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A very large fetal pericardial teratoma was diagnosed at 28 weeks gestation, prompting urgent multidisciplinary expert consultations to weigh the risks and benefits of various prenatal invasive procedures and preterm delivery for postnatal surgical management. Ultimately, the infant was born by planned cesarean section and underwent immediate cardiopulmonary bypass and surgical resection.

In people living with HIV, Kaposi Sarcoma (KS), a vascular neoplasm caused by KS herpesvirus (KSHV/HHV-8), remains one of the most common malignancies worldwide. Individuals living with HIV, receiving otherwise effective antiretroviral therapy, may present with extensive disease requiring chemotherapy. Hence, new therapeutic approaches are needed. The Wilms' tumor 1 (WT1) protein is overexpressed and associated with poor prognosis in several hematologic and solid malignancies and has shown promise as an immunotherapeutic target. We found that WT1 was overexpressed in >90% of a total 333 KS biopsies, as determined by immunohistochemistry and image analysis. Our largest cohort from ACTG, consisting of 294 cases was further analyzed demonstrating higher WT1 expression was associated with more advanced histopathologic subtypes. There was a positive correlation between the proportion of infected cells within KS tissues, assessed by expression of the KSHV-encoded latency-associated nuclear antigen (LANA), and WT1 positivity. Areas with high WT1 expression showed sparse T-cell infiltrates, consistent with an immune evasive tumor microenvironment. We show that major oncogenic isoforms of WT1 are overexpressed in primary KS tissue and observed WT1 upregulation upon de novo infection of endothelial cells with KSHV. KSHV latent viral FLICE-inhibitory protein (vFLIP) upregulated total and major isoforms of WT1, but upregulation was not seen after expression of mutant vFLIP that is unable to bind IKKƴ and induce NFκB. siRNA targeting of WT1 in latent KSHV infection resulted in decreased total cell number and pAKT, BCL2 and LANA protein expression. Finally, we show that ESK-1, a T cell receptor-like monoclonal antibody that recognizes WT1 peptides presented on MHC HLA-A0201, demonstrates increased binding to endothelial cells after KSHV infection or induction of vFLIP expression. We propose that oncogenic isoforms of WT1 are upregulated by KSHV to promote tumorigenesis and immunotherapy directed against WT1 may be an approach for KS treatment.

Key Clinical Message Multidisciplinary team collaboration in the diagnosis of rare tumors such as parosteal lipoma is highly important, especially when suspicious of malignancy. The use of radiological and physical examinations is imperative to monitor recurrence and quality of life.

A very large fetal pericardial teratoma was diagnosed at 28 weeks’ gestation, prompting urgent multidisciplinary expert consultations to weigh the risks and benefits of various prenatal invasive procedures and preterm delivery for postnatal surgical management. Ultimately, the infant was born by planned cesarean section and underwent immediate cardiopulmonary bypass and surgical resection.

In people living with HIV, Kaposi Sarcoma (KS), a vascular neoplasm caused by KS herpesvirus (KSHV/HHV-8), remains one of the most common malignancies worldwide. Individuals living with HIV, receiving otherwise effective antiretroviral therapy, may present with extensive disease requiring chemotherapy. Hence, new therapeutic approaches are needed. The Wilms' tumor 1 (WT1) protein is overexpressed and associated with poor prognosis in several hematologic and solid malignancies and has shown promise as an immunotherapeutic target. We found that WT1 was overexpressed in >90% of a total 333 KS biopsies, as determined by immunohistochemistry and image analysis. Our largest cohort from ACTG, consisting of 294 cases was further analyzed demonstrating higher WT1 expression was associated with more advanced histopathologic subtypes. There was a positive correlation between the proportion of infected cells within KS tissues, assessed by expression of the KSHV-encoded latency-associated nuclear antigen (LANA), and WT1 positivity. Areas with high WT1 expression showed sparse T-cell infiltrates, consistent with an immune evasive tumor microenvironment. We show that major oncogenic isoforms of WT1 are overexpressed in primary KS tissue and observed WT1 upregulation upon de novo infection of endothelial cells with KSHV. KSHV latent viral FLICE-inhibitory protein (vFLIP) upregulated total and major isoforms of WT1, but upregulation was not seen after expression of mutant vFLIP that is unable to bind IKKƴ and induce NFκB. siRNA targeting of WT1 in latent KSHV infection resulted in decreased total cell number and pAKT, BCL2 and LANA protein expression. Finally, we show that ESK-1, a T cell receptor-like monoclonal antibody that recognizes WT1 peptides presented on MHC HLA-A0201, demonstrates increased binding to endothelial cells after KSHV infection or induction of vFLIP expression. We propose that oncogenic isoforms of WT1 are upregulated by KSHV to promote tumorigenesis and immunotherapy directed against WT1 may be an approach for KS treatment.

We use phenomenology to reflect on the experience of being with others as mediated by screens through videoconferencing platforms, a phenomenon accelerated by the Covid-19 pandemic and social isolation measures. We explore two directions to explain the intersubjective experience of a videoconference. One direction introduces a conceptual background based on previous contributions in phenomenology, while the other one is more speculative: we introduce the novel idea of a phantom other. First, we understand this phenomenon either as a correlate of image consciousness or as a paradoxical perception. Then, we introduce the phantom other using ideas offered in phenomenological descriptions in which the phantom limb appears as a quasi-presence. The phantom other is the same flesh and blood body with whom I co-constitute senses of the world. In a videoconference, the other appears as a whole body with which I coordinate, although she appears as a phantom other.

OBJECTIVE: Sudden gains (SGs) have been found to occur during randomized controlled trials (RCTs) for social anxiety disorder (SAD). Evidence is mixed whether SGs relate to treatment outcome in SAD. We examined SGs in two RCTs for SAD. METHOD: Study 1 (N = 68) examined SGs in individual cognitive-behavioral therapy (CBT), and Study 2 (N = 100) compared SGs in group CBT and Mindfulness-Based Stress Reduction (MBSR). Weekly ratings of social anxiety were used to calculate SGs. The Liebowitz Social Anxiety Scale-Self-Report and the Social Interaction Anxiety Scale were completed at pretreatment, posttreatment, and follow-up to assess outcome. RESULTS: In Study 1, 17.6% of participants experienced a SG. Participants with SGs started and ended treatment with lower social anxiety. SGs were not associated with greater decreases in social anxiety from pre-to posttreatment or 12-month follow-up. In Study 2, SGs occurred in 27% of participants and at comparable rates in MBSR and group CBT. SGs were not associated with changes in social anxiety during treatment in either condition. CONCLUSION: SGs occurred during treatment for SAD. In both RCTs, participants improved regardless of experiencing a SG, suggesting that SGs are not predictive of greater improvement during treatment for SAD.

One of the core features of social anxiety disorder (SAD) is the persistent fear of being evaluated. Fear of evaluation includes fear of negative evaluation (FNE) and fear of positive evaluation (FPE). Few studies have examined the relationship between self-reported FNE and FPE and neural responses to simulated negative and positive social evaluation. In the current study, 56 participants, 35 with SAD and 21 healthy controls, completed questionnaires to assess dimensions of social anxiety including FNE and FPE, as well as symptoms of anxiety and depression. Participants also completed a social evaluation task, which involved viewing people delivering criticism and praise, and a control task, which involved counting asterisks, during functional magnetic resonance imaging. Although whole-brain analyses did not reveal significant associations between self-reported constructs and neural responses to social evaluation, region of interest analyses for the sample as a whole revealed that both FNE and social anxiety symptoms were associated with greater neural responses to both criticism and praise in emotion-processing brain regions, including the amygdala and anterior insula. There were no significant associations between FPE or depressive symptoms and neural responses to criticism or praise for the sample as a whole. Future research should examine the relationship between FNE, FPE, and neural responses to self-referent social evaluation in an unselected sample to assess a full range of fear of evaluation.

Background and Objectives: Poor sleep is prevalent among individuals with social anxiety disorder (SAD) and may affect treatment outcome. We examined whether: (1) individuals with SAD differed from healthy controls (HCs) in sleep quality, (2) baseline sleep quality moderated the effects of treatment (Cognitive-behavioral group therapy [CBGT] vs. mindfulness-based stress reduction [MBSR] vs. waitlist [WL]) on social anxiety, (3) sleep quality changed over treatment, and (4) changes in sleep quality predicted anxiety 12-months post-treatment. Design: Participants were 108 adults with SAD from a randomized controlled trial of CBGT vs. MBSR vs. WL and 38 HCs. Methods: SAD and sleep quality were assessed pre-treatment and post-treatment; SAD was assessed again 12-months post-treatment. Results: Participants with SAD reported poorer sleep quality than HCs. The effect of treatment condition on post-treatment social anxiety did not differ as a function of baseline sleep quality. Sleep quality improved in MBSR, significantly more than WL, but not CBGT. Sleep quality change from pre- to post-treatment in CBGT or MBSR did not predict later social anxiety. Conclusions: MBSR, and not CBGT, improved sleep quality among participants. Other results were inconsistent with prior research; possible explanations, limitations, and implications for future research are discussed. ClinicalTrials.gov identifier: NCT02036658.

This study explores the narratives of eight students who served as journal reviewers on a non-course-related service activity. The aim of this study was to develop an understanding of their experiences. The review board was multi-disciplinary in composition; the majority of its student and faculty members were from communities historically excluded from, and marginalized within, structures of U.S. higher education. Student engagement in learning how to manage an online journal fostered academic socialization through collaboration and collective learning. Students' perceptions of the benefits of working on the journal were categorized across five themes: Academic Career Enhancement, Practicing Faculty Work, Illuminating Faculty Roles, Demystifying Writing for Publication, and Grappling with Prioritization. The benefits and challenges of promoting academic socialization through service learning and mentorship, as well as showing how service engagement can be integrated in academic and personal identities, are discussed.

ObjectivesBlack and Hispanic/Latinx individuals experience a greater burden of mental health symptoms as compared to White individuals in the general population. Examination of ethnoracial disparities and mechanisms explaining these disparities among veterans is still in its nascence. The current study examined perceived everyday discrimination and income as parallel mediators of the association between race/ethnicity and PTSD, depression, and general anxiety symptoms in a sample of White, Black, and Hispanic/Latinx veterans stratified by gender.MethodsA random sample of 3,060 veterans living across the U.S. (oversampled for veterans living in high crime communities) completed a mail-based survey. Veterans completed self-report measures of perceived discrimination via the Everyday Discrimination Scale, PTSD symptoms via the Posttraumatic Stress Disorder Checklist-5, depressive symptoms via the Patient Health Questionnaire, and anxiety symptoms via the Generalized Anxiety Disorder Questionnaire.ResultsModels comparing Black vs. White veterans found that the significant effect of race on PTSD, depression, and anxiety symptoms was mediated by both perceived discrimination and income for both male and female veterans. Results were less consistent in models comparing Hispanic/Latinx vs. White veterans. Income, but not perceived discrimination, mediated the relationship between ethnicity/race and depression and anxiety symptoms, but only among women.ConclusionsResults suggest that discrimination and socioeconomic status are important mechanisms through which marginalized social status negatively impacts mental health.

OBJECTIVE: Network analysis allows us to identify the most interconnected (i.e., central) symptoms, and multiple authors have suggested that these symptoms might be important treatment targets. This is because change in central symptoms (relative to others) should have greater impact on change in all other symptoms. It has been argued that networks derived from cross-sectional data may help identify such important symptoms. We tested this hypothesis in social anxiety disorder. METHOD: We first estimated a state-of-the-art regularized partial correlation network based on participants with social anxiety disorder (n = 910) to determine which symptoms were more central. Next, we tested whether change in these central symptoms were indeed more related to overall symptom change in a separate dataset of participants with social anxiety disorder who underwent a variety of treatments (n = 244). We also tested whether relatively superficial item properties (infrequency of endorsement and variance of items) might account for any effects shown for central symptoms. RESULTS: Centrality indices successfully predicted how strongly changes in items correlated with change in the remainder of the items. Findings were limited to the measure used in the network and did not generalize to three other measures related to social anxiety severity. In contrast, infrequency of endorsement showed associations across all measures. CONCLUSIONS: The transfer of recently published results from cross-sectional network analyses to treatment data is unlikely to be straightforward. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

BACKGROUND AND PURPOSE: Malignant glioma is a highly infiltrative malignancy that causes variable disruptions to the structure and function of the cerebrovasculature. While many of these structural disruptions have known correlative histopathologic alterations, the mechanisms underlying vascular dysfunction identified by resting-state blood oxygen level-dependent imaging are not yet known. The purpose of this study was to characterize the alterations that correlate with a blood oxygen level-dependent biomarker of vascular dysregulation. MATERIALS AND METHODS: Thirty-two stereotactically localized biopsies were obtained from contrast-enhancing (n = 16) and nonenhancing (n = 16) regions during open surgical resection of malignant glioma in 17 patients. Preoperative resting-state blood oxygen level-dependent fMRI was used to evaluate the relationships between radiographic and histopathologic characteristics. Signal intensity for a blood oxygen level-dependent biomarker was compared with scores of tumor infiltration and microvascular proliferation as well as total cell and neuronal density. RESULTS: Biopsies corresponded to a range of blood oxygen level-dependent signals, ranging from relatively normal (z = -4.79) to markedly abnormal (z = 8.84). Total cell density was directly related to blood oxygen level-dependent signal abnormality (P = .013, R2 = 0.19), while the neuronal labeling index was inversely related to blood oxygen level-dependent signal abnormality (P = .016, R2 = 0.21). The blood oxygen level-dependent signal abnormality was also related to tumor infiltration (P = .014) and microvascular proliferation (P = .045). CONCLUSIONS: The relationship between local, neoplastic characteristics and a blood oxygen level-dependent biomarker of vascular function suggests that local effects of glioma cell infiltration contribute to vascular dysregulation.

Abstract Azasugars are monosaccharide analogs in which the ring oxygen is replaced with a nitrogen atom. These well-known glycosidase inhibitors are of interest as therapeutics, yet several aspects of azasugars remain unknown including their distribution, structural diversity, and chemical ecology. The hallmark signature of bacterial azasugar biosynthesis is a three gene cluster (3GC) coding for aminotransferase, phosphatase, and dehydrogenase enzymes. Using the bioinformatics platform Enzyme Similarity Tool (EST), we identified hundreds of putative three gene clusters coding for azasugar production in microbial species. In the course of this work, we also report a consensus sequence for the aminotransferase involved in azasugar biosynthesis as being: SGNXFRXXXFPNXXXXXXXLXVPXPYCXRC. Most clusters are found in Bacillus and Streptomyces species which typically inhabit soil and the rhizosphere, but some clusters are found with diverse species representation such as Photorhabdus and Xenorhabdus which are symbiotic with entomopathogenic nematodes; the human skin commensal Cutibacterium acnes, and the marine Bacillus rugosus SPB7, a symbiont to the sea sponge Spongia officinalis. This pan-taxonomic survey of the azasugar 3GC signature may lead to the identification of new azasugar producers, facilitate studies of their natural functions, and lead to new potential therapeutics.

During the Space Telescope and Optical Reverberation Mapping Project observations of NGC 5548, the continuum and emission-line variability became decorrelated during the second half of the six-month-long observing campaign. Here we present Swift and Chandra X-ray spectra of NGC 5548 obtained as part of the campaign. The Swift spectra show that excess flux (relative to a power-law continuum) in the soft X-ray band appears before the start of the anomalous emission-line behavior, peaks during the period of the anomaly, and then declines. This is a model-independent result suggesting that the soft excess is related to the anomaly. We divide the Swift data into on- and off-anomaly spectra to characterize the soft excess via spectral fitting. The cause of the spectral differences is likely due to a change in the intrinsic spectrum rather than to variable obscuration or partial covering. The Chandra spectra have lower signal-to-noise ratios, but are consistent with the Swift data. Our preferred model of the soft excess is emission from an optically thick, warm Comptonizing corona, the effective optical depth of which increases during the anomaly. This model simultaneously explains all three observations: the UV emission-line flux decrease, the soft-excess increase, and the emission-line anomaly.

We conduct a multiwavelength continuum variability study of the Seyfert 1 galaxy NGC 5548 to investigate the temperature structure of its accretion disk. The 19 overlapping continuum light curves (1158 A oto 9157 A o) combine simultaneous Hubble Space Telescope, Swift, and ground-based observations over a 180 day period from 2014 January to July. Light-curve variability is interpreted as the reverberation response of the accretion disk to irradiation by a central time-varying point source. Our model yields the disk inclination i = 36° ±10° temperature T1 = 44 ±6 ) × 10 3 K at 1 light day from the black hole, and a temperatureradius slope (T ∞r-a) of a = 0.99 ±0.03. We also infer the driving light curve and find that it correlates poorly with both the hard and soft X-ray light curves, suggesting that the X-rays alone may not drive the ultraviolet and optical variability over the observing period. We also decompose the light curves into bright, faint, and mean accretion-disk spectra. These spectra lie below that expected for a standard blackbody accretion disk accreting at L LEdd = 0.1.

Faculty development programs are typically designed to broaden college/university faculty teaching expertise, increase research knowledge, or augment mentoring practice. Other than improved knowledge, skills and confidence levels, long-term benefits remain relatively unknown. The authors reviewed 414 empirical health professions faculty development studies published between 2006-2018; 97 that met inclusion criteria are reported. First, the authors read each paper to ensure a consistent understanding of its goals. Second, the authors provide a descriptive analysis of the categories, methods, and results. Third, the authors provide an overview of other characteristics such as the participants studied, researcher recommendations, elements of analysis, and critique the methods used. The findings showed that there were an overwhelming number of positive outcomes, which suggests that faculty development is beneficial. To improve data collection and increase the use of robust methods, the authors recommend strategies related to measurement types, data sources, research design, and researcher positionality. Improving study procedures may shed light on the creditable benefits of faculty development initiatives and lend support for continuous resource commitment.

The purpose of our study was to report the long-term impact or training efficacy of mentor training from the perspective of mentees at a single institution. Twelve mentees representing seven faculty graduates of a mentor training program were interviewed. Data were analyzed using grounded theory. Training resulted in improved goal setting and meeting frequency and increased attentiveness to career development. Results related to communication styles shared expectations, difficult conversations, and promoting scientific independence were mixed. Changes to instructional practices and the implementation of active learning experiences are recommended to enhance the efficacy of the program and to address mentee's professional developmental needs.

The purpose of our study was to assess how an academic health center (AHC) mentor academy program affected mentor competence and optimized the mentor-mentee relationship. Mixed methods were used to assess the effectiveness of an AHC mentor program at a clinical translational science institute (CTSI). Twenty biomedical research faculty mentors took a validated survey and submitted reflective writings to discover if they corroborated or refuted statistically significant survey results. There was a significant improvement in participants' confidence of mentor skills, integral mentoring quality, and the extent to which they fulfill mentees' expectations. Males provided constructive feedback and helped mentees develop goal strategies more often compared to females. Reflective writings supported these findings yet refuted two survey findings. The use of a mixed methods approach offers novel insight into how mentoring programs benefit translational research mentoring capacity building and raises questions about the sole use of surveys as evidence of program effectiveness.