University of San Francisco

Functional testers are designed to evaluate select pulse oximeter characteristics but are often misused to validate device accuracy, potentially providing false reassurance. This study evaluated whether the Fluke ProSim8 (FPS8) could accurately predict oximeter performance during human controlled desaturation studies or identify performance differences under low signal conditions. 12 oximeters were tested using two FPS8 protocols: (1) an 'SpO₂ plateau' protocol which mimicked controlled desaturation studies by evaluating device performance over a range of simulated SpO2 (70-100%), and (2) a 'signal space' protocol designed to assess device accuracy under varying modulation and transmission conditions. Each device also underwent controlled desaturation testing in healthy adults.Six of the 12 oximeters passed (ARMS ≤ 3%) the SpO₂ plateau protocol; however, three of these failed (ARMS > 3%) human testing. At lower simulated saturations, most devices overestimated SpO₂. In the signal space protocol, oximeters performed well under high signal conditions, but many failed to produce readings or showed SpO₂ errors > 3% under low signal conditions. On average, oximeters failed to generate a reading 20.2 ± 7.2 times out of 60 attempts. Ten devices passed (ARMS < 3%) the signal space protocol, but two of these failed human testing. Oximeter performance on the FPS8 did not correlate with human performance (R² = 0.08 for the plateau protocol; R² = 0.01 for the signal space protocol).The FPS8 did not reliably predict oximeter accuracy in human desaturation studies or under low signal conditions; current functional tester protocols are limited in predicting real-world oximeter performance.

Fibroblasts play critical roles in regulating cellular relationships during tissue homeostasis, immunity, and tumor biology at multiple sites. However, tools to perturb fibroblasts at just one site in vivo are limited, restricting our understanding of how these cellular relationships act locally. We optimized local gene editing of fibroblasts in mouse tumor models to investigate how fibroblast perturbations affect the tumor microenvironment (TME). By knocking out receptors Osmr, Tgfbr2, or Il1r1 on cancer-associated fibroblasts (CAFs), we uncover that TGFBR2 signaling loss induces the emergence of a new Col18a1hi CAF cell state that is associated with worse survival in pancreatic cancer patients. Combinatorial gene KOs in CAFs reveals a circuit where these Col18a1hi CAFs reshape the TME by recruiting Siglec-Fhi neutrophils via Cxcl5 expression, and where this Col18a1hi CAF cell state is dependent on TNFR1 and canonical Wnt signaling. Together, a fast, affordable, and modular engineering method is demonstrated, allowing discovery of modified fibroblast identities and local intercellular relationships in the TME.

Our research in this paper lies at the intersection of Generative AI (GenAI) and search-as-learning (SAL). GenAI technologies (e.g., ChatGPT) have revolutionized how people search for and interact with information. However, we do not yet fully understand how people use GenAI systems to learn about complex topics. SAL research has studied how different tools can support learning with traditional document retrieval systems. Our research closely relates to SAL work that has investigated the effects of goal-setting on learning during search. We explore the influence of goal-setting on learning during information-seeking sessions with a GenAI system. We report on a between-subjects crowdsourced study (N = 120) in which participants were asked to learn about a complex topic using a GenAI system. The study had four conditions that varied along two factors (a 2 × 2 design). The first factor involved displaying related web results in addition to the GenAI output. The second factor involved giving participants access to the Subgoal Manager (SM), a tool designed to help people develop subgoals and take notes. We investigated the effects of both factors on: (RQ1) perceptions; (RQ2) behaviors; (RQ3) learning and retention; (RQ4) the types of requests issued to the system; and (RQ5) participants’ motivations for engaging (or not engaging) with the related web results. Results found that participants with access to the SM had higher post-task learning outcomes, did less copy/pasting into their notes, perceived the task as more difficult, and requested more examples and support for differentiating concepts from the GenAI system.

The brain has the remarkable ability to guide the performance of complex tasks. Distinct prefrontal cortical areas make specific contributions to this ability, with the orbitofrontal cortex (OFC) critical for processing information related to trial outcomes and the dorsomedial prefrontal cortex (dmPFC) critical for sustained effort and selecting the right action at the right time. Yet, in both areas, neural activity represents both outcome- and action-related quantities. How similar neural representations support different functions remains unclear. Here, we compared OFC and dmPFC activity in rats performing a spatial alternation task. We show that, in contrast to other task-related variables, task progression is represented in both areas, but with distinct patterns of across-trial reliability that match each area's previously documented functional specialization. Our results indicate that the engagement of reliable, task-phase-specific activity patterns differs across prefrontal regions in a manner well suited to engage different computations at different times.

Liver cancer is a leading cause of cancer-related death due to the shortage of effective therapies, and MYC overexpression defines an aggressive and difficult-to-treat subset of patients. Given MYC's ability to reprogram cancer metabolism and the liver's role in coordinating systemic metabolism, we hypothesized that MYC induces metabolic dependencies that could be targeted to attenuate tumor growth. We discovered that MYC-driven liver cancers catabolize alanine in a GPT2-dependent manner. GPT2 is the predominant alanine-catabolizing enzyme expressed in MYC-driven liver tumors and genetic ablation of GPT2 limited liver tumorigenesis. In vivo isotope tracing identified alanine as a substrate for a repertoire of pathways including the tricarboxylic acid cycle and biosynthesis. Finally, treating a MYC-driven liver tumor model with L-cycloserine diminished the frequency of mouse tumor formation and attenuated the growth of established human liver tumors. Thus, we identify a targetable metabolic dependency that MYC-driven liver tumors usurp to ensure their survival.

Abstract Background Pregnant and lactating women with HIV are particularly vulnerable to the intersecting effects of HIV and poverty. In Zimbabwe, socioeconomic vulnerability among young women increases the risk of HIV acquisition and compromises treatment outcomes. Addressing poverty is therefore essential to improving maternal and child health outcomes in this population. This retrospective cross-sectional study examined the relationship between socioeconomic vulnerability and HIV-related health outcomes among pregnant and lactating women in Zimbabwe. Methods We surveyed 600 pregnant and lactating women living with HIV receiving care at community health centers across Zimbabwe. The survey captured sociodemographic and self-reported clinical data. Using generalized estimating equations, we assessed associations between viral load non-suppression, antiretroviral (ARV) treatment interruption, delayed presentation to antenatal care, and socioeconomic covariates including poverty level and participation in social protection programs. Results Among participants, 74.5% (n=447) were lactating and 25.5% (n=153) were pregnant. Over half (54.2%, n=325) reported at least one unmet social need; 47.2% (n=238) experienced food insecurity, 26.2% (n=157) lacked transportation funds, and 23.7% (n=142) lacked money for user fees or related health costs. Nearly half (49.5%, n=297) reported using negative financial coping strategies such as taking loans, selling assets, or withdrawing savings. Intimate partner violence was significantly associated with viral load non-suppression (RR 2.4, 95% CI 1.5–4.0, p&lt;0.005). Receipt of social protection benefits was associated with ARV treatment interruption (RR 2.3, 95% CI 1.3–4.2, p=0.006), while dissaving was associated with delayed antenatal care presentation (RR 1.8, 95% CI 1.4–2.3, p&lt;0.05). Conclusions Unmet social needs, poverty, and adverse financial coping strategies were associated with suboptimal HIV outcomes among pregnant and lactating women in Zimbabwe. Although social protection interventions aim to mitigate these vulnerabilities, their complex effects warrant further investigation to optimize design and implementation.

There is growing global recognition of the importance of viruses as a cause of lower respiratory tract infections (LRIs) from widespread outbreaks such as the recent COVID-19 pandemic, to seasonal viruses such as those caused by influenza and adenovirus. Worldwide, viruses are a common cause of respiratory infections and mortality due to LRIs. Advances in rapid virus detection have led to a greater understanding of their prevalence and importance as etiological agents of illness. With multiple epidemics and pandemics of viral pneumonia over the past several decades, there is an increasing need to understand the global variations and impacts of these viruses. This review summarizes recent global trends in viral pneumonias and provides an overview of current diagnostic, treatment, and imaging challenges in the setting of viral infections.

ABSTRACT This article illustrates how relational innovation leadership can enable strategic renewal, innovation continuity, and long‐term value creation in the fast‐moving digital technology sector. Drawing on an integrative leadership case of Lip‐Bu Tan's tenure at Cadence Design Systems, the article examines leadership practice through the complementary lenses of transformational, authentic, servant, and relational leadership, informed by cross‐theoretical and cross‐cultural perspectives. Tan's leadership—characterized by moral clarity, humility, and deep intercultural competence—supported Cadence's strategic turnaround while fostering a sustainable culture of innovation. In contrast to dominant individualistic and heroic leadership archetypes often associated with Silicon Valley, the case exemplifies a relationally embedded and ethically grounded approach to innovation leadership. By integrating insights from cross‐cultural management, including the influence of Asian leadership philosophies and global stakeholder engagement, the article offers a generative illustration of post‐heroic leadership in the era of digital transformation. This article highlights a relational innovation leadership paradigm and discusses implications for leadership practice, managerial learning, and global innovation strategy.