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Abstract Pulmonary fibrosis is characterized by pathological accumulation of scar tissue in the lung parenchyma. Many of the processes that are implicated in fibrosis, including increased extracellular matrix synthesis, also occur following pneumonectomy (PNX), but PNX instead results in regenerative compensatory growth of the lung. As fibroblasts are the major cell type responsible for extracellular matrix production, we hypothesized that comparing fibroblast responses to PNX and bleomycin (BLM) would unveil key differences in the role they play during regenerative versus fibrotic lung responses. RNA‐sequencing was performed on flow‐sorted fibroblasts freshly isolated from mouse lungs 14 days after BLM, PNX, or sham controls. RNA‐sequencing analysis revealed highly similar biological processes to be involved in fibroblast responses to both BLM and PNX, including TGF‐β1 and TNF‐α. Interestingly, we observed smaller changes in gene expression after PNX than BLM at Day 14, suggesting that the fibroblast response to PNX may be muted by expression of transcripts that moderate pro‐fibrotic pathways. Itpkc, encoding inositol triphosphate kinase C, was a gene uniquely up‐regulated by PNX and not BLM. ITPKC overexpression in lung fibroblasts antagonized the pro‐fibrotic effect of TGF‐β1. RNA‐sequencing analysis has identified considerable overlap in transcriptional changes between fibroblasts following PNX and those overexpressing ITPKC.

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal metastatic disease associated with robust activation of the coagulation and fibrinolytic systems. However, the potential contribution of the primary fibrinolytic protease plasminogen to PDAC disease progression has remained largely undefined. Mice bearing C57Bl/6‐derived KPC (KRasG12D, TRP53R172H) tumors displayed evidence of plasmin activity in the form of high plasmin–antiplasmin complexes and high plasmin generation potential relative to mice without tumors. Notably, plasminogen‐deficient mice (Plg‐) had significantly diminished KPC tumor growth in subcutaneous and orthotopic implantation models. Moreover, the metastatic potential of KPC cells was significantly diminished in Plg‐ mice, which was linked to reduced early adhesion and/or survival of KPC tumor cells. The reduction in primary orthotopic KPC tumor growth in Plg‐ mice was associated with increased apoptosis, reduced accumulation of pro‐tumor immune cells, and increased local proinflammatory cytokine production. Elimination of fibrin(ogen), the primary proteolytic target of plasmin, did not alter KPC primary tumor growth and resulted in only a modest reduction in metastatic potential. In contrast, deficiencies in the plasminogen receptors Plg‐RKT or S100A10 in tumor cells significantly reduced tumor growth. Plg‐RKT reduction in tumor cells, but not reduced S100A10, suppressed metastatic potential in a manner that mimicked plasminogen deficiency. Finally, tumor growth was also reduced in NSG mice subcutaneously or orthotopically implanted with patient‐derived PDAC tumor cells in which circulating plasminogen was pharmacologically reduced. Collectively, these studies suggest that plasminogen promotes PDAC tumor growth and metastatic potential, in part through engaging plasminogen receptors on tumor cells.

Abstract The vascular smooth muscle (VSM) of resistance blood vessels is a target of intrinsic autoregulatory responses to increased intraluminal pressure, the myogenic response. In the brain, the myogenic reactivity of cerebral arteries is critical to homeostatic blood flow regulation. Here we provide the first evidence to link the death‐associated protein kinase 3 (DAPK3) to the myogenic response of rat and human cerebral arteries. DAPK3 is a Ser/Thr kinase involved in Ca2+‐sensitization mechanisms of smooth muscle contraction. Ex vivo administration of a specific DAPK3 inhibitor (i.e., HS38) could attenuate vessel constrictions invoked by serotonin as well as intraluminal pressure elevation. The HS38‐dependent dilatation was not associated with any change in myosin light chain (LC20) phosphorylation. The results suggest that DAPK3 does not regulate Ca2+ sensitization pathways during the myogenic response of cerebral vessels but rather operates to control the actin cytoskeleton. A slow return of myogenic tone was observed during the sustained ex vivo exposure of cerebral arteries to HS38. Recovery of tone was associated with greater LC20 phosphorylation that suggests intrinsic signalling compensation in response to attenuation of DAPK3 activity. Additional experiments with VSM cells revealed HS38‐ and siDAPK‐dependent effects on the actin cytoskeleton and focal adhesion kinase phosphorylation status. The translational importance of DAPK3 to the human cerebral vasculature was noted, with robust expression of the protein kinase and significant HS38‐dependent attenuation of myogenic reactivity found for human pial vessels.

ABSTRACT Importance Despite the high burden of respiratory infections among children, the production of exhaled particles during common activities and the efficacy of face masks in children have not been sufficiently studied. Objective To determine the effect of type of activity and mask usage on exhaled particle production in children. Methods Healthy children were asked to perform activities that ranged in intensity (breathing quietly, speaking, singing, coughing, and sneezing) while wearing no mask, a cloth mask, or a surgical mask. The concentration and size of exhaled particles were assessed during each activity. Results Twenty‐three children were enrolled in the study. Average exhaled particle concentration increased by intensity of activity, with the lowest particle concentration during tidal breathing (1.285 particles/cm3 [95% CI 0.943, 1.627]) and highest particle concentration during sneezing (5.183 particles/cm3 [95% CI 1.911, 8.455]). High‐intensity activities were associated with an increase primarily in the respirable size (≤ 5 µm) particle fraction. Surgical and cloth masks were associated with lower average particle concentration compared to no mask (P = 0.026 for sneezing). Surgical masks outperformed cloth masks across all activities, especially within the respirable size fraction. In a multivariable linear regression model, we observed significant effect modification of activity by age and by mask type. Interpretation Similar to adults, children produce exhaled particles that vary in size and concentration across a range of activities. Production of respirable size fraction particles (≤ 5 µm), the dominant mode of transmission of many respiratory viruses, increases significantly with coughing and sneezing and is most effectively reduced by wearing surgical face masks.

Abstract The acute reduction in peripheral arterial stiffness during reactive hyperemia is assumed to be flow‐mediated; however, the mechanism remains unproven. We hypothesized that restricting the blood flow increase during reactive hyperemia would abolish the reduction in peripheral arterial stiffness. Fourteen healthy young adults (5 females, 25 ± 5 years, mean ± SD) underwent reactive hyperemia with a rapid‐release cuff on the upper arm inflated to 220 mmHg for 5 min: once with unrestricted blood flow and once with restricted blood flow by manually applying pressure to the brachial artery. Brachial–radial pulse wave velocity (PWV) was measured with tonometers over brachial and radial arteries before cuff inflation and at 5, 15, and 30 min after release. Brachial blood flow was monitored with Doppler ultrasound. Baseline brachial–radial PWV was similar between conditions (10.3 ± 1.8 vs. 10.7 ± 1.7 m/s). With unrestricted flow, PWV decreased 5 min post‐reactive hyperemia (8.6 ± 1.1 m/s; p 0.05) post‐reactive hyperemia. Reactive hyperemia acutely reduced peripheral arterial stiffness, but not when brachial artery blood flow increase was restricted. This suggests that the reduction in peripheral arterial stiffness during reactive hyperemia depends on increased blood flow.

Abstract The Reynolds Creek Experimental Watershed (RCEW) and Critical Zone Observatory (CZO), located south of the western Snake River Plain in the Intermountain West of the United States, is the site of over 60 years of research aimed at understanding integrated earth processes in a semi‐arid climate to aid sustainable use of environmental resources. Meteoric water lines (MWLs) are used to interpret hydrologic processes, though equilibrium and nonequilibrium processes affect the linear function and can reveal seasonal and climatological effects, necessitating the development of local meteoric water lines (LMWLs). At RCEW‐CZO, an RCEW LMWL was developed using non‐volume‐weighted, orthogonal regression with assumed error in both predictor and response variables from several years of precipitation (2015, 2017, 2019, 2020, and 2021) primarily at three different elevations (1203, 1585, and 2043 m). As most precipitation is evaporated or intercepted by vegetation in the driest months, an RCEW LMWL for groundwater recharge (RCEW LMWL‐GWR) was also developed using precipitation from the wettest months (November through April). The RCEW LMWL (δ2H = 7.41 × δ18O – 3.09) is different from the RCEW LMWL‐GWR (δ2H = 8.21 × δ18O + 9.95) and compares favorably to other LMWLs developed for the region and climate. Comparative surface, spring, and subsurface water datasets within the RCEW‐CZO are more similar to precipitation during the wettest months than dry months, illustrating that some semi‐arid hydrologic systems may most appropriately be compared to MWLs developed from precipitation only from the wettest season.

Abstract Species records from biological collections are becoming increasingly available online. This unprecedented availability of records has largely supported recent studies in taxonomy, biogeography, macroecology and biodiversity conservation. Biological collections vary in their documentation and notation standards, which have changed through time. For different reasons, neither collections nor data repositories perform the editing, formatting and standardisation of the data, leaving these tasks to the final users of the species records (e.g. taxonomists, ecologists and conservationists). These tasks are challenging, particularly when working with millions of records from hundreds of biological collections. To help collection curators and final users perform those tasks, we introduce plantR, an open‐source package that provides a comprehensive toolbox to manage species records from biological collections. The package is accompanied by the proposal of a reproducible workflow to manage this type of data in taxonomy, ecology and biodiversity conservation. It is implemented in R and designed to handle relatively large datasets as fast as possible. Initially designed to handle plant species records, many of the plantR features also apply to other groups of organisms, given that the data structure is similar. The plantR workflow includes tools to (a) download records from different data repositories, (b) standardise typical fields associated with species records, (c) validate the locality, geographical coordinates, taxonomic nomenclature and species identifications, including the retrieval of duplicates across collections, and (d) summarise and export records, including the construction of species lists with vouchers. Other R packages provide tools to tackle some of the workflow steps described above. But in addition to the new tools and resources related to data standardisation and validation, the greatest strength of plantR is to provide a comprehensive and user‐friendly workflow in one single environment, performing all tasks from data retrieval to export. Thus, plantR can help researchers better assess data quality and avoid data leakage in a wide variety of studies using species records.

Objective The objectives of this study are to identify patterns of anxiety symptomology over time among patients with systemic lupus erythematosus (SLE) and to assess the longitudinal relationship between SLE disease activity and anxiety symptomology. Methods Longitudinal data from 139 patients with American College of Rheumatology or Systemic Lupus International Collborating Clinic (SLICC)‐classified SLE were analyzed. Anxiety symptomology was assessed using the Patient‐Reported Outcomes Measurement Information System (PROMIS) Emotional Distress: Anxiety Short Form 8a. SLE disease activity was measured using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)‐2000 (S2K) and S2K Responder Index 50 (S2K RI‐50). Group‐based trajectory modeling (GBTM) identified longitudinal trajectories of anxiety symptomology. The relationship between disease activity and anxiety over time was assessed using multilevel linear regressions. Results The mean patient age was 40.2 years (standard deviation [SD], 12.7); 90.6% were female, and 56.1% were of Black race. All patients had at least three PROMIS anxiety scores over an average of 30.9 months (SD, 13.0). GBTM identified four trajectories of anxiety symptomology, labeled as the following: low (LA), average (AA), moderate (MA), and high anxiety (HA). Black patients were 2.47 (95% confidence interval: 1.19‐5.12) times as likely as White patients to be classified into the MA or HA groups compared with the LA or AA groups. On multivariable analysis, active SLE disease was not significantly associated with anxiety over time (P = 0.19). Conclusion Anxiety trajectories remained stable over time, and racial differences in anxiety severity were observed. SLE disease activity was not longitudinally associated with anxiety after controlling for depression and other factors. Further understanding of the factors that contribute to the persistence of anxiety among individuals with SLE is necessary.

Abstract Small mammals are key scatter hoarders in forest ecosystems, acting as both seed predators and dispersers. The outcome of their interactions (i.e., predation vs. dispersal) is determined by a series of decisions made by small mammals, such as the choice of seed, whether the seed is immediately consumed or cached, and where it is cached. These decisions are influenced by a variety of factors, including the intrinsic traits of the seed, the individual personality of the scatter hoarder, and the perceived risk of predation while foraging. Furthermore, these factors may all interact to dictate the fate of the seed, with consequences for forest regeneration. Nevertheless, the ways in which perceived predation risk and personality interact to affect the seed dispersal decisions of scatter hoarders are still poorly understood. To contribute in filling this knowledge gap, we tested the hypotheses that southern red‐backed voles (Myodes gapperi), an important scatter hoarder in forest ecosystems, would exhibit personality‐mediated foraging and that predation risk would alter associations between personality and seed dispersal. We conducted a large‐scale field experiment, offering seed trays at stations with altered risk levels and recorded foraging decisions of free‐ranging voles with known personalities. We found that personality and perceived predation risk influenced decisions made by foraging voles. Specifically, docility, and boldness predicted foraging site selection, boldness predicted seed species selection and the number of seeds individuals selected, and the tendency to explore of an individual predicted whether voles would remove or consume seeds. Predation risk, mediated by the amount of cover at a site and by moon illumination, affected which foraging site individuals chose, seed species selection, and the probability of removal versus consumption. We did not find support for an interaction between personality and predation risk in predicting foraging decisions. These findings highlight the importance of scatter hoarder personality and perceived predation risk in affecting foraging decisions, with important consequences for seed dispersal and implications for altered patterns of forest regeneration in areas with different small mammal personality distributions or landscapes of fear.