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Doxorubicin (DOX)-induced cardiotoxicity has been widely observed, yet the specific impact on cardiac fibroblasts is not fully understood. Additionally, the modulation of the transforming growth factor beta (TGF-β) signaling pathway by DOX remains to be fully elucidated. This study investigated DOX’s ability to modulate the expression of genes and proteins involved in the TGF-β signaling cascade in mouse fibroblasts from two sources by assessing the impact of DOX treatment on TGF-β inducible expression of pivotal genes and proteins within fibroblasts. Mouse embryonic fibroblasts (NIH3T3) and mouse primary cardiac fibroblasts (CFs) were treated with DOX in the presence of TGF-β1 to assess changes in protein levels by western blot and changes in mRNA levels by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Our results revealed a dose-dependent reduction in cellular communication network factor 2 (CCN2) protein levels upon DOX treatment in both NIH3T3 and CFs, suggesting an antifibrotic activity by DOX in these fibroblasts. However, DOX only inhibited the TGF-β1 induced expression of COL1 in NIH3T3 cells but not in CFs. In addition, we observed that DOX treatment reduced the expression of BMP1 in NIH3T3 but not primary cardiac fibroblasts. No significant changes in SMAD2 protein expression and phosphorylation in either cells were observed after DOX treatment. Finally, DOX inhibited the expression of Atf4 gene and increased the expression of Cdkn1a, Id1, Id2, Runx1, Tgfb1, Inhba, Thbs1, Bmp1, and Stat1 genes in NIH3T3 cells but not CFs, indicating the potential for cell-specific responses to DOX and its modulation of the TGF-β signaling pathway.

. [Display omitted] ► The relative stocking level of alternatives impacts consumer preferences. ► Consumers infer that less-stocked (scarcer) products are more popular. ► Consumers also infer that scarcer products are of higher quality. ► These inferences increase the choice share of scarcer products. ► The effect is overwhelmed by strong preferences and price promotions. Shelf-based scarcity in the form of relative stocking level depletion significantly affects consumer preferences ( van Herpen et al. 2009). While both popularity and quality inferences are induced by stocking-level depletion, this paper demonstrates that popularity (rather than quality) inferences are the primary driver of the effect. Shelf-based scarcity is shown to have an impact in the presence of other signals, such as brand names and quality ratings, which indicates its effect may be widespread. However, its effect on preferences is greatly decreased by the presence of strong prior preferences and/or price promotions, indicating that shelf-based scarcity is likely to affect choices when consumers lack strong prior preferences and under conditions where price promotions are either not present or are similar across alternatives.

Contemporary consumer behavior research largely conceptualizes post-decision evaluation processes in terms of decision confidence, anticipated regret and satisfaction, and decision and consumption satisfaction. The current research broadens this view, arguing that people additionally experience varying degrees of decision comfort that are distinct from other post-decision evaluations. The authors argue that comfort is a soft-positive emotion thus far unexamined in relation to decision processes and present nine studies that (1) develop and validate two scales to measure decision comfort, (2) demonstrate the discriminant validity of decision comfort relative to numerous other post-decision constructs, and (3) examine the unique downstream consequences of decision comfort. The results show that an individual may be quite comfortable with a decision despite being uncertain about the optimality and/or the anticipated consequences of that decision (e.g., satisfaction or regret). It is demonstrated that decision comfort responds to affect-relevant cues and tends to rely less on comparisons between the chosen and foregone options (i.e., it tends to be a less comparative evaluation). Decision comfort is also shown to account for a sizable proportion of consumers’ overall decision evaluations and to have meaningful downstream consequences on marketing-relevant variables (e.g., choice commitment and the likelihood of recommending).

We propose that autonomy is a crucial aspect of consumer choice. We offer a definition that situates autonomy among related constructs in philosophy and psychology, contrast actual with perceived autonomy in consumer contexts, examine the resilience of perceived autonomy, and sketch out an agenda for research into the role of perceived autonomy in an evolving marketplace increasingly characterized by automation.

High-energy ion beams are successfully used in cancer therapy and precisely deliver high doses of ionizing radiation to small deep-seated target volumes. A similar noninvasive treatment modality for cardiac arrhythmias was tested here. This study used high-energy carbon ions for ablation of cardiac tissue in pigs. Doses of 25, 40, and 55 Gy were applied in forced-breath-hold to the atrioventricular junction, left atrial pulmonary vein junction, and freewall left ventricle of intact animals. Procedural success was tracked by (1.) in-beam positron-emission tomography (PET) imaging; (2.) intracardiac voltage mapping with visible lesion on ultrasound; (3.) lesion outcomes in pathohistolgy. High doses (40–55 Gy) caused slowing and interruption of cardiac impulse propagation. Target fibrosis was the main mediator of the ablation effect. In irradiated tissue, apoptosis was present after 3, but not 6 months. Our study shows feasibility to use high-energy ion beams for creation of cardiac lesions that chronically interrupt cardiac conduction.

In this article, we document the evolution of research trends (concepts, methods, and aims) within the field of consumer behavior, from the time of its early development to the present day, as a multidisciplinary area of research within marketing. We describe current changes in retailing and real-world consumption and offer suggestions on how to use observations of consumption phenomena to generate new and interesting consumer behavior research questions. Consumption continues to change with technological advancements and shifts in consumers’ values and goals. We cannot know the exact shape of things to come, but we polled a sample of leading scholars and summarize their predictions on where the field may be headed in the next twenty years.

When companies plan to build multi-category brands by adding new products to their product lines, two questions loom large: (1) whether and (2) when brand extensions perceived as distant (comparatively dissimilar) from the company’s existing core line of products should be introduced. Since many real-world firms have introduced distant brand extensions, this paper focuses on the second question: when the company should introduce a distant extension within a series of other closer extensions—a decision for which there is little research-based guidance for managers. Building on theories of mental categorization, the authors argue that early (vs. late) introductions of distant brand extensions can be more beneficial for the brand. Three studies support this conclusion, demonstrating that early (vs. late) introductions of distant extensions can result in more positive final brand attitudes; that is, attitudes held after all the extensions have been introduced. This effect is driven by how easily the distant extension is integrated into consumers’ brand concepts and is moderated by overall brand positioning. Importantly, this effect on final brand attitudes is shown to influence behavioral measures of product preference and brand engagement.

Summary Climate change is dramatically altering the distribution and abundance of many species. An examination of traits may elucidate why some species respond more strongly to climate change than others, particularly when ecophysiological thresholds set range limits. Mangrove forests are expanding polewards. Although multiple environmental factors influence mangrove distributions, freeze tolerance is hypothesized to determine their poleward extent. To investigate how trait variation influences mangroves’ responses to a warming climate, we examined how freeze tolerance and associated traits varied along a latitudinal cline for three co‐occurring mangrove species. We sampled individuals along >200 km of Florida, USA's eastern coast, from the mangroves’ most northern populations, where freeze events were historically common, to southern populations where freeze events continue to be rare. We measured a suite of traits in field‐collected adults and their garden‐reared offspring, and assessed their responses to an experimentally imposed freeze event. We asked whether freeze tolerance and other traits varied predictably among species, with latitude, and between life stages. Species and populations varied dramatically in freeze tolerance, with the highest freeze tolerance in the northernmost species and populations, and the lowest freeze tolerance in the southernmost species and populations. Additionally, leaves of all three species were drier, tougher, thicker and more freeze‐tolerant at the range edge. Tolerance to freezing appears to set the range limits for these mangrove species. All three species converged on a similar phenotype at the range edge, but species‐level variation in freezing resistance was conserved. Thus, these species are likely to continue migrating at different rates in response to climate warming, potentially leading to the dissolution of typically co‐occurring species and creating ‘no analogue’ coastal mangrove–marsh communities. Lay Summary

Recent climate warming has led to asynchronous species migrations, with major consequences for ecosystems worldwide. In woody communities, localized microclimates have the potential to create feedback mechanisms that can alter the rate of species range shifts attributed to macroclimate drivers alone. Mangrove encroachment into saltmarsh in many areas is driven by a reduction in freeze events, and this encroachment can further modify local climate, but the subsequent impacts on mangrove seedling dynamics are unknown. We monitored microclimate conditions beneath mangrove canopies and adjacent open saltmarsh at a freeze-sensitive mangrove-saltmarsh ecotone and assessed survival of experimentally transplanted mangrove seedlings. Mangrove canopies buffered night time cooling during the winter, leading to interspecific differences in freeze damage on mangrove seedlings. However, mangrove canopies also altered biotic interactions. Herbivore damage was higher under canopies, leading to greater mangrove seedling mortality beneath canopies relative to saltmarsh. While warming-induced expansion of mangroves can lead to positive microclimate feedbacks, simultaneous fluctuations in biotic drivers can also alter seedling dynamics. Thus, climate change can drive divergent feedback mechanisms through both abiotic and biotic channels, highlighting the importance of vegetation-microclimate interactions as important moderators of climate driven range shifts.

Background Acute kidney injury ( AKI) is a common complication in patients hospitalized with COVID-19 and may require renal replacement therapy (RRT). Dipstick urinalysis is frequently obtained, but data regarding the prognostic value of hematuria and proteinuria for kidney outcomes is scarce. Methods Patients with positive severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) PCR, who had a urinalysis obtained on admission to one of 20 hospitals, were included. Nested models with degree of hematuria and proteinuria were used to predict AKI and RRT during admission. Presence of Chronic Kidney Disease (CKD) and baseline serum creatinine were added to test improvement in model fit. Results Of 5,980 individuals, 829 (13.9%) developed an AKI during admission, and 149 (18.0%) of those with AKI received RRT. Proteinuria and hematuria degrees significantly increased with AKI severity ( P  < 0.001 for both). Any degree of proteinuria and hematuria was associated with an increased risk of AKI and RRT. In predictive models for AKI, presence of CKD improved the area under the curve (AUC) (95% confidence interval) to 0.73 (0.71, 0.75), P  < 0.001, and adding baseline creatinine improved the AUC to 0.85 (0.83, 0.86), P  < 0.001, when compared to the base model AUC using only proteinuria and hematuria, AUC = 0.64 (0.62, 0.67). In RRT models, CKD status improved the AUC to 0.78 (0.75, 0.82), P  < 0.001, and baseline creatinine improved the AUC to 0.84 (0.80, 0.88), P  < 0.001, compared to the base model, AUC = 0.72 (0.68, 0.76). There was no significant improvement in model discrimination when both CKD and baseline serum creatinine were included. Conclusions Proteinuria and hematuria values on dipstick urinalysis can be utilized to predict AKI and RRT in hospitalized patients with COVID-19. We derived formulas using these two readily available values to help prognosticate kidney outcomes in these patients. Furthermore, the incorporation of CKD or baseline creatinine increases the accuracy of these formulas.