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The Mizoroki-Heck reaction is one of the most studied palladium-catalyzed cross-coupling reactions, representing a powerful method for forming C-C bonds between diverse substrates with broad functional group compatibility. However, the reductive variant has received considerably less attention. In this Review, we summarize distinct mechanistic aspects of the reductive Heck reaction, highlight recent contributions to the field, and discuss potential applications of the reductive Heck reaction in the pharmaceutical industry. With the potential to have a large impact in both academic and industrial settings, further development of the reductive Heck reaction is a promising area of future investigation.Chemo-resistant breast cancer is a major barrier to curative treatment for a significant number of women with breast cancer. Neoadjuvant chemotherapy (NACT) is standard first- line treatment for most women diagnosed with high-risk TNBC, HER2+, and locally advanced ER+ breast cancer. Current clinical prognostic tools evaluate four clinicopathological factors Tumor size, LN status, pathological stage, and tumor molecular subtype. However, many similarly treated patients with identical residual cancer burden (RCB) following NACT experience distinctly different tumor relapse rates, clinical outcomes and survival. This problem is particularly apparent for incomplete responders with a high-risk RCB classification following NACT. Therefore, there is a pressing need to identify new prognostic and predictive biomarkers, and develop novel curative therapies to augment current standard of care (SOC) treatment regimens to save more lives. Here, we will discuss these unmet needs and clinical challenges that stand in the way of precision medicine and personalized cancer therapy.Hibernating mammals exhibit an innate physiological ability to withstand dramatic fluctuations in blood flow that occurs during hibernation and arousal or experimental models of ischemia reperfusion without significant damage. These innate adaptations are of significance particularly to organs that are highly susceptible to energy deprivation, such as the brain and the heart. Among vertebrates, the arctic ground squirrel (AGS) is a species that tolerates ischemic/anoxic insult. During the process of entering hibernation, a state of prolonged torpor, the AGS undergoes a profound decrease in respiratory rate, heart rate, blood flow, cerebral perfusion, and body temperature (Tb). The reduced level of blood flow during torpor resembles an ischemic state, albeit without energy deficit. During the process of arousal or emergence from torpor, however, when Tb, respiratory rate, heart rate, and blood flow rapidly returns to pre-torpid levels, the rapid return of cerebral blood flow mimics aspects of reperfusion such as is seen after stroke or cardiac arrest. This sublethal ischemic/reperfusion insult experienced by AGS during the process of arousal may precondition AGS to tolerate otherwise lethal ischemic/reperfusion injury induced in the laboratory. In this review, we will summarize some of the mechanisms implemented by mammalian hibernators to combat ischemia/anoxia tolerance.Patient-related complications from invasive bedside procedures (IBPs) are attributed to the experience and proficiency of the operator. Furthermore, IBP complications by trainees may be due to practice variability and competency among IBP teachers. The use of gaze metrics technology to better understand the behaviors of IBP teachers may aid in the creation of faculty development checklists and, ultimately, reduce procedural complications. Prior research on gaze patterns has focused on the individual performing the procedure, but the goal of this pilot study was to assess gaze behaviors of supervising teachers of IBPs, which is a paradigm shift within procedural education. In this study, pulmonary and critical care medicine fellows placed a central venous catheter on a simulated task trainer as pulmonary and critical care medicine faculty supervised while wearing an eye-tracking device. Both quantitative and qualitative data were obtained. Gaze analysis was divided into 2 areas of interest (ultrasonography and procedure site) and 3 procedural tasks (venous puncture, dilation, and flushing the line). Study findings included the following (1) calibration was easy and took seconds to complete, (2) the device is relatively comfortable and did not interfere with tasks, (3) a trend toward a higher fixation frequency and dwell time on the ultrasound images during the puncture segment, and (4) variations in fixation frequency on the ultrasound images among supervising IBP teachers. This study documents the feasibility of the eye-tracking device for assessing behaviors of supervisory IBP teachers. There may be a signal suggesting differences in gaze patterns among supervisory teachers, which warrants further study.An understanding of the molecular basis of liver regeneration will open new horizons for the development of novel therapies for chronic liver failure. Such therapies would solve the drawbacks associated with liver transplant, including the shortage of donor organs, long waitlist time, high medical costs, and lifelong use of immunosuppressive agents. Regeneration after partial hepatectomy has been studied in animal models, particularly fumarylacetoacetate hydrolase-deficient (FAH -/-) mice and pigs. The process of regeneration is distinctive, complex, and well coordinated, and it depends on the interplay among several signaling pathways (eg, nuclear factor κβ, Notch, Hippo), cytokines (eg, tumor necrosis factor α, interleukin 6), and growth factors (eg, hepatocyte growth factor, epidermal growth factor, vascular endothelial growth factor), and other components. Furthermore, endocrinal hormones (eg, norepinephrine, growth hormone, insulin, thyroid hormones) also can influence the aforementioned pathways and factors. We believe that these endocrinal hormones are important hepatic mitogens that strongly induce and accelerate hepatocyte proliferation (regeneration) by directly and indirectly triggering the activity of the involved signaling pathways, cytokines, growth factors, and transcription factors. The subsequent induction of cyclins and associated cyclin-dependent kinase complexes allow hepatocytes to enter the cell cycle. In this review article, we comprehensively summarize the current knowledge regarding the roles and mechanisms of these hormones in liver regeneration. read more Articles used for this review were identified by searching MEDLINE and EMBASE databases from inception through June 1, 2019.
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