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When her genius Asperger's syndrome colleague rules a friend's suspicious death a homicide in spite of police opinions, St. Louis attorney Rachel Gold investigates clues that lead her into the heart of a dark criminal enterprise.

The 2022 Decadal Plan for Science, Technology and Innovation intends to shape innovation activities and their contribution to development out to 2031, serving as government master plan and pivoting the National System of Innovation to mitigate the socio-economic, health and environmental challenges of times that are volatile, uncertain, complex and ambiguous. But in trying to be all things to all people, the Decadal Plan avoids prioritisation, reading more as a Vision Statement than an Implementation Plan.

Attorney Rachel Gold--reluctantly representing a working class neighborhood against a developer intent on bulldozing homes to erect a gated community and investigating the death of rehabber Nick Moran, who's demise--his sister believes--was the result of foul play--begins to suspect the two cases may be related.

Throughout our life, long‐lived somatic stem cells (SSC) regenerate adult tissues both during homeostatic processes and repair after injury. The role of aberrant regulation of SSC has also recently gained prominence in the field of cancer research. Following malignant transformation, so termed cancer stem cells (CSC), endowed with the same properties as SSC (i.e. the ability to both self‐renew and generate differentiated progenitors), play a major part in tumor initiation, therapy resistance and ultimately relapse. The same signaling pathways involved in regulating SSC maintenance are involved in the regulation of CSC. CSC exist in a wide array of tumor types, including leukemias, and brain, breast, prostate and colon tumors. Consequently, one of the key goals in cancer research over the past decade has been to develop therapeutic strategies to safely eliminate the CSC population without damaging the endogenous SSC population. A major hurdle to this goal lies in the identification of the key mechanisms that distinguish CSC from the normal endogenous tissue stem cells. This review will discuss the discovery of the specific CBP/catenin antagonist ICG‐001 and the ongoing clinical development of the second generation CBP/catenin antagonist PRI‐724. Importantly, specific CBP/catenin antagonists appear to have the ability to safely eliminate CSC by taking advantage of an intrinsic differential preference in the way SSC and CSC divide. The same signaling pathways involved in regulating somatic stem cells (SSC) are also involved in the regulation of cancer stem cells (CSC). Consequently, one of the key goals in cancer research over the past decade has been to develop therapeutic strategies to safely eliminate the CSC population without damaging the endogenous SSC population. This review focusses on the discovery of specific CBP/catenin antagonists that appear to have the ability to safely eliminate CSCs by taking advantage of an intrinsic differential preference in the way SSCs and CSCs divide.

\"Every law firm has its backroom bench of brilliant workaholic nerds ferocious in their commitment to the law and to their clients. Such a player is Milton Bernstein of Abbott & Windsor ... Milton's younger brother Hal is his polar opposite--strikingly handsome, a high-school baseball legend in St. Louis who was on his way to the major leagues until he destroyed his prospects in a motorcycle accident ... But the lives of both brothers are about to change. Cherry, the bombshell third wife of St. Louis' most shark-like litigator, Lester Pitt, unexpectedly turns Hal's advances around. They become lovers. Coincidentally, Milton becomes the attack dog behind litigation to nail Pitt for running an insurance scam on his injured clients\"--Cover flap.

Key Points WNT signalling is a complex cascade and there is extensive crosstalk with other pathways. WNT signalling has crucial roles in both normal homeostasis and disease, and thereby there has been considerable difficulty in safely targeting the WNT pathway, thus hampering development to date. There are multiple points of intervention in the WNT signalling cascade that have been investigated; however, many of them may be limited from the standpoint of therapeutic efficacy owing to on-target side effects. WNT signalling has crucial roles in stem cells — both normal and cancer stem cells — in both the maintenance of potency and initiation of differentiation. Currently, several specific inhibitors and modulators of WNT signalling have entered clinical trials. Preliminary results and future prospects are discussed. The WNT pathway has a vast array of functions and aberrant WNT signalling is correspondingly implicated in numerous diseases, including cancer, fibrosis and nervous system disorders. Kahn discusses our understanding of this developmentally important pathway, the complexities associated with safely targeting it therapeutically and WNT-modulating agents that are currently being investigated. WNT–β-catenin signalling is involved in a multitude of developmental processes and the maintenance of adult tissue homeostasis by regulating cell proliferation, differentiation, migration, genetic stability and apoptosis, as well as by maintaining adult stem cells in a pluripotent state. Not surprisingly, aberrant regulation of this pathway is therefore associated with a variety of diseases, including cancer, fibrosis and neurodegeneration. Despite this knowledge, therapeutic agents specifically targeting the WNT pathway have only recently entered clinical trials and none has yet been approved. This Review examines the problems and potential solutions to this vexing situation and attempts to bring them into perspective.

The Covid-19 pandemic offers an opportunity for doctors to recognize more readily facts that can otherwise take years to learn: that we’re no different from our patients and that interacting with them as human beings can be gratifying for them and freeing for us.

This paper builds on a long-standing and well-articulated science, technology, innovation and knowledge (STIK) partnership between Canada and South Africa. It provides an historical overview of the origins and development of the STIK partnership since 1994 with the early efforts of Canada's International Development Research Centre and the new ANC government in framing a green and white paper for South Africa's national science and technology policy. It suggests an opportunity within the context of the G7 and G20 Summits being hosted by Canada and South Africa, respectively, in 2025, and argues for enhanced research opportunities in science diplomacy and science policy exchanges.

Key Points Preclinical models provide evidence of cancer stem cells (CSCs) contributing to cancer proliferation, relapse and metastasis; this theory is being examined and validated in the clinical setting, currently in advanced malignancies Over the past few years, new investigational agents have been developed to block the Notch, Hedgehog (HH) or Wnt signalling pathways for targeting CSCs To date, robust antitumour activity has not been observed by targeting CSCs using Notch, HH or Wnt inhibitors, either as single agents or in combination with standard chemotherapy, in clinical trials Combination approaches to overcome the crosstalk among Notch, HH and Wnt pathways, as well as other signalling pathways, has been examined mostly in preclinical models, with promising results The success of the combination therapy in clinical trials might depend on CSC–tumour microenvironment interactions, perhaps in the context of the genotypes and phenotypes of the bulk tumour, CSCs, and the tumour microenvironment A number of clinical trials have incorporated surrogate CSC assays to measure the effects of an investigational agent on CSCs, but further technological improvements in assays are needed Cancer stem cell (CSC) populations are increasingly recognized in most malignancies and are hypothesized to contribute to cancer proliferation, relapse, and metastasis. Thus, the highly conserved stem-cell signal transduction pathways involved in development and tissue homeostasis that are frequently active in CSCs represent prime targets for targeted therapies against this characteristically treatment-resistant and highly tumorigenic cell population. This Review provides a update on the clinical development of therapies targeting Wnt, Notch, and Hedgehog, three prominent stem-cell signalling pathways that are upregulated in CSCs. During the past decade, cancer stem cells (CSCs) have been increasingly identified in many malignancies. Although the origin and plasticity of these cells remain controversial, tumour heterogeneity and the presence of small populations of cells with stem-like characteristics is established in most malignancies. CSCs display many features of embryonic or tissue stem cells, and typically demonstrate persistent activation of one or more highly conserved signal transduction pathways involved in development and tissue homeostasis, including the Notch, Hedgehog (HH), and Wnt pathways. CSCs generally have slow growth rates and are resistant to chemotherapy and/or radiotherapy. Thus, new treatment strategies targeting these pathways to control stem-cell replication, survival and differentiation are under development. Herein, we provide an update on the latest advances in the clinical development of such approaches, and discuss strategies for overcoming CSC-associated primary or acquired resistance to cancer treatment. Given the crosstalk between the different embryonic developmental signalling pathways, as well as other pathways, designing clinical trials that target CSCs with rational combinations of agents to inhibit possible compensatory escape mechanisms could be of particular importance. We also share our views on the future directions for targeting CSCs to advance the clinical development of these classes of agents.