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

Exploring Child Welfare Workers\u27 Attitudes and Practice With Fathers

This cross-sectional study explored child welfare agency workers\u27 attitudes and practice regarding working with fathers whose children are at-risk for abuse and neglect. Agency workers completed a questionnaire about their attitudes towards working with fathers, their knowledge of barriers to fathers\u27 engagement, and their experiences with their own fathers. They also completed open-ended items about services and supports they felt would be most helpful to fathers. A content analysis of the data revealed critical themes for four areas that workers felt could be enhanced to effectively engage fathers: (a) use diligent efforts that ensure fathers are present to contribute, (b) provide equitable services, supports, and policies for fathers, (c) address father-specific needs, and (d) promote a positive worker-father relationship. The findings provide insight into ways that social workers can maximize fathers\u27 strengths and reduce their challenges

Discrepant Alcohol Use, Intimate Partner Violence, and Relationship Adjustment Among Lesbian Women and Their Same-Sex Intimate Partners

This study examined the association between relationship adjustment and discrepant alcohol use among lesbian women and their same-sex intimate partners after controlling for verbal and physical aggression. Lesbian women (N = 819) who were members of online marketing research panels completed an online survey in which they reported both their own and same-sex intimate partner\u27s alcohol use, their relationship adjustment, and their own and their partner\u27s physical aggression and psychological aggression (i.e., verbal aggression and dominance/isolation). Partners\u27 alcohol use was moderately correlated. Discrepancy in alcohol use was associated with poorer relationship adjustment after controlling for psychological aggression and physical aggression. Results are discussed in terms of the similarity and differences with previous literature primarily focused on heterosexual couples

Nematode Spatial and Ecological Patterns from Tropical and Temperate Rainforests

Large scale diversity patterns are well established for terrestrial macrobiota (e.g. plants and vertebrates), but not for microscopic organisms (e.g. nematodes). Due to small size, high abundance, and extensive dispersal, microbiota are assumed to exhibit cosmopolitan distributions with no biogeographical patterns. This assumption has been extrapolated from local spatial scale studies of a few taxonomic groups utilizing morphological approaches. Recent molecularly-based studies, however, suggest something quite opposite. Nematodes are the most abundant metazoans on earth, but their diversity patterns are largely unknown. We conducted a survey of nematode diversity within three vertical strata (soil, litter, and canopy) of rainforests at two contrasting latitudes in the North American meridian (temperate: the Olympic National Forest, WA, U.S.A and tropical: La Selva Biological Station, Costa Rica) using standardized sampling designs and sample processing protocols. To describe nematode diversity, we applied an ecometagenetic approach using 454 pyrosequencing. We observed that: 1) nematode communities were unique without even a single common species between the two rainforests, 2) nematode communities were unique among habitats in both rainforests, 3) total species richness was 300% more in the tropical than in the temperate rainforest, 4) 80% of the species in the temperate rainforest resided in the soil, whereas only 20% in the tropics, 5) more than 90% of identified species were novel. Overall, our data provided no support for cosmopolitanism at both local (habitats) and large (rainforests) spatial scales. In addition, our data indicated that biogeographical patterns typical of macrobiota also exist for microbiota

Inseguro: Policiamento sob o capitalismo racial

This paper outlines the nature of policing under racial capitalism in the USA and makes a case for the abolition of the police. It reviews the history of the police in the country, focusing particularly on racist ideas and practices against African Americans. It includes analysis of recent cases of police murders of black people and discusses the diverse movements for racial justice, including Black Lives Matter. It relies on an ample base of historical and contemporary evidence and widely utilizes both the academic literature in history, sociology and political science and journalistic sources. Tradução inédita em português do artigo originalmente publicado em Spectre: A Marxist Journal em 2020.Traduzido por Sean PurdyEste artigo descreve a natureza do policiamento sob o capitalismo racial nos EUA e defende a abolição da polícia. Ele faz um levantamento da história da polícia no país, concentrando-se principalmente nas ideias e práticas racistas contra os afro-americanos. Inclui a análise de casos recentes de assassinatos de negros pela polícia e discute os diversos movimentos por justiça racial, incluindo Black Lives Matter. A análise se baseia em uma ampla base de evidências históricas e contemporâneas e utiliza a literatura acadêmica em história, sociologia e ciência política, bem como fontes jornalísticas

Bigger Than You Think: The Economic Impact of Microbusinesses in the U.S.

AEO embarked on a two-year study to build the data and the evidence base that documents the economic impact of microbusiness in the U.S. The evidence gathered paints a compelling portrait of a remarkably vigorous microbusiness community that plays an essential role in American economic productivity

Structural diversity in tetrakis(4-pyridyl)porphyrin supramolecular building blocks

The authors would like to thank the University of Alabama Department of Chemistry and the University of Missouri-Columbia Department of Chemistry for support of this work.In memory of a pioneer in crystal engineering, Prof. Israel Goldberg, we report a series of new framework solids, based on the ligand tetrakis(4–pyridyl)porphyrin (TPyP). Spontaneous reactions of TPyP with seven different metal salts under liquid-liquid diffusion at ambient temperature show that the formation of ionic compounds is preferred to coordination polymers due to increased conformational freedom. Two coordination networks, {(HgI2)2(TPyP)}n·4nCHCl3∙2nTCE (TCE = 1,1,2,2–tetrachloroethane), and {(Ba(μ1,1–NCS)(μ1,1,3–NCS)(H2O)(MeCN))2(TPyP)}n·4nH2O, displayed a new isomeric form of the known [(HgI2)2(TPyP)]∞ polymeric motif, and a two-dimensional honeycomb polymeric motif linked by hydrogen-bonding into a three dimensional moganite (mog) net, respectively. Four protonated porphyrinic salts, [H3TPyP][PF6]3∙0.5TCE, [H2TPyP][I3]2·2MeOH, [H4TPyP][UO2Cl4]2·6MeCN, and [H4TPyP][Th(NO3)6][NO3]2, were observed which hydrogen bond to give one- or two-dimensional networks, or in the case of [H4TPyP][UO2Cl4]2·6MeCN, a discrete dinuclear hydrogen-bonded complex. In one case, a neutral, hydrogen-bonded complex, Ce(NO3)3(MeOH)3(H2O)·TPyP·TCE·H2O, was formed which adopts a three-dimensional, self-penetrated variant of the face-centered cubic (fcc) network. These new structures represent hybrid organic-inorganic crystalline compounds in which the multidentate porphyrin units, having both hydrogen bonding, as well as coordination functionalities, are interlinked through the inorganic connectors into self-assembled three-dimensional architectures. This work shows the relative stability of noncovalently bound vs. coordination networks as well as the effective potential of the TPyP building block to construct supramolecular assemblies in the presence or absence of coordinating ions as linkers.PostprintPeer reviewe

Empirical Investigation of a Model of Sexual Minority Specific and General Risk Factors for Intimate Partner Violence Among Lesbian Women

Objective: This study proposed and tested the first conceptual model of sexual minority specific (discrimination, internalized homophobia) and more general risk factors (perpetrator and partner alcohol use, anger, relationship satisfaction) for intimate partner violence among partnered lesbian women. Method: Selfidentified lesbian women (N = 1,048) were recruited from online market research panels. Participants completed an online survey that included measures of minority stress, anger, alcohol use and alcohol-related problems, relationship satisfaction, psychological aggression, and physical violence. Results: The model demonstrated good fit and significant links from sexual minority discrimination to internalized homophobia and anger, from internalized homophobia to anger and alcohol problems, and from alcohol problems to intimate partner violence. Partner alcohol use predicted partner physical violence. Relationship dissatisfaction was associated with physical violence via psychological aggression. Physical violence was bidirectional. Conclusions: Minority stress, anger, alcohol use, and alcohol-related problems play an important role in perpetration of psychological aggression and physical violence in lesbian women\u27s intimate partner relationships. The results of this study provide evidence of potentially modifiable sexual minority specific and more general risk factors for lesbian women\u27s partner violence

Gene Expression Associated with Disease Resistance and Long-Term Growth in a Reef-Building Coral

Rampant coral disease, exacerbated by climate change and other anthropogenic stressors, threatens reefs worldwide, especially in the Caribbean. Physically isolated yet genetically connected reefs such as Flower Garden Banks National Marine Sanctuary (FGBNMS) may serve as potential refugia for degraded Caribbean reefs. However, little is known about the mechanisms and trade-offs of pathogen resistance in reef-building corals. Here, we measure pathogen resistance in Montastraea cavernosa from FGBNMS. We identified individual colonies that demonstrated resistance or susceptibility to Vibrio spp. in a controlled laboratory environment. Long-term growth patterns suggest no trade-off between disease resistance and calcification. Predictive (pre-exposure) gene expression highlights subtle differences between resistant and susceptible genets, encouraging future coral disease studies to investigate associations between resistance and replicative age and immune cell populations. Predictive gene expression associated with long-term growth underscores the role of transmembrane proteins involved in cell adhesion and cell-cell interactions, contributing to the growing body of knowledge surrounding genes that influence calcification in reef-building corals. Together these results demonstrate that coral genets from isolated sanctuaries such as FGBNMS can withstand pathogen challenges and potentially aid restoration efforts in degraded reefs. Furthermore, gene expression signatures associated with resistance and long-term growth help inform strategic assessment of coral health parameters