Sprouty2 loss‐induced IL6 drives castration‐resistant prostate cancer through scavenger receptor B1

Metastatic castration‐resistant prostate cancer (mCRPC) is a lethal form of treatment‐resistant prostate cancer and poses significant therapeutic challenges. Deregulated receptor tyrosine kinase (RTK) signalling mediated by loss of tumour suppressor Sprouty2 (SPRY2) is associated with treatment resistance. Using pre‐clinical human and murine mCRPC models, we show that SPRY2 deficiency leads to an androgen self‐sufficient form of CRPC. Mechanistically, HER2‐IL6 signalling axis enhances the expression of androgen biosynthetic enzyme HSD3B1 and increases SRB1‐mediated cholesterol uptake in SPRY2‐deficient tumours. Systemically, IL6 elevated the levels of circulating cholesterol by inducing host adipose lipolysis and hepatic cholesterol biosynthesis. SPRY2‐deficient CRPC is dependent on cholesterol bioavailability and SRB1‐mediated tumoral cholesterol uptake for androgen biosynthesis. Importantly, treatment with ITX5061, a clinically safe SRB1 antagonist, decreased treatment resistance. Our results indicate that cholesterol transport blockade may be effective against SPRY2‐deficient CRPC

Advanced Glycation End Product Interventions Reduce Diabetes-Accelerated Atherosclerosis

Advanced glycation end product (AGE) formation may contribute to the progression of atherosclerosis, particularly in diabetes. The present study explored atherosclerosis in streptozotocin-induced diabetic apolipoprotein E–deficient (apoE�/�) mice that were randomized (n � 20) to receive for 20 weeks no treatment, the AGE cross-link breaker ALT-711, or the inhibitor of AGE formation aminoguanidine (AG). A sixfold increase in plaque area with diabetes was attenuated by 30 % with ALT-711 and by 40 % in AG-treated mice. Regional distribution of plaque demonstrated no reduction in plaque area or complexity within the aortic arch with treatment, in contrast to the thoracic and abdominal aortas, where significant attenuation was seen. Diabetes-associated accumulation of AGEs in aorta

Uniaxially aligned electrospun fibers for advanced nanocomposites based on a model PVOH-epoxy system

This work demonstrates the potential of aligned electrospun fibers as the sole reinforcement in nanocom- posite materials. Poly(vinyl alcohol) and epoxy resin were selected as a model system and the effect of electrospun fiber loading on polymer properties was examined in conjunction with two manufacturing methods. A proprietary electrospinning technology for production of uniaxially aligned electrospun fiber arrays was used. A conventional wet lay-up fabrication method is compared against a novel, hybrid electrospinning–electrospraying approach. The structure and thermomechanical properties of resulting composite materials were examined using scanning electron microscopy, dynamic mechanical analysis, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, and tensile testing. The result demonstrate that using aligned electrospun fibers significantly enhances material properties compared to unreinforced resin, especially when manufactured using the hybrid electrospinning–electrospraying method. For example, tensile strength of such a material containing only 0.13 vol% of fiber was increased by �700%, and Young’s modulus by �250%, with concomitant increase in ductility

Do Shareholders Value Green Information Technology Announcements?

Using the natural resource-based view (NRBV) and signaling theory, we conducted an event study using the Fama-French four-factor (FFM4) model to determine how shareholders react to company announcements about adopting information technology (IT) to address environmental issues. We found that green IT announcements generate positive abnormal returns and increase share trading volume. Initiatives that use IT to support decision making (ITDSS) cause positive stock market reactions. Firms with good environmental performance records enjoy positive market returns from ITDSS and direct IT assets and infrastructure (ITASSETS) announcements. In contrast, shareholders react negatively to announcements regarding sustainable products and services (SPDTSVC). Combining the NRBV with signaling theory provides deeper theoretical insights than either theory alone. The findings could serve as the basis for further research and theory development on the different types of green IT and impacts on market value. The results help explain how firm characteristics and different types of green IT announcements impact market value, and they have significant implications for how firms plan and allocate their resources to support green initiatives

Sustainable Information Systems: Does It Matter?

Using the Natural Resource Based View (NRBV) as our theoretical lens, green IS or sustainable IS is conceptualized as comprising the different dimensions of sustainability practices that can create competitive advantage for the organization. This study examines (i) the impact of adoption of sustainable IS on organizational performance; and (ii) the impact of the extent of adoption of sustainable IS on organizational performance. Analyzing secondary data on sustainable IS and performance measures of 115 global organizations, we find that the adoption of sustainable IS is positively associated with market valuation and innovativeness but not with profitability. However, sustainable IS organizations that have greater extent of adoption realize better profitability, market valuation and innovativeness. Implications of results for research and practice are discussed

Establishing a core outcome set for peritoneal dialysis : report of the SONG-PD (standardized outcomes in nephrology-peritoneal dialysis) consensus workshop

Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified: life participation as a main goal of PD, impact of fatigue, empowerment for preparation and planning, and separation of contributing factors from core factors. Considerations for implementation were identified: standardizing patient-reported outcomes, requiring a validated and feasible measure, simplicity of binary outcomes, responsiveness to interventions, and using positive terminology. All stakeholders supported inclusion of PD-related infection, cardiovascular disease, mortality, technique survival, and life participation as the core outcome domains for PD