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Summary: Ferroptosis is a type of regulated cell death driven by the iron-dependent accumulation of oxidized polyunsaturated fatty acid-containing phospholipids. There is no reliable way to selectively stain ferroptotic cells in tissue sections to characterize the extent of ferroptosis in animal models or patient samples. We address this gap by immunizing mice with membranes from lymphoma cells treated with the ferroptosis inducer piperazine erastin and screening ∼4,750 of the resulting monoclonal antibodies generated for their ability to selectively detect cells undergoing ferroptosis. We find that one antibody, 3F3 ferroptotic membrane antibody (3F3-FMA), is effective as a selective ferroptosis-staining reagent. The antigen of 3F3-FMA is identified as the human transferrin receptor 1 protein (TfR1). We validate this finding with several additional anti-TfR1 antibodies and compare them to other potential ferroptosis-detecting reagents. We find that anti-TfR1 and anti-malondialdehyde adduct antibodies are effective at staining ferroptotic tumor cells in multiple cell culture and tissue contexts. : Feng et al. find that 3F3-FMA detects ferroptotic cells by screening ∼4,750 antibodies generated from mice immunized with membranes from DLBCL cells undergoing ferroptosis. The antigen of 3F3-FMA is the TfR1 protein. 3F3-FMA and other anti-TfR1 antibodies can be used to detect ferroptosis in cell culture and in cancer models. Keywords: ferroptosis marker, ferroptosis-specific antibody, transferrin receptor, tissue staining, ferroptosis, ROS, iron, cell death, cancer, biomarker

The rise of technology-enabled ride-hailing services has affected individuals’ transportation-related decisions. The impact of these ride-hailing services likely varies across traveler segments that differ in their usage of various modes of transportation. In this paper, we develop and leverage a framework that allows us to examine the impact of ride-hailing services on the transportation mode choice for three traveler segments: drivers (who primarily use a personal automobile to travel), riders (who primarily use public transit to travel), and walkers (who primarily use non-motorized modes of transport). We first develop a framework outlining how the behavior of different traveler segments would be impacted by the introduction of ride-hailing services and show how this affects traffic congestion and public transportation ridership. To test the framework, we compiled a rich dataset, combining data on public transportation ridership, traffic congestion, and individual transportation mode choice. Employing a difference-in-differences methodology, we show that the Uber entry in a market enabled those who were walkers and riders prior to the entry of Uber to travel more conveniently, leading to an increase in traffic congestion, and induced those who were drivers to substitute their use of private automobiles with a combination of Uber and public transit. We introduced urban compactness to assess the heterogeneous impact of ride-hailing services for cities that differ in their distribution of traveler segments. We found that Uber entry increases traffic congestion and reduces public transit demand more in cities with higher levels of urban compactness, i.e., where the proportion of riders and walkers is higher than that of drivers. This work provides a holistic framework to understand the mechanism underlying the impact of ride-hailing services on public transit and traffic congestion. Urban planners and policy makers can leverage our framework, methodology, and empirical results to guide city planning decisions that have implications for sustainability. [ABSTRACT FROM AUTHOR]

Abstract Background Fall is a major health threat to older people. The lower-limb power and rate of torque or force development (RTD or RFD) are prominently affected by aging and are crucial for maintaining postural balance. However, there have been inconsistent findings regarding the association of such aspects of lower-limb strength with falls among community-dwelling older adults. Comprehensive synthesis and appraisal are needed to examine what deficits in lower-limb rapid force generation could identify the fallers (i.e., those with a fall history or prospective falls). Methods This systematic review searched six databases, including PubMed, Web of Science, EMBASE, Scopus, CINAHL, and Cochrane CENTRAL. Meta-analysis was conducted to aggregate standardized mean differences (SMD) or odds ratios (OR). The quality of evidence regarding each strength parameter’s ability to identify fallers was assessed using the GRADE approach. Results Twenty observational studies with 8,231 community-dwelling older adults were included (mean age: 73.5 years; male to female ratio: approximately 6:1). Moderate quality of evidence showed that the lower average leg-press power (SMD & 95% CI: -0.17 [-0.23, -0.12]; OR & 95% CI: 0.84 [0.79, 0.89]) and lower peak sit-to-stand power (Cohen’s d = 0.41) could predict prospective falls in older adults, especially the injurious/recurrent falls. Low quality of evidence showed that the lower peak sit-to-stand power could also discern fall history (SMD & 95% CI: -0.58 [-0.96, -0.20]). Conversely, low to very low quality of evidence showed that the RTD of a single muscle group could not predict prospective falls and was generally unable to identify fall history in older adults. Discussions and Conclusion The decline of entire lower-limb power appears a good indicator of prospective falls in community-dwelling older adults. Tests of entire lower-limb power required the cumulative and coordinated contractions of more leg muscles, possibly explaining why they could identify the fallers whereas the RTD or power of a single muscle group could not. Future studies are warranted to determine cut-point values of the entire lower-limb power measurements in fall-risk assessment and explore rapid force generation of a single muscle group in predicting the injurious falls among older adults. Trial registration Registration No.: CRD42021237091.

Subcrestal placement of implants may have interproximal bone proximity issues that interfere with the submucosal contour of implant-supported zirconia restorations during delivery of the restorations. Modification of the mesial distal submucosal areas may be necessary to fully seat the restoration without impingement of the interproximal bone. Our aim was to determine if modification of submucosal cervical contour of implant supported zirconia-titanium base (Zi-Ti base) restorations resulted in a significant change in fracture strength compared with Zi-Ti base restorations without any modification near the cervical submucosal area. Implant Zi-Ti base restorations designed in the form of a maxillary premolar were made for the Straumann implant lab analog. Zirconia samples were cemented onto the Ti-base and the test group (N = 20) underwent recontouring and polishing at the junction of the Zi-Ti base cervical areas. The control group (N = 20) did not undergo any modifications. All 40 samples underwent fracture testing with an Instron machine. We assessed differences between modified and unmodified implants restorations using a 2-tailed t test for independent samples. Fracture strength values (N) ranged from 4354.68 to 6412.49 in the test group (N = 20) and from 5400.31 to 6953.22 in the control group (N = 20). The average fracture strength in the control group (6154.84 ± 320.50) was higher than in the modified group (5593.13 ± 486.51; P <.001). Modification of submucosal contour significantly decreased fracture strength. However, the average fracture strength exceeded the masticatory forces of humans. [ABSTRACT FROM AUTHOR]

Abstract In this study, we develop and empirically test a valuation model for a commonly encountered option in office leases: a tenant’s option to renew at future market rent (a fair market value) with lease termination as the maturity date. The model integrates decision analysis with real options analysis and market risk with private risks. “Option value” is defined as the private value of the option to either party pre-contract, while “option price” assumes a fair agreement between transacting parties and can be positive (rental premium paid) or negative (rental discount offered). Without manifest expectations, an analysis of a sample of office leases supports the model’s logic with price estimates in a practical range. The tenants’ option price/value is shown to have a negative relationship with the original/renewal lease term; conversely, the landlords’ option value is positively related to the original/renewal term. Comparative analyses show that transaction costs have a positive effect on tenants’ option value and on prices, while vacancy costs and the vacancy period are both positively related to the landlords’ option value and negatively related to price. Market rent is found to have a negative relationship with option price. Overall, this study provides a theoretical analysis and empirical tests of the value of a real option that allows option holders to renew/extend their contracts at a fair market value.

Native Hawaiians (NH) are the original people of Hawai'i and today make up 21% of the islands' population.1 Nationwide, there are more than 560,000 Americans who identify as NH and are among the fastest-growing racial group in the United States.2 Despite their growth in the population, they suffer from some of the worst health disparities in the country. Based on these trends, Kaiser Permanente Hawai'i (KPHI) developed systems and programs to address this health inequity to service approximately 252,000 members across commercial, Medicare, and Medicaid health plans. [Extracted from the article]

BackgroundPsychological distress, isolation, feelings of powerlessness, and limited social support are realities faced by temporary migrant live-in caregivers in Canada. Furthermore, they experience multiple barriers in accessing mental health services due to their long work hours, limited knowledge of health resources, precarious employment, and immigration status. ObjectiveThe Women Empowerment - Caregiver Acceptance & Resilience E-Learning (WE2CARE) project is a pilot intervention research project that aims to promote the mental well-being and resiliency of migrant live-in caregivers. The objectives include exploring the effectiveness of this program in achieving the following: (1) reducing psychological distress (depression, anxiety, and stress); (2) promoting committed actions of self-care; and (3) building mutual support social networks. Further, participants’ satisfaction with the intervention and their perceived barriers to and facilitators of practicing the self-care strategies embedded in WE2CARE will be examined. MethodsA total of 36 live-in caregivers residing in the Greater Toronto Area will be recruited and randomly assigned to either the intervention or waitlist control group. The intervention group will receive a 6-week web-based psychosocial intervention that will be based on Acceptance and Commitment Therapy (ACT). Standardized self-reported surveys will be administered online preintervention, postintervention, and at 6 weeks postintervention to assess mental distress (Depression, Anxiety and Stress Scale), psychological flexibility (Acceptance and Action Questionnaire), mindfulness (Cognitive and Affective Mindfulness Scale – Revised), and resilience (Multi-System Model of Resilience Inventory). In addition, two focus groups will be held with a subset of participants to explore their feedback on the utility of the WE2CARE program. ResultsWE2CARE was funded in January 2019 for a year. The protocol was approved by the research ethics boards of Ryerson University (REB 2019-036) and the University of Toronto (RIS37623) in February and May 2019, respectively. Data collection started upon ethics approval and was completed by May 2020. A total of 29 caregivers completed the study and 20 participated in the focus groups. Data analyses are in progress and results will be published in 2021. ConclusionsWE2CARE could be a promising approach to reducing stress, promoting resilience, and providing a virtual space for peer emotional support and collaborative learning among socially isolated and marginalized women. The results of this pilot study will inform the adaptation of an ACT-based psychological intervention for online delivery and determine its utility in promoting mental health among disadvantaged and vulnerable populations. International Registered Report Identifier (IRRID)DERR1-10.2196/31211

BackgroundRapid urbanization, academic pressures, and developmental life transition stressors contribute to mental health stress for postsecondary students in China. Effective prevention, early identification, and timely intervention are challenged by stigma, a lack of mental health literacy, and inadequate mental health resources. ObjectiveOur implementation science (IS) research project is aimed at evaluating the use of an evidence-informed mental health promotion intervention named Acceptance and Commitment to Empowerment – Linking Youth and ‘Xin’ (hearts) (ACE-LYNX) to promote university student mental health in Jinan, China. MethodsWe will engage and collaborate with Shandong Mental Health Center, the provincial mental health center, and six local universities in different regions of Jinan. The ACE-LYNX intervention aims to reduce social stigma against mental illness, enhance mental health literacy, and improve access to quality mental health care by increasing interdisciplinary collaboration and forming a mental health network. It is based on two evidence-based approaches, Acceptance and Commitment Therapy (ACT) and Group Empowerment Psychoeducation (GEP), and it will be delivered through online learning and in-person group training. The project will train 90 interdisciplinary professionals using the model. They will in turn train 15 professionals and 20 students at each university. The project will adopt the Reach, Efficacy, Adoption, Implementation, and Maintenance (RE-AIM) framework, which provides a structure to examine the process and outcomes of implementation using mixed methods comprising quantitative and qualitative approaches along five dimensions: reach, efficacy, adoption, implementation, and maintenance. ResultsOver the course of the project, 720 champions will be directly trained. They will contribute to developing a formal and informal mental health network, strengthened by student-led mental health initiatives and professional-led initiatives to promote collaborative care and facilitated care pathways. We anticipate that our project will reach out to 11,000 to 18,000 students. ConclusionsThis IS protocol will outline our unique intervention model and key steps to contextualize, implement, and evaluate community-based mental health intervention. International Registered Report Identifier (IRRID)PRR1-10.2196/25592

The article presents information on three hepatitis C virus infection drugs including simeprevir, sofosbuvir and dolutegravir.

Libraries sign a wide variety of licensing agreements that specify terms of both access and use of a publisher’s electronic collections. Adding easily accessible licensing information to collections helps ensure that library users comply with these agreements. This article will describe the addition of licensing permissions to resource displays using Mondo by Queen’s University and Scholars Portal (a service of the Ontario Council of University Libraries). We will give a brief introduction to Mondo and explain how we improved Mondo to add the license permissions to different library systems. The systems we used are an ILS (Voyager), an OpenURL Link Resolver (360 Link), and a Discovery System (Summon). However, libraries can use Mondo to add the license permissions to other library systems which allow user configurations.

The design, synthesis and pharmacology of novel long-acting exenatide analogs for the treatment of metabolic diseases are described. These molecules display enhanced pharmacokinetic profile and potent glucoregulatory and weight lowering actions compared to native exenatide. [Leu(14)]exenatide-ABD is an 88 residue peptide amide incorporating an Albumin Binding Domain (ABD) scaffold. [Leu(14)]exenatide-ABP is a 53 residue peptide incorporating a short Albumin Binding Peptide (ABP). [Leu(14)]exenatide-ABD and [Leu(14)]exenatide-ABP exhibited nanomolar functional GLP-1 receptor potency and were metabolically stable in vitro in human plasma and in a pancreatic digestive enzyme mixture. Both molecules displayed picomolar and nanomolar binding association with albumin across multiple species and circulating half lives of 16 and 11 hours, respectively, post a single IV dose in rats. Unlike exenatide, both molecules elicited robust glucose lowering when injected 1 day prior to an oral glucose tolerance test, indicative of their extended duration of action. [Leu(14)]exenatide-ABD was compared to exenatide in a Lep (ob/ob) mouse model of diabetes. Twice-weekly subcutaneously dosed [Leu(14)]exenatide-ABD displayed superior glucose lowering and weight loss in diabetic mice when compared to continuously infused exenatide at the same total weekly dose. A single oral administration of each molecule via an enteric coated capsule to cynomolgus monkeys showed superior pharmacokinetics for [Leu(14)]exenatide-ABD as compared to [Leu(14)]exenatide-ABP with detectable exposure longer than 14 days. These studies support the potential use of these novel long acting exenatide analogs with different routes of administration for the treatment of type 2 diabetes.

TAp73 is a p53 tumor suppressor gene homologue that is known to be mainly involved in apoptosis. We report here that TAp73 is necessary for the cellular response to oxidative stress and that TAp73 functions as a downstream target of p53 in this process. We show that p53 physically interacts with the TAp 73 promoter under stress conditions that lead to cell death. Particularly, p53 binds to a palindromic site in the TAp73 promoter, activates the promoter of TAp 73, and selectively induces TAp 73 transcription. TAp73 expression is highly increased under oxidative stress in a p53-dependent manner. Furthermore, knock-down of TAp73 expression inhibits the cellular apoptotic response to oxidative damage. In contrast, the ectopic expression of TAp73 in p53-/- mouse embryonic fibroblasts induces oxidative cell death. Our findings demonstrate that p53 is a direct transcriptional regulator of TAp 73. Our data reveal a new pathway for cellular protection against oxidative damage and provide evidence that TAp73 is a stress-response gene and a downstream effector in the p53 pathway. [ABSTRACT FROM AUTHOR]