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Background The clinical success of immune checkpoint inhibitors demonstrates that reactivation of the human immune system delivers durable responses for some patients and represents an exciting approach for cancer treatment. An important class of preclinical in vivo models for immuno-oncology is immunocompetent mice bearing mouse syngeneic tumors. To facilitate translation of preclinical studies into human, we characterized the genomic, transcriptomic, and protein expression of a panel of ten commonly used mouse tumor cell lines grown in vitro culture as well as in vivo tumors. Results Our studies identified a number of genetic and cellular phenotypic differences that distinguish commonly used mouse syngeneic models in our study from human cancers. Only a fraction of the somatic single nucleotide variants (SNVs) in these common mouse cell lines directly match SNVs in human actionable cancer genes. Some models derived from epithelial tumors have a more mesenchymal phenotype with relatively low T-lymphocyte infiltration compared to the corresponding human cancers. CT26, a colon tumor model, had the highest immunogenicity and was the model most responsive to CTLA4 inhibitor treatment, by contrast to the relatively low immunogenicity and response rate to checkpoint inhibitor therapies in human colon cancers. Conclusions The relative immunogenicity of these ten syngeneic tumors does not resemble typical human tumors derived from the same tissue of origin. By characterizing the mouse syngeneic models and comparing with their human tumor counterparts, this study contributes to a framework that may help investigators select the model most relevant to study a particular immune-oncology mechanism, and may rationalize some of the challenges associated with translating preclinical findings to clinical studies.

Background Socio‐cultural and language‐appropriate study materials and instruments are critical for accurate assessment of cognitive function in people from diverse backgrounds. Most research uses cognitive tests based on Western, industrialized, English‐speaking cultures and may not reflect global experiences. The purpose of this study was to describe the translations of study materials and cultural adaptations that were developed for the Asian Cohort for Alzheimer’s Disease (ACAD). Methods Multi‐lingual researchers, clinicians, and community leaders with extensive practical translation experience created materials and instruments in accordance with World Health Organization (WHO) guidelines, using a translation process that consisted of preparing materials, translating materials, conducting a committee review, conducting a pretest (as appropriate), and conducting necessary revisions. The ACAD study population speaks Chinese (Simplified and Traditional), Korean, or Vietnamese. The majority of instruments in the protocol harmonize with the National Alzheimer’s Coordinating Center purposefully, warranting both literal and conceptually cultural‐appropriate translations for our older Asian American and Asian Canadian participants. Results We have developed Asian language versions of the ACAD informed consent, data collection packet, and community outreach materials for all our target groups. Many cognitive tools had been previously translated into Asian languages and made minor modifications. Some items required cultural adaptations to reflect the socio‐cultural background of the targeted Asian languages, e.g., the types of physical activities or dietary choices surveyed. Conclusion This multi‐stage translation process accounts for the distinctive socio‐cultural and language backgrounds of each Asian population. Alzheimer’s disease and related dementias researchers interested in engaging with these populations may apply this translation process to reduce health disparities in these underrepresented populations. To ensure fidelity across different languages, ACAD will continue to engage in this comprehensive translation process with our diverse community stakeholders.

When transporting yogurt, vibrations and sharp movements can damage its quality. This study developed a model to connect the changes in yogurt quality with the transportation distance as simulated by the total number of vibrations. Linear regression analysis showed that there was a significant negative correlation between the water holding capacity and hardness of the yogurt over the same transport distance (p < 0.05). The yogurt vibration model was established by combining principal component analysis with a Back-Propagation Artificial Neural Network model. The number of training iterations was 2669, with a correlation coefficient of 0.96611, indicating that the model was reliable. The optimal transportation distance was determined to be within the range from 20 rpm for 8 h to 100 rpm for 4 h.

Seroprevalence studies provide useful information about the proportion of the population either vaccinated against SARS-CoV-2, previously infected with the virus, or both. Numerous studies have been conducted in the United States, but differ substantially by dates of enrollment, target population, geographic location, age distribution, and assays used. This can make it challenging to identify and synthesize available seroprevalence data by geographic region or to compare infection-induced versus combined infection- and vaccination-induced seroprevalence. To facilitate public access and understanding, the National Institutes of Health and the Centers for Disease Control and Prevention developed the COVID-19 Seroprevalence Studies Hub (COVID-19 SeroHub, https://covid19serohub.nih.gov/ ), a data repository in which seroprevalence studies are systematically identified, extracted using a standard format, and summarized through an interactive interface. Within COVID-19 SeroHub, users can explore and download data from 178 studies as of September 1, 2022. Tools allow users to filter results and visualize trends over time, geography, population, age, and antigen target. Because COVID-19 remains an ongoing pandemic, we will continue to identify and include future studies. Measurement(s) SARS-CoV-2 seroprevalence Technology Type(s) serology assay Factor Type(s) geography • age • sex • race/ethnicity • Collection date Sample Characteristic - Organism Homo sapiens Sample Characteristic - Environment spatiotemporal region Sample Characteristic - Location United States of America

Compulsive gamblers and their family members have had a long, unsuccessful history of lawsuits against the gambling industry in the United States. With the emergence of online gambling and sports betting, the gambling industry is becoming less and less regulated, preying on compulsive gamblers and nurturing their addiction for profit. Although gambling is diagnosed as a legitimate addiction disorder in medicine, the law has been slow and even reluctant to recognize and grant legal protection to addicted gambler plaintiffs. However, the recent wave of litigation brought against a similar addiction-for-profit industry, the opioid industry, seems to suggest there is an alternative solution for compulsive gambler plaintiffs to seek relief for the gambling industry's fraudulent and deceptive practices. This Comment argues that compulsive gamblers should allege that the gambling industry used the United States mail system to defraud them in violation of the civil Racketeer Influenced and Corrupt Organizations Act (RICO). First, this Comment highlights the deceptive practices of the gambling industry and explains why it has continued to profit without any legal accountability thus far. Through the mutually beneficial relationship between the state governments and the casinos, state governments can receive a cut of revenue generated each year and even hold proprietary interests in the casino machines' software. In return, casinos are able to run their businesses with minimal regulations and legal immunity from self-exclusion programs. Next, this Comment breaks new ground by arguing that compulsive gamblers can leverage recent RICO litigation against opioid pharmaceutical companies in their own RICO claims. Compulsive gamblers bringing civil RICO claims against gambling companies can make comparisons between the opioid industry's fraudulent industry-wide tactics and the gambling industry's practices. Finally, this Comment highlights the new boom of sports betting after its legalization in 2018. Following the establishment of a new gambling industry, the timing is perfect for compulsive gambler plaintiffs to pursue legal accountability in the courts. Furthermore, the hidden tool of internal discovery documents released to the public will aid compulsive gamblers in fighting for legal recourse and government regulatory action to stop the manipulations of the gambling industry.

As the popular culture-driven “Korean Wave” (Hallyu) continues to gain attention worldwide, many attempts have been made to incorporate various other aspects of Korean culture within it, including traditional Korean music (kugak). Thus far, most top-down cultural policy has continued to focus on the initial contact with kugak rather than encouraging more in-depth engagement. However, local grassroots efforts have begun to develop into dedicated aficionado groups, who are not only expert listeners but also beginning to foray into performance. Addressing the case studies of the Francophone p’ansori (sung storytelling) scene and the K-Community Festival, I explore the potential for the kind of in-depth engagement seen at the grassroots level to also be employed on the cultural policy level.

Ophiostoma bicolor is a pathogenic fungus associated with bark beetles that can cause serious damage to host plants. In this study, a novel fungal virus, “Ophiostoma bicolor endornavirus 1” (ObEV1), was obtained from O. bicolor, and its complete genome sequence was determined. ObEV1 has a single-stranded positive-sense (+ ss) RNA genome of 10,119 nucleotides. Sequence annotation and comparison showed that the viral genome has a single large open reading frame (ORF) encoding a polyprotein of 362.48 kDa. The polyprotein contains seven conserved domains: RNA-dependent RNA polymerase (RdRp), viral RNA helicase 1 (VHel1), viral methyltransferase (VMet), DEAD-like helicase (DEXDc), gliding-GltJ (G1), large tegument protein UL36 (PHA), and YlqF-related-GTPase (Y). Sequence comparisons and phylogenetic analysis showed that ObEV1 is a novel mycovirus belonging to the genus Betaendornavirus of the family Endornaviridae. This is the first report of a mycovirus in the ophiostomatoid fungus O. bicolor.

Macroautophagy is a key stress-response pathway that can suppress or promote tumorigenesis depending on the cellular context. Notably, Kirsten rat sarcoma (KRAS)-driven tumors have been reported to rely on macroautophagy for growth and survival, suggesting a potential therapeutic approach of using autophagy inhibitors based on genetic stratification. In this study, we evaluated whether KRAS mutation status can predict the efficacy to macroautophagy inhibition. By profiling 47 cell lines with pharmacological and genetic loss-of-function tools, we were unable to confirm that KRAS-driven tumor lines require macroautophagy for growth. Deletion of autophagy-related 7 (ATG7) by genome editing completely blocked macroautophagy in several tumor lines with oncogenic mutations in KRAS but did not inhibit cell proliferation in vitro or tumorigenesis in vivo. Furthermore, ATG7 knockout did not sensitize cells to irradiation or to several anticancer agents tested. Interestingly, ATG7-deficient and -proficient cells were equally sensitive to the antiproliferative effect of chloroquine, a lysosomotropic agent often used as a pharmacological tool to evaluate the response to macroautophagy inhibition. Moreover, both cell types manifested synergistic growth inhibition when treated with chloroquine plus the tyrosine kinase inhibitors erlotinib or sunitinib, suggesting that the antiproliferative effects of chloroquine are independent of its suppressive actions on autophagy.

The tumor microenvironment of cancers has emerged as a crucial component in regulating cancer stemness and plays a pivotal role in cell-cell communication. However, the specific mechanisms underlying these phenomena remain poorly understood. We performed the single-cell RNA sequencing (scRNA-seq) on nine HBV-associated hepatocellular carcinoma (HCC) patients. The heterogeneity of the malignant cells in pathway functions, transcription factors (TFs) regulation, overall survival, stemness, as well as ligand-receptor-based intercellular communication with macrophages were characterized. The aggressive and stemness feature for the target tumor subclone was validated by the conduction of assays including sphere formation, proliferation, Annexin V apoptosis, flow cytometry, siRNA library screening assays, and multiple preclinical mouse models including mouse hepatoma cell and human HCC cell xenograft models with subcutaneous or orthotopic injection. Our analysis yielded a comprehensive atlas of 31,664 cells, revealing a diverse array of malignant cell subpopulations. Notably, we identified a stemness-related subclone of HCC cells with concurrent upregulation of CD24, CD47, and ICAM1 expression that correlated with poorer overall survival. Functional characterization both and validated S100A11 as one of the top downstream mediators for tumor initiation and stemness maintenance of this subclone. Further investigation of cell-cell communication within the tumor microenvironment revealed a propensity for bi-directional crosstalk between this stemness-related subclone and tumor-associated macrophages (TAMs). Co-culture study showed that this interaction resulted in the maintenance of the expression of cancer stem cell markers and driving M2-like TAM polarization towards a pro-tumorigenic niche. We also consolidated an inverse relationship between the proportions of TAMs and tumor-infiltrating T cells. Our study highlighted the critical role of stemness-related cancer cell populations in driving an immunosuppressive tumor microenvironment and identified the S100A11 gene as a key mediator for stemness maintenance in HCC. Moreover, our study provides support that the maintenance of cancer stemness is more attributed to M2 polarization than the recruitment of the TAMs.