Reprint of: Impact of a pharmacist-led weight management service in a cardiology clinic.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for weight management require frequent dose titration, patient education, and insurance coverage navigation, which pharmacists are well equipped to manage. Data are lacking regarding the benefit of a pharmacist-managed service using GLP-1 RAs for weight loss in a high-risk cardiac population. OBJECTIVE: This study aimed to evaluate the impact of a pharmacist-led weight loss service within a cardiology clinic using GLP-1 RAs and lifestyle counseling in patients with overweight and obesity. PRACTICE DESCRIPTION: An outpatient cardiology clinic employs clinical pharmacists who use collaborative practice agreements to provide cardiovascular risk reduction services that did not include weight management at baseline. PRACTICE INNOVATION: This is the first description of a pharmacist-led weight management clinic using solely GLP-1 RAs in a cardiology practice. Patients were referred to the clinical pharmacist, who initiated and titrated GLP-1 RA and provided lifestyle counseling. EVALUATION METHODS: This was a single-center, prospective, pre-post analysis of adults with a body mass index of at least 30 kg/m2 or 27 kg/m2 with a weight-related comorbidity, with a preceding failed dietary effort and insurance coverage for semaglutide (Wegovy, Novo Nordisk) or liraglutide (Saxenda, Novo Nordisk) and managed by a pharmacist. The primary outcome was patients achieving ≥ 5% weight loss at 6 months, assessed via descriptive statistics. RESULTS: Between March 2022 and March 2023, 204 patients were referred by their cardiologist, and 59 patients started treatment with semaglutide (Wegovy, Novo Nordisk) or liraglutide (Saxenda, Novo Nordisk). A total of 31 patients completed 6 months of treatment at time of study completion, and all achieved ≥ 5% weight loss at 6 months, with a mean weight loss of 12.6%. Glycated hemoglobin improved by 0.6%, low-density lipoprotein by 18 mg/dL, triglycerides by 29 mg/dL, systolic blood pressure by 9 mm Hg, and diastolic blood pressure by 2 mm Hg. CONCLUSION: Pharmacist-led management of GLP-1 RA in patients with obesity or overweight led to clinically meaningful weight loss and improvements in weight-related comorbidities.

A genome assembly of the American black bear, Ursus americanus, from California.

The American black bear, Ursus americanus, is a widespread and ecologically important species in North America. In California, the black bear plays an important role in a variety of ecosystems and serves as an important species for recreational hunting. While research suggests that the populations in California are currently healthy, continued monitoring is critical to maintaining healthy populations, with genomic analyses providing an important surveillance tool. Here we report a high-quality, near chromosome-level genome assembly from a U. americanus sample from California. The primary assembly has a total length of 2.5 Gb contained in 317 scaffolds, a contig N50 of 58.9 Mb, a scaffold N50 of 67.6 Mb, and a BUSCO completeness score of 96%. This U. americanus genome assembly from a California sample will provide an important resource for the targeted management of black bear populations in California, with the goal of achieving an appropriate balance between the recreational value of black bears and the maintenance of viable populations. The high quality of this genome assembly will also make it a valuable resource for comparative genomic analyses among black bear populations and among bear species.

Pharmacist optimization of lipid therapy in patients with peripheral vascular disease.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: American College of Cardiology/American Heart Association guidelines recommend high-intensity statin therapy and consideration for nonstatin therapy for patients with peripheral vascular disease (PVD); however, utilization rates remain suboptimal. The primary objective of this study was to determine whether pharmacist intervention for patients with PVD could improve the percentage of patients discharged on a high-intensity statin. METHODS: The study used a single-center pre/post design and included patients with PVD who underwent peripheral bypass during their admission. Postintervention patients managed with an order set including a preselected consult for a pharmacy lipid protocol were compared to preintervention patients managed using the order set without the consult. The primary outcome was the percentage of patients discharged on a high-intensity statin. Secondary outcomes included intensification of statin therapy, the addition of ezetimibe, and referral to an outpatient lipid clinic. RESULTS: A total of 175 patients were included in the analysis, with 94 patients in the preintervention group and 81 patients in the postintervention group. The primary outcome met statistical significance, with an increase in the percentage of patients discharged on a high-intensity statin in the postintervention group (70.4%) compared to the preintervention group (38.3%) (P < 0.001; 95% confidence interval, 1.37-2.46). Secondary outcomes that met statistical significance included an increase in the percentage of patients with any increase in statin intensity (35.8% vs 20.2%; P = 0.02). CONCLUSION: The addition of a pharmacist consult led to an increase in the percentage of patients discharged on a high-intensity statin and an increase in overall statin intensification.

Impact of a pharmacist-led weight management service in a cardiology clinic.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for weight management require frequent dose titration, patient education, and insurance coverage navigation, which pharmacists are well equipped to manage. Data are lacking regarding the benefit of a pharmacist-managed service using GLP-1 RAs for weight loss in a high-risk cardiac population. OBJECTIVE: This study aimed to evaluate the impact of a pharmacist-led weight loss service within a cardiology clinic using GLP-1 RAs and lifestyle counseling in patients with overweight and obesity. PRACTICE DESCRIPTION: An outpatient cardiology clinic employs clinical pharmacists who use collaborative practice agreements to provide cardiovascular risk reduction services that did not include weight management at baseline. PRACTICE INNOVATION: This is the first description of a pharmacist-led weight management clinic using solely GLP-1 RAs in a cardiology practice. Patients were referred to the clinical pharmacist, who initiated and titrated GLP-1 RA and provided lifestyle counseling. EVALUATION METHODS: This was a single-center, prospective, pre-post analysis of adults with a body mass index of at least 30 kg/m2 or 27 kg/m2 with a weight-related comorbidity, with a preceding failed dietary effort and insurance coverage for semaglutide (Wegovy, Novo Nordisk) or liraglutide (Saxenda, Novo Nordisk) and managed by a pharmacist. The primary outcome was patients achieving ≥ 5% weight loss at 6 months, assessed via descriptive statistics. RESULTS: Between March 2022 and March 2023, 204 patients were referred by their cardiologist, and 59 patients started treatment with semaglutide (Wegovy, Novo Nordisk) or liraglutide (Saxenda, Novo Nordisk). A total of 31 patients completed 6 months of treatment at time of study completion, and all achieved ≥ 5% weight loss at 6 months, with a mean weight loss of 12.6%. Glycated hemoglobin improved by 0.6%, low-density lipoprotein by 18 mg/dL, triglycerides by 29 mg/dL, systolic blood pressure by 9 mm Hg, and diastolic blood pressure by 2 mm Hg. CONCLUSION: Pharmacist-led management of GLP-1 RA in patients with obesity or overweight led to clinically meaningful weight loss and improvements in weight-related comorbidities.

The contribution of historical processes to contemporary extinction risk in placental mammals.

Species persistence can be influenced by the amount, type, and distribution of diversity across the genome, suggesting a potential relationship between historical demography and resilience. In this study, we surveyed genetic variation across single genomes of 240 mammals that compose the Zoonomia alignment to evaluate how historical effective population size (Ne) affects heterozygosity and deleterious genetic load and how these factors may contribute to extinction risk. We find that species with smaller historical Ne carry a proportionally larger burden of deleterious alleles owing to long-term accumulation and fixation of genetic load and have a higher risk of extinction. This suggests that historical demography can inform contemporary resilience. Models that included genomic data were predictive of species' conservation status, suggesting that, in the absence of adequate census or ecological data, genomic information may provide an initial risk assessment.

Evolutionary constraint and innovation across hundreds of placental mammals.

Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (~10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.

Glacial ice supports a distinct and undocumented polar bear subpopulation persisting in late 21st-century sea-ice conditions.

Polar bears are susceptible to climate warming because of their dependence on sea ice, which is declining rapidly. We present the first evidence for a genetically distinct and functionally isolated group of polar bears in Southeast Greenland. These bears occupy sea-ice conditions resembling those projected for the High Arctic in the late 21st century, with an annual ice-free period that is >100 days longer than the estimated fasting threshold for the species. Whereas polar bears in most of the Arctic depend on annual sea ice to catch seals, Southeast Greenland bears have a year-round hunting platform in the form of freshwater glacial mélange. This suggests that marine-terminating glaciers, although of limited availability, may serve as previously unrecognized climate refugia. Conservation of Southeast Greenland polar bears, which meet criteria for recognition as the world's 20th polar bear subpopulation, is necessary to preserve the genetic diversity and evolutionary potential of the species.

A polar bear paleogenome reveals extensive ancient gene flow from polar bears into brown bears.

Polar bears (Ursus maritimus) and brown bears (Ursus arctos) are sister species possessing distinct physiological and behavioural adaptations that evolved over the last 500,000 years. However, comparative and population genomics analyses have revealed that several extant and extinct brown bear populations have relatively recent polar bear ancestry, probably as the result of geographically localized instances of gene flow from polar bears into brown bears. Here, we generate and analyse an approximate 20X paleogenome from an approximately 100,000-year-old polar bear that reveals a massive prehistoric admixture event, which is evident in the genomes of all living brown bears. This ancient admixture event was not visible from genomic data derived from living polar bears. Like more recent events, this massive admixture event mainly involved unidirectional gene flow from polar bears into brown bears and occurred as climate changes caused overlap in the ranges of the two species. These findings highlight the complex reticulate paths that evolution can take within a regime of radically shifting climate.

Author Correction: 863 genomes reveal the origin and domestication of chicken.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

863 genomes reveal the origin and domestication of chicken.

Despite the substantial role that chickens have played in human societies across the world, both the geographic and temporal origins of their domestication remain controversial. To address this issue, we analyzed 863 genomes from a worldwide sampling of chickens and representatives of all four species of wild jungle fowl and each of the five subspecies of red jungle fowl (RJF). Our study suggests that domestic chickens were initially derived from the RJF subspecies Gallus gallus spadiceus whose present-day distribution is predominantly in southwestern China, northern Thailand and Myanmar. Following their domestication, chickens were translocated across Southeast and South Asia where they interbred locally with both RJF subspecies and other jungle fowl species. In addition, our results show that the White Leghorn chicken breed possesses a mosaic of divergent ancestries inherited from other subspecies of RJF. Despite the strong episodic gene flow from geographically divergent lineages of jungle fowls, our analyses show that domestic chickens undergo genetic adaptations that underlie their unique behavioral, morphological and reproductive traits. Our study provides novel insights into the evolutionary history of domestic chickens and a valuable resource to facilitate ongoing genetic and functional investigations of the world's most numerous domestic animal.

Author Correction: Puma genomes from North and South America provide insights into the genomic consequences of inbreeding.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Puma genomes from North and South America provide insights into the genomic consequences of inbreeding.

Pumas are the most widely distributed felid in the Western Hemisphere. Increasingly, however, human persecution and habitat loss are isolating puma populations. To explore the genomic consequences of this isolation, we assemble a draft puma genome and a geographically broad panel of resequenced individuals. We estimate that the lineage leading to present-day North American pumas diverged from South American lineages 300-100 thousand years ago. We find signatures of close inbreeding in geographically isolated North American populations, but also that tracts of homozygosity are rarely shared among these populations, suggesting that assisted gene flow would restore local genetic diversity. The genome of a Florida panther descended from translocated Central American individuals has long tracts of homozygosity despite recent outbreeding. This suggests that while translocations may introduce diversity, sustaining diversity in small and isolated populations will require either repeated translocations or restoration of landscape connectivity. Our approach provides a framework for genome-wide analyses that can be applied to the management of similarly small and isolated populations.

Depletion of Hemoglobin Transcripts and Long-Read Sequencing Improves the Transcriptome Annotation of the Polar Bear (Ursus maritimus).

Transcriptome studies evaluating whole blood and tissues are often confounded by overrepresentation of highly abundant transcripts. These abundant transcripts are problematic, as they compete with and prevent the detection of rare RNA transcripts, obscuring their biological importance. This issue is more pronounced when using long-read sequencing technologies for isoform-level transcriptome analysis, as they have relatively lower throughput compared to short-read sequencers. As a result, long-read based transcriptome analysis is prohibitively expensive for non-model organisms. While there are off-the-shelf kits available for select model organisms capable of depleting highly abundant transcripts for alpha (HBA) and beta (HBB) hemoglobin, they are unsuitable for non-model organisms. To address this, we have adapted the recent CRISPR/Cas9-based depletion method (depletion of abundant sequences by hybridization) for long-read full-length cDNA sequencing approaches that we call Long-DASH. Using a recombinant Cas9 protein with appropriate guide RNAs, full-length hemoglobin transcripts can be depleted in vitro prior to performing any short- and long-read sequencing library preparations. Using this method, we sequenced depleted full-length cDNA in parallel using both our Oxford Nanopore Technology (ONT) based R2C2 long-read approach, as well as the Illumina short-read based Smart-seq2 approach. To showcase this, we have applied our methods to create an isoform-level transcriptome from whole blood samples derived from three polar bears (Ursus maritimus). Using Long-DASH, we succeeded in depleting hemoglobin transcripts and generated deep Smart-seq2 Illumina datasets and 3.8 million R2C2 full-length cDNA consensus reads. Applying Long-DASH with our isoform identification pipeline, Mandalorion, we discovered ∼6,000 high-confidence isoforms and a number of novel genes. This indicates that there is a high diversity of gene isoforms within U. maritimus not yet reported. This reproducible and straightforward approach has not only improved the polar bear transcriptome annotations but will serve as the foundation for future efforts to investigate transcriptional dynamics within the 19 polar bear subpopulations around the Arctic.

Conservation of biodiversity in the genomics era.

"Conservation genomics" encompasses the idea that genome-scale data will improve the capacity of resource managers to protect species. Although genetic approaches have long been used in conservation research, it has only recently become tractable to generate genome-wide data at a scale that is useful for conservation. In this Review, we discuss how genome-scale data can inform species delineation in the face of admixture, facilitate evolution through the identification of adaptive alleles, and enhance evolutionary rescue based on genomic patterns of inbreeding. As genomic approaches become more widely adopted in conservation, we expect that they will have a positive impact on management and policy decisions.

Landscape genomic prediction for restoration of a Eucalyptus foundation species under climate change.

As species face rapid environmental change, we can build resilient populations through restoration projects that incorporate predicted future climates into seed sourcing decisions. Eucalyptus melliodora is a foundation species of a critically endangered community in Australia that is a target for restoration. We examined genomic and phenotypic variation to make empirical based recommendations for seed sourcing. We examined isolation by distance and isolation by environment, determining high levels of gene flow extending for 500 km and correlations with climate and soil variables. Growth experiments revealed extensive phenotypic variation both within and among sampling sites, but no site-specific differentiation in phenotypic plasticity. Model predictions suggest that seed can be sourced broadly across the landscape, providing ample diversity for adaptation to environmental change. Application of our landscape genomic model to E. melliodora restoration projects can identify genomic variation suitable for predicted future climates, thereby increasing the long term probability of successful restoration.

Complex modular architecture around a simple toolkit of wing pattern genes.

Identifying the genomic changes that control morphological variation and understanding how they generate diversity is a major goal of evolutionary biology. In Heliconius butterflies, a small number of genes control the development of diverse wing color patterns. Here, we used full genome sequencing of individuals across the Heliconius erato radiation and closely related species to characterize genomic variation associated with wing pattern diversity. We show that variation around color pattern genes is highly modular, with narrow genomic intervals associated with specific differences in color and pattern. This modular architecture explains the diversity of color patterns and provides a flexible mechanism for rapid morphological diversification.

Genomic diversity guides conservation strategies among rare terrestrial orchid species when taxonomy remains uncertain.

Background and Aims: Species are often used as the unit for conservation, but may not be suitable for species complexes where taxa are difficult to distinguish. Under such circumstances, it may be more appropriate to consider species groups or populations as evolutionarily significant units (ESUs). A population genomic approach was employed to investigate the diversity within and among closely related species to create a more robust, lineage-specific conservation strategy for a nationally endangered terrestrial orchid and its relatives from south-eastern Australia. Methods: Four putative species were sampled from a total of 16 populations in the Victorian Volcanic Plain (VVP) bioregion and one population of a sub-alpine outgroup in south-eastern Australia. Morphological measurements were taken in situ along with leaf material for genotyping by sequencing (GBS) and microsatellite analyses. Key Results: Species could not be differentiated using morphological measurements. Microsatellite and GBS markers confirmed the outgroup as distinct, but only GBS markers provided resolution of population genetic structure. The nationally endangered Diuris basaltica was indistinguishable from two related species ( D. chryseopsis and D. behrii ), while the state-protected D. gregaria showed genomic differentiation. Conclusions: Genomic diversity identified among the four Diuris species suggests that conservation of this taxonomically complex group will be best served by considering them as one ESU rather than separately aligned with species as currently recognized. This approach will maximize evolutionary potential among all species during increased isolation and environmental change. The methods used here can be applied generally to conserve evolutionary processes for groups where taxonomic uncertainty hinders the use of species as conservation units.

The gene cortex controls mimicry and crypsis in butterflies and moths.

The wing patterns of butterflies and moths (Lepidoptera) are diverse and striking examples of evolutionary diversification by natural selection. Lepidopteran wing colour patterns are a key innovation, consisting of arrays of coloured scales. We still lack a general understanding of how these patterns are controlled and whether this control shows any commonality across the 160,000 moth and 17,000 butterfly species. Here, we use fine-scale mapping with population genomics and gene expression analyses to identify a gene, cortex, that regulates pattern switches in multiple species across the mimetic radiation in Heliconius butterflies. cortex belongs to a fast-evolving subfamily of the otherwise highly conserved fizzy family of cell-cycle regulators, suggesting that it probably regulates pigmentation patterning by regulating scale cell development. In parallel with findings in the peppered moth (Biston betularia), our results suggest that this mechanism is common within Lepidoptera and that cortex has become a major target for natural selection acting on colour and pattern variation in this group of insects.

Divergence with gene flow across a speciation continuum of Heliconius butterflies.

BACKGROUND: A key to understanding the origins of species is determining the evolutionary processes that drive the patterns of genomic divergence during speciation. New genomic technologies enable the study of high-resolution genomic patterns of divergence across natural speciation continua, where taxa pairs with different levels of reproductive isolation can be used as proxies for different stages of speciation. Empirical studies of these speciation continua can provide valuable insights into how genomes diverge during speciation. METHODS: We examine variation across a handful of genomic regions in parapatric and allopatric populations of Heliconius butterflies with varying levels of reproductive isolation. Genome sequences were mapped to 2.2-Mb of the H. erato genome, including 1-Mb across the red color pattern locus and multiple regions unlinked to color pattern variation. RESULTS: Phylogenetic analyses reveal a speciation continuum of pairs of hybridizing races and incipient species in the Heliconius erato clade. Comparisons of hybridizing pairs of divergently colored races and incipient species reveal that genomic divergence increases with ecological and reproductive isolation, not only across the locus responsible for adaptive variation in red wing coloration, but also at genomic regions unlinked to color pattern. DISCUSSION: We observe high levels of divergence between the incipient species H. erato and H. himera, suggesting that divergence may accumulate early in the speciation process. Comparisons of genomic divergence between the incipient species and allopatric races suggest that limited gene flow cannot account for the observed high levels of divergence between the incipient species. CONCLUSIONS: Our results provide a reconstruction of the speciation continuum across the H. erato clade and provide insights into the processes that drive genomic divergence during speciation, establishing the H. erato clade as a powerful framework for the study of speciation.

Genomic variation across landscapes: insights and applications.

The distribution of genomic variation across landscapes can provide insights into the complex interactions between the environment and the genome that influence the distribution of species, and mediate phenotypic adaptation to local conditions. High throughput sequencing technologies now offer unprecedented power to explore these interactions, allowing powerful inferences about historical processes of colonization, gene flow and divergence, as well as the identification of loci that mediate local adaptation. These 'landscape genomic' approaches have been validated in model species and are now being applied to nonmodel organisms, including foundation species that have substantial effects on ecosystem processes. Here we review the growing field of landscape genomics from a very broad perspective. In particular, we describe the inferential power that is gained by taking a genome-wide view of genetic variation, strategies for study design to best capture adaptive variation, and how to apply this information to practical challenges, such as restoration.