Responses to 10 common criticisms of anti-racism action in STEMM

The wrongful murders of Black individuals during 2020 (including George Floyd, Breonna Taylor, Ahmaud Aubery, and others), compounded by a long history of similar incidents, inspired protests around the world against racism and police brutality. The growing anti-racism movement sparked conversations within science, technology, engineering, mathematics, and medicine (STEMM) surrounding ways to combat racial bias in our respective fields. A spotlight was placed on the discriminatory history of scientific research and medical practice, as well as the problematic modern-day policies that perpetuate the lack of racial diversity and equity in STEMM. While observing and participating in recent discussions about the racism that pervades institutions, departments, and scientific discourse, we have noticed a set of standard arguments against anti-racism action within STEMM. Ten of these arguments are laid out in this manuscript and paired with evidence-based counterarguments. Notably, while this manuscript is primarily centered around a United States perspective, most of our arguments and suggested actions remain applicable to other countries as well. It is crucial for a STEMM anti-racism movement to extend beyond national borders, reflecting the international nature of scientific research and collaboration. This team of authors represents a collaboration between scientists from historically marginalized groups and their allies. By compiling published academic literature, we hope to directly confront racist ideology in STEMM with evidence-based arguments while simultaneously amplifying the research and perspectives of scholars of color. Our broad goal in articulating this information is to facilitate more productive conversations (and, in turn, tangible systemic changes) toward addressing racial discrimination within STEMM

The p21-Dependent Radiosensitization of Human Breast Cancer Cells by MLN4924, an Investigational Inhibitor of NEDD8 Activating Enzyme

Radiotherapy is a treatment choice for local control of breast cancer. However, intrinsic radioresistance of cancer cells limits therapeutic efficacy. We have recently validated that SCF (SKP1, Cullins, and F-box protein) E3 ubiquitin ligase is an attractive radiosensitizing target. Here we tested our hypothesis that MLN4924, a newly discovered investigational small molecule inhibitor of NAE (NEDD8 Activating Enzyme) that inactivates SCF E3 ligase, could act as a novel radiosensitizing agent in breast cancer cells. Indeed, we found that MLN4924 effectively inhibited cullin neddylation, and sensitized breast cancer cells to radiation with a sensitivity enhancement ratio (SER) of 1.75 for SK-BR-3 cells and 1.32 for MCF7 cells, respectively. Mechanistically, MLN4924 significantly enhanced radiation-induced G2/M arrest in SK-BR-3 cells, but not in MCF7 cells at early time point, and enhanced radiation-induced apoptosis in both lines at later time point. However, blockage of apoptosis by Z-VAD failed to abrogate MLN4924 radiosensitization, suggesting that apoptosis was not causally related. We further showed that MLN4924 failed to enhance radiation-induced DNA damage response, but did cause minor delay in DNA damage repair. Among a number of tested SCF E3 substrates known to regulate growth arrest, apoptosis and DNA damage response, p21 was the only one showing an enhanced accumulation in MLN4924-radiation combination group, as compared to the single treatment groups. Importantly, p21 knockdown via siRNA partialy inhibited MLN4924-induced G2/M arrest and radiosensitization, indicating a causal role played by p21. Our study suggested that MLN4924 could be further developed as a novel class of radiosensitizer for the treatment of breast cancer

Towards a Framework for Understanding Fairtrade Purchase Intention in the Mainstream Environment of Supermarkets

© 2014, Springer Science+Business Media Dordrecht. Despite growing interest in ethical consumer behaviour research, ambiguity remains regarding what motivates consumers to purchase ethical products. While researchers largely attribute the growth of ethical consumerism to an increase in ethical consumer concerns and motivations, widened distribution (mainstreaming) of ethical products, such as fairtrade, questions these assumptions. A model that integrates both individual and societal values into the theory of planned behaviour is presented and empirically tested to challenge the assumption that ethical consumption is driven by ethical considerations alone. Using data sourced from fairtrade shoppers across the UK, structural equation modelling suggests that fairtrade purchase intention is driven by both societal and self-interest values. This dual value pathway helps address conceptual limitations inherent in the underlying assumptions of existing ethical purchasing behaviour m odels and helps advance understanding of consumers’ motivation to purchase ethical products

Management of Patients with Advanced Prostate Cancer. Part I: Intermediate-/High-risk and Locally Advanced Disease, Biochemical Relapse, and Side Effects of Hormonal Treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022.

BACKGROUND: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. OBJECTIVE: To present consensus voting results for select questions from APCCC 2022. DESIGN, SETTING, AND PARTICIPANTS: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members ("panellists") who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1-3. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. RESULTS AND LIMITATIONS: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. CONCLUSIONS: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions

Integrated use of fertilizer micro-dosing and Acacia tumida mulching increases millet yield and water use efficiency in Sahelian semi-arid environment

Limited availability of soil organic amendments and unpredictable rainfall, decrease crop yields drastically in the Sahel. There is, therefore, a need to develop an improved technology for conserving soil moisture and enhancing crop yields in the Sahelian semi-arid environment. A 2-year field experiment was conducted to investigate the mulching effects of Acacia tumida pruning relative to commonly applied organic materials in Niger on millet growth, yields and water use efficiency (WUE) under fertilizer micro-dosing technology. We hypothesized that (1) A. tumida pruning is a suitable mulching alternative for crop residues in the biomass-scarce areas of Niger and (2) combined application of A. tumida mulch and fertilizer micro-dosing increases millet yield and water use efficiency. Two fertilizer micro-dosing options (20 kg DAP ha−1, 60 kg NPK ha−1) and three types of organic mulches (millet straw, A. tumida mulch, and manure) and the relevant control treatments were arranged in factorial experiment organized in a randomized complete block design with four replications. Fertilizer micro-dosing increased millet grain yield on average by 28 %. This millet grain yield increased further by 37 % with combined application of fertilizer micro-dosing and organic mulch. Grain yield increases relative to the un-mulched control were 51 % for manure, 46 % for A. tumida mulch and 36 % for millet mulch. Leaf area index and root length density were also greater under mulched plots. Fertilizer micro-dosing increased WUE of millet on average by 24 %, while the addition of A. tumida pruning, manure and millet increased WUE on average 55, 49 and 25 %, respectively. We conclude that combined application of micro-dosing and organic mulch is an effective fertilization strategy to enhance millet yield and water use efficiency in low-input cropping systems and that A. tumida pruning could serve as an appropriate mulching alternative for further increasing crop yields and water use efficiency in the biomass-scarce and drought prone environment such as the Sahel. However, the economic and social implications and the long-term agronomic effects of this agroforestry tree in Sahelian millet based system have to be explored further

Distribution of Small Integrin-binding Ligand, N-linked Glycoproteins (SIBLING) in the Articular Cartilage of the Rat Femoral Head

The small integrin-binding ligand, N-linked glycoprotein (SIBLING) family is closely related to osteogenesis. Until recently, little was known about their existence in articular cartilage. In this study, we systematically evaluated the presence and distribution of four SIBLING family members in rat femoral head cartilage: dentin matrix protein 1 (DMP1), bone sialoprotein (BSP), osteopontin (OPN), and dentin sialophosphoprotein (DSPP). First, non-collagenous proteins were extracted and then separated by ion-exchange chromatography. Next, the protein extracts eluted by chromatography were analyzed by Stains-all staining and Western immunoblotting. IHC was used to assess the distribution of these four SIBLING family members in the femoral head cartilage. Both approaches showed that all the four SIBLING family members are expressed in the femoral head cartilage. IHC showed that SIBLING members are distributed in various locations throughout the articular cartilage. The NH2-terminal fragments of DMP1, BSP, and OPN are present in the cells and in the extracellular matrix, whereas the COOH-terminal fragment of DMP1 and the NH2-terminal fragment of DSPP are primarily intracellularly localized in the chondrocytes. The presence of the SIBLING family members in the rat femoral head cartilage suggests that they may play important roles in chondrogenesis. (J Histochem Cytochem 58:1033–1043, 2010

Highly efficient transfection of human induced pluripotent stem cells using magnetic nanoparticles

Megan A Yamoah,1 Maryam Moshref,1 Janhavi Sharma,1 Wei Chun Chen,1 Hannah A Ledford,1 Jeong Han Lee,2 Karen S Chavez,1 Wenying Wang,2 Javier E López,1 Deborah K Lieu,1 Padmini Sirish,1,3 Xiao-Dong Zhang1,3 1Department of Internal Medicine, University of California, Davis, CA, USA; 2Department of Physiology and Cell Biology, University of Nevada, Reno, NV, USA; 3Department of Veterans Affairs, Northern California Health Care System, Mather, CA, USA Purpose: The delivery of transgenes into human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) represents an important tool in cardiac regeneration with potential for clinical applications. Gene transfection is more difficult, however, for hiPSCs and hiPSC-CMs than for somatic cells. Despite improvements in transfection and transduction, the efficiency, cytotoxicity, safety, and cost of these methods remain unsatisfactory. The objective of this study is to examine gene transfection in hiPSCs and hiPSC-CMs using magnetic nanoparticles (NPs).Methods: Magnetic NPs are unique transfection reagents that form complexes with nucleic acids by ionic interaction. The particles, loaded with nucleic acids, can be guided by a magnetic field to allow their concentration onto the surface of the cell membrane. Subsequent uptake of the loaded particles by the cells allows for high efficiency transfection of the cells with nucleic acids. We developed a new method using magnetic NPs to transfect hiPSCs and hiPSC-CMs. HiPSCs and hiPSC-CMs were cultured and analyzed using confocal microscopy, flow cytometry, and patch clamp recordings to quantify the transfection efficiency and cellular function.Results: We compared the transfection efficiency of hiPSCs with that of human embryonic kidney (HEK 293) cells. We observed that the average efficiency in hiPSCs was 43%±2% compared to 62%±4% in HEK 293 cells. Further analysis of the transfected hiPSCs showed that the differentiation of hiPSCs to hiPSC-CMs was not altered by NPs. Finally, robust transfection of hiPSC-CMs with an efficiency of 18%±2% was obtained.Conclusion: The difficult-to-transfect hiPSCs and hiPSC-CMs were efficiently transfected using magnetic NPs. Our study offers a novel approach for transfection of hiPSCs and hiPSC-CMs without the need for viral vector generation. Keywords: human induced pluripotent stem cell-derived cardiomyocytes, therapy, pluripotency, efficienc