A comparison of the sociodemographic, medical, and psychosocial characteristics of adolescents and young adults diagnosed with cancer recruited in-person and online: A Canadian cross-sectional survey.

Introduction: Adolescents and young adults diagnosed with cancer (AYAs) are under-represented in research. The Internet and social media could increase the reach of recruitment efforts but may impact sample characteristics. This study evaluated the characteristics of AYAs recruited in-person at an urban hospital versus the Internet in terms of their sociodemographic and medical characteristics, and psychosocial wellbeing, and offers recommendation for increasing the inclusivity and representativeness of research samples. Methods: Participant data from a cross-sectional survey of AYAs in Canada were evaluated. In-person hospital recruitment used a registry to identify patients attending ambulatory clinics. Internet recruitment included notices on hospital, team members', and community partners' social media channels, and email newsletters. Independent sample t-tests and Chi-squared tests were used to identify differences in participant sociodemographic, medical, and psychosocial characteristics based on recruitment source. Results: Of 436 participants, 217 (49.8%) were recruited in-person and 219 (50.2%) online. Online participants were more likely: to be white (p < .001), women (p < .001), and Canadian-born (p < .001); to speak English at home (p < .001), live alone (p = .001) and live in rural settings (p = .014); and to be farther from diagnosis (p = .023), diagnosed with breast cancer (p < .001), and cancer free (p < .001) compared to the hospital sample. Online participants also reported higher anxiety, depression, and loneliness (p < .001), and lower social support (p < .001), self-efficacy for coping with cancer (p < .001), and life satisfaction (p = .006). Conclusions: Online recruitment yielded a more geographically diverse but less sociodemographically diverse sample of AYAs who were farther from diagnosis and had poorer psychosocial wellbeing than in-person recruitment at an urban hospital. Future research efforts should consider partnering with under-represented communities and using targeted and stratified online and in-person recruitment strategies to achieve an inclusive and representative sample of AYAs.

The organic cation transporter 2 regulates dopamine D1 receptor signaling at the Golgi apparatus.

Dopamine is a key catecholamine in the brain and kidney, where it is involved in a number of physiological functions such as locomotion, cognition, emotion, endocrine regulation, and renal function. As a membrane-impermeant hormone and neurotransmitter, dopamine is thought to signal by binding and activating dopamine receptors, members of the G protein coupled receptor (GPCR) family, only on the plasma membrane. Here, using novel nanobody-based biosensors, we demonstrate for the first time that the dopamine D1 receptor (D1DR), the primary mediator of dopaminergic signaling in the brain and kidney, not only functions on the plasma membrane but becomes activated at the Golgi apparatus in the presence of its ligand. We present evidence that activation of the Golgi pool of D1DR is dependent on organic cation transporter 2 (OCT2), a dopamine transporter, providing an explanation for how the membrane-impermeant dopamine accesses subcellular pools of D1DR. We further demonstrate that dopamine activates Golgi-D1DR in murine striatal medium spiny neurons, and this activity depends on OCT2 function. We also introduce a new approach to selectively interrogate compartmentalized D1DR signaling by inhibiting Gαs coupling using a nanobody-based chemical recruitment system. Using this strategy, we show that Golgi-localized D1DRs regulate cAMP production and mediate local protein kinase A activation. Together, our data suggest that spatially compartmentalized signaling hubs are previously unappreciated regulatory aspects of D1DR signaling. Our data provide further evidence for the role of transporters in regulating subcellular GPCR activity.

Peer Support Needs and Preferences for Digital Peer Navigation among Adolescent and Young Adults with Cancer: A Canadian Cross-Sectional Survey.

Adolescents and young adults (AYA) with cancer desire peer support and require support programs that address their unique needs. This study investigated the need for, and barriers to, peer support and preferences for digital peer navigation among AYA. A cross-sectional survey was administered to AYA, diagnosed with cancer between the ages of 15-39, at a cancer center and through social media. Descriptive summary statistics were calculated. Participants (n = 436) were on average 31.2 years (SD = 6.3), 3.3 years since-diagnosis (SD = 3.8), and 65% (n = 218) were women. Over three-quaters (n = 291, 76.6%) desired peer support from cancer peers, but 41.4% (n = 157) had not accessed peer support. Main access barriers were: Inconvenience of in-person support groups (n = 284, 76.1%), finding AYA with whom they could relate (n = 268, 72.4%), and finding AYA-specific support programs (n = 261, 70.4%). Eighty-two percent (n = 310) desired support from a peer navigator through a digital app, and 63% (n = 231) were interested in being a peer navigator. Participants indicated a greater need for emotional (n = 329, 90.1%) and informational support (n = 326, 89.1%) than companionship (n = 284, 78.0%) or practical support (n = 269, 73.6%) from a peer navigator. Foremost peer matching characteristics were cancer-type (n = 329, 88.4%), specific concerns (n = 317, 86.1%), and age-at-diagnosis (n = 316, 86.1%). A digital peer navigation program was desired by over 80% of a large Canadian sample of AYA and could potentially overcome the barriers AYA experience in accessing peer support. The design of a peer navigation program for AYA should consider the matching characteristics and multidimensional support needs of AYA.

WASP integrates substrate topology and cell polarity to guide neutrophil migration.

To control their movement, cells need to coordinate actin assembly with the geometric features of their substrate. Here, we uncover a role for the actin regulator WASP in the 3D migration of neutrophils. We show that WASP responds to substrate topology by enriching to sites of inward, substrate-induced membrane deformation. Superresolution imaging reveals that WASP preferentially enriches to the necks of these substrate-induced invaginations, a distribution that could support substrate pinching. WASP facilitates recruitment of the Arp2/3 complex to these sites, stimulating local actin assembly that couples substrate features with the cytoskeleton. Surprisingly, WASP only enriches to membrane deformations in the front half of the cell, within a permissive zone set by WASP's front-biased regulator Cdc42. While WASP KO cells exhibit relatively normal migration on flat substrates, they are defective at topology-directed migration. Our data suggest that WASP integrates substrate topology with cell polarity by selectively polymerizing actin around substrate-induced membrane deformations in the front half of the cell.

Identification of chlorophyll a-b binding protein AB96 as a novel TGFß1 neutralizing agent.

The discovery of compounds and proteins from plants has greatly contributed to modern medicine. Vernonia amygdalina Del. (Compositae) is used by humans and primates for a variety of conditions including parasitic infection. This paper describes the serendipitous discovery that V. amygdalina extract was able to bind to, and functionally inhibit, active TGFß1. The binding agent was isolated and identified as chlorophyll a-b binding protein AB96. Given that active TGFß1 contributes to the pathology of many infectious diseases, inhibiting these processes may explain some of the benefits associated with the ingestion of this species. This is the first plant-derived cytokine-neutralizing protein to be described and paves the way for further such discoveries.

Sterol and oxysterol synthases near the ciliary base activate the Hedgehog pathway.

Vertebrate Hedgehog signals are transduced through the primary cilium, a specialized lipid microdomain that is required for Smoothened activation. Cilia-associated sterol and oxysterol lipids bind to Smoothened to activate the Hedgehog pathway, but how ciliary lipids are regulated is incompletely understood. Here we identified DHCR7, an enzyme that produces cholesterol, activates the Hedgehog pathway, and localizes near the ciliary base. We found that Hedgehog stimulation negatively regulates DHCR7 activity and removes DHCR7 from the ciliary microenvironment, suggesting that DHCR7 primes cilia for Hedgehog pathway activation. In contrast, we found that Hedgehog stimulation positively regulates the oxysterol synthase CYP7A1, which accumulates near the ciliary base and produces oxysterols that promote Hedgehog signaling in response to pathway activation. Our results reveal that enzymes involved in lipid biosynthesis in the ciliary microenvironment promote Hedgehog signaling, shedding light on how ciliary lipids are established and regulated to transduce Hedgehog signals.

Improving Access to Standardized Fertility Preservation Information for Older Adolescents and Young Adults with Cancer: Using a User-Centered Approach with Young Adult Patients, Survivors, and Partners to Refine Fertility Knowledge Transfer.

Adolescent and young adult (AYA) cancer patients under 40 should be made aware of their fertility risks and preservation options throughout their care. However, discussions on fertility preservation (FP) do not routinely occur. With a dearth of FP resources, oncology providers may lack knowledge around FP. Thus, informational needs can be unmet, leading to anxiety and distress in patients. Provision of pertinent and timely information can help patients cope better with their diagnosis. FP pamphlets were developed for men and women with cancer. A cross-sectional in-house survey, using convenience sampling, evaluated the pamphlets' effectiveness and measured ease of understanding, acceptability, and perceived utility. Patients and partners were also asked to provide recommendations and complete the Short Test of Functional Health Literacy in Adults (S-TOFHLA) measuring health literacy level. This helps determine if health literacy influences perception of pamphlet effectiveness. All participants (n = 56) reviewed both pamphlets. Fifty-four participants (96 %) found the pamphlet for men useful, while 29 participants (52 %) improved their male fertility knowledge. The pamphlet for women was useful for 52 participants (93 %) and improved knowledge in 35 (63 %) of them. Although the majority of participants had adequate health literacy (98 %), there was insufficient sample diversity to determine if health literacy influenced the pamphlet's effectiveness. Participants indicated preference in receiving verbal (73 %) and written (66 %) information over watching videos or in-class education. They recommended including fertility clinics, financial resources, and statistics in the brochures. These FP pamphlets were concluded as effective in supporting patients in making FP decisions.

The positive effect of a dedicated adolescent and young adult fertility program on the rates of documentation of therapy-associated infertility risk and fertility preservation options.

PURPOSE: Minimal data exist regarding documentation of therapy-associated infertility risk (IR) and fertility preservation (FP) options during the initial oncology consultation prior to systemic therapy. This study investigated factors affecting IR/FP documentation and assessed the effect of implementation of an Adolescent and Young Adult (AYA) program on documentation rates. METHODS: A retrospective review of charts of patients receiving gonadotoxic therapy was undertaken for documentation of IR/FP pre- and post-implementation of an AYA program. Change in documentation rates was assessed using univariate and multiple logistic regression. RESULTS: A total of 173 charts were reviewed. On univariate analysis, IR/FP documentation was less likely if patients had metastatic disease (P < 0.01, P < 0.01), by tumor type (P < 0.01, P < 0.01), received less intensive chemotherapy (P = 0.03, P = 0.06), were older (P = 0.14, P < 0.01), had more children (P < 0.01, P < 0.01), or lacked AYA program involvement (P < 0.01, P < 0.01). FP discussion was more common in males (P = 0.02). On multivariable analysis, more children (P = 0.01, P = 0.03), older age (P < 0.01, P < 0.01), tumor type (P < 0.01, P = 0.01), stage (P = 0.02, NS), relationship (P = 0.03, NS), and lack of AYA involvement (P < 0.01, P < 0.01) were associated with lower rates of IR/FP documentation. Following AYA program implementation, IR/FP rates increased from 56% (CI 46-65%) to 85% (CI 74-92%, P < 0.01) and 54% (CI 45-64%) to 86% (CI 75-93%, P < 0.01), respectively. The effect of AYA program implementation on IR/FP documentation was most noticeable in leukemia, lymphoma, and breast groups (P < 0.01). CONCLUSIONS: Implementing an AYA consultation service at an adult cancer institution had a positive effect on the rates of IR/FP documentation. Specific programming can improve service delivery to AYA cancer patients, and fertility counseling should be integrated for patients undergoing gonadotoxic therapy.