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Model Intercomparison Projects (MIPs) are fundamental to our understanding of how the land surface responds to changes in climate. However, MIPs are challenging to conduct, requiring the organization of multiple, decentralized modeling teams throughout the world running common protocols. We explored centralizing these models on a single supercomputing system. We ran nine offline terrestrial biosphere models through the Terrestrial Biosphere Model Farm: CABLE, CENTURY, HyLand, ISAM, JULES, LPJ‐GUESS, ORCHIDEE, SiB‐3, and SiB‐CASA. All models were wrapped in a software framework driven with common forcing data, spin‐up, and run protocols specified by the Multi‐scale Synthesis and Terrestrial Model Intercomparison Project (MsTMIP) for years 1901–2100. We ran more than a dozen model experiments. We identify three major benefits and three major challenges. The benefits include: (a) processing multiple models through a MIP is relatively straightforward, (b) MIP protocols are run consistently across models, which may reduce some model output variability, and (c) unique multimodel experiments can provide novel output for analysis. The challenges are: (a) technological demand is large, particularly for data and output storage and transfer; (b) model versions lag those from the core model development teams; and (c) there is still a need for intellectual input from the core model development teams for insight into model results. A merger with the open‐source, cloud‐based Predictive Ecosystem Analyzer (PEcAn) ecoinformatics system may be a path forward to overcoming these challenges. Plain Language Summary Comparing models is fundamental to our understanding of how the land surface responds to changes in climate. However, these comparisons are challenging to conduct, requiring the organization of multiple, decentralized teams throughout the world. We explored centralizing these models on a single supercomputing system. The models were all run the same way. We ran more than a dozen model experiments. We identify three major benefits and three major challenges. The benefits include: (a) the centralized system takes a lot of burden off individual teams; (b) running models the same way helps to identify differences in how the world is represented in the models; and (c) the system allows us to run many model experiments relatively quickly. The challenges are: (a) lots of models require lots of data storage and transfer needs; (b) model versions lag those from the core model development teams; and (c) there is still a need for intellectual input from the core model development teams for insight into model results. Another system, called PEcAn, which has a lot of tools that can help overcome these challenges, can potentially be used in future work. Key Points We ran nine terrestrial biosphere models centralized on a common computing framework The Farm allows multiple MIP experiments to be run relatively quickly and uniformly Challenges included technological demand, model versioning, and interpretation of results

This software is used to locate Earth-science satellite data and climate-model analysis outputs in space and time. This enables the direct comparison of any set of data with different spatial and temporal resolutions. It is written in three separate modules that are clearly separated for their functionality and interface with other modules. This enables a fast development of supporting any new data set. In this updated version of the tool, several new front ends are developed for new products. This software finds co-locatable data pairs for given sets of data products and creates new data products that share the same spatial and temporal coordinates. This facilitates the direct comparison between the two heterogeneous datasets and the comprehensive and synergistic use of the datasets.

Purpose Cancer-related fatigue (CRF) is a prevalent and distressing side effect of cancer and its treatment that remains inadequately understood and poorly managed. A better understanding of the factors contributing to CRF could result in more effective strategies for the prevention and treatment of CRF. The objectives of this study were to examine the prevalence, severity, and potential predictors for the early onset of CRF after chemotherapy cycle 1 in breast cancer patients. Methods We report on a secondary data analysis of 548 female breast cancer patients from a phase III multi-center randomized controlled trial examining antiemetic efficacy. CRF was assessed by the Brief Fatigue Inventory at pre- and post-chemotherapy cycle 1 as well as by the four-day diary. Results The prevalence of clinically relevant post-CRF was 75%. Linear regression showed that pre-treatment CRF, greater nausea, disturbed sleep, and younger age were significant risk factors for post-CRF (adjusted R 2  = 0.39; P  < 0.0001). Path modeling showed that nausea severity influenced post-CRF both directly and indirectly by influencing disturbed sleep. Similarly, pre-treatment CRF influenced post-CRF directly as well as indirectly through both nausea severity and disturbed sleep. Pearson correlations showed that changes in CRF over time were significantly correlated with concurrent changes in nausea severity ( r  = 0.41; P  < 0.0001) and in disturbed sleep ( r  = 0.20; P  < 0.0001). Conclusion This study showed a high prevalence (75%) of clinically relevant CRF in breast cancer patients following their initial chemotherapy, and that nausea severity, disturbed sleep, pre-treatment CRF, and age were significant predictors of symptom.

Despite the well-documented action of growth hormone-releasing hormone (GHRH) on the stimulation of production and release of growth hormone (GH), the effects of GHRH in peripheral tissues are incompletely explored. In this study, we show that GHRH plays a role in wound healing and tissue repair by acting primarily on wound-associated fibroblasts. Mouse embryonic fibroblasts (MEFs) in culture and wound-associated fibroblasts in mice expressed a splice variant of the receptors for GHRH (SV1). Exposure of MEFs to 100 nM and 500 nM GHRH or the GHRH agonist JI-38 stimulated the expression of α-smooth muscle actin (αSMA) based on immunoblot analyses as well as the expression of an αSMA-β-galactosidase reporter transgene in primary cultures of fibroblasts isolated from transgenic mice. Consistent with this induction of αSMA expression, results of transwell-based migration assays and in vitro wound healing (scratch) assays showed that both GHRH and GHRH agonist JI-38 stimulated the migration of MEFs in vitro. In vivo, local application of GHRH or JI-38 accelerated healing in skin wounds of mice. Histological evaluation of skin biopsies showed that wounds treated with GHRH and JI-38 were both characterized by increased abundance of fibroblasts during the early stages of wound healing and accelerated reformation of the covering epithelium at later stages. These results identify another function of GHRH in promoting skin tissue wound healing and repair. Our findings suggest that GHRH may have clinical utility for augmenting healing of skin wounds resulting from trauma, surgery, or disease.

Abstract Global protein shortages and sustainability concerns have increased consumer demand for non-animal-derived protein. Dried whole-cell yeast (Saccharomyces cerevisiae) may be a suitable alternative to rendered protein meals in pet foods. The objective of this study was to investigate the effects of dried yeast in dog and cat foods on indicators that pet parents typically use to evaluate the suitability of a food for their pet. For this evaluation, two dog and two cat dry extruded diets were formulated. For each species, the test diet contained 10% dried yeast (Yeast) and the control diet was devoid of yeast (Control). Palatability, apparent total tract nutrient digestibility, and fecal quality of the foods were assessed in dogs and cats. Urine pH and specific gravity were measured in cats as indicators of urinary tract health. In dogs, the Yeast diet showed equivalent or better palatability compared to the Control diet based on total food consumption (P = 0.06), average daily consumption (day 1, P = 0.10; day 2, P = 0.54), and first choice preference over 2 consecutive days (P = 0.005). Cats showed a strong preference for the Yeast diet with more than double the consumption during the 2-d test period (P = 0.001). More cats showed a first-choice preference for the Yeast diet (24 vs. 16), but the difference was not statistically significant (P = 0.21). There were no significant differences in stool quality or nutrient digestibility when fed Yeast vs. Control diets to the dogs and cats (P > 0.05). All cats produced urine with pH and specific gravity values within the normal range, though specific gravity was lower in the Control group (P = 0.003). This study provides support for the acceptability and digestibility of dog and cat diets containing dried yeast as an alternative protein source.

Background: The mechanisms of recurrence have been under-studied in rare histologies of invasive epithelial ovarian cancer (EOC) (endometrioid, clear cell, mucinous, and low-grade serous). We hypothesised the existence of an expression signature predictive of outcome in the rarer histologies. Methods: In split discovery and validation analysis of 131 Mayo Clinic EOC cases, we used clustering to determine clinically relevant transcriptome classes using microarray gene expression measurements. The signature was validated in 967 EOC tumours (91 rare histological subtypes) with recurrence information. Results: We found two validated transcriptome classes associated with progression-free survival (PFS) in the Mayo Clinic EOC cases ( P =8.24 × 10 −3 ). This signature was further validated in the public expression data sets involving the rare EOC histologies, where these two classes were also predictive of PFS ( P =1.43 × 10 −3 ). In contrast, the signatures were not predictive of PFS in the high-grade serous EOC cases. Moreover, genes upregulated in Class-1 (with better outcome) were showed enrichment in steroid hormone biosynthesis (false discovery rate, FDR=0.005%) and WNT signalling pathway (FDR=1.46%); genes upregulated in Class-2 were enriched in cell cycle (FDR=0.86%) and toll-like receptor pathways (FDR=2.37%). Conclusions: These findings provide important biological insights into the rarer EOC histologies that may aid in the development of targeted treatment options for the rarer histologies.

Dogs with chronic giardiasis, histoplasmosis, or histiocytic ulcerative colitis, among other primary gastrointestinal diseases, may have similar results to the dogs labeled as “CE/IBD” and may have even been part of that group of dogs. [...]cohorts have been studied in detail, the authors' suggestion that a combination of ACA, ACNA, and AGA could aid in IBD diagnosis is unfounded or potentially even detrimental to the dogs diagnosed based on these biomarkers. While the work-up mentioned did include a minimum database and fecal examination for endoparasites, a standardized diagnostic work-up, including the outcome of broad-spectrum anthelminthic therapy or dietary trials, or tissue diagnosis, all essential for a diagnosis of IBD, are missing. [...]all we can conclude from the current study is that the panel of the three markers described has a 90% sensitivity and a 96% specificity in differentiating dogs with a variety of signs of chronic gastrointestinal disease from dogs that have signs of chronic gastrointestinal disease due to hypoadrenocorticism, EPI, possible pancreatitis, possible lymphoma, or healthy control dogs. [...]the authors state that the markers described in their study have been used as clinical tools for the diagnosis of gastrointestinal conditions in humans for decades.

A pilot safety study of focused microwave phased array thermotherapy in the treatment of primary breast carcinomas was conducted. Ten patients with breast carcinomas beneath the skin surface that ranged in maximal clinical size from 1 to 8 cm (mean, 4.3 cm) were treated with the breast compressed in the prone position. We planned to deliver a tumor thermal dose equivalent to 60 minutes at 43 degrees C. Breast imaging and pathology data were used to assess efficacy. For the 10 patients, the mean tumor equivalent thermal dose was 51.7 minutes, the mean peak tumor temperature was 44.9 degrees C, and the mean treatment time was 34.7 minutes. Ultrasound imaging demonstrated a significant reduction in tumor size (mean, 41%) 5 to 18 days after thermotherapy in 6 (60%) of 10 patients. A significant tumor response on the basis of reduction in tumor size or significant tumor cell kill occurred in 8 (80%) of 10 patients. With sufficient skin cooling, delivery of focused microwave phased array thermotherapy is safe in treating breast carcinomas when used alone, and some potential efficacy was demonstrated at the tumor thermal doses administered. Increased tumor thermal dose efficacy studies in larger patient populations for improved breast conservation should be investigated.