Conectar
by Drew Gorenz, Norbert Schwarz
People hear jokes live and pre-recorded in a variety of settings, from comedy clubs, bars, outdoor venues, cafes, to their own home or car. While a lot of research has analyzed the significance of the content of jokes, we know less about the significance of the setting one hears them in. Some settings can have interfering background noise or poor acoustics, reducing an audience’s ease of processing heard jokes. Would this affect how funny the jokes seem? Two experiments with audio clips of stand-up comedy performances show that participants found jokes less funny when background noise interfered with their listening.
by Okkeun Jung, Angelene Soto, Andrew L. Wolfe, Shahana S. Mahajan
KRAS mutations, which induce proliferative signaling driving many human cancers, are detectable in a small subset of osteosarcoma patients. The recently developed pan-KRAS inhibitor daraxonrasib, also known as RMC-6236, is capable of targeting a wide array of KRAS mutations and shows promise against pancreatic and lung cancers. However, the efficacy and mechanisms of action of daraxonrasib in osteosarcoma (OS) remain unclear. We evaluated the effects of daraxonrasib on the viability, proliferation, and metastatic potential of wild-type and KRAS mutant OS cells. We assayed the effects of treatment on downstream targets using qPCR, immunoblotting, and activity assays to explore the underlying mechanism by which daraxonrasib selectively suppresses the metastatic potential of KRAS mutant osteosarcoma. Finally, we investigated how the increased prevalence of GTP-bound KRAS enhanced the sensitivity of KRAS wild-type osteosarcoma cells to daraxonrasib using siRNA targeting RASA1. Daraxonrasib selectively attenuated the proliferation and migratory ability of KRAS mutant HOS-143B cells without affecting KRAS wild-type controls. Additionally, daraxonrasib suppressed the expression of the matrix metalloproteases MMP9 and MMP1, which promote cell motility and metastasis. Daraxonrasib selectively inhibited the AKT/ETS1 pathway in HOS-143B cells, whereas no such effect was observed in HOS cells. HOS cells were sensitized to daraxonrasib by knocking down the GTPase-activating protein RASA1. In osteosarcoma, KRAS inhibition decreased MMP1, MMP9, and AKT/ETS1 signaling. Daraxonrasib is a promising agent for treating osteosarcoma with KRAS mutations.
by Karishma K. Singh, Andrew J. Elliot, Elizabeth D. Handley, Jeremy P. Jamieson
Individuals embody various social identities that can impact how they interface with the social environment. Stigma theories suggest that members of low-status or marginalized groups possess devalued social identities, and therefore, experience more stress. While social identities can lead to increased stress, individuals’ appraisals of their identities are not necessarily perceived as harmful/demanding. Rather, social identities can also be appraised as resources or sources of strength bringing opportunities and facilitating goal attainment. Using the biopsychosocial (BPS) model of challenge and threat as a conceptual foundation, this research developed a novel measure to assess individuals’ appraisals of their social identities. In Study 1 (N = 575), confirmatory factor analysis (CFA) evaluated the theorized factor structure (i.e., resource and demand appraisals) and assessed the overall fit of the model. Structural equation modeling (SEM) tested for associations between the resource and demand latent factors. Individuals appraising their ethnic-racial identity as a resource exhibited improved self and intergroup outcomes, while those perceiving it as a demand reported worse self-based and intergroup outcomes, as well as more distress. Study 2 (N = 743 Black and White Americans), which was preregistered, examined group differences in appraisals of ethnic-racial identity. SEM revealed that Black participants were more likely than White participants to appraise their ethnic-racial identity as demanding, leading to worse social and intergroup outcomes. Even when Black participants perceived their ethnic-racial identity as a resource, they still reported higher levels of discrimination, intergroup anxiety, and behavioral avoidance compared to their White counterparts. Implications for theory development and application to the stress literature are discussed.
by Jack O. Thomas, Josiah K. To, Parsa Riazi Esfahani, Frithjof Kruggel, William C. Tang, Andrew W. Browne
PurposeThis study aims to explore the feasibility and performance of three-dimensional ultrasound (3DUS) imaging in ophthalmology using commercially available ultrasound probes adapted to a slit lamp.
SignificanceDespite ultrasound’s long-standing application in eye care for visualizing ocular components, the evolution of 3DUS technology has remained inactive, with limited development and commercial availability. This study introduces a novel method that could potentially enhance ophthalmic diagnostics and treatment planning by providing comprehensive 3D views of ocular structures using existing ultrasound probes adapted to the conventional slit lamp.
MethodsA custom system was designed for mounting a linear actuator to a slit lamp and enabling the horizontal actuation of any ultrasound probe. Ophthalmic and non-ophthalmic ultrasound probes were tested for their ability to reconstruct 3DUS images of the posterior pole. The study involved designing and evaluating three US phantoms ex vivo and performing in vivo imaging on human subjects to assess the system’s applicability.
ResultsThe system successfully acquired 3D volume scans of phantoms and live human eyes, demonstrating the system’s potential for detailed ocular imaging. The adaptability of the device allowed for compatibility with various ultrasound probes. In vivo imaging revealed the system’s capability to produce high-resolution 3D reconstructions of ocular structures, including eyes with pathological conditions.
ConclusionsThe introduction of a slit lamp-mounted 3DUS system represents a significant advancement in ophthalmic ultrasonography, offering a practical and accessible solution for comprehensive 3D ocular assessments. The device’s modularity and compatibility with existing ultrasound probes make it a versatile tool for a wide range of ophthalmic applications. Further research and clinical trials are needed to optimize the system’s performance and validate its clinical utility.
by Jasmine C. Mah, Olga Theou, Mario Ulises Perez-Zepeda, Jodie L. Penwarden, Judith Godin, Kenneth Rockwood, Melissa K. Andrew
BackgroundThe construct of social vulnerability attempts to understand social circumstances not merely as a descriptor, but as a predictor of adverse health events. It can be measured by aggregating social deficits in a social vulnerability index (SVI). We describe a standard procedure for constructing a multi-level SVI using two working examples.
MethodsFirst, we describe a six-step approach to constructing a SVI. Then, we conducted a secondary analysis of a clinical dataset (Canadian Immunization Research Network’s Serious Outcomes Surveillance Network (SOS)) and a population-based dataset (Canadian Longitudinal Study on Aging (CLSA)). In both datasets, we construct SVIs, use descriptive statistics to report distributions by age and sex, and perform a multivariable linear regression of social vulnerability on frailty.
ResultsProcedures for drafting a list of candidate social items, selecting deficits for inclusion, and screening deficits to meet inclusion criteria were applied to yield a 18-deficit SVI for the SOS and 74-deficit SVI for the CLSA. Deficits in each SVI were re-scored between 0 and 1, where 1 indicates the greater risk. Finally, the sum of all deficits is calculated into an index. In the SOS, SVI was associated with age only for females and was weakly associated with frailty (r = 0.26, p Conclusion
We present a standard method of constructing a SVI by incorporating factors from multiple social domains and levels in a social-ecological model. This SVI can be used to improve our understanding of social vulnerability and its impacts on the health of communities and individuals.
by Andrew D. Shelton, Jessica L. Allen, Vicki S. Mercer, Jeremy R. Crenshaw, Jason R. Franz
Rehabilitation to prevent falls should not only directly address intrinsic and extrinsic factors, but also the neuropsychology of falls to promote safe and independent mobility in our aging population. The purpose of this study was to determine the relation between falls self-efficacy and objective responses to a series of walking balance perturbations. 29 healthy younger adults and 28 older adults completed four experimental trials, including unperturbed walking and walking while responding to three perturbations: mediolateral optical flow, treadmill-induced slips, and lateral waist-pulls; and three self-reported questionnaires: Activity-specific Balance Confidence, Falls Efficacy Scale, and the Fear of Falling Questionnaire-Revised. We quantified stabilizing responses as a change in margin of stability from unperturbed walking. Older adults generally exhibited larger instability than younger adults in response to walking balance perturbations. Only the Fear of Falls Questionnaire-Revised showed an increase in perceived falls risk for older adults. We found no significant correlations for older adults between any balance perturbation response and questionnaires of self-perception. Given the disconnect between self-perceived falls risk and responses to walking balance perturbations, rehabilitation to prevent falls while maintaining mobility and independence will likely require personalized techniques that combine neuromuscular training with approaches for neurophysiological reeducation.
by Lianyu Shan, Mojdeh Matloubi, Ifeoma Okwor, Sam Kung, Mohamed Sadek Almiski, Sujata Basu, Andrew Halayko, Latifa Koussih, Abdelilah S. Gounni
Dendritic cells (DCs) are pivotal in regulating allergic asthma. Our research has shown that the absence of Sema3E worsens asthma symptoms in acute and chronic asthma models. However, the specific role of PlexinD1 in these processes, particularly in DCs, remains unclear. This study investigates the role of PlexinD1 in CD11c+ DCs using a house dust mite (HDM) model of asthma. We generated CD11c+ DC-specific PlexinD1 knockout (CD11cPLXND1 KO) mice and subjected them, alongside wild-type controls (PLXND1fl/fl), to an HDM allergen protocol. Airway hyperresponsiveness (AHR) was measured using FlexiVent, and immune cell populations were analyzed via flow cytometry. Cytokine levels and immunoglobulin concentrations were assessed using mesoscale and ELISA, while collagen deposition and mucus production were examined through Sirius-red and periodic acid Schiff (PAS) staining respectively. Our results indicate that CD11cPLXND1 KO mice exhibit significantly exacerbated AHR, characterized by increased airway resistance and tissue elastance. Enhanced mucus production and collagen gene expression were observed in these mice compared to wild-type counterparts. Flow cytometry revealed higher CD11c+ MHCIIhigh CD11b+ cell recruitment into the lungs, and elevated total and HDM-specific serum IgE levels in CD11cPLXND1 KO mice. Mechanistically, co-cultures of B cells with DCs from CD11cPLXND1 KO mice showed significantly increased IgE production compared to wild-type mice.These findings highlight the critical regulatory role of the plexinD1 signaling pathway in CD11c+ DCs in modulating asthma features.
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