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Rendering a common ligand scaffold anionic and then pairing it with a chiral cation represents an alternative strategy for developing enantioselective versions of challenging transformations, as has been recently demonstrated in the enantioselective borylation of arenes using a quinine-derived chiral cation. A significant barrier to the further generalization of this approach is the lack of understanding of the specific interactions involved between the cation, ligand, and substrate, given the complexity of the system. We have embarked on a detailed computational study probing the mechanism, the key noncovalent interactions involved, and potential origin of selectivity for the desymmetrizing borylation of two distinct classes of substrate. We describe a deconstructive, stepwise approach to tackling this complex challenge, which involves building up a detailed understanding of the pairwise components of the nominally three component system before combining together into the full 263-atom reactive complex. This approach has revealed substantial differences in the noncovalent interactions occurring at the stereodetermining transition state for C-H oxidative addition to iridium for the two substrate classes. Each substrate engages in a unique mixture of diverse interactions, a testament to the rich and privileged structure of the cinchona alkaloid-derived chiral cations. Throughout the study, experimental support is provided, and this culminates in the discovery that prochiral phosphine oxide substrates, lacking hydrogen bond donor functionality, can also give very encouraging levels of enantioselectivity, potentially through direct interactions with the chiral cation. We envisage that the findings in this study will spur further developments in using chiral cations as controllers in asymmetric transition-metal catalysis., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Catalytic enantioselective Minisci reactions have recently been developed but all instances so far utilize α-amino radical coupling partners. We report a substantial evolution of the enantioselective Minisci reaction that enables α-hydroxy radicals to be used, providing valuable enantioenriched secondary alcohol products. This is achieved through the direct oxidative coupling of two C-H bonds on simple alcohol and pyridine partners through a hydrogen atom transfer (HAT)-driven approach: a challenging process to achieve due to the numerous side reactions that can occur. Our approach is highly regioselective as well as highly enantioselective. Dicumyl peroxide, upon irradiation with 390 nm light, serves as both HAT reagent and oxidant whilst selectivity is controlled by use of a chiral phosphoric acid catalyst. Computational and experimental evidence provide mechanistic insight as to the origin of selectivity, revealing a stereodetermining deprotonation step distinct from the analogous reaction of amide-containing substrates., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Objective: To assess whether long-term cancer survivors (≥5 years after diagnosis) are at an increased risk of experiencing an opioid-related emergency department (ED) visit or hospitalization compared with persons without cancer., Methods: A 1:1 matched retrospective cohort study was performed using the Surveillance, Epidemiology, and End Results-Medicare linked data sets. The analysis was conducted from October 2020 to December 2020 in persons who lived 5 years or more after a breast, colorectal, lung, or prostate cancer diagnosis matched to noncancer controls on the basis of age, sex, race, pain conditions, and previous opioid use. Fine-Gray regression models were used to assess the relationship between cancer survivorship status and opioid-related ED visit or hospitalization., Results: The incidence of opioid-related ED visits and hospitalizations was 51.2 (95% CI, 43.5 to 59.8) and 62.2 (95% CI, 53.4 to 72.1) per 100,000 person-years among cancer survivors and matched noncancer controls, respectively. No significant association was observed between survivorship and opioid-related adverse event among opioid naive (hazard ratio, 0.79; 95% CI, 0.61 to 1.02) and non-naive (hazard ratio, 1.26; 95% CI, 0.84 to 1.89) cohorts., Conclusion: Cancer survivors and noncancer controls had a similar risk of an ED visit or inpatient admission. Guidelines and policies should promote nonopioid pain management approaches especially to opioid non-naive older adults, a population at high risk for an opioid-related ED visit or hospitalization., (Copyright © 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Older cancer survivors have high rates of long-term opioid therapy (≥90 days/year). However, the geographical and temporal variation in long-term opioid therapy rates for older cancer survivors is not known., Methods: A retrospective cohort study was conducted using SEER-Medicare data. Persons aged ≥66 years, diagnosed with breast, colorectal, lung, or prostate cancer from 1991 to 2011, and alive ≥5 years after diagnosis were included. Persons were followed from 1/1/2008 until 12/31/2016. Persons were assigned to a census region in their state of residence each year. Individuals who were covered by an opioid prescription for at least 90 days in a calendar year were classified as having received long-term opioid therapy. Multivariable analysis was conducted using generalized estimating equations., Results: Temporal trends significantly varied by region (p < 0.0001) and opioid-naïve status (p < 0.0001). Compared to 2013, opioid-naïve cancer survivors in the south and non-naïve survivors in the south and west experienced significant declines in long-term opioid therapy in 2015 and 2016. Significant declines were observed in 2016 for opioid-naïve and non-naïve cancer survivors residing in the northeast and among opioid-naïve cancer survivors living in the Midwest., Conclusion: The annual trends in the receipt of long-term opioid therapy significantly varied by region among older cancer survivors. Variation in a clinical practice suggests the need for more research and interventions to improve efficiency, process, cost, and quality of care., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Ocular disorders, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP), and glaucoma, can cause irreversible visual loss, and affect the quality of life of millions of patients. However, only very few 3D systems can mimic human ocular pathophysiology, especially the retinal degenerative diseases, which involve the loss of retinal ganglion cells (RGCs), photoreceptors, or retinal pigment epithelial cells (RPEs). In this review, we discuss current progress in the 3D modeling of ocular tissues, and review the use of the aforementioned technologies for optic neuropathy treatment according to the categories of associated disease models and their applications in drug screening, mechanism studies, and cell and gene therapies., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Unhealthy food environments may be associated with higher risks of developing diet-related cancers, such as, colorectal cancer. We conducted an ecological analysis to evaluate the relationship between the local food environment and colorectal cancer incidence overall and separately for males and females., Methods: Data from the Texas Cancer Registry was utilized to geocode individuals aged 40 years and older diagnosed with colorectal cancer from 2005 to 2015 to their residential 2010 census tract. Total number of establishments classified as Limited Service Restaurants for each census tract was retrieved from the 2005 Business Patterns Survey by using a crosswalk to map zip codes to census tract. Census tract unhealthy food availability was calculated by dividing the estimated number of Limited Service Restaurant establishments in each census tract by the census tract population and divided into quartiles. Generalized estimating equations were used to assess the association between unhealthy food availability quartiles and colorectal cancer incidence., Results: Adjusting for the census tract level sociodemographic characteristics, the incidence of colorectal cancer was slightly higher in unhealthy food availability quartile 2 (Incidence Rate Ratio (IRR) = 1.03, 95 % CI: 1.00-1.05), but not quartile 3 (IRR = 1.02, 95 % CI: 1.00-1.05), and quartile 4 (highest availability, IRR = 1.02, 95 % CI: 0.99-1.05) compared to census tracts with lowest unhealthy food availability., Conclusion: Colorectal cancer incidence was not strongly associated with census tracts with higher unhealthy food availability. Future observational studies should be conducted to examine the influence of the built environment on colorectal cancer risk., Competing Interests: Declaration of Competing Interest Derrick C Gibson has no conflicts of interest to disclose. John D. Prochaska has no conflicts of interest to disclose. Xiaoying Yu has no conflicts of interest to disclose. Sapna Kaul has no conflicts of interest to disclose., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Given concerns about suboptimal pain management for actively treated cancer patients following the 2014 federal reclassification of hydrocodone, we examined changes in patterns of opioid prescribing among surgical breast cancer patients., Materials and Methods: Data from a large nationally representative commercial health insurance program from 2009 to 2017 were used to identify women aged 18 years and older who were diagnosed with carcinoma in-situ or malignant breast cancer and received breast-conserving surgery or mastectomy from 2010 to 2016. Generalized linear mixed models were used to estimate the adjusted odds ratio (aOR) for receipt of ≥1-day, >30-day, or ≥ 90-day supply of opioids in the 12 months following surgery adjusting for demographics, cancer treatment-related characteristics, and preoperative opioid use., Results: A total of 60,080 patients were included in the study. Surgically treated breast cancer patients in 2015 (aOR = 0.90, 0.84-0.97) and 2016 (aOR = 0.80, 0.74-0.86) were less likely to receive ≥1-day supply of opioid prescriptions when compared with patients in 2013. Patients who had surgery in 2015 (aOR = 0.89, 0.81-0.98) and 2016 (aOR = 0.80, 0.73-0.87) were also less likely to receive >30-day supply of prescription opioids in the 12 months following surgery. However, only surgical breast cancer patients in 2016 were less likely to receive ≥90-day supply (aOR = 0.86, 0.76-0.98)., Conclusion: Surgically treated breast cancer patients are less likely to receive short- and long-term opioid prescriptions following the implementation of hydrocodone rescheduling. Further studies on the potential impact of federal policy on cancer patient pain management are needed., Implications for Practice: Clinicians and researchers with diverse perspectives should be included as stakeholders during policy development for restricting opioid prescriptions. Stakeholders can identify potential unintended consequences early and help identify methods to mitigate concerns, specifically as it relates to policy that influences how providers manage pain for actively treated cancer patients. This work shows how federal policy may have led to declines in opioid prescribing for breast cancer patients who underwent mastectomy or breast-conserving surgery., (© AlphaMed Press 2019.)

Chiral cations have been used extensively as organocatalysts, but their application to rendering transition metal-catalyzed processes enantioselective remains rare. This is despite the success of the analogous charge-inverted strategy in which cationic metal complexes are paired with chiral anions. We report here a strategy to render a common bipyridine ligand anionic and pair its iridium complexes with a chiral cation derived from quinine. We have applied these ion-paired complexes to long-range asymmetric induction in the desymmetrization of the geminal diaryl motif, located on a carbon or phosphorus center, by enantioselective C-H borylation. In principle, numerous common classes of ligand could likewise be amenable to this approach., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

This article presents a new framework for unobtrusive observation analytics of knowledge and skills-in-action through continuous collection of data from individuals while they interact with digital assets either as individuals or on problem-solving teams. The framework includes measures of the skill and knowledge areas of collaboration, creativity, personal learning, problem solving, and global sustainability, which are observed during natural production and use of communications, intentional artifacts, and resources in a digital learning space designed for self-directed and team-based learning challenges. The article describes the digital context for data collection and shows some example data and analyses.

Increasingly, higher education institutions are exploring the potential of learning analytics to predict student retention, understand learning behaviors, and improve student learning through providing personalized feedback and support. The technical development of learning analytics has outpaced consideration of ethical issues surrounding their use. Of particular concern is the absence of the student voice in decision-making about learning analytics. We explored higher education students' knowledge, attitudes, and concerns about big data and learning analytics through four focus groups ( N = 41). Thematic analysis of the focus group transcripts identified six key themes. The first theme, "Uninformed and Uncertain," represents students' lack of knowledge about learning analytics prior to the focus groups. Following the provision of information, viewing of videos and discussion of learning analytics scenarios three further themes; "Help or Hindrance to Learning," "More than a Number," and "Impeding Independence"; represented students' perceptions of the likely impact of learning analytics on their learning. "Driving Inequality" and "Where Will it Stop?" represent ethical concerns raised by the students about the potential for inequity, bias and invasion of privacy and the need for informed consent. A key tension to emerge was how "personal" vs. "collective" purposes or principles can intersect with "uniform" vs. "autonomous" activity. The findings highlight the need the need to engage students in the decision making process about learning analytics.