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Hepatocellular carcinoma (HCC) is among the most common cancers worldwide, and tumor recurrence following liver resection or transplantation is one of the highest contributors to mortality in HCC patients after surgery. Using artificial intelligence (AI), we developed an interdisciplinary model to predict HCC recurrence and patient survival following surgery. We collected whole-slide H&E images, clinical variables, and follow-up data from 300 patients with HCC who underwent transplant and 169 patients who underwent resection at the Cleveland Clinic. A deep learning model was trained to predict recurrence-free survival (RFS) and disease-specific survival (DSS) from the H&E-stained slides. Repeated cross-validation splits were used to compute robust C-index estimates, and the results were compared to those obtained by fitting a Cox proportional hazard model using only clinical variables. While the deep learning model alone was predictive of recurrence and survival among patients in both cohorts, integrating the clinical and histologic models significantly increased the C-index in each cohort. In every subgroup analyzed, we found that a combined clinical and deep learning model better predicted post-surgical outcome in HCC patients compared to either approach independently.

Liver transplantation is known to generate significant inflammation in the entire organ based on the metabolic profile and the tissue’s ability to recover from the ischemia-reperfusion injury (IRI). This cascade contributes to post-transplant complications, affecting both the synthetic liver function (immediate) and the scar development in the biliary tree. The new occurrence of biliary strictures, and the recurrence of malignant and benign liver diseases, such as cholangiocarcinoma (CCA) and primary sclerosing cholangitis (PSC), are direct consequences linked to this inflammation. The accumulation of toxic metabolites, such as succinate, causes undirected electron flows, triggering the releases of reactive oxygen species (ROS) from a severely dysfunctional mitochondrial complex 1. This initiates the inflammatory IRI cascade, with subsequent ischemic biliary stricturing, and the upregulation of pro-tumorigenic signaling. Such inflammation is both local and systemic, promoting an immunocompromised status that can lead to the recurrence of underlying liver disease, both malignant and benign in nature. The traditional treatment for CCA was resection, when possible, followed by cytotoxic chemotherapy. Liver transplant oncology is increasingly recognized as a potentially curative approach for patients with intrahepatic (iCCA) and perihilar (pCCA) cholangiocarcinoma. The link between IRI and disease recurrence is increasingly recognized in transplant oncology for hepatocellular carcinoma. However, smaller numbers have prevented similar analyses for CCA. The mechanistic link may be even more critical in this disease, as IRI causes the most profound damage to the intrahepatic bile ducts. This article reviews the underlying mechanisms associated with biliary inflammation and biliary pathology after liver transplantation. One main focus is on the link between transplant-related IRI-associated inflammation and the recurrence of cholangiocarcinoma and benign liver diseases of the biliary tree. Risk factors and protective strategies are highlighted.

Cells must access resources to survive, and the anatomy of multicellular structures influences this access. In diverse multicellular eukaryotes, resources are provided by internal conduits that allow substances to travel more readily through tissue than they would via diffusion. Microbes growing in multicellular structures, called biofilms, are also affected by differential access to resources and we hypothesized that this is influenced by the physical arrangement of the cells. In this study, we examined the microanatomy of biofilms formed by the pathogenic bacterium Pseudomonas aeruginosa and discovered that clonal cells form striations that are packed lengthwise across most of a mature biofilm's depth. We identified mutants, including those defective in pilus function and in O-antigen attachment, that show alterations to this lengthwise packing phenotype. Consistent with the notion that cellular arrangement affects access to resources within the biofilm, we found that while the wild type shows even distribution of tested substrates across depth, the mutants show accumulation of substrates at the biofilm boundaries. Furthermore, we found that altered cellular arrangement within biofilms affects the localization of metabolic activity, the survival of resident cells, and the susceptibility of subpopulations to antibiotic treatment. Our observations provide insight into cellular features that determine biofilm microanatomy, with consequences for physiological differentiation and drug sensitivity.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death and the sixth most diagnosed malignancy worldwide. Serum alpha-fetoprotein (AFP) is the traditional, ubiquitous biomarker for HCC. However, there has been an increasing call for the use of multiple biomarkers to optimize care for these patients. AFP, AFP-L3, and prothrombin induced by vitamin K absence II (DCP) have described clinical utility for HCC, but unfortunately, they also have well established and significant limitations. Circulating tumor DNA (ctDNA), genomic glycosylation, and even totally non-invasive salivary metabolomics and/or micro-RNAS demonstrate great promise for early detection and long-term surveillance, but still require large-scale prospective validation to definitively validate their clinical validity. This review aims to provide an update on clinically available and emerging biomarkers for HCC, focusing on their respective clinical strengths and weaknesses.

A hallmark of idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases is dysregulated repair of the alveolar epithelium. The Hippo pathway effector transcription factors YAP and TAZ are implicated as essential for type 1 and type 2 alveolar epithelial cell (AT1 and AT2) differentiation in the developing lung, yet aberrant activation of YAP/TAZ is a prominent feature of the dysregulated alveolar epithelium in IPF. In these studies, we sought to define the functional role of YAP/TAZ activity during alveolar regeneration. We demonstrated that Yap and Taz were normally activated in AT2 cells shortly after injury, and deletion of Yap/Taz in AT2 cells led to pathologic alveolar remodeling, failure of AT2-to-AT1 cell differentiation, increased collagen deposition, exaggerated neutrophilic inflammation, and increased mortality following injury induced by a single dose of bleomycin. Loss of Yap/Taz activity prior to an LPS injury prevented AT1 cell regeneration, led to intraalveolar collagen deposition, and resulted in persistent innate inflammation. These findings establish that AT2 cell Yap/Taz activity is essential for functional alveolar epithelial repair and prevention of fibrotic remodeling.

Introduction: Circulating tumor DNA (ctDNA) is emerging as a promising, non-invasive diagnostic and surveillance biomarker in solid organ malignancy. However, its utility before and after liver transplant (LT) for patients with primary and secondary liver cancers is still underexplored. Methods: Patients undergoing LT for hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and colorectal liver metastases (CRLM) with ctDNA testing were included. CtDNA testing was conducted pre-transplant, post-transplant, or both (sequential) from 11/2019 to 09/2023 using Guardant360, Guardant Reveal, and Guardant360 CDx. Results: 21 patients with HCC (n = 9, 43%), CRLM (n = 8, 38%), CCA (n = 3, 14%), and mixed HCC/CCA (n = 1, 5%) were included in the study. The median follow-up time was 15 months (range: 1–124). The median time from pre-operative testing to surgery was 3 months (IQR: 1–4; range: 0–5), and from surgery to post-operative testing, it was 9 months (IQR: 2–22; range: 0.4–112). A total of 13 (62%) patients had pre-transplant testing, with 8 (62%) having ctDNA detected (ctDNA+) and 5 (32%) not having ctDNA detected (ctDNA-). A total of 18 (86%) patients had post-transplant testing, 11 (61%) of whom were ctDNA+ and 7 (33%) of whom were ctDNA-. The absolute recurrence rates were 50% (n = 5) in those who were ctDNA+ vs. 25% (n = 1) in those who were ctDNA- in the post-transplant setting, though this difference was not statistically significant (p = 0.367). Six (29%) patients (HCC = 3, CCA = 1, CRLM = 2) experienced recurrence with a median recurrence-free survival of 14 (IQR: 6–40) months. Four of these patients had positive post-transplant ctDNA collected following diagnosis of recurrence, while one patient had positive post-transplant ctDNA collected preceding recurrence. A total of 10 (48%) patients had sequential ctDNA testing, of whom n = 5 (50%) achieved ctDNA clearance (+/−). The remainder were ctDNA+/+ (n = 3, 30%), ctDNA−/− (n = 1, 10%), and ctDNA−/+ (n = 1, 11%). Three (30%) patients showed the acquisition of new genomic alterations following transplant, all without recurrence. Overall, the median tumor mutation burden (TMB) decreased from 1.23 mut/Mb pre-transplant to 0.00 mut/Mb post-transplant. Conclusions: Patients with ctDNA positivity experienced recurrence at a higher rate than the ctDNA- patients, indicating the potential role of ctDNA in predicting recurrence after curative-intent transplant. Based on sequential testing, LT has the potential to clear ctDNA, demonstrating the capability of LT in the treatment of systemic disease. Transplant providers should be aware of the potential of donor-derived cell-free DNA and improved approaches are necessary to address such concerns.

Background: Immunotherapy has emerged as an improved systemic treatment for select patients with advanced unresectable HCC. Objective response is reported in 30% of patients, yet complete response (pCR) allowing for curative-intent resection is rare. Locoregional therapies (LRTs) seem to show synergistic effects with immunotherapy, though this effect has not been scientifically reported. We report a cohort of patients showing pCR to immunotherapy + LRT as a proof of concept for the proposed treatment approach for locally unresectable HCC. Methods: Patients with unresectable HCC treated with immunotherapy as an intended destination therapy from 2016 to 2023 were included. The electronic health record was queried for oncologic information, locoregional therapies, surgical interventions, and long-term outcomes. Circulating tumor DNA (ctDNA) testing was obtained using Guardant360, and tumor mutational burden (TMB) was defined as the number of somatic mutations per megabase. Results: Ninety-six patients with advanced HCC received immunotherapy + LRT as a destination therapy. In total, 11 of 96 patients showed a complete response according to mRECIST criteria. Four of these (36.4%) ultimately underwent curative-intent resection. The median follow-up was 24.9 (IQR 15.6–38.3) months. Overall survival rates in those with complete response at 1, 3, and 5 years were 100%, 91%, and 81.8%, respectively, which were significantly improved compared to those of the cohort not achieving pCR (p < 0.001). All four patients undergoing immunotherapy + LRT followed by curative-intent hepatectomy have no evidence of disease (NED). Of those undergoing surgery, ctDNA was cleared in 75% (n = 3), providing an additional objective measurement of complete response. All four patients were TMB+ before beginning this treatment course, with three being TMB-, indicating stable and complete disease response. Conclusions: Immunotherapy + locoregional therapy can help downstage a significant proportion of patients with initially unresectable HCC, allowing for curative-intent surgery. The survival benefit associated with complete response seems durable up to 3 years after achieving this response. ctDNA measurement was converted from positive to negative in this cohort, providing additional indication of response.

External stressors such as alcohol, caffeine, and vigorous exercise are known to alter cellular homeostasis, affecting the autonomic nervous system (ANS) and overall physiological function. However, little direct evidence exists quantifying the impact of these external stressors on physiological testing. We assessed the impact of the above-listed stressors on spontaneous baroreflex sensitivity (BRS), heart rate variability (HRV), heart rate asymmetry (HRA), and systolic blood pressure variability (BPV). Seventeen male university varsity American-style football athletes completed two identical assessments on separate days, once presenting with one or more stressors (recent intake of caffeine, alcohol, or exercise participation; contraindicated assessment) and another with no stressors present (repeat assessment). Both assessments were conducted within one week and at the same time of day. The testing protocol consisted of 5-min of rest followed by 5-min of a squat-stand maneuver (0.05 Hz). Continuous beat-to-beat blood pressure and electrocardiogram measurements were collected and allowed for calculations of BRS, HRV, HRA, and BPV. Significant decreases (p

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 and poor outcomes. Here the authors compare the transcriptomes of single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in these patients.

Trophic cascades, or indirect effects of predators on non-adjacent lower trophic levels, are a classic phenomenon in ecology, and are thought to be strongest in aquatic ecosystems. Most research on freshwater trophic cascades focused on temperate lakes, where fish are present and where Daphnia frequently dominate the zooplankton community. These studies identified that Daphnia often play a key role in facilitating trophic cascades by linking fish to algae with strong food web interactions. However, Daphnia are rare or absent in most tropical and subtropical lowland freshwaters, and fish are absent from small and temporary water bodies, where invertebrates fill the role of top predator. While invertebrate predators are ubiquitous in freshwater systems, most have received little attention in food web research. Therefore, we aimed to test whether trophic cascades are possible in small warmwater ponds where Daphnia are absent and small invertebrates are the top predators. We collected naturally occurring plankton communities from small fishless water bodies in central Texas and propagated them in replicate pond mesocosms. We removed zooplankton from some mesocosms, left the plankton community intact in others, and added one of two densities of the predaceous insect Neoplea striola to others. Following an incubation period, we then compared biomasses of plankton groups to assess food web effects between the trophic levels, including whether Neoplea caused a trophic cascade by reducing zooplankton. The zooplankton community became dominated by copepods which prefer large phytoplankton and exhibit a fast escape response. Perhaps due to these qualities of the copepods and perhaps due to other reasons such as high turbidity impairing predation, no evidence for food web effects were found other than somewhat weak evidence for zooplankton reducing large phytoplankton. More research is needed to understand the behavior and ecology of Neoplea, but trophic cascades may generally be weak or absent in fishless low latitude lowland water bodies where Daphnia are rare.

This exploratory qualitative research focuses on the experiences of those who facilitate lesbian, gay, bisexual, transgender, queer/questioning (LGBTQ+) social justice educational interventions (SJEIs), such as safe zone, safe space, and ally training. Although persistent in higher education LGBTQ+ SJEIs remain an understudied area for empirical research, especially how facilitators describe the benefits and challenges of this role. Findings reveal how these benefits and challenges are paradoxical in that participants are hopeful for the impact of the work while burdened by the endeavor. Implications illuminate how participants approach engagement with campus communities through SJEIs as a potential opportunity for increasing inclusion efforts and how participants act as tempered radicals within this facilitator role in higher education.

Several worlds in our solar system are thought to hold oceans of liquid water beneath their frozen surfaces. These subsurface ice and ocean environments are promising targets in the search for life beyond Earth, but they also present significant new technical challenges to planetary exploration. With a focus on Jupiter’s moon Europa, here we (1) identify major benefits and challenges to subsurface ocean world science, (2) provide a multidisciplinary survey of relevant sample handling and life detection technologies, and (3) integrate those perspectives into the Subsurface Science and Search for Life in Ocean Worlds (SSSLOW) concept payload. We discuss scientific goals across three complementary categories: (1) search for life, (2) assess habitability, and (3) investigate geological processes. Major mission challenges considered include submerged operation in high-pressure environments, the need to sample fluids with a range of possible chemical conditions, and detection of biosignatures at low concentrations. The SSSLOW addresses these issues by tightly integrated instrumentation and sample handling systems to enable sequential, complementary measurements while prioritizing preservation of sample context. In this work, we leverage techniques and technologies across several fields to demonstrate a path toward future subsurface exploration and life detection in ice and ocean worlds.

Current methods to diagnose concussions are subjective and difficult to confirm. A variety of physiological biomarkers have been reported, but with conflicting results. This study assessed heart rate variability (HRV), spontaneous baroreflex sensitivity (BRS), and systolic blood pressure variability (BPV) in concussed athletes. The assessment consisted of a 5-min seated rest followed by a 5-min (0.1 Hz) controlled breathing protocol. Thirty participants completed baseline assessments. The protocol was repeated during the post-injury acute phase (days one to five). Total (p = 0.02) and low-frequency (p = 0.009) BPV spectral power were significantly decreased during the acute phase of concussion. BRS down-sequence (p = 0.036) and up-sequence (p = 0.05) were significantly increased in the acute phase of concussion, with a trend towards an increased BRS pooled (p = 0.06). Significant decreases in HRV were also found. Acute concussion resulted in altered BRS and BPV dynamics compared to baseline. These findings highlight objective physiological parameters that could aid concussion diagnosis and return-to-play protocols.

Targeting proteins to specific subcellular destinations is essential in prokaryotes, eukaryotes, and the viruses that infect them. Chimalliviridae phages encapsulate their genomes in a nucleus-like replication compartment composed of the protein chimallin (ChmA) that excludes ribosomes and decouples transcription from translation. These phages selectively partition proteins between the phage nucleus and the bacterial cytoplasm. Currently, the genes and signals that govern selective protein import into the phage nucleus are unknown. Here, we identify two components of this protein import pathway: a species-specific surface-exposed region of a phage intranuclear protein required for nuclear entry and a conserved protein, PicA (Protein importer of chimalliviruses A), that facilitates cargo protein trafficking across the phage nuclear shell. We also identify a defective cargo protein that is targeted to PicA on the nuclear periphery but fails to enter the nucleus, providing insight into the mechanism of nuclear protein trafficking. Using CRISPRi-ART protein expression knockdown of PicA, we show that PicA is essential early in the chimallivirus replication cycle. Together, our results allow us to propose a multistep model for the Protein Import Chimallivirus pathway, where proteins are targeted to PicA by amino acids on their surface and then licensed by PicA for nuclear entry. The divergence in the selectivity of this pathway between closely related chimalliviruses implicates its role as a key player in the evolutionary arms race between competing phages and their hosts.

Mechanical ventilation is a primary therapy for patients with respiratory failure. However, incorrect ventilator settings can cause lung damage. Optimising ventilation while minimising risk is complex in practice. A common lung protective strategy is to titrate positive end-expiratory pressure (PEEP) to the point of minimum elastance. This process can result in additional available lung volume due to alveolar recruitment but comes with the risk of subjecting the lungs to excessive pressure and lung damage. Predictive elastance models can mitigate this risk by estimating airway pressure at a higher PEEP level. Due to the increased risk of barotrauma during inspiration, many models exclude expiration data. However, this section of the breath can include useful information about lung mechanics. This research investigates the impact that including expiration data into the fitting of a validated predictive elastance model will have on its ability to predict peak inspiratory pressure. Results showed that expiration data did not improve the efficacy of the model in this case with an increase in error (median (%)) of predicting peak inspiratory pressure through an increase in PEEP of 8 cmH2O from 6% to 16%.

The optimized wound healing (OWID) project provides technical support of wound healing processes. Advanced biophysical treatment therapies using light (photobiomodulation), negative pressure wound therapy (NPWT), and electrical stimulation show biological effects. Specifically, a biphasic dose-response curve is observed where lower doses activate cells, while above a threshold, higher doses are inhibitory. However, no standard protocols and no multi-modal treatment studies determine specific therapy needs. The OWID project aims to develop a multi-modal treatment device and modelbased therapy for individualized wound healing. This work presents the OWID project status. Currently, a photobiomodulation prototype delivers red, green, and blue light ‘medicine’ at prescribed therapeutic ‘doses’. The calculation of incident light necessarily considers transmission properties of the intervening cell culture plate. Negative pressure wound therapy (NPWT) and electrical impedance tomography (EIT) hardware are being adapted for use in vitro. Development of mathematical models of wound healing and therapy control are supported by treatment experiment outcome measures conducted in a wounded 3D tissue model. Parameter sensitivity analysis conducted on an existing mathematical model of reepithelialization results in changing parameter values influencing cellular movement rates. Thus, the model is robust to fit model parameters to observed reepithelialization rates under treatment conditions impacting cellular activation, inhibition, and untreated controls. Developed image analysis techniques have not captured changes in wound area after photobiomodulation treatment experiments. Alternatively, EIT will be tested for wound area analysis. Additionally, live dyes will be introduced to non-invasively visualize the reepithelialization front on a smaller, cellular scale. Finally, an overall therapeutic feedback control model uses model reference adaptive control to incorporate the intrinsic biological reepithelialization mechanism, treatment loops, and treatment controller modulation at a wound state. Currently, the OWID project conducts photobiomodulation treatment experiments in vitro and has developed mathematical models. Future work includes the incorporation of multi-modal wound healing treatment experiments.

College expansion throughout the twentieth century was accompanied by the growth of a profession centered on supporting student learning and development. Higher Education and Student Affairs (HESA) programs multiplied across the United States to train these professionals with a focus on administration, leadership, and student affairs. As recommended by the Council for the Advancement of Standards in Higher Education and related professional organizations, the more than 280 programs in existence today typically include a course on the history of higher education. For the vast majority of HESA students, this is the only graduate-level history course they will take. For this study, the research team consisted of two faculty members -- one a historian and one a higher education professional -- and two graduate students who collaborated with the intention of deepening student engagement with history through an authentic digital assessment. This article examines the impact of the authentic digital assessment on student engagement, inquiry, research skills, and awareness of audience within the broader context of the history of higher education in the United States.

Using Ahmed's (2012) scholarship on diversity work and institutional life as a conceptual framework, we examine how LGBTQ+ social justice educational intervention (SJEI) facilitators described the challenges of their role. We found LGBTQ+ SJEI facilitators descriptions of their role revealed institutional dynamics that undermine purported support of equity-based work. Institutional realities that facilitators faced were neither intentionally malicious nor hostile, and encapsulated by the descriptor of benign neglect. Our findings expose how LGBTQ+ SJEIs operate as non-performatives treated with benign neglect through unenforceable authority, administrative gaslighting, and resource scarcity.

Using scholarly personal narratives as a research tool, we explored how the director of an LGBTQ+ living-learning program (LLP) created community within the constructs of an otherwise cis- and heteronormative residential environment. We reviewed the first author's reflections about community experiences and analyzed them for opportunities to upend assumptions, practices, and operations for more liberatory futures. Students participating in LLPs tend to have higher levels of engagement and belonging, but those with marginalized identities may benefit even more from this kind of involvement. The first author's personal narratives about serving as an LGBTQ+ LLP program director revealed that many of the residents appreciated the feelings of affinity and safety offered by this residential community, and they were uninterested in engaging in community in many of the expected ways (i.e., program attendance). Our exploration offers liberatory possibilities for queering institutional transformation, with the recognition that campus housing professionals should reconsider their expectations for all LLPs, and higher education institutions must make strong commitments to provide support that resists assumptions about queerness and community. The stability and growth of this LLP requires specific support that allows it to evolve into configurations that reflect the needs of its divergent communities while still being centered in queerness. [Discussion questions prepared by Kaleb Scott.]

This paper explores the experiences of nonbinary and trans (NBT) facilitators of Safe Zone workshops, what we call LGBTQ+ social justice educational interventions (SJEIs). Despite their prevalence in higher education for over 3 decades, there remains a paucity of research about them and those who facilitate them. This research focused on 33 NBT participants, a subpopulation within the larger 87 participants, to explore their preparation for LGBGTQ+ SJEI facilitation and how they use their gender in their facilitation. Using grassroots leadership as our conceptual framework, we raise concerns about what it means for identities to serve as preparation for leadership, and how these leaders give of themselves even to the detriment of themselves.

Social and economic inequality are chronic stressors that continually erode the mental and physical health of marginalized groups, undermining overall societal resilience. In this comprehensive review, we synthesize evidence of greater increases in mental health symptoms during the COVID-19 pandemic among socially or economically marginalized groups in the United States, including (a) people who are low income or experiencing homelessness, (b) racial and ethnic minorities, (c) women and lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ+) communities, (d) immigrants and migrants, (e) children and people with a history of childhood adversity, and (f) the socially isolated and lonely. Based on this evidence, we propose that reducing social and economic inequality would promote population mental health and societal resilience to future crises. Specifically, we propose concrete, actionable recommendations for policy, intervention, and practice that would bolster five "pillars" of societal resilience: (1) economic safety and equity, (2) accessible healthcare, including mental health services, (3) combating racial injustice and promoting respect for diversity, equity, and inclusion, (4) child and family protection services, and (5) social cohesion. Although the recent pandemic exposed and accentuated steep inequalities within our society, efforts to rebuild offer the opportunity to re-envision societal resilience and policy to reduce multiple forms of inequality for our collective benefit.

In this conceptual article, we explore allyship as the intended result of participation in LGBTQ+ social justice education interventions on college campuses, often called Safe Zone or Safe Space trainings. We contextualize how these trainings align with Boyer's (1990) concepts of teaching and learning in student affairs practice. We argue how the token of completion (sticker or other symbol) distracts from a transformative educational experience to a commodification of allyship. We offer Love's (2018) liberatory consciousness as a more expansive conceptualization of allyship to sustain efforts for individuals to grapple with dynamics of power, privilege, and oppression.

Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1+ profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.

ObjectiveThis study aimed to understand how periodic shifts in financial cutbacks and fears of contracting COVID-19 contributed to children's externalizing behaviors due to increases in maternal stress among low-income Latina mothers during the first 10 months of the COVID-19 pandemic.BackgroundThe COVID-19 pandemic caused widespread health, economic, and psychological consequences for families and children. The Latino community is particularly vulnerable to the economic and health risks of this pandemic as a consequence of systemic oppression. The family stress model suggests that these family stressors will have psychological repercussions to parents, and downstream behavioral consequences to children.MethodWe examined both the within- and between-person impacts of worry surrounding contracting the virus and the economic consequences of the pandemic on maternal stress and child externalizing behaviors. Participants were 73 Latina mothers who completed assessments an average eight times across the first  10 months of the COVID-19 pandemic. At each assessment time, the mother was asked about worries surrounding contracting the virus, economic cutbacks the family was making, her perceived stress, and her child's externalizing behaviors during a brief phone call.ResultsBetween-families, higher economic cutbacks indirectly increased child externalizing behaviors through maternal stress. The within-family model revealed that at assessments when mothers expressed greater worry about contracting the COVID-19 virus, they also reported greater stress. Further, at the within-person level, a mother's greater experience of stress was associated with greater reports of child externalizing behaviors, though the indirect association between COVID-19 contract worry and child externalizing behaviors through maternal stress was not significant.ConclusionsAcross the first 10 months of the COVID-19 pandemic, the children in Latino families participating in this research exhibited more externalizing behaviors among families that engaged in more financial cutbacks as a function maternal stress. However, periodic spikes in Latina mothers' fears of contracting COVID-19 contributed to periodic spikes in stress, which predicted periodic spikes in child externalizing behaviors.ImplicationsGreater effort toward social policy that provides economic support for vulnerable families before periods of increased societal stress and greater protections for workers with limited sick leave and schedule flexibility will help promote resilience to future crises among low-income Latino families.

Today, close to 300 graduate-level higher education and student affairs (HESA) programs exist nationally, and the Council for the Advancement of Standards (CAS) recommends studying the historical context of higher education as part of the curriculum. The strong social justice emphasis within HESA programs offers a valuable hook for introducing the complexities of the past and the craft of the historian. Research on the history of higher education has expanded in the last decade and is beginning to reshape the field, including current explorations of the relationship between institutions of higher education, slavery, and racism. For this study, the authors surveyed HESA programs nationally to understand the current landscape of history of higher education courses and conducted follow-up interviews with twenty-eight faculty. Drawing upon this rich data, this article examines the ways in which history of higher education instructors worked through the lens of social justice to make history relevant for graduate students outside of the discipline of history and to foster an appreciation of history as an iterative process involving analysis, evaluation, and interpretation of past events.

Actions that are chosen have properties that distinguish them from actions that are not. Of the nearly infinite possible actions that can achieve any given task, many of the unchosen actions are irrelevant, incorrect, or inappropriate. Others are relevant, correct, or appropriate but are disfavored for other reasons. Our research focuses on the question of what distinguishes actions that are chosen from actions that are possible but are not chosen. We review studies that use simple preference methods to identify factors that contribute to action choices, especially for object manipulation tasks. We can determine which factors are especially important through simple behavioral experiments.

Activation of PI3K/AKT pathway correlates with poor prognosis in patients with neuroblastoma. Our previous studies have demonstrated that PI3K/AKT signaling is critical for the oncogenic transformations induced by gastrin-releasing peptide (GRP) and its receptor, GRP-R, in neuroblastoma. Moreover, PI3K/AKT-dependent oncogenic transformations require N-myc, an extensively studied oncogene in neuroblastoma. Whether AKT directly regulates the expression of N-myc oncogene is yet to be determined. Here, we report a novel finding that of the three AKT isoforms, AKT2 specifically regulated N-myc expression in neuroblastoma cells. We also confirmed that GRP-R is upstream of AKT2 and in turn, regulated N-myc expression via AKT2 in neuroblastoma cells. Functional assays demonstrated that attenuation of AKT2 impaired cell proliferation and anchorage-independent cell growth, and decreased the secretion of angiogenic factor VEGF in vitro. Furthermore, silencing AKT2 inhibited migration and invasion of neuroblastoma cells in vitro. Xenografts established by injecting AKT2 silenced human neuroblastoma cells into murine spleen expressed decreased levels of AKT2 and resulted in fewer liver metastases compared to controls in vivo. Hence, our study highlights the potential molecular mechanism(s) mediating the oncogenic role of GRP/GRP-R and demonstrates a novel role for AKT2 in neuroblastoma tumorigenesis, indicating that targeting the GRP/GRP-R/AKT2 axis may be important for developing novel therapeutics in the treatment of clinically aggressive neuroblastoma.