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Non-suppressible HIV-1 viremia (NSV) is defined as persistent low-level viremia on antiretroviral therapy (ART) without evidence of ART non-adherence or significant drug resistance. Unraveling the mechanisms behind NSV would broaden our understanding of HIV-1 persistence. Here we analyzed plasma virus sequences in eight ART-treated individuals with NSV (88% male) and show that they are composed of large clones without evidence of viral evolution over time in those with longitudinal samples. We defined proviruses that match plasma HIV-1 RNA sequences as 'producer proviruses', and those that did not as 'non-producer proviruses'. Non-suppressible viremia arose from expanded clones of producer proviruses that were significantly larger than the genome-intact proviral reservoir of ART-suppressed individuals. Integration sites of producer proviruses were enriched in proximity to the activating H3K36me3 epigenetic mark. CD4+ T cells from participants with NSV demonstrated upregulation of anti-apoptotic genes and downregulation of pro-apoptotic and type I/II interferon-related pathways. Furthermore, participants with NSV showed significantly lower HIV-specific CD8+ T cell responses compared with untreated viremic controllers with similar viral loads. We identified potential critical host and viral mediators of NSV that may represent targets to disrupt HIV-1 persistence.

Introduction Maternal feeding practices may be linked to infant obesogenic outcomes, but research to date has focused primarily on infant growth as an outcome of maternal feeding practices rather than exploring additional obesogenic outcomes like infant appetite and diet. Therefore, the current study examined the association between maternal feeding practices and beliefs and infant growth, diet, and appetite simultaneously at a critical timepoint for obesity risk development (i.e., 3-months-old). Methods Thirty-two 3-month-old infants and their mothers participated in this cross-sectional study. Infant anthropometrics were collected by trained staff and mothers completed questionnaires regarding maternal feeding practices and beliefs and infant diet and appetite. The data were analyzed by Spearman correlations. Results Statistically significant correlations were identified between maternal feeding practices (e.g., using food to calm, concern about infant weight) and infant satiety, appetite, food responsiveness, slow eating, and kilocalories consumed. Infant weight-for-length was related to maternal concern about infant underweight and mother-infant social interaction during feeding. Discussion These findings highlight the importance of the mother-infant feeding relationship and how these associations may influence responsive feeding practices and infant weight-related outcomes., Author(s): Angela Combs [sup.1] , Katlyn Garr [sup.1] , Christopher Bolling [sup.2] , Taylor Gates [sup.1] , Veronica Mehl [sup.1] , Taylor Adams [sup.1] , Krystin Turner [sup.3] , Cathleen [...]

Collagen-producing cells maintain the complex architecture of the lung and drive pathologic scarring in pulmonary fibrosis. Here we perform single-cell RNA-sequencing to identify all collagen-producing cells in normal and fibrotic lungs. We characterize multiple collagen-producing subpopulations with distinct anatomical localizations in different compartments of murine lungs. One subpopulation, characterized by expression of Cthrc1 (collagen triple helix repeat containing 1), emerges in fibrotic lungs and expresses the highest levels of collagens. Single-cell RNA-sequencing of human lungs, including those from idiopathic pulmonary fibrosis and scleroderma patients, demonstrate similar heterogeneity and CTHRC1-expressing fibroblasts present uniquely in fibrotic lungs. Immunostaining and in situ hybridization show that these cells are concentrated within fibroblastic foci. We purify collagen-producing subpopulations and find disease-relevant phenotypes of Cthrc1-expressing fibroblasts in in vitro and adoptive transfer experiments. Our atlas of collagen-producing cells provides a roadmap for studying the roles of these unique populations in homeostasis and pathologic fibrosis.

Precision management of fibrotic lung diseases is challenging due to their diverse clinical trajectories and lack of reliable biomarkers for risk stratification and therapeutic monitoring. Here, we validated the accuracy of CMKLR1 as an imaging biomarker of the lung inflammation-fibrosis axis. By analyzing single-cell RNA sequencing datasets, we demonstrated CMKLR1 expression as a transient signature of monocyte-derived macrophages (MDMf) enriched in patients with idiopathic pulmonary fibrosis (IPF). Consistently, we identified MDMf as the major driver of the uptake of CMKLR1-targeting peptides in a murine model of bleomycin-induced lung fibrosis. Furthermore, CMKLR1- targeted positron emission tomography in the murine model enabled quantification and spatial mapping of inflamed lung regions infiltrated by CMKLR1-expressing macrophages and emerged as a robust predictor of subsequent lung fibrosis. Last, high CMKLR1 expression by bronchoalveolar lavage cells identified an inflammatory endotype of IPF with poor survival. Our investigation supports the potential of CMKLR1 as an imaging biomarker for endotyping and risk stratification of fibrotic lung diseases. [ABSTRACT FROM AUTHOR]

Introduction: The objective was to evaluate the use of a minimally invasive surgical (MIS) approach to perform hemilaminectomies in chondrodystrophic dogs with thoracolumbar intervertebral disc extrusions (IVDE). Additionally, we aimed to evaluate the degree of soft tissue trauma using the endoscopic procedure compared to the standard open approach. Methods: Eight client-owned dogs presented to the Colorado State University Veterinary Teaching Hospital with acute onset thoracolumbar IVDE were included in this study. This was a prospective, randomized case-series. Patients were assigned to undergo an endoscopic (group 1; n = 4) or a standard open approach (group 2; n = 4) for a hemilaminectomy. A post-operative MRI was performed in all cases. Results: Conversion to an open approach was not necessary for any case in group 1. All cases had adequate spinal cord decompression on post-operative MRI. There was no significant difference in soft tissue changes noted on post-operative MRI between the two groups. Discussion: The MIS approach to hemilaminectomies in chondrodystrophic dogs with thoracolumbar IVDE can successfully be performed to decompress the neural tissue and appears to lead to similar clinical outcomes in the early postoperative period compared to the standard open approach. Larger studies are needed to determine the potential advantages of the MIS technique compared to the standard open approach in veterinary medicine. [ABSTRACT FROM AUTHOR]

Alveolarization ensures sufficient lung surface area for gas exchange, and during bulk alveolarization in mice (postnatal day [P] 4.5-14.5), alpha-smooth muscle actin (SMA)+ myofibroblasts accumulate, secrete elastin, and lay down alveolar septum. Herein, we delineate the dynamics of the lineage of early postnatal SMA+ myofibroblasts during and after bulk alveolarization and in response to lung injury. SMA+ lung myofibroblasts first appear at ~ P2.5 and proliferate robustly. Lineage tracing shows that, at P14.5 and over the next few days, the vast majority of SMA+ myofibroblasts downregulate smooth muscle cell markers and undergo apoptosis. Of note, ~8% of these dedifferentiated cells and another ~1% of SMA+ myofibroblasts persist to adulthood. Single cell RNA sequencing analysis of the persistent SMA-cells and SMA+ myofibroblasts in the adult lung reveals distinct gene expression profiles. For instance, dedifferentiated SMA-cells exhibit higher levels of tissue remodeling genes. Most interestingly, these dedifferentiated early postnatal myofibroblasts re-express SMA upon exposure of the adult lung to hypoxia or the pro-fibrotic drug bleomycin. However, unlike during alveolarization, these cells that re-express SMA do not proliferate with hypoxia. In sum, dedifferentiated early postnatal myofibroblasts are a previously undescribed cell type in the adult lung and redifferentiate in response to injury. [ABSTRACT FROM AUTHOR]

Objective: To determine signalment, injury type, trauma severity score, and outcome of canine trauma patients undergoing surgical (emergency room [ER] or operating room [OR]) and nonsurgical treatment in addition to time to surgery, specialty services involved, and cost in the OR surgery population. Design: Retrospective evaluation of medical record and hospital trauma registry data on canine trauma cases. Setting: University teaching hospital. Animals: One thousand six hundred and thirty dogs presenting for traumatic injury between May 2017 and July 2020. Interventions: None. Measurements and Main Results: Demographics and outcome were compared for canine trauma patients undergoing OR surgery (12.8%, 208/1630), ER surgery (39.1%, 637/1630), or no surgical intervention (48.2%, 785/1630). Among the 2 surgical groups, 98.9% (836/845) survived to discharge compared with 92.2% (724/785) of the nonsurgical group (P < 0.0001). The OR surgical group had significantly higher median Animal Trauma Triage scores (2 vs 1, P < 0.0001) and median days in hospital (2 vs < 1, P < 0.0001) compared with the other groups. For the OR surgical cohort, electronic medical records were reviewed to determine the specialty surgery service involved, time to and duration of anesthesia and surgery, and visit cost. The most common surgery services involved were orthopedics (45.2%, 94/208) and general surgery (26.9%, 56/208). Neurology and general surgery cases required the longest median length of stay in hospital, and ophthalmology and dentistry cases required the shortest. The median cost of visit was highest in neurology ($10,032) and lowest in ophthalmology ($2305) and dentistry ($2404). Conclusions: Surgical intervention in canine trauma patients appears to be associated with higher survival rates, and among the surgery groups, mortality was highest in the ER and general surgery groups. OR surgical intervention, in particular general surgery and neurology, was associated with increased length of hospitalization, increased cost, and higher Animal Trauma Triage scores. [ABSTRACT FROM AUTHOR]

VISTA (V domain immunoglobulin suppressor of T cell activation, also called PD-1H [programmed death-1 homolog]), a novel immune regulator expressed on myeloid and T lymphocyte lineages, is upregulated in mouse and human idiopathic pulmonary fibrosis (IPF). However, the significance of VISTA and its therapeutic potential in regulating IPF has yet to be defined. To determine the role of VISTA and its therapeutic potential in IPF, the expression profile of VISTA was evaluated from human single-cell RNA sequencing data (IPF Cell Atlas). Inflammatory response and lung fibrosis were assessed in bleomycin-induced experimental pulmonary fibrosis models in VISTA-deficient mice compared with wild-type littermates. In addition, these outcomes were evaluated after VISTA agonistic antibody treatment in the wild-type pulmonary fibrosis mice. VISTA expression was increased in lung tissue-infiltrating monocytes of patients with IPF. VISTA was induced in the myeloid population, mainly circulating monocyte-derived macrophages, during bleomycin-induced pulmonary fibrosis. Genetic ablation of VISTA drastically promoted pulmonary fibrosis, and bleomycin-induced fibroblast activation was dependent on the interaction between VISTA-expressing myeloid cells and fibroblasts. Treatment with VISTA agonistic antibody reduced fibrotic phenotypes accompanied by the suppression of lung innate immune and fibrotic mediators. In conclusion, these results suggest that VISTA upregulation in pulmonary fibrosis may be a compensatory mechanism to limit inflammation and fibrosis, and stimulation of VISTA signaling using VISTA agonists effectively limits the fibrotic innate immune landscape and consequent tissue fibrosis. Further studies are warranted to test VISTA as a novel therapeutic target for the IPF treatment. [ABSTRACT FROM AUTHOR]

We use a multi‐year record of Pandora‐derived NO2 total column abundance in Boston to examine the influence of atmospheric transport on column NO2 and its surface concentrations during the warm season in a coastal urban environment. We derive tropospheric NO2 estimates from the total column with a measurement‐model fusion approach using near‐real‐time estimates of stratospheric NO2 from NASA's Goddard Earth Observing System Composition Forecast model system and find the average influence of stratospheric NO2 at this urban site can be 30%–70% depending on season and time of day. Sea breeze days tend to exhibit rapid temporal variability in the column that which can go in the opposite direction of changes in surface NO2 concentrations. By comparing tropospheric NO2 with surface concentrations, we constrain the role of boundary layer entrainment processes in the evolution of surface NO2 concentrations, while highlighting the value of column measurements in identifying sea breeze frontal dynamics. We estimate an apparent equal mixing layer height of NO2 and infer that surface NOx emissions remain concentrated near the surface regardless of atmospheric stability regime. When comparing the Pandora‐ to TROPOMI‐derived column NO2 measurements, we find that sea breeze days present a unique challenge likely due to higher spatial heterogeneity in NO2 and the meteorology involved that is not well represented in retrieval inputs. Our observations provide new insights into column and surface variability of NO2 which will be relevant to interpreting geostationary observations, especially in coastal urban locations. Plain Language Summary: Relating satellite‐derived observations of nitrogen dioxide (NO2) to ground‐level air quality has long been an area of research with important applications to human and environmental welfare. Here, we use new remote sensing observations from ground‐ and satellite‐based instruments, along with ground‐level air quality monitoring and meteorological observations, to gain new insight into the relationship of NO2 total column abundance and surface concentrations in a costal urban environment. We show how the total columns (the NO2 between the surface and top of the atmosphere) derived from remote sensing are sensitive to different processes than surface concentrations (the amount of NO2 at a point near the surface), which complicate the interpretation of surface air quality from satellite observations. We also find evidence that the mixing of surface emissions in our urban environment is slow relative to the NOx lifetime even under conditions when the boundary layer is expected to be well‐mixed. We find that sea breeze systems common to coastal environments present particularly challenging circumstances, due to higher spatial and temporal variability in pollutant concentrations. Our results should provide some insights into the interpretation of new geostationary air quality observations. Key Points: Tropospheric NO2 column measurements capture rapid changes in horizontal advection of pollutionCollocated column and in situ measurements constrain the dominant role of vertical entrainment in NO2 surface concentrationsSea breezes pose a challenge to satellite retrievals of NO2 due to heterogeneity in NO2 and meteorology [ABSTRACT FROM AUTHOR]