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Digital technologies can lead to the provision of innovative opportunities for academic entrepreneurship. However, investigations on the rationale for the adoption of digital technologies for academic entrepreneurship, particularly in emerging economies, remain limited. As a result, the determinants of digital technology adoption for academic entrepreneurship are not fully understood. Drawing on technology adoption and entrepreneurship literature, we propose a research model to investigate the adoption of social media -- a type of digital technology - for entrepreneurial activities among students in academic settings. Based on survey data collected from 312 participants, and a partial least square structural equation modeling technique for analysis, this study shows that computer self-efficacy and perceived enjoyment significantly influence perceived ease of use. In addition, perceived job relevance and perceived ease of use significantly influence perceived usefulness. Furthermore, perceived ease of use and students' perceived entrepreneurial feasibility significantly affect behavioral intention. Moreover, the study shows that behavioral intention significantly affects actual usage. Through these findings, our study advances knowledge on the antecedents of social media adoption for entrepreneurship in academic settings in emerging economies.

A youth mental health crisis has been exacerbated significantly by the COVID-19 pandemic. Teachers are often front-line support for students in need. Yet teachers themselves are struggling, making it difficult to help their students. Cognitive behavioral interventions (CBIs) have been shown to reduce mental health symptoms in school settings. Learning and implementing a psychological intervention, however, places undue burden on teachers who are already struggling. This project aimed to develop and assess the acceptability and feasibility of a brief, web-based training for educators on cognitive behavioral tools that can be implemented in classrooms without additional psychological or practical burden. Attendees (n = 193) attended one of two 1-h trainings on applying cognitive behavioural therapy (CBT) in classrooms. Attendees completed pre- and posttraining surveys on their knowledge and comfort using CBT. Following the course, attendees reported increases in knowledge and comfort using CBT skills, with large effect sizes. Attendees reported being highly satisfied with the course and likely to recommend the course to colleagues. Limitations of this work include a relatively small, homogenous sample and a low rate of completing both pre- and posttraining measures. Suggestions for future research include measuring change in practice as a result of the training. Implications of our findings are discussed.

BackgroundAlthough ~18 million people live within a mile from active oil and gas development (OGD) sites in the United States, epidemiological research on how OGD affects the health of nearby urban residents is sparse. Thousands of OGD sites are spread across Los Angeles (LA) County, California, home to the largest urban oil production in the country. Air pollution and noise from OGD may contribute to cardiovascular morbidity.ObjectiveWe examined the association between proximity to OGD and blood pressure in a diverse cohort of residents in LA.MethodsWe recruited residents in South LA who lived

The United Nations Human Rights Committee’s 2022 Decision, Daniel Billy et al. v. Australia (“Daniel Billy” or “the Decision”), brought by Indigenous Peoples residing on the Torres Strait Islands off the coast of Australia, is the first case before an international human rights body to find that a State’s failure to adopt timely climate adaptation measures violates the human rights of Indigenous Peoples living in that State. In Daniel Billy, the Human Rights Committee (“the Committee”) found a violation of the right to privacy, family, and home and the right to culture; but not the right to life. Drawing on the International Covenant on Civil and Political Rights (“the Covenant”), the United Nations Declaration of the Rights of Indigenous Peoples (UNDRIP), and recent developments in the field of climate change and international human rights law (IHRL), this Comment discusses the significance and the limitations of Daniel Billy regarding the protection of the rights of Indigenous Peoples and others affected by climate change. We find that the advancements made in Daniel Billy are a big step toward holding states accountable for inadequateclimate adaptation measures.In our analysis of the Decision’s shortcomings, however, we argue that Daniel Billy promises more than it delivers on two accounts. First, we argue that the failure of the Committee to clearly determine that states have a positive obligation to adopt climate change mitigation measures, in addition to adaptation measures is a significant limitation of the Decision. Without climate change mitigation, it will not be possible for Indigenous peoples on low-lyingi slands or in other climate-vulnerable locations to protect their land and way of life, the basis for several human rights. Further, climate change is perpetuated by industrialized states, but its effects are most keenly felt by communities, like that of the Torres Strait Islanders, who have contributed little to climate change. Neglecting to link states’ duty to mitigate climate change to human rights violations therefore ignores the colonial nature of climate change. Second, we argue that the Committee failed to consider the interconnectedness of the right to life with dignity in the context of climate change and Indigenous Peoples’ right to enjoy their culture when it rejected the Torres Strait Islanders’claim that Australia’s (in)action on climate change mitigation and adaptation violated the Islanders’ right to life with dignity. Notwithstanding these limitations, we conclude that the precedent set in Daniel Billy et a. v Australia will have a long-lasting positive impact in the fields of international environmental and human rights law.

BackgroundMetastatic prostate cancer (PC) is highly lethal. The ability to identify primary tumors capable of dissemination is an unmet need in the quest to understand lethal biology and improve patient outcomes. Previous studies have linked chromosomal instability (CIN), which generates aneuploidy following chromosomal missegregation during mitosis, to PC progression. Evidence of CIN includes broad copy number alterations (CNAs) spanning > 300 base pairs of DNA, which may also be measured via RNA expression signatures associated with CNA frequency. Signatures of CIN in metastatic PC, however, have not been interrogated or well defined. We examined a published 70-gene CIN signature (CIN70) in untreated and castration-resistant prostate cancer (CRPC) cohorts from The Cancer Genome Atlas (TCGA) and previously published reports. We also performed transcriptome and CNA analysis in a unique cohort of untreated primary tumors collected from diagnostic prostate needle biopsies (PNBX) of localized (M0) and metastatic (M1) cases to determine if CIN was linked to clinical stage and outcome.MethodsPNBX were collected from 99 patients treated in the VA Greater Los Angeles (GLA-VA) Healthcare System between 2000 and 2016. Total RNA was extracted from high-grade cancer areas in PNBX cores, followed by RNA sequencing and/or copy number analysis using OncoScan. Multivariate logistic regression analyses permitted calculation of odds ratios for CIN status (high versus low) in an expanded GLA-VA PNBX cohort (n = 121).ResultsThe CIN70 signature was significantly enriched in primary tumors and CRPC metastases from M1 PC cases. An intersection of gene signatures comprised of differentially expressed genes (DEGs) generated through comparison of M1 versus M0 PNBX and primary CRPC tumors versus metastases revealed a 157-gene "metastasis" signature that was further distilled to 7-genes (PC-CIN) regulating centrosomes, chromosomal segregation, and mitotic spindle assembly. High PC-CIN scores correlated with CRPC, PC-death and all-cause mortality in the expanded GLA-VA PNBX cohort. Interestingly, approximately 1/3 of M1 PNBX cases exhibited low CIN, illuminating differential pathways of lethal PC progression.ConclusionsMeasuring CIN in PNBX by transcriptome profiling is feasible, and the PC-CIN signature may identify patients with a high risk of lethal progression at the time of diagnosis.

We analyze the transcriptome of baseline and on-therapy tumor biopsies from 101 patients with advanced melanoma treated with nivolumab (anti-PD-1) alone or combined with ipilimumab (anti-CTLA-4). We find that T cell infiltration and interferon-γ (IFN-γ) signaling signatures correspond most highly with clinical response to therapy, with a reciprocal decrease in cell-cycle and WNT signaling pathways in responding biopsies. We model the interaction in 58 human cell lines, where IFN-γ in vitro exposure leads to a conserved transcriptome response unless cells have IFN-γ receptor alterations. This conserved IFN-γ transcriptome response in melanoma cells serves to amplify the antitumor immune response. Therefore, the magnitude of the antitumor T cell response and the corresponding downstream IFN-γ signaling are the main drivers of clinical response or resistance to immune checkpoint blockade therapy.

Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR = 0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR = 1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features.

Nonrhabdomyosarcoma soft-tissue sarcomas (STSs) are a class of 50+ cancers arising in muscle and soft tissues of children, adolescents, and adults. Rarity of each subtype often precludes subtype-specific preclinical research, leaving many STS patients with limited treatment options should frontline therapy be insufficient. When clinical options are exhausted, personalized therapy assignment approaches may help direct patient care. Here, we report the results of an adult female STS patient with relapsed undifferentiated pleomorphic sarcoma (UPS) who self-drove exploration of a wide array of personalized Clinical Laboratory Improvement Amendments (CLIAs) level and research-level diagnostics, including state of the art genomic, proteomic, ex vivo live cell chemosensitivity testing, a patient-derived xenograft model, and immunoscoring. Her therapeutic choices were also diverse, including neoadjuvant chemotherapy, radiation therapy, and surgeries. Adjuvant and recurrence strategies included off-label and natural medicines, several immunotherapies, and N-of-1 approaches. Identified treatment options, especially those validated during the in vivo study, were not introduced into the course of clinical treatment but did provide plausible treatment regimens based on FDA-approved clinical agents.

As the most abundant animals on earth, nematodes are a dominant component of the soil community. They play critical roles in regulating biogeochemical cycles and vegetation dynamics within and across landscapes and are an indicator of soil biological activity. Here, we present a comprehensive global dataset of soil nematode abundance and functional group composition. This dataset includes 6,825 georeferenced soil samples from all continents and biomes. For geospatial mapping purposes these samples are aggregated into 1,933 unique 1-km pixels, each of which is linked to 73 global environmental covariate data layers. Altogether, this dataset can help to gain insight into the spatial distribution patterns of soil nematode abundance and community composition, and the environmental drivers shaping these patterns.

This study sought to investigate the key factors that influence teenage reproductive and sexual behaviours and how these behaviours are likely to be influenced by parenting styles of primary caregivers of adolescents in Suhum, in Eastern Ghana. The study aimed to identify risky sexual and reproductive behaviours and their underlying factors among in-school and out-of-school adolescents and how parenting styles might play a role. While the data from the study provided a useful snapshot and a clear picture of sexual and reproductive behaviours of the teenagers surveyed, it did not point to any strong association between parental styles and teens' sexual reproductive behaviours.

To understand the genetic drivers of immune recognition and evasion in colorectal cancer, we analyzed 1,211 colorectal cancer primary tumor samples, including 179 classified as microsatellite instability-high (MSI-high). This set includes The Cancer Genome Atlas colorectal cancer cohort of 592 samples, completed and analyzed here. MSI-high, a hypermutated, immunogenic subtype of colorectal cancer, had a high rate of significantly mutated genes in important immune-modulating pathways and in the antigen presentation machinery, including biallelic losses of B2M and HLA genes due to copy-number alterations and copy-neutral loss of heterozygosity. WNT/β-catenin signaling genes were significantly mutated in all colorectal cancer subtypes, and activated WNT/β-catenin signaling was correlated with the absence of T-cell infiltration. This large-scale genomic analysis of colorectal cancer demonstrates that MSI-high cases frequently undergo an immunoediting process that provides them with genetic events allowing immune escape despite high mutational load and frequent lymphocytic infiltration and, furthermore, that colorectal cancer tumors have genetic and methylation events associated with activated WNT signaling and T-cell exclusion.Significance: This multi-omic analysis of 1,211 colorectal cancer primary tumors reveals that it should be possible to better monitor resistance in the 15% of cases that respond to immune blockade therapy and also to use WNT signaling inhibitors to reverse immune exclusion in the 85% of cases that currently do not. Cancer Discov; 8(6); 730-49. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 663.

Lack of tumor infiltration by immune cells is the main mechanism of primary resistance to programmed cell death protein 1 (PD-1) blockade therapies for cancer. It has been postulated that cancer cell-intrinsic mechanisms may actively exclude T cells from tumors, suggesting that the finding of actionable molecules that could be inhibited to increase T cell infiltration may synergize with checkpoint inhibitor immunotherapy. Here, we show that p21-activated kinase 4 (PAK4) is enriched in non-responding tumor biopsies with low T cell and dendritic cell infiltration. In mouse models, genetic deletion of PAK4 increased T cell infiltration and reversed resistance to PD-1 blockade in a CD8 T cell-dependent manner. Furthermore, combination of anti-PD-1 with the PAK4 inhibitor KPT-9274 improved anti-tumor response compared with anti-PD-1 alone. Therefore, high PAK4 expression is correlated with low T cell and dendritic cell infiltration and a lack of response to PD-1 blockade, which could be reversed with PAK4 inhibition.

BackgroundCancer patients with advanced disease routinely exhaust available clinical regimens and lack actionable genomic medicine results, leaving a large patient population without effective treatments options when their disease inevitably progresses. To address the unmet clinical need for evidence-based therapy assignment when standard clinical approaches have failed, we have developed a probabilistic computational modeling approach which integrates molecular sequencing data with functional assay data to develop patient-specific combination cancer treatments.MethodsTissue taken from a murine model of alveolar rhabdomyosarcoma was used to perform single agent drug screening and DNA/RNA sequencing experiments; results integrated via our computational modeling approach identified a synergistic personalized two-drug combination. Cells derived from the primary murine tumor were allografted into mouse models and used to validate the personalized two-drug combination. Computational modeling of single agent drug screening and RNA sequencing of multiple heterogenous sites from a single patient's epithelioid sarcoma identified a personalized two-drug combination effective across all tumor regions. The heterogeneity-consensus combination was validated in a xenograft model derived from the patient's primary tumor. Cell cultures derived from human and canine undifferentiated pleomorphic sarcoma were assayed by drug screen; computational modeling identified a resistance-abrogating two-drug combination common to both cell cultures. This combination was validated in vitro via a cell regrowth assay.ResultsOur computational modeling approach addresses three major challenges in personalized cancer therapy: synergistic drug combination predictions (validated in vitro and in vivo in a genetically engineered murine cancer model), identification of unifying therapeutic targets to overcome intra-tumor heterogeneity (validated in vivo in a human cancer xenograft), and mitigation of cancer cell resistance and rewiring mechanisms (validated in vitro in a human and canine cancer model).ConclusionsThese proof-of-concept studies support the use of an integrative functional approach to personalized combination therapy prediction for the population of high-risk cancer patients lacking viable clinical options and without actionable DNA sequencing-based therapy.

A significantly higher proportion of patients with nonalcoholic steatohepatitis (NASH) who received obeticholic acid (OCA) had histological improvement relative to placebo in the FLINT (farnesoid X nuclear receptor ligand obeticholic acid for noncirrhotic, NASH treatment) trial. However, genetic predictors of response to OCA are unknown. We conducted a genome-wide association study (GWAS) in FLINT participants to identify variants associated with NASH resolution and fibrosis improvement. Genotyping was performed using the Omni2.5 content GWAS chip. To avoid false positives introduced by population stratification, we focused our GWAS on white participants. Six regions on chromosomes 1, 4, 6, 7, 15, and 17 had multiple single nucleotide polymorphisms (SNPs) with suggestive association (P