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Leptospirosis (caused by pathogenic bacteria in the genus Leptospira ) is prevalent worldwide but more common in tropical and subtropical regions. Transmission can occur following direct exposure to infected urine from reservoir hosts, or a urine-contaminated environment, which then can serve as an infection source for additional rats and other mammals, including humans. The brown rat, Rattus norvegicus , is an important reservoir of Leptospira spp. in urban settings. We investigated the presence of Leptospira spp. among brown rats in Boston, Massachusetts and hypothesized that rat population dynamics in this urban setting influence the transportation, persistence, and diversity of Leptospira spp. We analyzed DNA from 328 rat kidney samples collected from 17 sites in Boston over a seven-year period (2016–2022); 59 rats representing 12 of 17 sites were positive for Leptospira spp. We used 21 neutral microsatellite loci to genotype 311 rats and utilized the resulting data to investigate genetic connectivity among sampling sites. We generated whole genome sequences for 28 Leptospira spp. isolates obtained from frozen and fresh tissue from some of the 59 positive rat kidneys. When isolates were not obtained, we attempted genomic DNA capture and enrichment, which yielded 14 additional Leptospira spp. genomes from rats. We also generated an enriched Leptospira spp. genome from a 2018 human case in Boston. We found evidence of high genetic structure among rat populations that is likely influenced by major roads and/or other dispersal barriers, resulting in distinct rat population groups within the city; at certain sites these groups persisted for multiple years. We identified multiple distinct phylogenetic clades of L. interrogans among rats that were tightly linked to distinct rat populations. This pattern suggests L. interrogans persists in local rat populations and its transportation is influenced by rat population dynamics. Finally, our genomic analyses of the Leptospira spp. detected in the 2018 human leptospirosis case in Boston suggests a link to rats as the source. These findings will be useful for guiding rat control and human leptospirosis mitigation efforts in this and other similar urban settings.

Leptospirosis (caused by pathogenic bacteria in the genus Leptospira ) is prevalent worldwide but more common in tropical and subtropical regions. Transmission can occur following direct exposure to infected urine from reservoir hosts, or a urine-contaminated environment, which then can serve as an infection source for additional rats and other mammals, including humans. The brown rat, Rattus norvegicus , is an important reservoir of Leptospira spp. in urban settings. We investigated the presence of Leptospira spp. among brown rats in Boston, Massachusetts and hypothesized that rat population dynamics in this urban setting influence the transportation, persistence, and diversity of Leptospira spp. We analyzed DNA from 328 rat kidney samples collected from 17 sites in Boston over a seven-year period (2016–2022); 59 rats representing 12 of 17 sites were positive for Leptospira spp. We used 21 neutral microsatellite loci to genotype 311 rats and utilized the resulting data to investigate genetic connectivity among sampling sites. We generated whole genome sequences for 28 Leptospira spp. isolates obtained from frozen and fresh tissue from some of the 59 positive rat kidneys. When isolates were not obtained, we attempted genomic DNA capture and enrichment, which yielded 14 additional Leptospira spp. genomes from rats. We also generated an enriched Leptospira spp. genome from a 2018 human case in Boston. We found evidence of high genetic structure among rat populations that is likely influenced by major roads and/or other dispersal barriers, resulting in distinct rat population groups within the city; at certain sites these groups persisted for multiple years. We identified multiple distinct phylogenetic clades of L. interrogans among rats that were tightly linked to distinct rat populations. This pattern suggests L. interrogans persists in local rat populations and its transportation is influenced by rat population dynamics. Finally, our genomic analyses of the Leptospira spp. detected in the 2018 human leptospirosis case in Boston suggests a link to rats as the source. These findings will be useful for guiding rat control and human leptospirosis mitigation efforts in this and other similar urban settings.

Leptospirosis (caused by pathogenic bacteria in the genus ) is prevalent worldwide but more common in tropical and subtropical regions. Transmission can occur following direct exposure to infected urine from reservoir hosts, such as rats, or a urine-contaminated environment, which then can serve as an infection source for additional rats and other mammals, including humans. The brown rat, , is an important reservoir of leptospirosis in urban settings. We investigated leptospirosis among brown rats in Boston, Massachusetts and hypothesized that rat dispersal in this urban setting influences the movement, persistence, and diversity of . We analyzed DNA from 328 rat kidney samples collected from 17 sites in Boston over a seven-year period (2016-2022); 59 rats representing 12 of 17 sites were positive for . We used 21 neutral microsatellite loci to genotype 311 rats and utilized the resulting data to investigate genetic connectivity among sampling sites. We generated whole genome sequences for 28 isolates obtained from frozen and fresh tissue from some of the 59 -positive rat kidneys. When isolates were not obtained, we attempted genomic DNA capture and enrichment, which yielded 14 additional genomes from rats. We also generated an enriched genome from a 2018 human case in Boston. We found evidence of high genetic structure and limited dispersal among rat populations that is likely influenced by major roads and/or other unknown dispersal barriers, resulting in distinct rat population groups within the city; at certain sites these groups persisted for multiple years. We identified multiple distinct phylogenetic clades of among rats, with specific clades tightly linked to distinct rat populations. This pattern suggests persists in local rat populations and movement of leptospirosis in this urban rat community is driven by rat dispersal. Finally, our genomic analyses of the 2018 human leptospirosis case in Boston suggests a link to rats as the source. These findings will be useful for guiding rat control and human leptospirosis mitigation efforts in this and other urban settings.

INTRODUCTION This post hoc analysis of the Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial examined associations between dulaglutide, Alzheimer's disease and related dementia (ADRD) biomarkers, and substantive cognitive impairment (SCI). METHODS Participants (dulaglutide, n = 3741; placebo, n = 3627) completed cognitive tests and provided blood samples at baseline and 2 years, with additional cognitive tests at 5‐year and final visits. Analysis of covariance and Cox models tested associations between dulaglutide, SCI, and plasma neurofilament light chain (NfL), phosphorylated tau217 (p‐tau217), and glial fibrillary acidic protein (GFAP) biomarkers. RESULTS Dulaglutide‐associated changes in biomarkers or SCI were nonsignificant overall. Participants with NfL ≥56 pg/mL had a dulaglutide‐associated 2‐year reduction in NfL (−27.4% vs −14.2%; p = 0.003). Participants with p‐tau217 ≥25 pg/mL had a dulaglutide‐associated SCI reduction (hazard ratio = 0.78; p = 0.0064). DISCUSSION Dulaglutide reduced NfL and SCI in participants with select elevated plasma ADRD biomarkers, with limited 2‐year effects on p‐tau217 and GFAP. Future studies with longer follow‐up should explore incretin‐related cognitive changes. CLINICAL TRIAL REGISTRATION INFORMATION NCT01394952, registered July 15, 2011. Highlights Treatment‐related 5‐year reduction in subjective cognitive impairment (SCI) occurred in a sub‐group of participants. The 22% reduction in SCI was significant in those with baseline phosphorylated tau217 (p‐tau17) ≥0.25 mg/dL. Over 2 years, dulaglutide reduced plasma NfL in those with baseline NfL ≥56 pg.ml.

Adipose tissue (AT) is a complex connective tissue with a high relative proportion of adipocytes, which are specialized cells with the ability to store lipids in large droplets. AT is found in multiple discrete depots throughout the body, where it serves as the primary repository for excess calories. In addition, AT has an important role in functions as diverse as insulation, immunity and regulation of metabolic homeostasis. The Human Cell Atlas Adipose Bionetwork was established to support the generation of single-cell atlases of human AT as well as the development of unified approaches and consensus for cell annotation. Here, we provide a first roadmap from this bionetwork, including our suggested cell annotations for humans and mice, with the aim of describing the state of the field and providing guidelines for the production, analysis, interpretation and presentation of AT single-cell data. In this Review, the authors present a roadmap towards achieving consensus on development, analysis and interpretation of single-cell transcriptomics data in adipose tissue, including discussion of roadblocks, best practices and ideal cell-type markers for annotation of adipose tissue cell types in mice and humans.