 days, respectively (p = 0.124). To conclude, tenting is associated with procedural outcomes and should be considered during screening for interventional TR therapy.

Octreotide is the first synthetic peptide hormone, consisting of eight amino acids, that mimics the activity of somatostatin, a natural hormone in the body. During the past decades, advanced instrumentation and crystallographic software have established X-Ray Powder Diffraction (XRPD) as a valuable tool for extracting structural information from biological macromolecules. The latter was demonstrated by the successful structural determination of octreotide at a remarkably high d-spacing resolution (1.87 Å) (PDB code: 6vc1). This study focuses on the response of octreotide to different humidity levels and temperatures, with a particular focus on the stability of the polycrystalline sample. XRPD measurements were accomplished employing an Anton Paar MHC-trans humidity-temperature chamber installed within a laboratory X’Pert Pro diffractometer (Malvern Panalytical). The chamber is employed to control and maintain precise humidity and temperature levels of samples during XRPD data collection. Pawley analysis of the collected data sets revealed that the octreotide polycrystalline sample is remarkably stable, and no structural transitions were observed. The compound retains its orthorhombic symmetry (space group: P212121, a = 18.57744(4) Å, b = 30.17338(6) Å, c = 39.70590(9) Å, d ~ 2.35 Å). However, a characteristic structural evolution in terms of lattice parameters and volume of the unit cell is reported mainly upon controlled relative humidity variation. In addition, an improvement in the signal-to-noise ratio in the XRPD data under a cycle of dehydration/rehydration is reported. These results underline the importance of considering the impact of environmental factors, such as humidity and temperature, in the context of structure-based drug design, thereby contributing to the development of more effective and stable pharmaceutical products.

Abstract Changes in protein turnover play an important role in dynamic physiological processes, including skeletal muscle regeneration, which occurs as an essential part of tissue repair after injury. The inability of muscle tissue to recapitulate this regenerative process can lead to the manifestation of clinical symptoms in various musculoskeletal diseases, including muscular dystrophies and pathological atrophy. Here, we employed a workflow that couples deuterated water (2H2O) administration with mass spectrometry (MS) to systematically measure in-vivo protein turnover rates across the muscle proteome in 8-week-old male C57BL6/J mice. We compared the turnover kinetics of over 100 proteins in response to cardiotoxin (CTX) induced muscle damage and regeneration at unique sequential stages along the regeneration timeline. This analysis is compared to gene expression data from mRNA-sequencing (mRNA-seq) from the same tissue. The data reveals quantitative protein flux signatures in response to necrotic damage, in addition to sequential differences in cell proliferation, energy metabolism, and contractile gene expression. Interestingly, the mRNA changes correlated poorly with changes in protein synthesis rates, consistent with post-transcriptional control mechanisms. In summary, the experiments described here reveal the signatures and timing of protein flux changes during skeletal muscle regeneration, as well as the inability of mRNA expression measurements to reveal changes in directly measured protein turnover rates. The results of this work described here provide a better understanding of the muscle regeneration process and could help to identify potential biomarkers or therapeutic targets.

Abstract Critical illness can significantly alter the composition and function of the human microbiome, but few studies have examined these changes over time. Here, we conduct a comprehensive analysis of the oral, lung, and gut microbiota in 479 mechanically ventilated patients (223 females, 256 males) with acute respiratory failure. We use advanced DNA sequencing technologies, including Illumina amplicon sequencing (utilizing 16S and ITS rRNA genes for bacteria and fungi, respectively, in all sample types) and Nanopore metagenomics for lung microbiota. Our results reveal a progressive dysbiosis in all three body compartments, characterized by a reduction in microbial diversity, a decrease in beneficial anaerobes, and an increase in pathogens. We find that clinical factors, such as chronic obstructive pulmonary disease, immunosuppression, and antibiotic exposure, are associated with specific patterns of dysbiosis. Interestingly, unsupervised clustering of lung microbiota diversity and composition by 16S independently predicted survival and performed better than traditional clinical and host-response predictors. These observations are validated in two separate cohorts of COVID-19 patients, highlighting the potential of lung microbiota as valuable prognostic biomarkers in critical care. Understanding these microbiome changes during critical illness points to new opportunities for microbiota-targeted precision medicine interventions.

The use of cargo bikes for last-mile deliveries has seen renewed interest, as more sustainable modes are needed to meet the carbon reduction strategies. Furthermore, cargo-bikes contain possibly the greatest co-benefits of any emission reduction strategies for the freight sector. With the goal of informing state, regional, and local government efforts for transforming local goods movement, researchers at the University of California, Davis synthesized the literature on cargo bikes for goods movement with a specific focus on the challenges facing California. Key findings from the research are summarized in this brief.

This white paper presents the synthesis of the literature on the use of cargo bikes for urban goods movement with a particular focus on four barrier and opportunity domains: physical and spatial; economic; political and legal; and social and cultural. It also includes research particularly relevant to California cities, although many of the studies reported were conducted outside California because we found a lack of evidence within California. The barriers to shifting from trucks and vans to cargo bikes for a variety of good movements remain tall in California. They include, among many, a need for a significant shift in the delivery landscape that requires collaboration across different organizations, and support from the local and state level that includes the development of urban consolidation hubs, investment in bike infrastructure, and strict restrictions on larger delivery vehicles. In addition, it may also require initial incentives to freight operators to offset the costs of shifting to cargo bike logistics. Although the barriers are large, the need is paramount, given the rise in e-commerce and local goods movement. Motivated by this need, and with targeted efforts to overcome these barriers, synergistic benefits are possible including a safer and more bike-friendly road network supportive of both personal active transportation and cargo-bike goods movement. These outcomes will help achieve wide-ranging goals in transportation planning, including GHG reduction, improvements to public health through physical activity, and emission reductions, among others.

Local and state electric bike (e-bike) incentive programs offering point-of-sale or post-sale monetary discounts to consumers have been implemented across the United States since 2018. As yet, however, little is known about their effectiveness in changing travel behavior. To understand the outcomes of these incentive programs, UC Davis researchers analyzed survey data from rebate recipients in Northern California two months and one year after they acquired e-bikes. The rebate programs were evaluated for effects of e-bike ownership on travel behavior, including changes in bicycling, driving, and use of transit, and on greenhouse gas emissions. The team also suggest areas for future research. View the NCST Project Webpage

Academic researchers in the U.S. and Canada have partnered with genealogical organizations and statistical agencies to create massive new scientific data collections from census enumerations. These data are creating new opportunities for research across the social and health sciences. By linking individuals and families across censuses, analysts can create national longitudinal panels that trace the characteristics of individuals over their lives and families over multiple generations. IPUMS disseminates full count census enumerations for ten U.S. census years from 1850 to 1950. These full count data cover almost 800 million individual records and the IPUMS Multigenerational Longitudinal Panel (MLP) project links individuals' records across censuses. IPUMS data can be combined with data from the U.S. Census Bureau’s data linkage infrastructure to link historical records to numerous recent censuses, surveys and administrative data that measure social, economic and health outcomes. The Canadian Peoples (TCP) is a comprehensive public research database of 40 million coded and georeferenced records found in Canadian censuses from the middle of the nineteenth century until after the First World War. The data include personal, family and household characteristics of every individual enumerated in each census from 1852 to 1921. TCP investigators are exploring record linkage technology to solve challenges presented with these historical records. The workshop included one presentation from each organization, with these objectives: introduce the data collections, explain the challenges and opportunities of census linkage, describe the linking strategies, and provide an overview on how to access the data.

Reduced natural killer (NK) cell cytotoxicity is the most consistent immune finding in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Meta-analysis of the published literature determined the effect size of the decrement in ME/CFS. Databases were screened for papers comparing NK cell cytotoxicity in ME/CFS and healthy controls. A total of 28 papers and 55 effector:target cell ratio (E:T) data points were collected. Cytotoxicity in ME/CFS was significantly reduced to about half of healthy control levels, with an overall Hedges’ g of 0.96 (0.75–1.18). Heterogeneity was high but was explained by the range of E:T ratios, different methods, and potential outliers. The outcomes confirm reproducible NK cell dysfunction in ME/CFS and will guide studies using the NK cell model system for pathomechanistic investigations.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024542140.

Over the past five years, the IPUMS Multigenerational Longitudinal Panel (MLP) has constructed a massive longitudinal population panel by linking together American censuses, surveys, administrative sources, and vital records spanning the period from 1850 to the present. MLP is designed as a general-purpose resource for studying longitudinal processes and long-run social and economic change. By linking individuals across generations from birth through death using data from multiple sources, MLP enables reproducible research on shifting patterns of life course patterns and intergenerational processes. The large scale of the MLP database allows researchers both to study particular communities and small dispersed populations and to conduct big studies spanning many places and periods. Data that allow investigators to examine simultaneously the broad sweep of time and fine spatial detail will yield new insights into ongoing transformations of demographic behavior. The presentation will describe the creation of the IPUMS MLP database and the current MLP linking strategy. We then detail our plans for expansion and improvement of MLP over the next five years, including the incorporation of additional data sources, the development of a “linkage hub” to connect MLP with other major record linkage efforts, and the refinement of our technology and dissemination efforts. We will conclude by describing a few early examples of MLP-based research.

Background: Obesity is a multifactorial neurohormonal disease that results from dysfunction within energy regulation pathways and is associated with increased morbidity, mortality, and reduced quality of life. The most common form is polygenic obesity, which results from interactions between multiple gene variants and environmental factors. Highly penetrant monogenic and syndromic obesities result from rare genetic variants with minimal environmental influence and can be differentiated from polygenic obesity depending on key symptoms, including hyperphagia; early-onset, severe obesity; and suboptimal responses to nontargeted therapies. Timely diagnosis of monogenic or syndromic obesity is critical to inform management strategies and reduce disease burden. We outline the physiology of weight regulation, role of genetics in obesity, and differentiating characteristics between polygenic and rare genetic obesity to facilitate diagnosis and transition toward targeted therapies. Methods: In this narrative review, we focused on case reports, case studies, and natural history studies of patients with monogenic and syndromic obesities and clinical trials examining the efficacy, safety, and quality of life impact of nontargeted and targeted therapies in these populations. We also provide comprehensive algorithms for diagnosis of patients with suspected rare genetic causes of obesity. Results: Patients with monogenic and syndromic obesities commonly present with hyperphagia (ie, pathologic, insatiable hunger) and early-onset, severe obesity, and the presence of hallmark characteristics can inform genetic testing and diagnostic approach. Following diagnosis, specialized care teams can address complex symptoms, and hyperphagia is managed behaviorally. Various pharmacotherapies show promise in these patient populations, including setmelanotide and glucagon-like peptide-1 receptor agonists. Conclusion: Understanding the pathophysiology and differentiating characteristics of monogenic and syndromic obesities can facilitate diagnosis and management and has led to development of targeted pharmacotherapies with demonstrated efficacy for reducing body weight and hunger in the affected populations.

Background: Coronary plaque is common among people with HIV (PWH) with low-to-moderate traditional atherosclerotic cardiovascular disease (ASCVD) risk. Objectives: The purpose of this study was to determine the association of high-sensitivity cardiac troponin T (hs-cTnT) levels with coronary plaque characteristics and evaluate if hs-cTnT improves identification of these features beyond traditional ASCVD risk factors among PWH. Methods: Among PWH receiving stable antiretroviral therapy with low-to-moderate ASCVD risk and no known history of ASCVD, hs-cTnT levels and measures of plaque by coronary computed tomography angiography were assessed. Primary outcomes included the association of hs-cTnT level with the presence of any plaque, vulnerable plaque, coronary artery calcium (CAC) score, and Leaman score. Assessment of model discrimination of hs-cTnT for plaque characteristics was also performed. Results: The cohort included 708 U.S. participants with a mean age of 51 ± 6 years, 119 (17%) females, a median ASCVD risk score of 4.4% (Q1-Q3: 2.5%-6.6%), and a median hs-cTnT level of 6.7 ng/L (detectable level ≥6 ng/L in 61%). Any plaque was present in 341 (48%), vulnerable plaque in 155 (22%), CAC>100 in 68 (10%), and a Leaman score >5 in 105 (15%). After adjustment for ASCVD risk score, participants with hs-cTnT >9.6 ng/L (highest category) versus an undetectable level (100 (2.58, 95% CI: 1.37-4.83), and Leaman score >5 (2.13, 95% CI: 1.32-3.46). The addition of hs-cTnT level modestly improved the discrimination of ASCVD risk score to identify critical plaque features. Conclusions: In PWH without known ASCVD, hs-cTnT levels were strongly associated with and improved prediction of subclinical coronary plaque. (Evaluating the Use of Pitavastatin to Reduce the Risk of Cardiovascular Disease in HIV-Infected Adults [REPRIEVE]; NCT02344290)

Background: In 2023, the Obesity Medicine Association (OMA) published “Compounded peptides: An Obesity Medicine Association Position Statement.” Since this publication, the use of compounded peptides for the treatment of obesity has continued to evolve, leading to additional confusion and questions from obesity medicine clinicians and their patients. Methods: This frequently asked questions (FAQ) document and “Call for Action” commentary is based upon the existing evidence and practical clinical experiences of the authors. Results: This FAQ is intended to provide insights beyond the original 2023 OMA Position Statement regarding the use of “compounded peptides” for treating obesity. Three obstacles impair patient access to highly effective peptide anti-obesity medications: insufficient production especially during times of high demand, high costs, and lack of clarity surrounding the role of compounded peptides. Solutions to enhance patient access to these medications lie within the existing legal and regulatory framework and Food and Drug Administration policies. Implementing these solutions necessitates dispelling misinformation and providing clear guidance on the appropriate prescribing and administration of compounded peptides, particularly during times of acknowledged shortage. Conclusion: Among stakeholders with aligned priorities, challenges can often be overcome by collaboration and communication. Towards the goal of providing patient-centered care, the OMA calls on applicable stakeholders (e.g., pharmaceutical companies, compounding pharmacy organizations, health insurance companies, and the Food and Drug Administration) to work collaboratively to achieve a consensus that improves patient access to safe anti-obesity medications. The purpose of this “Call to Action” is to ask stakeholders to provide clinicians and their patients clarity regarding the role of compounded peptide anti-obesity medications during times of FDA-acknowledged shortages. Finally, this FAQ review provides clinicians with a simple and practical checklist respective to the potential use of compounded peptides.

The cell type-specific expression of key transcription factors is central to development. Brachyury/T/TBXT is a major transcription factor for gastrulation, tailbud patterning, and notochord formation; however, how its expression is controlled in the mammalian notochord has remained elusive. Here, we identify the complement of notochord-specific enhancers in the mammalian Brachyury/T/TBXT gene. Using transgenic assays in zebrafish, axolotl, and mouse, we discover three Brachyury -controlling notochord enhancers T3, C , and I in human, mouse, and marsupial genomes. Acting as Brachyury-responsive, auto-regulatory shadow enhancers, deletion of all three enhancers in mouse abolishes Brachyury/T expression selectively in the notochord, causing specific trunk and neural tube defects without gastrulation or tailbud defects. Sequence and functional conservation of Brachyury -driving notochord enhancers with the brachyury/tbxtb loci from diverse lineages of fishes dates their origin to the last common ancestor of jawed vertebrates. Our data define the enhancers for Brachyury/T/TBXTB notochord expression as ancient mechanism in axis development.