Immunotherapy in hepatocellular carcinoma: the complex interface between inflammation, fibrosis, and the immune response.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide and confers a poor prognosis. Beyond standard systemic therapy with multikinase inhibitors, recent studies demonstrate the potential for robust and durable responses from immune checkpoint inhibition in subsets of HCC patients across disease etiologies. The majority of HCC arises in the context of chronic inflammation and from within a fibrotic liver, with many cases associated with hepatitis virus infections, toxins, and fatty liver disease. Many patients also have concomitant cirrhosis which is associated with both local and systemic immune deficiency. Furthermore, the liver is an immunologic organ in itself, which may enhance or suppress the immune response to cancer arising within it. Here, we explore the immunobiology of the liver from its native state to chronic inflammation, fibrosis, cirrhosis and then to cancer, and summarize how this unique microenvironment may affect the response to immunotherapy

Local Bureaucrats and Climate Change Adaptation

In local communities across the United States, local government officials – specifically local bureaucrats – are faced with the realities of a changing climate which include severe storms, prolonged droughts, larger and more damaging floods, and more. Simultaneously, the issue of climate change is incredibly polarized in US politics with one side claiming it is not happening (or if it is happening it is not human caused) and the other framing the issue as the direst threat (or close to it) facing the planet. This dissertation examines a empirical puzzle, asking whether and how local bureaucrats respond to the threat of climate change in their communities. I find that many, but not all, local bureaucrats are responding by developing climate adaptation plans and considering policies which might help their communities avoid the consequences of climate change. They are not acting alone, they work with support from the federal or state government, other bureaucrats, or multi-stakeholder organizations which allow them to access resources and gain political support when they would otherwise not have it. Climate change adaptation, like other emergency and disaster management policies, does not garner much attention from local politicians unless there currently is a disaster the community is responding to or recovering from that forces their attention. Throughout this project, I examine how local bureaucrats step out of their conventional role as policy implementors to shape local agendas and formulate policy – policymaking roles often dominated by elected politicians, members of the media, and advocacy organizations. I argue that local bureaucrats occupy the perfect institutional role for shaping the development of climate adaptation in local governments. They have issue-specific knowledge, making them emergency management and climate adaptation experts (or at least the actors with the most expertise of this kind in local government). This often leads to elected officials deferring to bureaucrats when policies and plans need to be written, like emergency management plans, land use plans. When bureaucrats write these plans, they have the opportunity to incorporate climate adaptation provisions. Local bureaucrats also hold institutional knowledge in local governments. They are more likely to know state and federal policies and requirements, which may encourage climate adaptation (e.g. the Obama Administration’s efforts through the Federal Emergency Management Agency (FEMA) to encourage local adaptation policy). Local bureaucrats are also more motivated than elected officials to address climate change. I find that the bureaucrats in this study were aware of the political debates around climate change, but they often adopted a position which separated local adaptation efforts from the polarizing debate around what causes climate change (i.e. who or what is responsible for the problem). This enabled them to address their communities’ needs to adapt without drawing opposition from conservative members of their communities who do not think climate change is happening or caused by human activities. I also address the intergovernmental environment local bureaucrats respond to: specifically, their relationship with their state governments and the federal government. Even though states and the federal government wield significant influence over local governments – mostly through the control of resources – local bureaucrats do not avoid climate adaptation solely because the state government disapproves. A few cases demonstrate that state governments’ and FEMA’s encouragement to address climate adaptation impacted local bureaucrats’ decisions to create adaptation policies. However, it was not the only or the most important influence in local bureaucrats’ decision-making. In sum, this project demonstrates that local bureaucrats are important actors in the development of local climate adaptation policy. Local bureaucrats’ efforts alone are not enough to adapt to climate change, but they are an important first step when politicians cannot or will not act. While only climate adaptation policy was studied in this project, these findings speak to the important role bureaucrats play in creating policy when elected officials do not – either because the issues have low saliences, are highly technical, or are politically polarized

Being a Prison Chaplain in a Godless Country: An Exploration of the Czech Correctional Chaplaincy

Prison chaplaincy, along with religiosity in the criminal justice system, are widely researched in the US (e.g.,Maruna, Wilson, & Curran, 2006; Sundt & Cullen, 1998). The Czech Republic remains one of the most secular countries in the world; about 72% of the population does not identify with any religion or church (Pew Research Center, 2017). The religious landscape in the country lead to prison chaplains being a largely unexplored population, existing in the tension between a total institution and their church. Due to the lack of research concerning this population in the Czech republic, this study aims to examine the position and identify the role of a prison chaplain in the context of Czech prisons.https://digitalscholarship.unlv.edu/gcua_symposium/1009/thumbnail.jp

Expressions 2011

https://openspace.dmacc.edu/expressions/1023/thumbnail.jp

Annotated Bibliography of Research in the Teaching of English

Since 2003, RTE has published the annual “Annotated Bibliography of Research in the Teaching of English,” a list of curated and annotated works reviewed and selected by a large group of dedicated educator-scholars in our field. The goal of the annual bibliography is to offer a synthesis of the research published in the area of English language arts within the past year for RTE readers’ consideration. Abstracted citations and those featured in the “Other Related Research” sections were published, either in print or online, between June 2020 and June 2021. The bibliography is divided into nine sections, with some changes to the categories this year in response to the ever-evolving nature of research in the field. Small teams of scholars with diverse research interests and background experiences in preK–16 educational settings reviewed and selected the manuscripts for each section using library databases and leading scholarly journals. Each team abstracted significant contributions to the body of peer-reviewed studies that addressed the current research questions and concerns in their topic area

COVID-19 related experiences among college students with and without disabilities: Psychosocial impacts, supports, and virtual learning environments

This cross-sectional analysis estimated differences, based on disability status, in college students' (n = 777) experiences during the COVID-19 pandemic. Data were modeled using t-tests and logistic regression. Most participants were white (86.2%), and women (66.4%). The mode age was 23. A third (35.6%) had at least one disability. Students reported high rates of psychosocial distress, like fear of contracting (59.7%) and spreading (74.3%) COVID-19, worry about friends and family (83.7%), and increased anxiety (72.5%), depression (59.9%), and substance use (24.7%). Forty-two percent (42.2%) were scared they would miss out on their education through virtual classes. About a third feared forgetting assignments (34.1%) and making mistakes (33.9%). Fewer students expressed apprehension about (27.9%) and intimidation by (26.3%) virtual learning. Only 17.2% would continue taking virtual classes after the pandemic. Students with disabilities (M = 12.4, SD = 4.1) experienced more psychosocial stressors compared to students without disabilities (M = 9.9, SD = 4.2), [t(775) = 7.86, p < 0.001]. In adjusted models, disabled students were more than twice as likely to experience worry about medical bills (OR = 2.29), loneliness (OR = 2.09), and increased anxiety (OR = 2.31). They were also more than three times as likely to report increased depression (OR = 3.51) and changes in sexual activity (OR = 3.12). However, students with disabilities (M = 1.5, SD = 1.1) also reported receiving more support compared to their non-disabled classmates (M = 1.1, SD = 1.1), [t(775) = 6.06, p < 0.001]. Disabled students were more likely to feel a sense of contributing to society by following precautions (OR = 1.80) and receive support from family and others (emotional support: OR = 2.01, financial support: OR = 2.04). Interestingly, no significant differences were found in students' feelings associated with online or virtual learning [t(526.08) = 0.42, p = 0.68]. Students with disabilities, though, trended toward reporting negative experiences with virtual learning. In conclusion, students with disabilities were disproportionately affected by COVID-19 stressors, but also expressed more support and a sense of contributing to the common good.Peer reviewedCommunity Health Sciences, Counseling and Counseling PsychologyEducational PsychologyIntegrative Biolog

Annotated Bibliography of Research in the Teaching of English

Since 2003, RTE has published the annual “Annotated Bibliography of Research in the Teaching of English,” and we are proud to share these curated and annotated citations once again. The goal of the annual bibliography is to offer a synthesis of the research published in the area of English language arts within the past year that may be of interest to RTE readers. Abstracted citations and those featured in the “Other Related Research” sections were published, either in print or online, between June 2019 and June 2020. The bibliography is divided into nine subject area sections. A three-person team of scholars with diverse research interests and background experiences in preK–16 educational settings reviewed and selected the manuscripts for each section using library databases and leading empirical journals. Each team abstracted significant contributions to the body of peer-reviewed studies that addressed the current research questions and concerns in their topic area

Trust in and use of COVID-19 information sources differs by health literacy among college students

People’s health information-seeking behaviors differ by their health literacy levels. This study assessed the relationship between health literacy and college students’ levels of trust in and use of a range of health information sources of COVID-19. We collected data from August to December 2020 among college students (n = 763) through an online survey. We used a health literacy measure containing three self-reported survey questions, developed by the CDC. We assessed the extent to which participants trusted and used any of the sixteen different sources of information about COVID-19. Respondents reported high levels of trusting and using COVID-19 information from the CDC, health care providers, the WHO, state/county/city health departments, and official government websites when compared to other sources. After controlling for demographic characteristics (i.e., gender, age, race, ethnicity, and income), those who reported having lower health literacy were significantly less likely to trust and use COVID-19 information from these health authorities when compared to participants who reported having higher health literacy. Students with lower self-reported health literacy indicated not trusting or using official health authority sources for COVID-19 information. Relying on low-quality information sources could create and reinforce people’s misperceptions regarding the virus, leading to low compliance with COVID-19-related public health measures and poor health outcomes.Hlth Sci, Couns and Couns Psyc (HCCP

Neuromuscular Electrical Stimulation as a Method to Maximize the Beneficial Effects of Muscle Stem Cells Transplanted into Dystrophic Skeletal Muscle

Cellular therapy is a potential approach to improve the regenerative capacity of damaged or diseased skeletal muscle. However, its clinical use has often been limited by impaired donor cell survival, proliferation and differentiation following transplantation. Additionally, functional improvements after transplantation are all-too-often negligible. Because the host microenvironment plays an important role in the fate of transplanted cells, methods to modulate the microenvironment and guide donor cell behavior are warranted. The purpose of this study was to investigate whether the use of neuromuscular electrical stimulation (NMES) for 1 or 4 weeks following muscle-derived stem cell (MDSC) transplantation into dystrophic skeletal muscle can modulate the fate of donor cells and enhance their contribution to muscle regeneration and functional improvements. Animals submitted to 4 weeks of NMES after transplantation demonstrated a 2-fold increase in the number of dystrophin+ myofibers as compared to control transplanted muscles. These findings were concomitant with an increased vascularity in the MDSC+NMES group when compared to non-stimulated counterparts. Additionally, animals subjected to NMES (with or without MDSC transplantation) presented an increased maximal specific tetanic force when compared to controls. Although cell transplantation and/or the use of NMES resulted in no changes in fatigue resistance, the combination of both MDSC transplantation and NMES resulted in a faster recovery from fatigue, when compared to non-injected and non-stimulated counterparts. We conclude that NMES is a viable method to improve MDSC engraftment, enhance dystrophic muscle strength, and, in combination with MDSC transplantation, improve recovery from fatigue. These findings suggest that NMES may be a clinically-relevant adjunct approach for cell transplantation into skeletal muscle. © 2013 Distefano et al

Harnessing peripheral DNA methylation differences in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to reveal novel biomarkers of disease

Background Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease impacting an estimated 44 million adults worldwide. The causal pathology of AD (accumulation of amyloid-beta and tau), precedes hallmark symptoms of dementia by more than a decade, necessitating development of early diagnostic markers of disease onset, particularly for new drugs that aim to modify disease processes. To evaluate differentially methylated positions (DMPs) as novel blood-based biomarkers of AD, we used a subset of 653 individuals with peripheral blood (PB) samples in the Alzheimer’s disease Neuroimaging Initiative (ADNI) consortium. The selected cohort of AD, mild cognitive impairment (MCI), and age-matched healthy controls (CN) all had imaging, genetics, transcriptomics, cerebrospinal protein markers, and comprehensive clinical records, providing a rich resource of concurrent multi-omics and phenotypic information on a well-phenotyped subset of ADNI participants. Results In this manuscript, we report cross-diagnosis differential peripheral DNA methylation in a cohort of AD, MCI, and age-matched CN individuals with longitudinal DNA methylation measurements. Epigenome-wide association studies (EWAS) were performed using a mixed model with repeated measures over time with a P value cutoff of 1 × 10−5 to test contrasts of pairwise differential peripheral methylation in AD vs CN, AD vs MCI, and MCI vs CN. The most highly significant differentially methylated loci also tracked with Mini Mental State Examination (MMSE) scores. Differentially methylated loci were enriched near brain and neurodegeneration-related genes (e.g., BDNF, BIN1, APOC1) validated using the genotype tissue expression project portal (GTex). Conclusions Our work shows that peripheral differential methylation between age-matched subjects with AD relative to healthy controls will provide opportunities to further investigate and validate differential methylation as a surrogate of disease. Given the inaccessibility of brain tissue, the PB-associated methylation marks may help identify the stage of disease and progression phenotype, information that would be central to bringing forward successful drugs for AD